Antiviral pyrazolopyridinone compounds

Abstract

To provide a method for treating a disease.SOLUTION: The invention provides compounds of Formula (I), along with pharmaceutically acceptable salts, pharmaceutical compositions containing such compounds, and methods to use these compounds, salts and compositions for treating viral infections, particularly infections caused by herpesviruses. The present invention relates to novel bicyclic pyrazolopyridione compounds that are inhibitors of herpesvirus replication, and are thus useful to treat herpesvirus infections. The compounds inhibit viral DNA polymerases of various herpesviruses, including cytomegalovirus (CMV), herpes simplex viruses, and others.SELECTED DRAWING: None

Description

[Technical Field]

[0001] (Related applications) This application claims priority to U.S. Provisional Patent Application No. 62 / 906,664, filed on 26 September 2019, the contents of which are incorporated herein by reference.

[0002] (Field of invention) This invention relates to novel bicyclic pyrazolopyridione compounds that are inhibitors of herpesvirus replication and are therefore useful for treating herpesvirus infections. These compounds inhibit the viral DNA polymerase of various herpesviruses, including cytomegalovirus (CMV) and herpes simplex virus. This invention provides novel bicyclic pyrazolopyridione compounds disclosed herein, pharmaceutical compositions containing such compounds, and methods of using these compounds and compositions in the treatment and prevention of herpesvirus diseases. [Background technology]

[0003] Human CMV, also known as human herpesvirus 5 (HHV-5), is a beta-herpesvirus that affects all populations worldwide, including adults and children with normal or impaired immune systems. While often asymptomatic in healthy individuals, CMV can be life-threatening in immunocompromised individuals. CMV is also a concern during pregnancy, as it can be transmitted from mother to fetus, causing severe birth defects. There are no approved treatments to prevent or treat congenital CMV infection. In transplant settings, current anti-CMV treatments include the nucleoside analogs valganciclovir (valGCV), ganciclovir (GCV), and cidofovir (CDV), as well as the pyrophosphate analog foscarnet (FOS). Each of the therapies inhibits CMV DNA polymerase, a protein encoded by the UL54 gene, which is an essential enzyme for viral replication (PNAS (2003) Vol. 100 No. 24 pp. 14223-14228; International Publication 2013 / 152063; International Publication 2005 / 012545). In solid organ transplant recipients, the first-line treatment consists of either prophylactic or preemptive treatment using GCV or the orally bioavailable prodrug valGCV. GCV is a risk factor for the disease. These drugs can significantly reduce the risk of developing CMV infections and effectively treat active CMV infections. However, the drugs are poorly tolerated. GCV and valGCV can cause severe myelosuppression in stem cell transplant recipients, leading to a risk of poor engraftment. Second-line therapies such as CDV and FOS are associated with severe nephrotoxicity. Furthermore, resistance to current anti-CMV nucleoside analogs is a significant cause of treatment failure. Therefore, a novel class of CMV therapeutic agents, particularly non-nucleoside compounds, is needed to provide safer CMV treatment and combat herpesviruses resistant to known classes of antiviral drugs.

[0004] In addition to CMV, other herpes viruses that cause widespread human viral infections include Epstein-Barr virus (EBV) and varicella-zoster virus. Examples include Varicella zoster virus (VZV), as well as herpes simplex viruses HSV-1 and HSV-2. Other herpesviruses that cause disease in humans include human herpesvirus 6, human herpesvirus 7, and Kaposi's sarcoma-associated herpesvirus. Herpesvirus infections are not only widespread, but they can also persist in the host for life during the incubation period. One estimate suggests that over 90% of adults have a latent infection with at least one herpesvirus that can reactivate years later. Shingles (herpes zoster) is one example. Shingles typically occurs when the varicella-zoster virus (VZV) reactivates from its incubation period, years after the original infection (chickenpox) has been suppressed. Shingles is a painful condition that primarily affects the elderly and immunocompromised individuals. A complication is postherpetic neuralgia, a potentially debilitating chronic pain syndrome that responds little to anti-VZV inhibitors (nucleosides). Immunocompromised individuals, such as transplant patients, are at high risk of herpesvirus reactivation, including CMV, HSV, or VZV. Therefore, safe and potent viral inhibitors with broad herpesvirus activity would be extremely beneficial. This invention provides novel compounds active against several herpesviruses, including CMV, HSV, VZV, and EBV. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] International Publication No. 2013 / 152063 [Patent Document 2] International Publication No. 2005 / 012545 [Non-patent literature]

[0006] [Non-Patent Document 1] PNAS (2003) Vol. 100 No. 24 No. 14223-14228 [Overview of the project] [Means for solving the problem]

[0007] The present invention provides novel non-nucleoside compounds that inhibit herpesvirus DNA polymerase, exhibiting potent antiviral activity in vitro. The compounds are active against several herpesviruses, including CMV, HSV, VZV, and EBV. Potent non-nucleoside polymerase inhibitors offer significant advantages over current anti-CMV agents. Firstly, unlike nucleoside analogs, the compounds are not incorporated by human polymerase and are therefore expected to have a better safety profile than current anti-CMV drugs. Secondly, the compounds described herein are active against GCV-resistant viruses and therefore have potential as salvage therapy in patients with cross-resistance to nucleoside analogs. Finally, the compounds are active against several human herpesviruses and offer opportunities for broad clinical use. The present invention also provides pharmaceutical compositions containing the novel compounds, as well as methods for using the compounds and compositions to inhibit herpesvirus replication or reactivation and treat disease conditions associated with or caused by herpesviruses. Further objects of the present invention are described in the following description and examples.

[0008] In one embodiment, the present invention provides a compound of formula (I), [ka] During the ceremony: X is [ka] 5-6 member heteroaryls, N, NH, NR having 1-4 heteroatoms independently selected from N, O, and S as ring members. 17 A 5-6 member heterocycloalkyl group containing 1-4 ring members independently selected from O, or S, or N, NH, NR 17 , a 5-6 member heterocycline containing 1-4 ring members independently selected from O or S; Y is a combination. [ka] and wherein Y's * represents a point of attachment to X, and Y's * * represents a point of attachment to R B ; q is 0 or 1; when q is 1, L MC is * -((CR 11 R 12 ) n O) m (CR 11 R 12 ) p - ** , * -C(=O)NR 15 ((CR 11 R 12 ) n O) m (CR 11 R 12 ) p - ** , * -(CR 11 R 12 ) n NR 15 ((CR 11 R 12 ) n O) m (CR 11 R 12 ) p -<00​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​- ** 、 * -C(=O)NR 15 (CR 11 R 12 ) n - ** 、 * -O(CR 11 R 12 ) n - ** 、又は * -NR 15 (CR 11 R 12 ) n - ** where L MC 's * indicates the attachment point to Z, and L MC 's ** indicates the attachment point to A; When q is 1, L MC exists, A is a bond, and Z is

Chemical formula

[0009] Another aspect of the present invention relates to the compound of the present invention, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable A pharmaceutical composition comprising a carrier to be encapsulated. In one embodiment of this aspect, the pharmaceutical composition according to the present invention further comprises a therapeutically effective amount of at least one other antiviral agent.

[0010] Another aspect of the present invention relates to a method for treating or preventing herpesvirus disease and / or infection in humans, comprising administering to a human being, either together or separately, an antiviral effective amount of the compound of the present invention, a pharmaceutically acceptable salt thereof, or the composition described above, either alone or in combination with at least one other antiviral agent.

[0011] Another aspect of the present invention relates to a method for treating or preventing herpesvirus disease and / or infection in humans, comprising administering to a human being, either together or separately, a compound of the present invention, a pharmaceutically acceptable salt thereof, or the composition described above, either alone or in combination with at least one other antiviral agent.

[0012] A further aspect of the present invention relates to a method for inhibiting the replication of CMV or another herpesvirus, comprising exposing the virus to an effective amount of the compound of the present invention or a pharmaceutically acceptable salt thereof under conditions that inhibit viral replication. This method can be carried out in vitro or in vivo.

[0013] Another aspect of the present invention is the use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical for the treatment or prevention of herpesvirus diseases and / or infections in humans, including CMV.

[0014] Another embodiment of the present invention provides, as a pharmaceutical product, the above-mentioned compound or a pharmaceutically acceptable salt thereof.

[0015] Another aspect of the present invention is the use of the above-described pharmaceutical composition for the treatment of CMV infection or other herpesviruses in a person who has CMV infection or is at risk of CMV infection.

[0016] Another aspect of the present invention is the use of the above-described pharmaceutical composition for the treatment of CMV disease or other herpesvirus infections in humans who have CMV disease or are at risk of developing CMV disease.

[0017] Another aspect of the present invention relates to a method for treating a viral disease and / or infection in a human, comprising administering to a human, alone or in combination with at least one other antiviral agent, an antiviral effective amount of the compound of the present invention, a pharmaceutically acceptable salt thereof, or the composition described above, either together or separately, wherein the viral disease or infection is CMV infection, congenital CMV, genital herpes, oral herpes (cold sores), herpetic keratitis, neonatal herpes, herpetic encephalitis, varicella (chickenpox), herpes zoster (shingles), infectious mononucleosis, post-transplant lymphoproliferative disease (P) in immunocompromised patients (e.g., transplant recipients). The method involves selecting from TLD, Castelman's disease, and hemophagocytic lymphohistiocytosis.

[0018] Another aspect of the present invention is a method for treating disorders that may be induced / exacerbated / promoted by herpesvirus infection in humans, comprising administering to a human being, alone or in combination with at least one other antiviral agent, an effective amount of the compound of the present invention, a pharmaceutically acceptable salt thereof, or the above composition, either together or separately, wherein the disorder is Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (SLE) The procedure involves selecting from the following conditions: sis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes.

[0019] Another aspect of the present invention is a method for treating disorders that may be induced / exacerbated / promoted by herpesvirus infection in humans, comprising administering to a human being, alone or in combination with at least one other antiviral agent, an effective amount of the compound of the present invention, a pharmaceutically acceptable salt thereof, or the above composition, either together or separately, wherein the disorder is one of Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), atherosclerosis (AS), celiac disease, and type 1 diabetes. To be selected, with a method.

[0020] Another aspect of the present invention is the use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical product for treating or preventing a disorder that may be induced / exacerbated / promoted by a herpesvirus infection, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes.

[0021] Another aspect of the present invention is the use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical product for treating or preventing a disorder that may be induced / exacerbated / promoted by a herpesvirus infection, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), atherosclerosis (AS), celiac disease, and type 1 diabetes.

[0022] Another aspect of the present invention is the use of the pharmaceutical compositions described herein for the treatment of viral diseases and / or infections in humans, wherein the viral disease or infection is selected from CMV infection, congenital CMV, genital herpes, oral herpes (herpes simplex), herpetic keratitis, neonatal herpes, herpes encephalitis, varicella (chickenpox), herpes zoster (herpes zoster), infectious mononucleosis, post-transplant lymphoproliferative disorder (PTLD), Castelman's disease, and hemophagocytic lymphohistiocytosis in immunocompromised patients (e.g., transplant recipients).

[0023] Another aspect of the present invention is the use of the pharmaceutical compositions described herein for the treatment of disorders that may be induced / exacerbated / promoted by herpesvirus infection, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes.

[0024] Another aspect of the present invention is the use of the pharmaceutical compositions described herein for the treatment of disorders that may be induced / exacerbated / promoted by herpesvirus infection, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), atherosclerosis (AS), celiac disease, and type 1 diabetes. [Modes for carrying out the invention]

[0025] Various listed embodiments of the present invention are described herein. It will be recognized that certain features may be combined with other specific features to provide further embodiments of the present invention. definition

[0026] For the purposes of interpreting this specification, the following definitions apply, and wherever used in the singular, the plural form is also included. Terms used herein have the following meanings unless the context clearly indicates otherwise.

[0027] As used herein, the term "alkyl" refers to a fully saturated branched or straight-chain hydrocarbon. In certain embodiments, alkyl groups include "C1-C2 alkyl," "C1-C3 alkyl," "C1-C4 alkyl," "C1-C5 alkyl," "C1-C6 alkyl," "C1-C7 alkyl," "C1-C8 alkyl," "C1-C9 alkyl," or "C1-C 10 Alkyl, where the terms "C1-C2 alkyl", "C1-C3 alkyl", "C1-C4 alkyl", "C1-C5 alkyl", "C1-C6 alkyl", "C1-C7 alkyl", "C1-C8 alkyl", "C1-C9 alkyl", and "C1-C 10As used herein, "alkyl" refers to an alkyl group containing at least one and up to two, three, four, five, six, seven, eight, nine, or ten carbon atoms. Non-limiting examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n-heptyl, n-octyl, n-nonyl, and n-decyl.

[0028] As used herein, the term “alkoxy” refers to an -O-alkyl or -alkyl-O- group, where the “alkyl” group is as defined herein. In certain embodiments, the alkoxy group may be a “C1-C2 alkoxy”, a “C1-C3 alkoxy”, a “C1-C4 alkoxy”, a “C1-C5 alkoxy”, a “C1-C6 alkoxy”, a “C1-C7 alkoxy”, a “C1-C8 alkoxy”, a “C1-C9 alkoxy”, or a “C1-C 10 Alkoxy is the term "C1-C2 alkoxy", and here the terms "C1-C2 alkoxy", "C1-C3 alkoxy", "C1-C4 alkoxy", "C1-C5 alkoxy", "C1-C6 alkoxy", "C1-C7 alkoxy", "C1-C8 alkoxy", "C1-C9 alkoxy", and "C1-C 10 As used herein, "alkoxy" refers to -O-C1~C2 alkyl, -O-C1~C3 alkyl, -O-C1~C4 alkyl, -O-C1~C5 alkyl, -O-C1~C6 alkyl, -O-C1~C7 alkyl, -O-C1~C8 alkyl, -O-C1~C9 alkyl, or -O~C1~C 10 This refers to alkyl groups. Non-exclusive examples of "alkoxy" groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, hexoxy, heptoxy, octoxy, nonoxy, and decoxy.

[0029] When used herein, the term "alkylene" refers to a saturated branched or linear divalent hydrocarbon group derived from an alkyl group as defined herein. In certain embodiments, the alkylene group may be "C1-C3 alkylene", "C1-C4 alkylene", "C1-C5 alkylene", "C1-C6 alkylene", "C1-C7 alkylene", "C1-C8 alkylene", "C1-C9 alkylene", or "C1-C 10 "Alkylene," where the terms "C1-C3 alkylene," "C1-C4 alkylene," "C1-C5 alkylene," "C1-C6 alkylene," "C1-C7 alkylene," and "C1-C8 alkylene," as used herein, refer to an alkylene group containing at least one and up to three, four, five, six, seven, eight, nine, or ten carbon atoms, respectively. Non-limiting examples of alkylene groups as used herein include methylene, ethylene, n-propyl Examples include pyrene, isopropylene, n-butylene, isobutylene, sec-butylene, t-butylene, n-pentylene, isopentylene, hexylene, heptylene, octylene, nonylene, and decylene.

[0030] In certain embodiments, the alkylene group is "C1-C2 alkylene," which refers to an alkylene group containing at least one and up to two carbon atoms.

[0031] As used herein, the term "C3-C8 cycloalkyl" refers to a fully saturated monocyclic hydrocarbon ring system having 3 to 8 carbon atoms as ring members. Non-limiting examples of such "C3-C8 cycloalkyl" groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups.

[0032] As used herein, the term "C3-C6 cycloalkyl" refers to a fully saturated monocyclic hydrocarbon ring system having 3 to 6 carbon atoms as ring members. Non-limiting examples of such "C3-C8 cycloalkyl" groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups.

[0033] As used herein, the term "C5-C8 cycloalkyl" refers to a fully saturated monocyclic hydrocarbon ring system having 5 to 8 carbon atoms as ring members. Non-limiting examples of such "C5-C8 cycloalkyl" groups include cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups.

[0034] The term "haloalkyl," as used herein, refers to an alkyl group as defined herein, wherein at least one hydrogen atom of the alkyl group is replaced by a halo group as defined herein. A haloalkyl group may be a monohaloalkyl group, a dihaloalkyl group, a trihaloalkyl group, or a polyhaloalkyl group comprising a perhaloalkyl group. A monohaloalkyl group may have one iodo, bromo, chloro, or fluoro group within the alkyl group. A dihaloalkyl group may have two polyhaloalkyl groups, each containing two or more identical halo atoms or combinations of different halo groups within the alkyl group. Typically, a polyhaloalkyl group contains up to six, or four, or three, or two halo groups. Non-limiting examples of haloalkyl groups include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, and dichloropropyl. Perhaloalkyls refer to alkyl groups in which all hydrogen atoms are replaced by halo atoms, such as trifluoromethyl. Typical haloalkyl groups, unless otherwise specified, include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, and tert-butyl, which have at least one hydrogen atom substituted with a halogen. For example, when the halogen is fluorine, these include F3CF2-, (CF3)2CH-, CH3-CF2-, CF3CF2-, CF3, CF2H-, CF3CF2CH(CF3)-, or CF3CF2CF2CF2-.

[0035] When used herein, the term "C1-C3 haloalkyl" refers to the corresponding "C1-C3" as defined herein, wherein at least one of the hydrogen atoms of the "C1-C3 alkyl" is replaced by a halo atom. A C1-C3 haloalkyl can be a mono-C1-C3 haloalkyl, where such a C1-C3 haloalkyl has one iodine, one bromo, one chloro, or one fluoro. In addition, a C1-C3 haloalkyl can be a di-C1-C3 haloalkyl, where such a C1-C3 haloalkyl may have two halo atoms independently selected from iodine, bromo, chloro, or fluoro. Furthermore, a C1-C3 haloalkyl can be a poly-C1-C3 haloalkyl, where such a C1-C3 haloalkyl has the same A polyC1-C3 haloalkyl group may have two or more dihalo atoms or combinations of two or more different halo atoms. Such a polyC1-C3 haloalkyl group may be a perhaloC1-C3 haloalkyl group, in which all hydrogen atoms of each C1-C3 alkyl group are replaced by halo atoms, and these halo atoms may be the same or a combination of different halo atoms. Non-limiting examples of the "C1-C3 haloalkyl" group include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, difluoropropyl, dichloroethyl, and dichloropropyl.

[0036] The term "haloalkoxy," as used herein, refers to an -O-alkyl group, where the "alkyl" group is as defined herein, provided that at least one hydrogen atom of the alkyl group is replaced by a halo group as defined herein to become "haloalkyl." Haloalkoxys can be polyhaloalkoxys, including monohaloalkoxys, dihaloalkoxys, trihaloalkoxys, or perhaloalkoxys. Monohaloalkoxys may have one iodo, bromo, chloro, or fluoro group within the alkyl group. Dihaloalkoxys may have two polyhaloalkoxy groups, each having two or more identical halo atoms or combinations of different halo groups within the alkyl group. Typically, polyhaloalkoxys contain up to six, or four, or three, or two halo groups. Non-limiting examples of haloalkoxys include fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy, trichloromethoxy, pentafluoroethoxy, heptafluoropropoxy, difluorochloromethoxy, dichlorofluoromethoxy, difluoroethoxy, difluoropropoxy, dichloroethoxy, and dichloropropoxy. Perhaloalkoxys refer to alkoxys in which all hydrogen atoms are replaced by halo atoms, such as trifluoromethoxy. Typical haloalkoxy groups, unless otherwise specified, include monofluoro, difluoro, and trifluoro-substituted methoxy and ethoxy groups, such as -OCF3, -OCHF2, -OCH2F, -OCH2CHF2, and -OCH2CF3.

[0037] The term "C1-C4 haloalkoxy," as used herein, refers to an -O-C1-C4 alkyl group, where the "alkyl" group is as defined herein, except that at least one hydrogen atom of the "C1-C4 alkyl" is replaced by a halo atom as defined herein to become "haloalkyl." A C1-C4 haloalkoxy group can be a mono-C1-C4 haloalkoxy, such a C1-C4 haloalkoxy group having one iodine, one bromo, one chloro, or one fluoro. In addition, a C1-C4 haloalkoxy group can be a di-C1-C4 haloalkoxy, such a C1-C4 haloalkoxy group may have two halo atoms independently selected from iodine, bromo, chloro, or fluoro. Furthermore, the C1-C4 haloalkoxy group may be a poly-C1-C4 haloalkoxy, where such a C1-C4 haloalkoxy group may have two or more of the same halo atom or a combination of two or more different halo atoms. Such a poly-C1-C4 haloalkoxy may be a perhalo-C1-C4 alkoxy, where all hydrogen atoms of each C1-C4 alkoxy are replaced by halo atoms, which may be a combination of the same or different halo atoms. Non-limiting examples of the "C1-C4 haloalkoxy" group include fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy, trichloromethoxy, pentafluoroethoxy, heptafluoropropoxy, difluorochloromethoxy, dichlorofluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, difluoroethoxy, difluoropropoxy, dichloroethoxy, and dichloropropoxy.

[0038] As used herein, the terms "halo" or "halogen" refer to fluoro(F), chloro(Cl), bromo(Br), or iodine(I).

[0039] The term "heteroaryl" as used herein means (i) A 5-6 membered heteroaryl having 1-4 heteroatoms independently selected from heteroatoms N, O, and S as ring members, which refers to an aromatic 5-6 membered monocyclic ring system having 1-4 heteroatoms independently selected from heteroatoms N, O, and S as ring members, but the heteroaryl ring often contains one or less divalent O or S in the ring, (ii) A 5-6 membered heteroaryl having 1-3 heteroatoms independently selected from heteroatoms N, O, and S as ring members, which refers to an aromatic 5-6 membered monocyclic ring system having 1-3 heteroatoms independently selected from heteroatoms N, O, and S as ring members, (iii) A 5-6 membered heteroaryl having 1-2 heteroatoms independently selected from heteroatoms N, O, and S as ring members, which refers to an aromatic 5-6 membered monocyclic ring system having 1-2 heteroatoms independently selected from heteroatoms N, O, and S as ring members, (iv) A five-membered heteroaryl having 1 to 4 heteroatoms independently selected from heteroatoms N, O, and S as ring members, which refers to an aromatic five-membered monocyclic ring system having 1 to 4 heteroatoms independently selected from heteroatoms N, O, and S as ring members, (v) A six-membered heteroaryl having 1 to 4 heteroatoms independently selected from heteroatoms N, O, and S as ring members, which refers to an aromatic six-membered monocyclic ring system having 1 to 4 heteroatoms independently selected from heteroatoms N, O, and S as ring members, (vi) A 5-6 member heteroaryl having 1-4 nitrogen atoms as ring members, which refers to an aromatic 5-6 member monocyclic ring system having 1-4 nitrogen atoms as ring members, (vii) A 9-10 membered bicyclic heteroaryl having 1-2 heteroatoms independently selected from heteroatoms N, O, and S as ring members, which refers to an aromatic condensed 9-10 membered bicyclic ring system having 1-2 heteroatoms independently selected from heteroatoms N, O, and S as ring members, 9-10 membered bicyclic heteroaryl, and (viii) A 9-10 membered bicyclic heteroaryl having 1-3 heteroatoms independently selected from heteroatoms N, O, and S as ring members, which refers to an aromatic condensed 9-10 membered bicyclic ring system having 1-3 heteroatoms independently selected from heteroatoms N, O, and S as ring members.

[0040] As used herein, non-limiting examples of heteroaryl groups include benzofuranyl, benzo[c]thiophenyl, benzothiophenyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, cinnolinyl, flazanyl, furyl, imidazolyl, indolyl, indollidinyl, indazolyl, isoindolyl, isoquinolinyl, isoxazolyl, isothiazolyl, oxazolyl, oxaindolyl, oxadiazolyl, pyrazolyl, pyrrolyl, phthalazinyl, pyridyl, pyridazinyl, pyridinyl, pyrimidinyl, quinoxalinyl, quinolinyl, quinazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thienyl, triazinyl, and triazolyl.

[0041] The terms "heteroatoms" or "hetero atoms" as used herein refer to nitrogen (N), oxygen (O), or sulfur (S) atoms.

[0042] The term "heterocycloalkyl" as used herein refers to N, NH, NR 17 This refers to a cycloalkyl group as defined herein, having 1 to 2 carbon atoms in a ring structure that is replaced by 1 to 2 groups independently selected from , O, or -S-, where R 17 These are H, C1-C6 alkyl, or C3-C8 cycloalkyl. In particular, heterocycloalkyl is (i) N, NH, NR 17This refers to a 4-6 membered heterocycloalkyl having 1-2 ring members independently selected from N, O, or -S-, and having a fully saturated monocyclic hydrocarbon ring structure with 4-6 ring members, where 1-2 of the ring members are N, NH, NR 17 Selected independently from O, or -S-, R 17 This is a 4-6 member heterocycloalkyl group, which is H, C1-C6 alkyl, or C3-C8 cycloalkyl. (ii) N, NH, NR 17 This refers to a 5-6 membered heterocycloalkyl having 1-2 ring members independently selected from N, O, or -S-, and having a fully saturated monocyclic hydrocarbon ring structure with 5-6 ring members, where 1-2 of the ring members are N, NH, NR 17 Selected independently from O, or -S-, R 17 This is a 5-6 member heterocycloalkyl group, which is H, C1-C6 alkyl, or C3-C8 cycloalkyl. and (iii) N, NH, NR 17 This refers to an 8-10 member heterocycloalkyl having 1-2 ring members independently selected from N, O, or -S-, and having a fully saturated condensed bicyclic ring structure with 8-10 ring members, where 1-2 of the ring members are N, NH, NR 17 Selected independently from O, or -S-, R 17 This can be an 8-10 member heterocycloalkyl group, which is a C1-C6 alkyl group or a C3-C8 cycloalkyl group.

[0043] Non-limiting examples of heterocycloalkyl groups, as used herein, include azetidinyl, azetazin-1-yl, azetazin-2-yl, azetazin-3-yl, oxetanyl, oxetan-2-yl, oxetan-3-yl, oxetan-4-yl, thietanyl, thietan-2-yl, thietan-3-yl, thietan-4-yl, pyrrolidinyl, pyrrolidine-1-yl, pyrrolidine-2-yl, pyrrolidine-3-yl, pyrrolidine-4-yl, pyrrolidine-5-yl, tetrahydrofuranyl, tetrahydrofuran-2-yl, and tetrahydrofuranyl. -3-yl, tetrahydrofuran-4-yl, tetrahydrofuran-5-yl, tetrahydrothienyl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, tetrahydrothien-4-yl, tetrahydrothien-5-yl, piperidinyl, piperidine-1-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, piperidine-5-yl, piperidine-6-yl, tetrahydropyranyl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydropyran-5-yl Tetrahydropyran-6-yl, tetrahydrothiopyranil, tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl, tetrahydrothiopyran-6-yl, piperazinyl, piperazine-1-yl, piperazine-2-yl, piperazine-3-yl, piperazine-4-yl, piperazine-5-yl, piperazine-6-yl, morpholinyl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-5-yl, morpholin-6-yl, thio Omorpholinyl, thiomorpholin-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl, thiomorpholin-5-yl, thiomorpholin-6-yl, oxatianyl, oxatian-2-yl, oxatian-3-yl, oxatian-5-yl, oxatian-6-yl, dithianyl, dithian-2-yl, dithian-3-yl, dithian-5-yl, dithian-6-yl, dioxolanil, dioxolan-2-yl, dioxolan-4-yl, dioxolan-5-yl, thioxanyl, thioxan-2-yl, thioxan-3-yl, thio Examples include xan-4-yl, thioxan-5-yl, dithiolanyl, dithiolan-2-yl, dithiolan-4-yl, dithiolan-5-yl, pyrazolidinyl, pyrazolidine-1-yl, pyrazolidine-2-yl, pyrazolidine-3-yl, pyrazolidine-4-yl, pyrazolidine-5-yl, 2-azabicyclo[4.2.0]octanyl, octahydro-1H-cyclopenta[b]pyridine, and decahydroquinoline.

[0044] The terms "hydroxy" or "hydroxyl" refer to the -OH group.

[0045] As used herein, the term "oxo" refers to the "=O" group.

[0046] The term "heterocyclyl" is used herein with respect to N, NH, and NR. 36 This refers to a 4-14 member saturated or partially saturated hydrocarbon ring structure having 1-7, 1-5, 1-3, or 1-2 ring members independently selected from O, or S, where R 36 These are C1-C6 alkyl or C3-C8 cycloalkyl groups. The term "heterocyclyl" includes monocyclic, bicyclic, fused, spirocyclic, and bridging ring groups. Heterocyclic groups can be bonded to another group at nitrogen or carbon atoms. In particular, heterocyclyls are (i) N, NH, NR 17 A 4-6 member heterocycline containing 1-2 ring members independently selected from O, or S, wherein R 17 However, H, C1-C6 alkyl, or C3-C8 cycloalkyl, 4-6 membered heterocycline, (ii) N, NH, NR 17 A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, wherein R 17 However, H, C1-C6 alkyl, or C3-C8 cycloalkyl, 4-7 membered heterocycline, (iii) N, NH, NR 17A 5-6 member heterocycline containing 1-4 ring members independently selected from O, or S, wherein R 17 However, H, C1-C6 alkyl, or C3-C8 cycloalkyl, 5-6 membered heterocycline, (iv) N, NH, NR 17 A 5-6 member heterocycline containing 1-2 ring members independently selected from O, or S, wherein R 17 However, it is a 5-6 member heterocycline which is H, C1-C6 alkyl, or C3-C8 cycloalkyl, (v)N, NH, NR 17 An 8-10 member condensed bicyclic heterocycline containing 1-3 ring members independently selected from O, or S, wherein R 17 However, the 8-10 membered condensed bicyclic heterocycline is H, C1-C6 alkyl, or C3-C8 cycloalkyl. and (vi)N, NH, NR 17 An 8-10 member condensed tricyclic heterocycline containing 1-4 ring members independently selected from O, or S, wherein R 17 However, it may be an 8-10 membered condensed tricyclic heterocycline, which is H, C1-C6 alkyl, or C3-C8 cycloalkyl.

[0047] Non-limiting examples of heterocycloalkyl groups, as used herein, include dihydrobenzofuranyl, dihydrobenzo[c]thiophenyl, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrobenzothiazolyl, dihydrobenzimidazolyl, dihydrosinnolinyl, dihydroflazanyl, dihydrofuryl, dihydroimidazolyl, dihydroindolyl, dihydroindolidinyl, dihydroindazolyl, dihydroisoindolyl, dihydroisoquinolinyl, dihydroisoxazolyl, dihydroisothiazolyl, dihydrooxazolyl, and dihydrooxa Indolyl, dihydrooxadiazolyl, dihydropyrazolyl, dihydropyrrolyl, dihydrophthalazinyl, dihydropyridazinyl, dihydropyridazinyl, dihydropyrimidinyl, dihydroquinoxalinyl, dihydroquinolinyl, dihydroquinazolinyl, dihydrotetrazolyl, dihydrothiazolyl, dihydrothiadiazolyl, dihydrothienyl, dihydrotriazinyl, dihydrotriazolyl, tetrahydrobenzofuranyl, tetrahydrobenzo[c]thiophenyl, tetrahydrobenzothiophenyl, tetrahydrobenzooxazolyl, tetrahydroben Zothiazolyl, tetrahydrobenzimidazolyl, tetrahydrosinnolinyl, tetrahydroindyl, tetrahydroindazolyl, tetrahydroisoindyl, tetrahydroisoquinolinyl, tetrahydrooxaindyl, tetrahydrophthalazinyl, tetrahydropyridyl, tetrahydropyridazinyl, tetrahydropyridinyl, tetrahydropyrimidinyl, tetrahydroquinoxalinyl, tetrahydroquinolinyl, tetrahydroquinazolinyl, tetrahydrotriazinyl, hexahydrobenzofuranyl, hexahydrobenzo[c]thiophenyl, hexahydrobenzothiophenyl, Examples include hexahydrobenzoxazolyl, hexahydrobenzothiazolyl, hexahydrobenzimidazolyl, hexahydrosinnolinyl, hexahydroindolyl, hexahydroindazolyl, hexahydroisoindolyl, hexahydroisoquinolinyl, hexahydrooxaindolyl, hexahydrophthalazinyl, hexahydroquinoxalinyl, hexahydroquinolinyl, hexahydroquinazolyl, octahydrosinnolinyl, octahydroisoquinolinyl, octahydrophthalazinyl, octahydroquinoxalinyl, octahydroquinolinyl, and octahydroquinazolyl.

[0048] As used herein, the term “subject” refers to an animal. In certain embodiments, an animal is a mammal. A subject can also refer to, for example, primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, mice, fish, and birds. In certain embodiments, a subject is a human. As used herein, “patient” refers to a human subject.

[0049] As used herein, the term "linker" refers to a divalent chemical moiety that can covalently bond together two separated chemical moieties.

[0050] As used herein, the terms “inhibit” or “to inhibit” mean the reduction or suppression of a given condition, symptom, disorder, or disease, or a decrease in the baseline activity of a biological activity or process.

[0051] The terms "optical isomer" or "stereoisomer" refer to any of the various stereoisomer configurations that may exist for a given compound of the present invention, including geometric isomers. Substituents are understood to be bonded to the chiral center of a carbon atom. The term "chiral" refers to a molecule that possesses non-superimposability relative to its enantiomer partner. On the other hand, the term "achiral" refers to molecules that can be superimposed on their enantiomer partners. Therefore, the present invention includes enantiomers, diastereomers, or racemates of compounds. An "enantiomer" is a pair of stereoisomers that are mirror images of each other and cannot be superimposed. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. This term is used as appropriate to refer to a racemic mixture. A "diastereoisomer" is a stereoisomer that has at least two chiral atoms but is not a mirror image of each other. Absolute stereochemistry is specified according to the Kahn-Ingold-Prelogue RS system. If a compound is a pure enantiomer, the stereochemistry at each chiral carbon may be specified by either R or S. A split compound whose absolute configuration is unknown may be designated (+) or (-) depending on the direction in which it rotates plane polarization at the wavelength of the sodium D line (dextrorotatory or levorotatory). Certain compounds described herein contain one or more chiral centers or axes and may therefore give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined as (R)- or (S)- with respect to absolute stereochemistry.

[0052] As used herein, the terms “to treat” or “to cure” any disease or disorder mean, in one embodiment, to improve the disease or disorder (i.e., to delay, halt, or reduce the progression of the disease or at least one of its clinical symptoms). In some embodiments, “to treat” or “treatment” means to alleviate or improve at least one physical parameter, including one that may not be recognizable by the patient. In yet another embodiment, “to treat” or “treatment” means to modulate a disease or disorder, either physically (e.g., stabilization of recognizable symptoms), physiologically (e.g., stabilization of physical parameters), or both. In yet another embodiment, “to treat” or “treatment” means to prevent or delay the onset, development, or progression of a disease or disorder.

[0053] The compound names provided herein were obtained using ChemDraw Ultra version 12.0 (CambridgeSoft®) or JChem version 5.3.1 (ChemAxon).

[0054] All methods described herein may be carried out in any preferred order, unless otherwise specified herein or unless the context clearly contradicts it. The use of any and all examples or exemplary phrases (e.g., "etc.") provided herein is intended solely to further illustrate the invention and not to limit the scope of the claimed invention.

[0055] "Arbitrarily substituted" means that the group mentioned can be substituted at one or more positions by any one or any combination of the groups listed thereafter. The number, arrangement, and selection of substituents are understood to include only those substitutions that a professional chemist would reasonably expect to be stable, and therefore "oxo" means, for example, a single carbon atom that is not a substituent on an aryl or heteroaryl ring will not have three hydroxyl or amino substituents.

[0056] The group can be substituted at the same position that links the rest of the defined molecule. For example, the group may be substituted with cyclopropyl, which may then be substituted with another group at the same carbon that links it to the rest of the molecule.

[0057] Unless otherwise specified, the terms "compounds of the present invention," "compounds of the invention," or "provided herein" are used. The term "compounds provided herein" refers to compounds of formula (I), formula (II), This refers to compounds of formulas (IIa), (IIb), (IIIa), (IIIb), (IIIc), (IVa), (IVb), (IVc), (IVd), (Va), (Vb), (Vc), (VI), (VII), and (VIII), as well as pharmaceutically acceptable salts, stereoisomers (including diastereoisomers and enantiomers), rotational isomers, tautomers, and isotope-labeled compounds (including deuterium substitutions), and essentially formed moieties.

[0058] When used herein, “a,” “an,” “the,” and similar terms (especially in the context of the claims) should be construed to encompass both singular and plural forms unless otherwise specified herein or unless the context clearly contradicts this.

[0059] All methods described herein may be carried out in any preferred order, unless otherwise specified herein or unless the context clearly contradicts it. The use of any and all examples or exemplary phrases (e.g., "etc.") provided herein is intended solely to further illustrate the invention and not to limit the scope of the claimed invention. Compound of the present invention

[0060] The present invention provides a compound having the structure of formula (I), or a pharmaceutically acceptable salt thereof. [ka] During the ceremony: X is [ka] 5-6 member heteroaryls, N, NH, NR having 1-4 heteroatoms independently selected from N, O, and S as ring members. 17 A 5-6 member heterocycloalkyl group containing 1-4 ring members independently selected from O, or S, or N, NH, NR 17 , a 5-6 member heterocycline containing 1-4 ring members independently selected from O or S; Y is a combination. [ka] And in the formula, Y * This indicates the connection point to X, and Y ** That is, R B Show the connection point to; q is either 0 or 1; If q is 1, L MC teeth, * -((CR 11 R 12 ) n O) m (CR 11 R 12 ) p - ** , * -C(=O)NR 15 (CR 11 R 12 ) n O) m (CR 11 R 12 ) p - ** , * -(CR 11 R 12 ) n NR 15 (CR 11 R 12 ) n O) m (CR 11 R 12 ) p - ** , * -(CR 11 R 12 ) n -** , * -((CR 11 R 12 ) n NR 15 ) m (CR 11 R 12 ) p - ** , * -(CR 11 R 12 )C(=O)NR 15 (CR 11 R 12 ) n - ** , * -C(=O)NR 15 (CR 11 R 12 ) n - ** , * -O(CR 11 R 12 ) n - ** , or * -NR 15 (CR 11 R 12 ) n - ** And here, L MC of * This indicates a connection point to Z, and L MC of ** This indicates the connection point to A; If q is 1, L MC It exists, A is a combination, and Z is [ka] And in the formula, Z * This indicates the connection point to the LMC, and Z ** This indicates the connection point to L; m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; Each n is independently selected from 1, 2, 3, 4, 5, 7, 8, 9, and 10; p is 1, 2, 3, 4, 5, or 6; If q is 0, L MC It does not exist, Z is W, and A is R4 and; R B R is H, C1-C6 alkyl, phenyl, pyridinyl, thiophenyl, pyrimidinyl, or 5-8 membered cycloalkyl, where R B This is 1 to 3 R 5 It can be arbitrarily substituted in the base; R 1 H, C 1~ C3 alkyl and C substituted with 1-3 -OH groups 1~ Selected from C3 alkyl groups; R 2 H, C 1~ C3 alkyl and C substituted with 1-3 -OH groups 1~ Selected from C3 alkyl groups; Or, R 1 and R 2 These can, together with the carbon atoms to which they are bonded, form a 3- to 6-membered cycloalkyl ring; t is 0, 1, or 2; Each R 3 If present, -LZ is a substituent on the ring to which it is directly bonded, where each R 3 , Haro, CN, C 1~ C3 alkoxy, C 1~ C3alkyl, C(=O)OR 10 , and C(=O)NR 13 R 14 Selected independently of; R 4 H, C 1~ C3 alkyl, C 3~ C6 cycloalkyl, -(CH2)2O(CH2)2Br, or -OH, -C(=O)R 15 , and R 10 C substituted with 1-2 groups independently selected from 1~ It is a C3 alkyl group; Each R 5 These are halo, -CN, hydroxy, and -NR. 13 R 14 , C 3~ C6 cycloalkyl, C 1~ C3 alkoxy, C 1~ C3 haloalkyl and 1-3 R 6C arbitrarily substituted in R 1~ Independently selected from C3 alkyl groups, where R B This is two R 5 Replaced by each R 5 This is 1 to 3 R 6 A C arbitrarily substituted in the base 1~ It is a C3 alkyl group, and when directly bonded to the same carbon atom, both atoms together form 1 to 3 R atoms. 6 It can form a 3- to 5-membered cycloalkyl ring optionally substituted with a group; Each R 6 is halo, hydroxy, CN, C 1~ C3 alkoxy, C 1~ C3 alkyl, and C 3~ Independently selected from C5 cycloalkyl groups, Alternatively, two R 6 The group contains O, N, or S as ring members, together with the carbon atoms to which both are directly bonded, and is oxo and C 1~ They can form a 3- to 5-membered cycloalkyl ring or a 4- to 6-membered heterocycle, optionally substituted with 1-2 groups independently selected from the C3 alkyl group; L is a C1-C4 linear or branched alkylene linker, or if W is an optionally substituted ring, L may be a C1-C4 linear or branched alkylene linker or bond; W is H, -OH, -OR 10 -C(=O)NR 13 R 14 , -C(=O)OR 13 , -NR 13 R 14 , -NR 13 C(=O)OR 10 , -NR 13 C(=O)R 10 , -SO2R 10 -SO2NR 13 R 14 , -NR 13 SO2R 10 , -P(=O)(OR 13 )2, -S(=O)R 10 -S(=O)(=NR 13 )R 10 ,-CR11 R 12 C(=O)NR 13 R 14 ,-CR 11 R 12 C(=O)OR 13 ,-CR 11 R 12 NR 13 R 14 ,-CR 11 R 12 NR 13 C(=O)OR 10 ,-CR 11 R 12 NR 13 C(=O)R 10 ,-CR 11 R 12 SO2R 10 ,-CR 11 R 12 SO2NR 13 R 14 ,-CR 11 R 12 NR 13 SO2R 10 ,-CR 11 R 12 P(=O)(OR 13 )2, -CR 11 R 12 S(=O)R 10 ,-CR 11 R 12 S(=O)(=NR 13 )R 10 , 3-6 member cycloalkyl, phenyl, N, NH, NR 17 5-6 member heterocycloalkyl, N, NH, NR, containing one or two ring members independently selected from O, or S. 17 A 5-6 member heterocycline containing one or two ring members independently selected from O or S, or a 5-member heteroaryl having 1-4 heteroatoms selected as ring members from N, O, and S, which can be optionally condensed with phenyl. Here, W consists of 3-6 member cycloalkyls, phenyls, 5-6 member heterocycloalkyls, 5-6 member heterocyclines, and 5 member heteroaryls, respectively, C 1~ C3 alkyl, oxo, halo, C 1~ C3 haloalkyl, -L2 OH, -L 2 Ure 10 , -L 2 OC(=O)N R 13 R 14 , -L 2 SO2R 10 , -L 2 SO2NR 14 R 10 , -L 2 SO2NR 13 R 14 , -L 2 SO2N=CR 13 NR 13 R 14 , -L 2 SO2NR 13 C(=O)R 10 , -L 2 C(=O)NR 13 SO2R 10 , -L 2 S(=O)R 10 , -L 2 S(=O)(=NR 13 )R 10 , -L 2 NR 13 SO2NR 13 R 14 , -L 2 NR 13 SO2R 10 , -L 2 NR 13 R 14 , -L 2 NR 13 C(=O)R 13 , -L 2 NR 13 C(=O)OR 10 , -L 2 C(=O)NR 13 R 14 , and -L 2 C(=O)OR 13 It is arbitrarily replaced by 1 to 3 elements selected independently of it; R 10 C 1~ C5 alkyl, C 1~C3 haloalkyl, 3-6 membered cycloalkyl, phenyl, N, O, and S, having 1-4 heteroatoms independently selected as ring members, 5-6 membered heteroaryl, N, NH, NR 17 4-6 member heterocycloalkyls containing one or two ring members independently selected from O or S, and N, NH, NR 17 Selected from 4-6 membered heterocyclines containing 1-2 ring members independently selected from O, or S; Here, each R 10 C 1~ C4alkyl, deuterium, C 1~ C4 haloalkoxy, -L 3 OH, -L 3 CN, -L 3 OC(=O)R 14 , -L 3 Ure 13 , C 1~ C2-haloalkyl, oxo, -L 3 Halo, -L 3 C 1~ C3 alkoxy, -L 3 OC(=O)NR 13 R 14 , -L 3 SO2R 13 , -L 3 SO2NR 13 R 14 , -L 3 SO2NR 13 C(=O)R 13 , -L 3 C(=O)NR 13 SO2R 13 , -L 3 S(=O)R 13 , -L 3 S(=O)(=NR 14 )R 13 , -L 3 NR 13 SO2NR 13 R 14 , -L 3 NR 13 SO2R 13 , -L 3 NR 13 R 14 , -L 3 NR 14 C(=O)R13 , -L 3 NR 14 C(=O)OR 13 , -L 3 C(=O)NR 13 R 14 , -L 3 C(=O)OR 13 , -L 3 -(N, NH, NR 17 A 4-7 member heterocycloalkyl group containing 1-2 ring members independently selected from O, or S, (O or S), -L 3 -(N, NH, NR 17 A 4-7 member heterocycline containing 1-2 ring members independently selected from O, or S, -L 3 -C 3~ C5 cycloalkyl, and -L 3 -Optionally substituted with 1 to 5 groups independently selected from (a 5-6 membered heteroaryl ring having 1 to 4 heteroatoms, containing 1 to 4 nitrogen atoms, 0 or 1 oxygen atom, and 0 or 1 sulfur atom as ring members), where C 1~ C4 alkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocyclyl, C 3~ C5 cycloalkyl and 5-6 membered heteroaryl rings are, respectively, halo and C 1~ C3 alkyl, C 1~ C3 haloalkyl, -L 4 Ure 13 , -L 4 CN, and -L 4 NR 13 R 14 It is further optionally replaced by 1 to 3 bases, which are independently selected from; R 11 and R 12 H and C, respectively. 1~ Selected independently from C4 alkyl; Each R 13 H, C 1~ C4 alkyl, N, NH, NR 17 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S. 17A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C 3~ Independently selected from C6 cycloalkyl groups, where C 1~ C4 alkyl, heterocycloalkyl, heterocyclyl, and C 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , -C(=O)OR 15 , C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group; R 14 H, C 1~ C4 alkyl, and C 3~ Selected from C6 cycloalkyl, where C 1~ C4 alkyl and C 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group; Or, R 13 and R 14 Both, together with the nitrogen atom to which they are directly bonded, optionally contain additional N, O, or S as ring members, and C 1~ C2 alkyl, C 1~ It can form a 4-6 membered ring, optionally substituted with 1-3 groups selected from C2 alkoxy, oxo, and hydroxyl groups; R 15 and R 16 H and C, respectively. 1~ Selected independently from C4 alkyl; Each L 2 and L 3 and L 4 These are independently linked, or linear or branched C 1~ C3 Alki It is Ren; and [ka] This represents a single bond or a double bond.

[0061] Various embodiments of the compounds of the present invention are described herein. It will be recognized that certain features in each embodiment may be combined with other specific features to provide further embodiments. The embodiments listed below are representative of the compounds of formula (I) of the present invention. Embodiment 1.X is, [ka] A compound of formula (I) or a pharmaceutically acceptable salt thereof. Embodiment 2.X is, [ka] A compound of formula (I) or a pharmaceutically acceptable salt thereof. Embodiment 3.X is, [ka] A compound of formula (I) or a pharmaceutically acceptable salt thereof. Embodiment 4.X is, [ka] A compound of formula (I) or a pharmaceutically acceptable salt thereof. Embodiment 5.X is a compound of formula (I) or a pharmaceutically acceptable salt thereof, which is a 5- to 6-membered heteroaryl having 1 to 4 heteroatoms independently selected from N, O, and S as ring members. Embodiment 6.X is N, NH, NR 17 A compound of formula (I) or a pharmaceutically acceptable salt thereof, which is a 5-6 member heterocycloalkyl containing 1-4 ring members independently selected from , O, or S. Embodiment 7.X is N, NH, NR 17A compound of formula (I) or a pharmaceutically acceptable salt thereof, which is a 5-6 membered heterocycline containing 1-4 ring members independently selected from , O, or S. Embodiment 8.Y is, [ka] The compound of formula (I) or the compound described in any one of embodiments 1 to 7 or the Pharmaceutically acceptable salts. Embodiment 9.Y is, [ka] And in the formula, Y * This indicates the connection point to X, and Y ** However, R B A compound of formula (I) or a compound described in any one of embodiments 1 to 7, or a pharmaceutically acceptable salt thereof, that exhibits a bonding site to . Embodiment 10. A compound of formula (I) or a compound described in any one of Embodiments 1 to 7, or a pharmaceutically acceptable salt thereof, wherein Y is -O-. Embodiment 11.Y is, [ka] And in the formula, Y * This indicates the connection point to X, and Y ** However, R B A compound of formula (I) or a compound described in any one of embodiments 1 to 7, or a pharmaceutically acceptable salt thereof, that exhibits a bonding site to . Embodiment 12. A compound of formula (I) or a compound described in any one of Embodiments 1 to 7, or a pharmaceutically acceptable salt thereof, wherein Y is a bond. Embodiment 13.q is 1, L MC A compound of formula (I) or a compound described in any one of embodiments 1 to 12, or a pharmaceutically acceptable salt thereof, wherein A is a bond. Embodiment 14.q is 1, A is a bond, L MC but, * -((CR 11 R 12 )n O) m (CR 11 R 12 ) p - ** , * -C(=O)NR 15 (CR 11 R 12 ) n O) m (CR 11 R 12 ) p - ** , or * -(CR 11 R 12 ) n NR 15 (CR 11 R 12 ) n O) m (CR 11 R 12 ) p - ** And in the formula, L MC of * However, it indicates a connection point to Z, L MC of ** A compound of formula (I) or a compound described in any one of embodiments 1 to 13, or a pharmaceutically acceptable salt thereof, which exhibits a bonding site to A. Embodiment 15.q is 1, A is a bond, L MC but, [ka] And in the formula, L MC of * However, it indicates a connection point to Z, L MC of ** A compound of formula (I) or a compound described in any one of embodiments 1 to 14, or a pharmaceutically acceptable salt thereof, which exhibits a bonding site to A. Embodiment 16.q is 1, A is a bond, L MC but, [ka] And in the formula, L MC of * However, it indicates a connection point to Z, L MCof ** A compound of formula (I) or a compound described in any one of embodiments 1 to 14, or a pharmaceutically acceptable salt thereof, which exhibits a bonding site to A. Embodiment 17.q is 1, A is a combination, L MC but, [ka] And in the formula, L MC of * However, it indicates a connection point to Z, L MC of ** A compound of formula (I) or a compound described in any one of embodiments 1 to 14, or a pharmaceutically acceptable salt thereof, which exhibits a bonding site to A. Embodiment 18.q is 1, and Z is [ka] And in the formula, Z * However, L MC It shows the connection point to Z ** A compound of formula (I) or a compound described in any one of embodiments 1 to 17, or a pharmaceutically acceptable salt thereof, which exhibits a bonding site to L. Embodiment 19.q is 1, and Z is [ka] And in the formula, Z * However, L MC It shows the connection point to Z ** A compound of formula (I) or a compound described in any one of embodiments 1 to 17, or a pharmaceutically acceptable salt thereof, which exhibits a bonding site to L. Embodiment 20.q is 0, L MC However, a compound of formula (I) or a compound described in any one of embodiments 1 to 12, or a pharmaceutically acceptable salt thereof, wherein Z is not present and Z is W. Embodiment 21. A compound of formula (I) having the structure of formula (II) or a pharmaceutically acceptable salt thereof, [ka] In the formula, W, L, t, R 1 , R 2 , R 3 , R 4 , and R B A compound of formula (I) having the structure of formula (II), as defined in formula (I), or a pharmaceutically acceptable salt thereof. Embodiment 22. R B However, R is a phenyl, pyridinyl, thiophenyl, pyrimidinyl, or 5-8 membered cycloalkyl, where R B However, 1 to 3 R 5 It can be arbitrarily substituted in the base; R 1 However, H, C 1~ C3 alkyl and C substituted with 1-3 -OH groups 1~ Selected from C3 alkyl groups; R 2 However, H, C 1~ C3 alkyl and C substituted with 1-3 -OH groups 1~ Selected from C3 alkyl groups; Or, R 1 and R 2 However, together with the carbon atoms to which they are bonded, they can form a 3- to 6-membered cycloalkyl ring; t is 0, 1, or 2; Each R 3 However, if present, -LW is a substituent on the ring to which it is directly bonded, where each R 3 However, Hello, CN, C 1~ C3 alkoxy, C 1~ C3alkyl, C(=O)OR 10 , and C(=O)NR 13 R 14 Selected independently of; R 4 However, H, C 1~ C3 alkyl, C 3~ C6 cycloalkyl, -(CH2)2O(CH2)2Br, or -OH, -C(=O)R 15 , and R 10 C substituted with 1-2 groups independently selected from 1~ It is a C3 alkyl group; Each R 5However, halo, -CN, hydroxy, -NR 13 R 14 , C 3~ C6 cycloalkyl, C 1~ C3 alkoxy, C 1~ C3 haloalkyl and 1-3 R 6 A C arbitrarily substituted in the base 1~ Independently selected from C3 alkyl groups, where R B However, two R 5 Replaced by each R 5 However, 1 to 3 R 6 A C arbitrarily substituted in the base 1~ It is a C3 alkyl group, and when directly bonded to the same carbon atom, both atoms together form 1 to 3 R atoms. 6 It can form a 3- to 5-membered cycloalkyl ring optionally substituted with a group; Each R 6 However, halo, hydroxy, CN, C 1~ C3 alkoxy, C 1~ C3 alkyl, and C 3~ From C5 cycloalkyl groups, each occurrence is independently selected. Alternatively, two R 6 The group contains O, N, or S as ring members, together with the carbon atoms to which both are directly bonded, and includes oxo and C 1~ They can form a 3- to 5-membered cycloalkyl ring or a 4- to 6-membered heterocycle, optionally substituted with 1-2 groups independently selected from the C3 alkyl group; If L is a C1-C4 linear or branched alkylene linker, or if L is a ring in which W is optionally substituted, then L may be a C1-C4 linear or branched alkylene linker or bond; W is H, -OH, -OR 10 -C(=O)NR 13 R 14 , -C(=O)OR 13 , -NR 13 R 14 , -NR 13 C(=O)OR 10 , -NR 13 C(=O)R 10 , -SO2R 10 -SO2NR 13R 14 、 -NR 13 SO2R 10 、 -P(=O)(OR 13 )2、 -S(=O)R 10 、 -S(=O)(=NR 13 )R 10 、 -CR 11 R 12 C(=O)NR 13 R 14 、 -CR 11 R 12 C(=O)OR 13 、 -CR 11 R 12 NR 13 R 14 、 -CR 11 R 12 NR 13 C(=O)OR 10 、 -CR 11 R 12 NR 13 C(=O)R 10 、 -CR 11 R 12 SO2R 10 、 -CR 11 R 12 SO2NR 13 R 14 [[ID=6……]]、 -CR 11 R 12 NR 13 SO2R 10 …… 、 -CR 11 R 12 P(=O)(OR 13 )2、 -CR 11 R 12 S(=O)R 10 、 -CR 11 R 12 S(=O)(=NR 13 )R 10 、 3 - 6 member cycloalkyl, phenyl, N, NH, NR 17 、 O, or S, a 5 - 6 member heterocycloalkyl containing 1 or 2 ring members independently selected from N, NH, NR 17A 5-6 member heterocycline containing one or two ring members independently selected from O or S, or a 5-member heteroaryl having 1-4 heteroatoms selected as ring members from N, O, and S, which can be optionally condensed with phenyl. Here, W consists of a 3-6 member cycloalkyl, a phenyl, a 5-6 member heterocycloalkyl, a 5-6 member heterocyclyl, and a 5 member heteroaryl, respectively, C 1~ C3 alkyl, oxo, halo, C 1~ C3 haloalkyl, -OH, -OR 10 -OC(=O)NR 13 R 14 , -SO2R 10 -SO2NR 14 R 10 -SO2NR 13 R 14 -SO2N=CR 13 NR 13 R 14 -SO2NR 13 C(=O)R 10 -C(=O)NR 13 SO2R 10 -S(=O)R 10 -S(=O)(=NR 13 )R 10 , -NR 13 SO2NR 13 R 14 , -NR 13 SO2R 10 , -NR 13 R 14 , -NR 13 C(=O)R 13 , -NR 13 C(=O)OR 10 -C(=O)NR 13 R 14 , and -C(=O)OR 13 It is arbitrarily substituted with 1 to 3 bases, independently selected from; R 10 However, C 1~ C5 alkyl, C 1~ C3 haloalkyl, 3-6 membered cycloalkyl, phenyl, N, O, and S, having 1-4 heteroatoms independently selected as ring members, 5-6 membered heteroaryl, N, NH, NR17 A 4- to 6-membered heterocycloalkyl containing one or two ring members independently selected from N, NH, NR 17 A 4- to 6-membered heterocycle containing one or two ring members independently selected from N, O, or S selected from; where each R 10 is C 1~ C4 alkyl, deuterium, C 1~ C4 haloalkoxy, -OH, -CN, -OC(=O)R 14 , -L 3 OR 13 C 1~ C2 haloalkyl, oxo, -halo, -C 1~ C3 alkoxy, -OC(=O)NR 13 R 14 , -SO2R 13 , -SO2NR 13 R 14 , -SO2NR 13 C(=O)R 13 , -C(=O)NR 13 SO2R 13 , -S(=O)R 13 , -S(=O)(=NR 14 )R 13 , -NR 13 SO2NR 13 R 14 , -NR 13 SO2R 13 , -NR 13 R 14 , -NR 14 C(=O)R 13 , -NR 14 C(=O)OR 13 , -C(=O)NR 13 R 14 , -C(=O)OR 13 , (a 4- to 7-membered heterocycloalkyl containing one or two ring members independently selected from N, NH, NR 17 , O, or S, O or S), -(a 4- to 7-membered heterocyclyl containing one or two ring members independently selected from N, NH, NR 17 , O, or S), -C 3~C5 cycloalkyl and C5-6 membered heteroaryl rings having 1-4 heteroatoms and containing 1-4 nitrogen atoms, 0 or 1 oxygen atom, and 0 or 1 sulfur atom as ring members are optionally substituted with 1-5 groups independently selected from C5 cycloalkyl and C5 cycloalkyl, C5-6 membered heteroaryl rings, where C1-C4 alkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocyclyl, C3-C5 cycloalkyl, and C5-6 membered heteroaryl rings are each a halo, C5 cycloalkyl and C5 cycloalkyl rings, respectively. 1~ C3 alkyl, C 1~ C3 haloalkyl, -OR 13 -CN and -NR 13 R 14 It is further optionally replaced by 1 to 3 bases, which are independently selected from; R 11 and R 12 However, H and C respectively 1~ Selected independently from C4 alkyl; Each R 13 However, H, C 1~ C4 alkyl, N, NH, NR 17 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S. 17 A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C 3~ Independently selected from C6 cycloalkyl groups, where C 1~ C4 alkyl, heterocyclyl, and C 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , -C(=O)OR 15 , C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group; R 14 However, H, C 1~ C4 alkyl, and C 3~ Selected from C6 cycloalkyl, where C 1~ C4 alkyl and C 3~ C6 cycloalkyl, 1~C4 alkyl, halo, -OH, -NR 15 R 16 , C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group; Or, R 13 and R 14 However, together with the nitrogen atom to which both are directly bonded, they optionally contain additional N, O, or S as ring members, and C 1~ C2 alkyl, C 1~ It can form a 4-6 membered ring, optionally substituted with 1-3 groups selected from C2 alkoxy, oxo, and hydroxyl groups; R 15 and R 16 However, H and C respectively 1~ Selected independently from C4 alkyl; L 3 However, the bond, or the linear or branched chain C 1~ It is a C3 alkylene; and [ka] A compound of formula (II) as described in any one of Embodiments 1 to 21, or a pharmaceutically acceptable salt thereof, which represents a single bond or a double bond. Embodiment 23. R B However, R is phenyl, pyridinyl, thiophenyl, or a 5-8 membered cycloalkyl, where R B However, 1 to 3 R 5 It can be arbitrarily substituted in the base; R 1 However, H, C 1~ C3 alkyl and C substituted with 1-3 -OH groups 1~ Selected from C3 alkyl groups; R 2 However, H is; t is 0, 1, or 2; Each R 3 However, if present, -LW is a substituent on the ring to which it is directly bonded, where each R 3 However, C 1~Selected independently from C3 alkyl groups; R 4 However, H, C 1~ C3 alkyl, C 3~ C6 cycloalkyl, -(CH2)2O(CH2)2Br, or -OH, -C(=O)R 15 , and R 10 C substituted with 1-2 groups independently selected from 1~ It is a C3 alkyl group; Each R 5 However, Hello, -CN, C 1~ C3 alkoxy and C 1~ Selected independently from C3 alkyl groups; If L is a C1-C4 linear or branched alkylene linker, or if L is a ring in which W is optionally substituted, then L may be a C1-C4 linear or branched alkylene linker or bond; W is a 3- to 6-membered cycloalkyl group, where the 3- to 6-membered cycloalkyl group is -SO2R 10 -SO2NR 14 R 10 -SO2NR 13 R 14 , and -SO2N=CR 13 NR 13 R 14 Replaced by 1 to 3 elements, independently selected from; R 10 However, C 1~ C5 alkyl, C 1~ C3 haloalkyl, 3-6 membered cycloalkyl, phenyl, N, O, and S, having 1-4 heteroatoms independently selected as ring members, 5-6 membered heteroaryl, N, NH, NR 17 4-6 member heterocycloalkyls containing one or two ring members independently selected from O, or S, as well as N, NH, NR 17 Selected from 4-6 membered heterocyclines containing 1-2 ring members independently selected from O, or S; Here, each R 10 However, C 1~ C4alkyl, deuterium, C 1~ C4 halokoxy-OH, -CN, -OC(=O)R 14 , -L 3 Ure13 , -NR 13 R 14 , -NR 14 C(=O)R 13 , -NR 14 C(=O)OR 13 -C(=O)NR 13 R 14 , -C(=O)OR 13 , (N, NH, NR 17 (4-7 member heterocycloalkyls containing 1-2 ring members, independently selected from O, or S), (N, NH, NR) 17 A 4-7 member heterocycline containing 1-2 ring members, independently selected from O, or S, and -C 3~ It is optionally substituted with 1 to 5 groups independently selected from C5 cycloalkyl groups, where C 1~ C4 alkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocyclyl, and C 3~ C5 cycloalkyl groups are represented by halo, -OR, respectively. 13 , and -NR 13 R 14 It is optionally further replaced by 1 to 3 bases selected independently from it; R 11 and R 12 However, H and C respectively 1~ Selected independently from C4 alkyl; Each R 13 However, H, C 1~ C4 alkyl, N, NH, NR 17 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S. 17 A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C 3~ Independently selected from C6 cycloalkyl groups, where C 1~ C4 alkyl, heterocyclyl, and C 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , -C(=O)OR 15 , and C substituted with 1-2 hydroxyl groups 1~Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group; R 14 However, H and C 1~ Selected from C4 alkyl; R 15 and R 16 However, H and C respectively 1~ Selected independently from C4 alkyl; L 3 However, the bond, or the linear or branched chain C 1~ It is a C3 alkylene; and [ka] A compound of formula (II) as described in any one of Embodiments 1 to 22, or a pharmaceutically acceptable salt thereof, which represents a single bond or a double bond. Embodiment 24. A compound of formula (I) or formula (II) having the structure of formula (IIIa), formula (IIIb), or formula (IIIc), or a pharmaceutically acceptable salt thereof, [ka] During the ceremony: W, L, t, R 1 , R 3 , and R 5 This is defined for equation (I); Alternatively, W, L, t, R 1 , R 3 , and R 5 This is as defined in Embodiment 22, Alternatively, W, L, t, R 1 , R 3 , and R 5 This refers to a compound of formula (I) or formula (II) having the structure of formula (IIIa), formula (IIIb), or formula (IIIc), as defined in Embodiment 23, or a pharmaceutically acceptable salt thereof. Embodiment 25. A compound of formula (I) or formula (II) having the structure of formula (IIIa), or a pharmaceutically acceptable salt thereof, [ka] During the ceremony: W, L, t, R 1 , R 3 , and R 5 This is defined for equation (I); Alternatively, W, L, t, R 1 , R 3 , and R 5 This is as defined in Embodiment 22, Alternatively, W, L, t, R 1 , R 3 , and R 5 This refers to a compound of formula (I) or formula (II) having the structure of formula (IIIa), or a pharmaceutically acceptable salt thereof, as defined in Embodiment 23. Embodiment 26. R 1 However, H, C 1~ Selected from C3 alkyl groups and C1-C3 alkyl groups substituted with one -OH group; t is 0, 1, or 2; Each R 3 However, if present, -LW is a substituent on the ring to which it is directly bonded, where each R 3 However, Hello, CN, C 1~ C3 alkoxy, C 1~ C3alkyl, C(=O)OR 10 , and C(=O)NR 13 R 14 Selected independently of; Each R 5 However, Hello, CN, C 1~ C3 alkyl, and C 1~ Selected independently of C3 alkoxy; L is a C1-C4 linear or branched alkylene linker; W, -SO2R 10 -SO2NR 13 R 14 , -NR 14 SO2R 10 ,-CR 11 R 12 SO2R 10 ,-CR 11 R 12 SO2NR 13 R 14,-CR 11 R 12 NR 14 SO2R 10 , or optionally substituted 3- to 6-membered cycloalkyl groups; Here, any substituent for the arbitrarily substituted cycloalkyl is C 1~ C3 alkyl, oxo, halo, -OH, -SO2R 10 -SO2NR 13 R 14 , -SO2N R 14 R 10 , -NR 13 SO2NR 13 R 14 , -NR 13 SO2R 10 , -NR 13 R 14 , -OR 10 , -NR 13 C(=O)OR 10 -C(=O)NR 13 R 14 , and C(=O)OR 13 One to three bases are selected independently from, R 10 However, C 1~ 5-6 membered heteroaryls having 1-4 heteroatoms independently selected from C5 alkyl, 3-6 membered cycloalkyl, phenyl, N, O, and S as ring members, N, NH, NR 17 4-6 member heterocycloalkyls containing one or two ring members independently selected from O, or S, as well as N, NH, NR 17 Selected from 4-6 membered heterocyclines containing 1-2 ring members independently selected from O, or S; Here, each R 10 However, C 1~ C3 alkyl, oxo, CN, halo, C 1~ C3alkyl, OH, and C 3~ Optionally substituted with 1 to 4 groups selected from C5 cycloalkyl groups; R 11 and R 12 However, H and C respectively 1~ Selected independently from C4 alkyl; Each R 13 However, H, and halo, -OH, or C 1~ C arbitrarily substituted with C2alkoxy 1~ Selected independently from C4 alkyl groups; R 14 However, H and C 1~ Selected from C4 alkyl; Or, R 13 and R 14 However, together with the nitrogen atom to which both are directly bonded, they optionally contain additional N, O, or S as ring members, and C 1~ C2 alkyl, C 1~ A compound according to any one of Embodiments 1 to 25 or a pharmaceutically acceptable salt thereof, which can form a 4- to 6-membered ring, optionally substituted with 1-2 groups selected from C2-alkoxy, oxo, and hydroxyl groups. Embodiment 27. R 1 However, it is H, methyl, or methyl substituted with one -OH group; t is 0, 1, or 2; Each R 3 However, if present, -LW is a substituent on the ring to which it is directly bonded, where each R 3 However, it is selected independently of methyl; Each R 5 However, it is independently selected from Cl, F, -CN, methyl, and -OCH3; L is -CH2- or -CH2CH2-; W, -SO2R 10 -SO2NR 13 R 14 , or -SO2NR 14 R 10 It is a cyclopropyl substituted with; R 10 However, it is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, cyclopropyl, cyclobutyl, pyridinyl, pyrazolyl, isoxazolyl, oxetanyl, tetrahydrofuranil, tetrahydropyranil, morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, and azetidinyl. Here, each R 10However, methyl, ethyl, deuterium, -OCH3, -OH, -OCHF2, -CN, -NH2, -NHCH3, -N(CH3)2, -NHR 13 , -NHCH(=O), -NHC(=O)CH3, -NHC(=O)OCH3, -NHC(=O)CH2NH2, -NHC(=O)CH2N(CH3)2, -NHC(=O)CH(CH3)NH2, -NHC(=O)C(CH3)2NH2, -OCH2CH2OH, -OCH2CH (CH3)OH, -OCH2CH(CH3)2OH, -OCH(F)CH2OH, -OCF2CH2OH, -OCH2CH2NH2, -OCH2CH(CH3)NH2, -OCH2C(CH3)2NH2, -OCH2CH2NHCH3, -OCH2CH2N(CH3)2, -OCH( F) Optionally substituted with 1 to 4 groups independently selected from CH2NH2, -OCF2CH2NH2, -CH2OCH2CH2NH2, -CH2CH2OH, -CH2OH, -CH2NH2, -O-azetidinyl, -C(=O)NH2, -C(=O)NHCH3, -OC(=O)CH3, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl, Here, methyl, ethyl, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabi Cyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl are each optionally further substituted with 1 to 3 groups independently selected from F, -OH, -OCH3, -NH2, and methyl; R 13 However, the ring members include a 4-7 membered heterocycline containing 1-2 heteroatoms independently selected from H, methyl, ethyl, isopropyl, propyl, butyl, isobutyl, pentyl, N, O, or S, and C 3~ Selected from C6 cycloalkyl groups, Here, methyl, ethyl, isopropyl, propyl, butyl, isobutyl, pentyl heterocyclyl, and C 3~ C6 cycloalkyl groups include methyl, ethyl, propyl, isopropyl, F, -OH, -NH2, -N(CH3)2, -C(=O)OH, and C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group, and R 14 However, a compound according to any one of Embodiments 1 to 25, selected from H and methyl, or a pharmaceutically acceptable salt thereof. Embodiment 28. A compound of formula (I) or formula (II) having the structure of formula (IVa), formula (IVb), or formula (IVc), or a pharmaceutically acceptable salt thereof, [ka] During the ceremony: L, R 1 , R 5 , R 10 , R 11 , and R 12 This is defined above in equation (I); Or, L, R 1 , R 5 , R 10 , R 11 , and R 12 This is as defined in Embodiment 22; Or, L, R 1 , R 5 , R 10 , R 11 , and R 12 This is as defined in Embodiment 23; Or, L, R 1 , R 5 , R 10 , R 11 , and R 12 This is as defined in Embodiment 26; Or, L, R 1 , R 5 , R 10 , R 11, and R 12 This refers to a compound of formula (I) or formula (II) having the structure of formula (IVa), formula (IVb), or formula (IVc), as defined in Embodiment 27, or a pharmaceutically acceptable salt thereof. Embodiment 29. A compound of formula (I) or formula (II) having the structure of formula (IVa), or a pharmaceutically acceptable salt thereof, [ka] During the ceremony: L, R 1 , R 5 , R 10 , R 11 , and R 12 This is defined above in equation (I); Or, L, R 1 , R 5 , R 10 , R 11 , and R 12 This is as defined in Embodiment 22; Or, L, R 1 , R 5 , R 10 , R 11 , and R 12 This is as defined in Embodiment 23; Or, L, R 1 , R 5 , R 10 , R 11 , and R 12 This is as defined in Embodiment 26; Or, L, R 1 , R 5 , R 10 , R 11 , and R 12 This refers to a compound of formula (I) or formula (II) having the structure of formula (IVa), as defined in Embodiment 27, or a pharmaceutically acceptable salt thereof. Embodiment 30. A compound of formula (I) or formula (II) having the structure of formula (Va), formula (Vb), or formula (Vc), or a pharmaceutically acceptable salt thereof, [ka] During the ceremony: L, R 1 , R 5 , and R 10 This is defined above in equation (I); Or, L, R 1 , R 5 , and R 10 This is as defined in Embodiment 22; Or, L, R 1 , R 5 , and R 10 This is as defined in Embodiment 23; Or, L, R 1 , R 5 , and R 10 This is as defined in Embodiment 26; Or, L, R 1 , R 5 , and R 10 This refers to a compound of formula (I) or formula (II) having the structure of formula (Va), formula (Vb), or formula (Vc), as defined in Embodiment 27, or a pharmaceutically acceptable salt thereof. Embodiment 31. A compound of formula (I) or formula (II) having the structure of formula (Va), or a pharmaceutically acceptable salt thereof, [ka] During the ceremony: L, R 1 , R 5 , and R 10 This is defined above in equation (I); Or, L, R 1 , R 5 , and R 10 This is as defined in Embodiment 22; Or, L, R 1 , R 5 , and R 10 This is as defined in Embodiment 23; Or, L, R 1 , R 5 , and R 10 This is as defined in Embodiment 26; Or, L, R1 , R 5 , and R 10 This refers to a compound of formula (I) or formula (II) having the structure of formula (Va), as defined in Embodiment 27, or a pharmaceutically acceptable salt thereof. Embodiment 32. R 1 However, it is H, methyl, or methyl substituted with one -OH group; Each R 5 However, it is selected independently from Cl, F, and -CN; L is a bond, or CH2 or CH2CH2; R 10 However, it is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, cyclopropyl, cyclobutyl, pyridinyl, pyrazolyl, isoxazolyl, oxetanyl, tetrahydrofuranil, tetrahydropyranil, morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, and azetidinyl. Here, each R 10 However, methyl, ethyl, deuterium, -OCH3, -OH, -OCHF2, -CN, -NH2, -NHCH3, -N(CH3)2, -NHR 13, -NHCH(=O), -NHC(=O)CH3, -NHC(=O)OCH3, -NHC(=O)CH2NH2, -NHC(=O)CH2N(CH3)2, -NHC(=O)CH(CH3)NH2, -NHC(=O)C(CH3)2NH2, -OCH2CH2OH, -OCH2CH (CH3)OH, -OCH2CH(CH3)2OH, -OCH(F)CH2OH, -OCF2CH2OH, -OCH2CH2NH2, -OCH2CH(CH3)NH2, -OCH2C(CH3)2NH2, -OCH2CH2NHCH3, -OCH2CH2N(CH3)2, -OCH( F) Optionally substituted with 1 to 4 groups independently selected from CH2NH2, -OCF2CH2NH2, -CH2OCH2CH2NH2, -CH2CH2OH, -CH2OH, -CH2NH2, -O-azetidinyl, -C(=O)NH2, -C(=O)NHCH3, -OC(=O)CH3, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl, Here, methyl, ethyl, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl are each optionally further substituted with 1 to 3 groups independently selected from F, -OH, -OCH3, and -NH2. and R 11 and R 12 However, each independently represents H or methyl, the compound according to any one of Embodiments 1 to 31 or a pharmaceutically acceptable salt thereof. Embodiment 33. R 1 However, it is H, methyl, or methyl substituted with one -OH group; Each R 5 However, it is selected independently from Cl, F, and -CN; L is a bond, or CH2 or CH2CH2; and R 10 However, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl Selected from cyclopropyl, cyclobutyl, pyridinyl, pyrazolyl, isoxazolyl, oxetanyl, tetrahydrofuranil, tetrahydropyranil, morpholinil, piperidinil, piperazinil, pyrrolidinil, and azetidinil, Here, each R 10 However, methyl, ethyl, deuterium, -OCH3, -OH, -OCHF2, -CN, -NH2, -NHCH3, -N(CH3)2, -NHR 13 , -NHCH(=O), -NHC(=O)CH3, -NHC(=O)OCH3, -NHC(=O)CH2NH2, -NHC(=O)CH2N(CH3)2, -NHC(=O)CH(CH3)NH2, -NHC(=O)C(CH3)2NH2, -OCH2CH2OH, -OCH2CH (CH3)OH, -OCH2CH(CH3)2OH, -OCH(F)CH2OH, -OCF2CH2OH, -OCH2CH2NH2, -OCH2CH(CH3)NH2, -OCH2C(CH3)2NH2, -OCH2CH2NHCH3, -OCH2CH2N(CH3)2, -OCH( F) Optionally substituted with 1 to 4 groups independently selected from CH2NH2, -OCF2CH2NH2, -CH2OCH2CH2NH2, -CH2CH2OH, -CH2OH, -CH2NH2, -O-azetidinyl, -C(=O)NH2, -C(=O)NHCH3, -OC(=O)CH3, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl, Herein, methyl, ethyl, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl are each optionally further substituted with 1 to 3 groups independently selected from F, -OH, -OCH3, and -NH2, respectively, the compounds described in any one of Embodiments 1 to 32 or pharmaceutically acceptable salts thereof. Embodiment 34. A compound of formula (I) having the structure of formula (VI) or a pharmaceutically acceptable salt thereof, [ka] During the ceremony: W, L, t, R 3 , R 4 , and R B A compound of formula (I) having the structure of formula (VI), as defined for formula (I), or a pharmaceutically acceptable salt thereof. Embodiment 35. A compound of formula (VII) or a pharmaceutically acceptable salt thereof, [ka] During the ceremony: R C This is 1 to 3 R 6 It is an H or C1-C6 alkyl group optionally substituted with a group; t is 0, 1, or 2; Each R 3 If present, -LW is a substituent on the ring to which it is directly bonded, where Each R 3 However, Hello, CN, C 1~ C3 alkoxy, C 1~ C3alkyl, C(=O)OR 10 , and C(=O)NR 13 R 14 Selected independently of; R 4 is H, halo, or C 1~3 It is alkyl; L is a C1-C4 linear or branched alkylene linker, or bond; W is H, -OH, -OR 10 -C(=O)NR 13 R 14 , -C(=O)OR 13 , -NR 13 R 14 , -NR 13 C(=O)OR 10 , -NR 13 C(=O)R 10 , -SO2R 10 -SO2NR 13 R 14 , -NR 13 SO2R 10 , -P(=O)(OR 13 )2, -S(=O)R 10 -S(=O)(=NR 13 )R 10 ,-CR 11 R 12 C(=O)NR 13 R 14 ,-CR 11 R 12 C(=O)OR 13 ,-CR 11 R 12 NR 13 R 14 ,-CR 11 R 12 NR 13 C(=O)OR 10 ,-CR 11 R 12 NR 13 C(=O)R 10 ,-CR 11 R 12 SO2R 10 ,-CR 11 R 12 SO2NR 13 R 14 ,-CR 11 R 12 NR 13 SO2R 10 ,-CR 11 R 12 P(=O)(OR 13 )2, -CR 11 R 12 S(=O)R 10 ,-CR11 R 12 S(=O)(=NR 13 )R 10 , 3-6 member cycloalkyl, phenyl, N, NH, NR 17 5-6 member heterocycloalkyl, N, NH, NR, containing one or two ring members independently selected from O, or S. 17 A 5-6 member heterocycline containing one or two ring members independently selected from O or S, or a 5-member heteroaryl having 1-4 heteroatoms selected as ring members from N, O, and S, which can be optionally condensed with phenyl. Here, W consists of 3-6 member cycloalkyls, phenyls, 5-6 member heterocycloalkyls, 5-6 member heterocyclines, and 5 member heteroaryls, respectively, C 1~ C3 alkyl, oxo, halo, C 1~ C3 haloalkyl, -OH, -OR 10 -OC(=O)NR 13 R 14 , -SO2R 10 -SO2NR 14 R 10 -SO2NR 13 R 14 -SO2N=CR 13 NR 13 R 14 -SO2NR 13 C(=O)R 10 -C(=O)NR 13 SO2R 10 -S(=O)R 10 -S(=O)(=NR 13 )R 10 , -NR 13 SO2NR 13 R 14 , -NR 13 SO2R 10 , -NR 13 R 14 , -NR 13 C(=O)R 13 , -NR 13 C(=O)OR 10 -C(=O)NR 13 R 14 , and -C(=O)OR 13It is arbitrarily substituted with 1 to 3 bases, independently selected from; R 10 C 1~ C5 alkyl, C 1~ C3 haloalkyl, 3-6 membered cycloalkyl, phenyl, N, O, and S, having 1-4 heteroatoms independently selected as ring members, 5-6 membered heteroaryl, N, NH, NR 17 4-6 member heterocycloalkyls containing one or two ring members independently selected from O, or S, as well as N, NH, NR 17 Selected from 4-6 membered heterocyclines containing 1-2 ring members independently selected from O, or S; Here, each R 10 C 1~ C4alkyl, deuterium, C 1~ C4 haloalkoxy, -OH, -CN, -OC(=O)R 14 , -L 3 Ure 13 , C 1~ C2 haloalkyl, oxo, -halo, -C 1~ C3 alkoxy, -OC(=O)NR 13 R 14 , -SO2R 13 -SO2NR 13 R 14 -SO2NR 13 C(=O)R 13 -C(=O)NR 13 SO2R 13 -S(=O)R 13 -S(=O)(=NR 14 )R 13 , -NR 13 SO2NR 13 R 14 , -NR 13 SO2R 13 , -NR 13 R 14 , -NR 14 C(=O)R 13 , -NR 14 C(=O)OR 13 -C(=O)NR 13 R 14 , -C(=O)OR 13 , (N, NH, NR 174-7 membered heterocycloalkyl groups containing 1-2 ring members independently selected from O, or S (O or S), (N, NH, NR) 17 (4-7 member heterocycline containing 1-2 ring members independently selected from O, or S), -C 3~ C5 cycloalkyl and (a 5-6 membered heteroaryl ring having 1-4 heteroatoms and containing 1-4 nitrogen atoms, 0 or 1 oxygen atom, and 0 or 1 sulfur atom as ring members) are optionally substituted with 1-5 groups independently selected from C5 cycloalkyl and C5 cycloalkyl, C5 cycloalkyl, and C5 cycloaryl rings, where C1-C4 alkyl, C4-7 membered heterocycloalkyl, C4-7 membered heterocyclyl, C3-C5 cycloalkyl, and C5-6 membered heteroaryl rings are each a halo, C5 cycloalkyl and C5 cycloalkyl rings, respectively. 1~ C3 alkyl, C 1~ C3 haloalkyl, -OR 13 -CN and -NR 13 R 14 Selected independently from, 1 ~3 more bases may be arbitrarily substituted; R 11 and R 12 H and C, respectively. 1~ Selected independently from C4 alkyl; Each R 13 is H, halo, -OH, amino, or C 1~2 C arbitrarily substituted with alkoxy 1~4 Alkyl, and halo, -OH, amino, or C 1~2 C arbitrarily substituted with alkoxy 3~6 Independently selected from alkyl groups; R 14 is H, halo, -OH, amino, or C 1~2 C arbitrarily substituted with alkoxy 1~4 Alkyl, and halo, -OH, amino, or C 1~2 C arbitrarily substituted with alkoxy 3~6 Selected independently from alkyl groups, Or, R 13 and R 14 Both, together with the nitrogen atom to which they are directly bonded, optionally contain additional N, O, or S as ring members, and C 1~2 Alkyl, C 1~2It can form a 4-6 membered ring, optionally substituted with 1-3 groups selected from alkoxy, oxo, and hydroxyl groups; L 3 This refers to a bond, or a linear or branched chain C. 1~3 It is alkylene; Each R 6 is halo, hydroxy, CN, C 1~ C3 alkoxy, C 1~ C3 alkyl, and C 3~ From C5 cycloalkyl groups, each occurrence is independently selected. or 2 R 6 The group contains O, N, or S as ring members, together with the carbon atoms to which both are directly bonded, and is oxo and C 1~ A compound of formula (VII) or a pharmaceutically acceptable salt thereof, which can form a 3- to 5-membered cycloalkyl ring or a 4- to 6-membered heterocycle, optionally substituted with one or two groups independently selected from a C3 alkyl group. Embodiment 36.R C A compound of formula (VII) described in Embodiment 35 or a pharmaceutically acceptable salt thereof, wherein the compound is H, methyl, ethyl, propyl, isopropyl, t-butyl, or n-butyl. Embodiment 37. L is a C1-C4 linear or branched alkylene linker; W, -SO2R 10 -SO2NR 13 R 14 , -NR 14 SO2R 10 ,-CR 11 R 12 SO2R 10 ,-CR 11 R 12 SO2NR 13 R 14 ,-CR 11 R 12 NR 14 SO2R 10 or optionally substituted C1-C3 alkyl, or optionally substituted 3-6 membered cycloalkyl; Here, the arbitrarily substituted C 1~Any substituent for C3 alkyl and optionally substituted cycloalkyl is C 1- C3 alkyl, oxo, halo, -OH, -SO2R 10 -SO2NR 13 R 14 -SO2NR 14 R 10 , -NR 13 SO2NR 13 R 14 , -NR 13 SO2R 10 , -NR 13 R 14 , -OR 10 , -NR 13 C(=O)OR 10 -C(=O)NR 13 R 14 , and C(=O)OR 13 One to three bases selected independently from; R 10 However, C 1~ 5-6 membered heteroaryls having 1-4 heteroatoms independently selected from C5 alkyl, 3-6 membered cycloalkyl, phenyl, N, O, and S as ring members, N, NH, NR 17 4-6 member heterocycloalkyls containing one or two ring members independently selected from O, or S, as well as N, NH, NR 17 Selected from 4-6 membered heterocyclines containing 1-2 ring members independently selected from O, or S; Here, each R 10 However, C 1~ C3 alkyl, oxo, CN, halo, C 1~ C3alkyl, OH, and C 3~ Optionally substituted with 1 to 4 groups selected from C5 cycloalkyl groups; R 11 and R 12 However, H and C respectively 1~ Selected independently from C4 alkyl; Each R 13 However, H, and halo, -OH, or C 1~ C arbitrarily substituted with C2alkoxy 1~ Selected independently from C4 alkyl groups; R14 However, H and C 1~ Selected from C4 alkyl; Or, R 13 and R 14 However, together with the nitrogen atom to which both are directly bonded, they optionally contain additional N, O, or S as ring members, and C 1~ C2 alkyl, C 1~ Optionally substituted with 1-2 groups selected from C2 alkoxy, oxo, and hydroxyl, 4- A compound according to any one of embodiments 34 to 36, or a pharmaceutically acceptable salt thereof, that can form a six-membered ring. Embodiment 38.R B However, these are selected from phenyl, pyridinyl, thiophenyl, and cyclohexyl, each of which has 1 to 3 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is optionally substituted with a group. Embodiment 39.R B However, 1 to 3 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a pyridinyl optionally substituted with a group. Embodiment 40.R B However, 1 to 3 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, wherein pyridine-3-yl is optionally substituted with a group. Embodiment 41.R B However, 1 to 3 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, wherein pyridine-2-yl is optionally substituted with a group. Embodiment 42.R B However, 1 to 3 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a thiophenyl optionally substituted with a group. Embodiment 43.R B However, 1 to 3 R 5A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a thiophene-2-yl optionally substituted with a group. Embodiment 44.R B However, 1 to 3 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a cyclohexyl optionally substituted with a group. Embodiment 45.R B However, 1 to 3 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, wherein the compound is a phenyl optionally substituted with a group. Embodiment 46.R B However, it is selected from phenyl, pyridinyl, thiophenyl, and cyclohexyl, each of which is a halo, C 1~ C3 alkoxy, C 1~ One to three R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is optionally substituted with a group. Embodiment 47.R B However, 1 to 3 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, wherein pyridine-3-yl is optionally substituted with a group. Embodiment 48.R B But, hello, C 1~ C3 alkoxy, C 1~ One to three R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is pyridine-2-yl optionally substituted with a group. Embodiment 49.R B But, hello, C 1~ C3 alkoxy, C 1~ One to three R molecules independently selected from C3 alkyl and -CN. 5A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a thiophenyl optionally substituted with a group. Embodiment 50.R B But, hello, C 1~ C3 alkoxy, C 1~ One to three R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is thiophene-2-yl optionally substituted with a group. Embodiment 51.R B But, hello, C 1~ C3 alkoxy, C 1~ One to three R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a cyclohexyl compound optionally substituted with a group. Embodiment 52.R B But, hello, C 1~ C3 alkoxy, C 1~ C3 alkyl and -C 1 to 3 R selected independently from N 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a phenyl compound optionally substituted with a group. Embodiment 53.R B However, each of these is selected from phenyl, pyridinyl, thiophenyl, and cyclohexyl, and each of these is independently selected from Cl, F, -OCH3, methyl, and -CN, with 1 to 3 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is optionally substituted with a group. Embodiment 54.R B However, 1 to 3 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is pyridine-2-yl optionally substituted with a group. Embodiment 55.R B However, 1 to 3 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a thiophenyl optionally substituted with a group. Embodiment 56.R B However, 1 to 3 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is thiophene-2-yl optionally substituted with a group. Embodiment 57.R B However, 1 to 3 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a cyclohexyl compound optionally substituted with a group. Embodiment 58.R B However, 1 to 3 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a phenyl compound optionally substituted with a group. Embodiment 59.R B However, it is selected from phenyl, pyridinyl, thiophenyl, and cyclohexyl, each of which is a halo, C 1~ C3 alkoxy, C 1~ One to two R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is optionally substituted with a group. Embodiment 60.R B However, 1-2 R 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, wherein pyridine-3-yl is optionally substituted with a group. Embodiment 61.R B But, hello, C 1~C3 alkoxy, C 1~ One to two R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is pyridine-2-yl optionally substituted with a group. Embodiment 62.R B But, hello, C 1~ C3 alkoxy, C 1~ One to two R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a thiophenyl optionally substituted with a group. Embodiment 63.R B But, hello, C 1~ C3 alkoxy, C 1~ One to two R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is thiophene-2-yl optionally substituted with a group. Embodiment 64.R B But, hello, C 1~ C3 alkoxy, C 1~ One to two R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a cyclohexyl compound optionally substituted with a group. Embodiment 65.R B But, hello, C 1~ C3 alkoxy, C 1~ One to two R molecules independently selected from C3 alkyl and -CN. 5 A compound of formula (I) which is phenyl optionally substituted with a group, or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable compound thereof. Salt. Embodiment 66.R B However, 1-2 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is pyridine-2-yl optionally substituted with a group. Embodiment 67.R B However, 1-2 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a thiophenyl optionally substituted with a group. Embodiment 68.R B However, 1-2 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is thiophene-2-yl optionally substituted with a group. Embodiment 69.R B However, 1-2 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a cyclohexyl compound optionally substituted with a group. Embodiment 70.R B However, 1-2 R molecules are independently selected from Cl, F, -OCH3, methyl, and -CN. 5 A compound of formula (I) or a compound described in any one of embodiments 1 to 34, or a pharmaceutically acceptable salt thereof, which is a phenyl compound optionally substituted with a group. Embodiment 71. Phenylen ring R B A compound according to any one of Embodiments 38, 45, 46, 52, 53, 58, 59, 65, or 70, or a pharmaceutically acceptable salt thereof, wherein the upper substituent is located at the meta and / or para positions of the phenyl ring. Embodiment 72.R B but, [ka] A compound or a pharmaceutically acceptable salt thereof, selected from any one of embodiments 1 to 34, 38, 45, 46, 52, 53, 58, 59, 65, or 70. Embodiment 73.R B but, [ka] A compound or a pharmaceutically acceptable salt thereof, selected from any one of Embodiments 1 to 34, 38, 45, 46, 52, 53, 58, 59, 65, or 70. Embodiment 74.R 1 A compound of formula (I) or a compound described in any one of embodiments 1 to 73, or a pharmaceutically acceptable salt thereof, wherein H is present. Embodiment 75.R 1 However, C 1~ A compound of formula (I) that is a C3 alkyl compound, or a compound described in any one of embodiments 1 to 73, or a pharmaceutically acceptable salt thereof. Embodiment 76.R 1 A compound of formula (I) or a compound described in any one of embodiments 1 to 73, or a pharmaceutically acceptable salt thereof, wherein the compound is methyl. Embodiment 77.R 1 However, C substituted with 1 to 3 -OH groups 1~ A compound of formula (I) that is a C3 alkyl compound, or a compound described in any one of embodiments 1 to 73, or a pharmaceutically acceptable salt thereof. Embodiment 78.R 1 The compound of formula (I) or any one of the compounds described in Embodiments 1 to 73, or a pharmaceutically acceptable salt thereof, wherein the compound is -CH2OH. Embodiment 79.R 2 A compound of formula (I) or a compound described in any one of embodiments 1 to 78, or a pharmaceutically acceptable salt thereof, wherein H is present. Embodiment 80.R 2 However, C 1~ A compound of formula (I) or a compound described in any one of embodiments 1 to 78, or a pharmaceutically acceptable salt thereof, which is a C3 alkyl compound. Embodiment 81.R 2 A compound of formula (I) or a compound described in any one of embodiments 1 to 78, or a pharmaceutically acceptable salt thereof, wherein the compound is methyl. Embodiment 82.R 2However, C substituted with 1 to 3 -OH groups 1~ A compound of formula (I) or a compound described in any one of embodiments 1 to 78, or a pharmaceutically acceptable salt thereof, which is a C3 alkyl compound. Embodiment 83.R 2 The compound of formula (I) or any one of embodiments 1 to 78, or a pharmaceutically acceptable salt thereof, wherein the compound is -CH2OH. Embodiment 84. Each R 3 However, Hello, CN, C 1~ C3 alkoxy, C 1~ C3alkyl, C(=O)OR 10 , and C(=O)NR 13 R 14 A compound of formula (I) or a compound described in any one of embodiments 1 to 83, or a pharmaceutically acceptable salt thereof, independently selected from the above. Embodiment 85. Each R 3 However, Hello, CN, C 1~ C3 alkoxy and C 1~ A compound of formula (I) independently selected from C3 alkyl groups, or a compound described in any one of embodiments 1 to 83, or a pharmaceutically acceptable salt thereof. Embodiment 86. Each R 3 However, a compound of formula (I) or a compound described in any one of embodiments 1 to 83, or a pharmaceutically acceptable salt thereof, independently selected from Cl, F, CN, -OCH3, and methyl. Embodiment 87.R 3 A compound of formula (I) or a compound described in any one of embodiments 1 to 83, or a pharmaceutically acceptable salt thereof, wherein the compound is methyl. Embodiment 88.R 3 However, the compound of formula (I) or the compound described in any one of embodiments 1 to 83, or a pharmaceutically acceptable salt thereof, does not exist. Embodiment 89.R 4 However, H, C 1~ C3 alkyl, C 3~ C6 cycloalkyl, or -OH, -C(=O)R 15 and R 10 C substituted with 1-2 groups independently selected from 1~A compound of formula (I) that is a C3 alkyl compound, or a compound described in any one of embodiments 1 to 88, or a pharmaceutically acceptable salt thereof. Embodiment 90.R 4 However, H, methyl, cyclopropyl, [ka] A compound of formula (I) or a compound described in any one of embodiments 1 to 88, or a pharmaceutically acceptable salt thereof. Embodiment 91.R 4 However, H or C 1~ A compound of formula (I) that is a C3 alkyl compound, or a compound described in any one of embodiments 1 to 88, or a pharmaceutically acceptable salt thereof. Embodiment 92.R 4 A compound of formula (I) or a compound described in any one of embodiments 1 to 88, or a pharmaceutically acceptable salt thereof, wherein the compound is H or methyl. Embodiment 93.R 4 A compound of formula (I) or a compound described in any one of embodiments 1 to 88, or a pharmaceutically acceptable salt thereof, wherein H is present. Embodiment 94.R 4 A compound of formula (I) or a compound described in any one of embodiments 1 to 88, or a pharmaceutically acceptable salt thereof, wherein the compound is methyl. Embodiment 95.R 4 However, -OH, -C(=O)R 15 , and R 10 C substituted with 1-2 groups independently selected from 1~ A compound of formula (I) that is a C3 alkyl compound, or a compound described in any one of embodiments 1 to 88, or a pharmaceutically acceptable salt thereof. Embodiment 96.R 4 but, [ka] A compound of formula (I) or a compound described in any one of embodiments 1 to 88, or a pharmaceutically acceptable salt thereof. Embodiment 97.R 4 However, C 3~A compound of formula (I) that is a C6 cycloalkyl compound, or a compound described in any one of embodiments 1 to 88, or a pharmaceutically acceptable salt thereof. Embodiment 98.R 4 The compound of formula (I) or any one of the compounds described in Embodiments 1 to 87, or a pharmaceutically acceptable salt thereof, which is cyclopropyl. Embodiment 99. Each R 5 However, halo, -CN, hydroxy, -NR 13 R 14 , C 3~ C6 cycloalkyl, C 1~ C3 alkoxy, C 1~ C3 haloalkyl and 1-3 R 6 C is arbitrarily substituted in the base. 1~ Independently selected from C3 alkyl groups, where 1 to 3 R groups 6 The C that is arbitrarily substituted in the base 1~ When two C3 alkyl groups are directly bonded to the same carbon atom, they combine with the bonded carbon to form 1 to 3 atoms. 6 A compound of formula (I) or a compound described in any one of embodiments 1 to 98, or a pharmaceutically acceptable salt thereof, which can form a 3- to 5-membered cycloalkyl ring optionally substituted with a group. Embodiment 100. Each R 5 However, Hello, -CN, C 1~ C3 alkoxy and C 1~ A compound of formula (I) independently selected from C3 alkyl groups, or a compound described in any one of embodiments 1 to 98, or a pharmaceutically acceptable salt thereof. Embodiment 101. Each R 5 However, a compound of formula (I) or a compound described in any one of embodiments 1 to 98, or a pharmaceutically acceptable salt thereof, independently selected from Cl, F, -CN, -OCH3, and methyl. Embodiment 102. Each R 5 However, a compound of formula (I) or a compound described in any one of embodiments 1 to 98, or a pharmaceutically acceptable salt thereof, independently selected from Cl and -CN. Embodiment 103. Each R 6 However, each time it appears, Halo, Hydroxy, CN, C1~ C3 alkoxy, C 1~ C3 alkyl, and C 3~ A compound of formula (I) independently selected from C5 cycloalkyl groups, or a compound described in any one of Embodiments 1 to 102, or a pharmaceutically acceptable salt thereof. Embodiment 104. Each R 6 A compound of formula (I) or a compound described in any one of embodiments 1 to 102, or a pharmaceutically acceptable salt thereof, wherein the compound is hydroxyl. Embodiment 105. W is H, -OH, -OR, -C(=O)NR 13 R 14 , -C(=O)OR 13 , -NR 13 R 14 , -NR 13 C(=O)OR 10 , -NR 13 C(=O)R 10 , -SO2R 10 -SO2NR 13 R 14 , -NR 13 SO2R 10 , -P(=O)(OR 13 )2, -S(=O)R 10 -S(=O)(=NR 13 )R 10 ,-CR 11 R 12 C(=O)NR 13 R 14 ,-CR 11 R 12 C(=O)OR 13 ,-CR 11 R 12 NR 13 R 14 ,-CR 11 R 12 NR 13 C(=O)OR 10 ,-CR 11 R 12 NR 13 C(=O)R 10 ,-CR 11 R 12 SO2R 10 ,-CR 11 R 12 SO2NR13 R 14 ,-CR 11 R 12 NR 13 SO2R 10 ,-CR 11 R 12 P(=O)(OR 13 )2, -CR 11 R 12 S(=O)R 10 ,-CR 11 R 12 S(=O)(=NR 13 )R 10 , 3-6 member cycloalkyl, phenyl, N, NH, NR 17 5-6 member heterocycloalkyl, N, NH, NR, containing one or two ring members independently selected from O, or S. 17 A 5-6 member heterocycline containing one or two ring members independently selected from O or S, or a 5-member heteroaryl having 1-4 heteroatoms selected as ring members from N, O, and S, which can be optionally condensed with phenyl. Here, W consists of a 3-6 member cycloalkyl, a phenyl, a 5-6 member heterocycloalkyl, a 5-6 member heterocyclyl, and a 5 member heteroaryl, respectively, C 1~ C3 alkyl, oxo, halo, C 1~ C3 haloalkyl, -L 2 OH, -L 2 Ure 10 , -L 2 OC(=O)NR 13 R 14 , -L 2 SO2R 10 , -L 2 SO2NR 14 R 10 , -L 2 SO2NR 13 R 14 , -L 2 SO2N=CR 13 NR 13 R 14 , -L 2 SO2NR 13 C(=O)R 10 , -L 2 C(=O)NR 13 SO2R10 , -L 2 S(=O)R 10 , -L 2 S(=O)(=NR 13 )R 10 , -L 2 NR 13 SO2NR 13 R 14 , -L 2 NR 13 SO2R 10 , -L 2 NR 13 R 14 , -L 2 NR 13 C(=O)R 13 , -L 2 NR 13 C(=O)OR 10 , -L 2 C(=O)NR 13 R 14 , and -L 2 C(=O)OR 13 A compound of formula (I) or a compound according to any one of embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, which is optionally substituted with 1 to 3 groups independently selected from . Embodiment 106. W is H, -OH, -OR, -C(=O)NR 13 R 14 , -C(=O)OR 13 , -NR 13 R 14 , -NR 13 C(=O)OR 10 , -NR 13 C(=O)R 10 , -SO2R 10 -SO2NR 13 R 14 , -NR 13 SO2R 10 , -P(=O)(OR 13 )2, -S(=O)R 10 -S(=O)(=NR 13 )R 10 ,-CR 11 R 12 C(=O)NR 13 R 14 ,-CR 11 R 12C(=O)OR 13 ,-CR 11 R 12 NR 13 R 14 ,-CR 11 R 12 NR 13 C(=O)OR 10 ,-CR 11 R 12 NR 13 C(=O)R 10 ,-CR 11 R 12 SO2R 10 ,-CR 11 R 12 SO2NR 13 R 14 ,-CR 11 R 12 NR 13 SO2R 10 ,-CR 11 R 12 P(=O)(OR 13 )2, -CR 11 R 12 S(=O)R 10 , or -CR 11 R 12 S(=O)(=NR 13 )R 10 A compound of formula (I) or a compound described in any one of embodiments 1 to 104, or a pharmaceutically acceptable salt thereof. Embodiment 107. W is a 3-6 member cycloalkyl, phenyl, N, NH, NR 17 5-6 member heterocycloalkyl, N, NH, NR containing one or two ring members independently selected from O, or S. 17 , a 5-6 membered heterocycline containing one or two ring members independently selected from O or S, or a 5-membered heteroaryl having 1 to 4 heteroatoms selected from N, O, and S as ring members condensed to phenyl, Here, W consists of a 3-6 member cycloalkyl, a phenyl, a 5-6 member heterocycloalkyl, a 5-6 member heterocyclyl, and a 5 member heteroaryl, respectively, C 1~ C3 alkyl, oxo, halo, C 1~ C3 haloalkyl, -L2 OH, -L 2 Ure 10 , -L 2 OC(=O)NR 13 R 14 , -L 2 SO2R 10 , -L 2 SO2NR 14 R 10 , -L 2 SO2NR 13 R 14 , -L 2 SO2N=CR 13 NR 13 R 14 , -L 2 SO2NR 13 C(=O)R 10 , -L 2 C(=O)NR 13 SO2R 10 , -L 2 S(=O)R 10 , -L 2 S(=O)(=NR 13 )R 10 , -L 2 NR 13 SO2NR 13 R 14 , -L 2 NR 13 SO2R 10 , -L 2 NR 13 R 14 , -L 2 NR 13 C(=O)R 13 , -L 2 NR 13 C(=O)OR 10 , -L 2 C(=O)NR 13 R 14 , and -L 2 C(=O)OR 13 A compound of formula (I) or a compound according to any one of embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, which is optionally substituted with 1 to 3 groups independently selected from . Embodiment 108. W, C 1- C3 alkyl, oxo, halo, C 1~ C3 haloalkyl, -L2 OH, -L 2 Ure 10 , -L 2 OC(=O)NR 13 R 14 , -L 2 SO2R 10 , -L 2 SO2NR 14 R 10 , -L 2 SO2NR 13 R 14 , -L 2 SO2N=CR 13 NR 13 R 14 , -L 2 SO2NR 13 C(=O)R 10 , -L 2 C(=O)NR 13 SO2R 10 , -L 2 S(=O)R 10 , -L 2 S(=O)(=NR 13 )R 10 , -L 2 NR 13 SO2NR 13 R 14 , -L 2 NR 13 SO2R 10 , -L 2 NR 13 R 14 , -L 2 NR 13 C(=O)R 13 , -L 2 NR 13 C(=O)OR 10 , -L 2 C(=O)NR 13 R 14 , and -L 2 C(=O)OR 13 Compounds of formula (I) or embodiments 1-104, which are 3-6 membered cycloalkyls optionally substituted with 1-3 groups independently selected from the above. A compound or a pharmaceutically acceptable salt thereof as described in any one of the items. Embodiment 109. W is -O2R 10 -SO2NR14 R 10 -SO2NR 13 R 14 , or -SO2N=CR 13 NR 13 R 14 -SO2NR 13 C(=O)R 10 -C(=O)NR 13 SO2R 10 -S(=O)R 10 -S(=O)(=NR 13 )R 10 , -NR 13 SO2NR 13 R 14 , -NR 13 SO2R 10 , -NR 13 R 14 , -NR 13 C(=O)R 13 , -NR 13 C(=O)OR 10 -C(=O)NR 13 R 14 , and -C(=O)OR 13 A compound of formula (I) or a compound described in any one of embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, which is a cyclopropyl substituted with . Embodiment 110. W, -SO2R 10 -SO2NR 14 R 10 -SO2NR 13 R 14 , or -SO2N=CR 13 NR 13 R 14 A compound of formula (I) or a compound described in any one of embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, which is a cyclopropyl substituted with . Embodiment 111.WL--part, [ka] A compound of formula (I) or a compound described in any one of embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, selected from the above. Embodiment 112.W is, [ka] [ka] [ka] A compound of formula (I) or a compound described in any one of embodiments 1 to 104, or a pharmaceutically acceptable salt thereof, selected from the above. Embodiment 113.R 10 However, C 1~ C4 alkyl, C 1~ C3 haloalkyl, 3-6 membered cycloalkyl, phenyl, 5-6 membered heteroaryl having 1-4 heteroatoms independently selected from N, O, and S as ring members, N, NH, NR 17 A 4-6 member heterocycloalkyl group containing one or two ring members independently selected from O, or S, and bi N, NH, NR 17 Selected from 4-6 membered heterocyclyl rings containing 1-2 ring members independently selected from O or S, Here, each R 10 However, C 1~ C4alkyl, deuterium, C 1~ C4 haloalkoxy, -OH, -CN, -OC(=O)R 14 , -L 3 Ure 13 , C 1~ C2 haloalkyl, oxo, -halo, -C 1~ C3 alkoxy, -OC(=O)NR 13 R 14 , -SO2R 13 -SO2NR 13 R 14 -SO2NR 13 C(=O)R 13 -C(=O)NR 13 SO2R 13 -S(=O)R 13 -S(=O)(=NR 14 )R 13 , -NR 13 SO2NR13 R 14 , -NR 13 SO2R 13 , -NR 13 R 14 , -NR 14 C(=O)R 13 , -NR 14 C(=O)OR 13 -C(=O)NR 13 R 14 , -C(=O)OR 13 -(4-7 membered heterocycline containing 1-2 heteroatoms independently selected from N, O, or S as ring members), -C 3~ C5 cycloalkyl and optionally substituted with 1 to 5 groups independently selected from -(a 5-6 membered heteroaryl ring having 1 to 4 heteroatoms, containing 1 to 4 nitrogen atoms, 0 or 1 oxygen atom, and 0 or 1 sulfur atom as ring members), where C 1~ C4 alkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocyclyl, C 3~ C5 cycloalkyl and 5-6 membered heteroaryl rings are, respectively, halo and C 1~ C3 alkyl, C 1~ C3 haloalkyl, -L 4 Ure 13 , -L 4 CN, and -L 4 NR 13 R 14 A compound of formula (I) or a compound according to any one of embodiments 1 to 112, or a pharmaceutically acceptable salt thereof, which is optionally further substituted with 1 to 3 groups independently selected from the above. Embodiment 114.R 10 However, C 1~ C4 alkyl, C 1~ C3 haloalkyl, 3-6 membered ring cycloalkyl, 5-6 membered ring heteroaryl having 1-4 heteroatoms independently selected from N, O, and S as ring members, N, NH, NR 17 4-6 member heterocycloalkyls containing one or two ring members independently selected from O, or S, and N, NH, NR 17 Selected from 4-6 membered heterocyclyl rings containing 1-2 ring members independently selected from O or S, Here, each R 10 However, C 1~ C4alkyl, deuterium, C 1~ C4 haloalkoxy, -OH, -CN, -OC(=O)R 14 , -L 3 Ure 13 , -NR 13 R 14 , -NR 14 C(=O)R 13 , -NR 14 C(=O)OR 13 -C(=O)NR 13 R 14 , -C(=O)OR 13 , (N, NH, NR 17 (4-7 member heterocycloalkyls containing 1-2 ring members, independently selected from O, or S), (N, NH, NR) 17 A 4-7 member heterocycline containing 1-2 ring members, independently selected from O, or S, and -C 3~ It is optionally substituted with 1 to 5 groups independently selected from C5 cycloalkyl groups, where C 1~ C4 alkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocyclyl, and C 3~ C5 cycloalkyl groups are represented by halo, -OR, respectively. 13 -CN and -NR 13 R 14 A compound of formula (I) or a compound according to any one of embodiments 1 to 112, or a pharmaceutically acceptable salt thereof, which is optionally further substituted with 1 to 3 groups independently selected from the above. Embodiment 115. R 10 However, it is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, cyclopropyl, cyclobutyl, pyridinyl, pyrazolyl, isoxazolyl, oxetanyl, tetrahydrofuranil, tetrahydropyranil, morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, and azetidinyl. Here, each R 10 However, methyl, ethyl, deuterium, -OCH3, -OH, -OCHF2, -CN, -NH2, -NHCH3, -N(CH3)2, -NHR 13, -NHCH(=O), -NHC(=O)CH3, -NHC(=O)OCH3, -NHC(=O)CH2NH2, -NHC(=O)CH2N(CH3)2, -NHC(=O)CH(CH3)NH2, -NHC(=O)C(CH3)2NH2, -OCH2CH2OH, -OCH2CH(CH3)OH, -OCH2CH(CH 3)2OH, -OCH(F)CH2OH, -OCF2CH2OH, -OCH2CH2NH2, -OCH2CH(CH3)NH2, -OCH2C(CH3)2NH2, -OCH2CH2NHCH3, -OCH2CH2N(CH3)2, -OCH(F)CH2NH2, -OCF2CH2NH2, -CH2OCH2CH2NH2, Optionally substituted with 1 to 4 groups independently selected from -CH2CH2OH, -CH2OH, -CH2NH2, -O-azetidinyl, -C(=O)NH2, -C(=O)NHCH3, -OC(=O)CH3, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl, Herein, methyl, ethyl, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl are each optionally further substituted with 1 to 3 groups independently selected from F, -OH, -OCH3, -NH2, and methyl, respectively, the compound of formula (I) or the compound described in any one of embodiments 1 to 110 or a pharmaceutically acceptable salt thereof. Embodiment 116. R 10 However, it is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and pentyl. Here, each R 10 However, methyl, ethyl, deuterium, -OCH3, -OH, -OCHF2, -CN, -NH2, -NHCH3, -N(CH3)2, -NHR 13, -NHCH(=O), -NHC(=O)CH3, -NHC(=O)OCH3, -NHC(=O)CH2NH2, -NHC(=O)CH2N(CH3)2, -NHC(=O)CH(CH3)NH2, -NHC(=O)C(CH3)2NH2, -OCH2CH2OH, -OCH2CH (CH3)OH, -OCH2CH(CH3)2OH, -OCH(F)CH2OH, -OCF2CH2OH, -OCH2CH2NH2, -OCH2CH(CH3)NH2, -OCH2C(CH3)2NH2, -OCH2CH2NHCH3, -OCH2CH2N(CH3)2, -OCH( F) Optionally substituted with 1 to 4 groups independently selected from CH2NH2, -OCF2CH2NH2, -CH2OCH2CH2NH2, -CH2CH2OH, -CH2OH, -CH2NH2, -O-azetidinyl, -C(=O)NH2, -C(=O)NHCH3, -OC(=O)CH3, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl, Herein, methyl, ethyl, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl are each optionally further substituted with 1 to 3 groups independently selected from F, -OH, -OCH3, -NH2, and methyl, respectively, the compound of formula (I) or the compound described in any one of embodiments 1 to 112 or a pharmaceutically acceptable salt thereof. Embodiment 117. R 10 However, selected from cyclopropyl and cyclobutyl, Here, each R 10 However, methyl, ethyl, deuterium, -OCH3, -OH, -OCHF2, -CN, -NH2, -NHCH3, -N(CH3)2, -NHR 13, -NHCH(=O), -NHC(=O)CH3, -NHC(=O)OCH3, -NHC(=O)CH2NH2, -NHC(=O)CH2N(CH3)2, -NHC(=O)CH(C H3)NH2, -NHC(=O)C(CH3)2NH2, -OCH2CH2OH, -OCH2CH(CH3)OH, -OCH2CH(CH3)2OH, -OCH(F)CH2OH, - OCF2CH2OH, -OCH2CH2NH2, -OCH2CH(CH3)NH2, -OCH2C(CH3)2NH2, -OCH2CH2NHCH3, -OCH2CH2N(CH3) 2, -OCH(F)CH2NH2, -OCF2CH2NH2, -CH2OCH2CH2NH2, -CH2CH2OH, -CH2OH, -CH2NH2, -O-azetidinyl, -C(=O ) Optionally substituted with 1 to 4 groups independently selected from NH2, -C(=O)NHCH3, -OC(=O)CH3, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl, Herein, methyl, ethyl, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl are each optionally further substituted with 1 to 3 groups independently selected from F, -OH, -OCH3, -NH2, and methyl, respectively, the compound of formula (I) or the compound described in any one of embodiments 1 to 112 or a pharmaceutically acceptable salt thereof. Embodiment 118. R 10 However, selected from pyridinyl, pyrazolyl, and isoxazolyl, Here, each R 10 However, methyl, ethyl, deuterium, -OCH3, -OH, -OCHF2, -CN, -NH2, -NHCH3, -N(CH3)2, -NHR 13, -NHCH(=O), -NHC(=O)CH3, -NHC(=O)OCH3, -NHC(=O)CH2NH2, -NHC(=O)CH2N(CH3)2, -NHC(=O)CH(CH3)NH2, -NHC(=O)C(CH3)2NH2, -OCH2CH2OH, -OCH2CH (CH3)OH, -OCH2CH(CH3)2OH, -OCH(F)CH2OH, -OCF2CH2OH, -OCH2CH2NH2, -OCH2CH(CH3)NH2, -OCH2C(CH3)2NH2, -OCH2CH2NHCH3, -OCH2CH2N(CH3)2, -OCH( F) Optionally substituted with 1 to 4 groups independently selected from CH2NH2, -OCF2CH2NH2, -CH2OCH2CH2NH2, -CH2CH2OH, -CH2OH, -CH2NH2, -O-azetidinyl, -C(=O)NH2, -C(=O)NHCH3, -OC(=O)CH3, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl, Herein, methyl, ethyl, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl are each optionally further substituted with 1 to 3 groups independently selected from F, -OH, -OCH3, -NH2, and methyl, respectively, the compound of formula (I) or the compound described in any one of embodiments 1 to 112 or a pharmaceutically acceptable salt thereof. Embodiment 119. R 10 However, selected from oxetanil, tetrahydrofuranil, tetrahydropyranil, morpholinil, piperidinil, piperazinil, pyrrolidinil, and azetidinil, Here, each R 10 However, methyl, ethyl, deuterium, -OCH3, -OH, -OCHF2, -CN, -NH2, -NHCH3, -N(CH3)2, -NHR 13, -NHCH(=O), -NHC(=O)CH3, -NHC(=O)OCH3, -NHC(=O)CH2NH2, -NHC(=O)CH2N(CH3)2, -NHC(=O)CH(CH3)NH2, -NH C(=O)C(CH3)2NH2, -OCH2CH2OH, -OCH2CH(CH3)OH, -OCH2CH(CH3)2OH, -OCH(F)CH2OH, -OCF2CH2OH, -OCH2CH2NH 2, -OCH2CH(CH3)NH2, -OCH2C(CH3)2NH2, -OCH2CH2NHCH3, -OCH2CH2N(CH3)2, -OCH(F)CH2NH2, -OCF2CH2NH2, -CH2OCH2CH2NH2, -CH2CH2OH, -CH2OH, -CH2NH2, -O-azetidinyl, -C(=O)NH2, -C(=O)NHCH3, -OC(=O)CH3, cyclopropyl, azetidinyl Optionally substituted with 1 to 4 groups independently selected from nyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl, Herein, methyl, ethyl, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl are each optionally further substituted with 1 to 3 groups independently selected from F, -OH, -OCH3, -NH2, and methyl, respectively, the compound of formula (I) or the compound described in any one of embodiments 1 to 112 or a pharmaceutically acceptable salt thereof. Embodiment 120.R 10 but, [ka] [ka] A compound of formula (I) or a compound described in any one of embodiments 1 to 112, or a pharmaceutically acceptable salt thereof, selected from the above. Embodiment 121.R 11 and R 12 However, a compound of formula (I) or a compound described in any one of embodiments 1 to 120, or a pharmaceutically acceptable salt thereof, independently selected from H and methyl. Embodiment 122. Each R 13 However, H, C 1~ C4 alkyl, N, NH, NR 17 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S. 17 A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C 3~ Independently selected from C6 cycloalkyl groups, where C 1~ C4 alkyl, heterocyclyl, and C 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , -C(=O)OR 15 , C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ A compound of formula (I) or a compound according to any one of embodiments 1 to 121, or a pharmaceutically acceptable salt thereof, optionally substituted with 1 to 3 groups independently selected from a C4 alkyl group. Embodiment 123. Each R 13 However, H, C 1~ C4 alkyl, N, NH, NR 17 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S. 17 A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C 3~ Independently selected from C6 cycloalkyl groups, where C 1~ C4 alkyl, heterocyclyl, and C 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR15 R 16 , -C(=O)OR 15 , and C substituted with 1-2 hydroxyl groups 1~ Optionally, 1 to 3 groups independently selected from the C4 alkyl group can be placed. A compound of formula (I) or a compound described in any one of embodiments 1 to 121, or a pharmaceutically acceptable salt thereof. Embodiment 124. Each R 13 However, H or C 1~ Independently selected from C4 alkyl, where C 1~ C4 alkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , -C(=O)OR 15 , and C substituted with 1-2 hydroxyl groups 1~ A compound of formula (I) or a compound described in any one of embodiments 1 to 121, or a pharmaceutically acceptable salt thereof, which is optionally substituted with 1 to 3 groups independently selected from a C4 alkyl group. Embodiment 125. Each R 13 However, N, NH, NR 17 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S. 17 A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C 3~ Independently selected from C6 cycloalkyls, where heterocyclyl and C6 cycloalkyls are selected. 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , -C(=O)OR 15 , and C substituted with 1-2 hydroxyl groups 1~ A compound of formula (I) or a compound according to any one of embodiments 1 to 121, or a pharmaceutically acceptable salt thereof, optionally substituted with 1 to 3 groups independently selected from a C4 alkyl group. Embodiment 126. Each R 13 However, H, methyl, -CHF2, [ka] A compound of formula (I) or a compound described in any one of embodiments 1 to 121, or a pharmaceutically acceptable salt thereof, independently selected from the above. Embodiment 127.R 14 However, H, C 1~ C4 alkyl, and C 3~ Selected from C6 cycloalkyl, where C 1~ C4 alkyl and C 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ A compound of formula (I) or a compound according to any one of embodiments 1 to 126, or a pharmaceutically acceptable salt thereof, optionally substituted with 1 to 3 groups independently selected from a C4 alkyl group. Embodiment 128.R 14 However, H and C 1~ A compound of formula (I) selected from C4 alkyl groups, or a compound described in any one of embodiments 1 to 126, or a pharmaceutically acceptable salt thereof. Embodiment 129.R 14 A compound of formula (I) or a compound described in any one of embodiments 1 to 126, or a pharmaceutically acceptable salt thereof, wherein the compound is H or methyl. Embodiment 130.R 15 However, H and C 1~ A compound of formula (I) selected from C4 alkyl groups, or a compound described in any one of embodiments 1 to 130, or a pharmaceutically acceptable salt thereof. Embodiment 131.R 15 A compound of formula (I) or a compound described in any one of embodiments 1 to 130, or a pharmaceutically acceptable salt thereof, wherein the compound is H or methyl. Embodiment 132.R 16 However, H and C 1~ A compound of formula (I) selected from C4 alkyl groups, or a compound described in any one of embodiments 1 to 131, or a pharmaceutically acceptable salt thereof. Embodiment 133.R16 A compound of formula (I) or a compound described in any one of embodiments 1 to 131, or a pharmaceutically acceptable salt thereof, wherein the compound is H or methyl. Embodiment 134.L 2 However, linked, or linear or branched C 1~ A compound of formula (I) or a compound described in any one of embodiments 1 to 133, or a pharmaceutically acceptable salt thereof, which is a C3 alkylene. Embodiment 135.L 2 A compound of formula (I) or a compound described in any one of embodiments 1 to 133, or a pharmaceutically acceptable salt thereof, wherein the compound is bonded, -CH2-, or -CH2CH2-. Embodiment 136.L 2 The compound of formula (I) or any of the compounds described in Embodiments 1 to 133, or a pharmaceutically acceptable salt thereof, which is a bond. Embodiment 137.L 3 However, linked, or linear or branched C 1~ A compound of formula (I) or a compound described in any one of embodiments 1 to 136, or a pharmaceutically acceptable salt thereof, which is a C3 alkylene. Embodiment 138.L 3 A compound of formula (I) or a compound described in any one of embodiments 1 to 136, or a pharmaceutically acceptable salt thereof, wherein the compound is bonded, -CH2-, or -CH2CH2-. Embodiment 139.L 3 The compound of formula (I) or any of the compounds described in Embodiments 1 to 136, or a pharmaceutically acceptable salt thereof, which is a bond. Embodiment 140.L 4 However, linked, or linear or branched C 1~ A compound of formula (I) or a compound described in any one of embodiments 1 to 139, or a pharmaceutically acceptable salt thereof, which is a C3 alkylene. Embodiment 141.L 4 A compound of formula (I) or a compound described in any one of embodiments 1 to 139, or a pharmaceutically acceptable salt thereof, wherein the compound is bonded, -CH2-, or -CH2CH2-. Embodiment 142.L 4The compound of formula (I) or any of the compounds described in Embodiments 1 to 139, or a pharmaceutically acceptable salt thereof, which is a bond. Embodiment 143. A compound of formula (I) or a compound according to any one of Embodiments 1 to 142, wherein when W is an optionally substituted ring, L may be a C1-C4 straight chain or branched alkylene linker or bond. Embodiment 144. A compound of formula (I) or a compound according to any one of Embodiments 1 to 142, wherein L is a C1-C4 linear or branched alkylene linker. Embodiment 145. A compound of formula (I) or a compound according to any one of Embodiments 1 to 142, wherein L is -CH2- or -CH2CH2-. Embodiment 146. A compound of formula (I) or a compound according to any one of Embodiments 1 to 142, wherein L is -CH2-. Embodiment 147. A compound of formula (I) or any one of the compounds described in Embodiments 1 to 111, wherein W is an optionally substituted ring, and L is a bond. Embodiment 148. A compound of formula (I) having the structure of formula (II) or a pharmaceutically acceptable salt thereof, [ka] During the ceremony, W is -SO2R 10 -SO2NR 13 R 14 , or -SO2NR 14 R 10 It is a cyclopropyl substituted with; R 10 R is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropyl, and pyridinyl; where R 10 It is optionally substituted with 1 to 4 groups independently selected from methyl, ethyl, -OH, -NH2, -CH2OH, and -CH2NH2; L is a C1-C4 linear or branched alkylene linker; R 1 H and C 1~ Selected from C3 alkyl groups; R2 H is; t is 0, and R 3 It does not exist; R 4 H, C 1~ C3 alkyl, or C substituted with 1-2 groups independently selected from -OH and methyl 1~ It is a C3 alkyl group; Each R 13 and R 14 H and C 1~ Selected independently from C4 alkyl; Furthermore, R B This is 1 to 3 R 5 Phenyl is optionally substituted with a group; and each R 5 These are independently: Haro, -CN, C 1~ C3alkyl, or C 1~ A compound of formula (I) having the structure of formula (II) and being a C3 alkyl group, or a pharmaceutically acceptable salt thereof. Embodiment 149. A compound of formula (I) having the structure of formula (II) or a pharmaceutically acceptable salt thereof, [ka] During the ceremony, W is -SO2R 10 or -SO2NR 14 R 10 It is a cyclopropyl substituted with; R 10 R is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, cyclopropyl, and pyridinyl; where R 10 It is optionally substituted with one or two groups independently selected from methyl, -OH, -NH2, -CH2OH, and -CH2NH2; L is either -CH2- or -CH2CH2; R 1 H and C 1~ Selected from C3 alkyl groups; R 2 H is; t is 0, and R 3 It does not exist; R4 H, C 1~ C3 alkyl, or C substituted with 1-2 groups independently selected from -OH and methyl 1~ It is a C3 alkyl group; R 14 H is; Furthermore, R B This is one R 5 Phenyl is optionally substituted with a group; and, R 5 is a compound of formula (I) having the structure of formula (II), or a pharmaceutically acceptable salt thereof, which is a halo or -CN. Embodiment 150. A compound of formula (I) having the structure of formula (II) or a pharmaceutically acceptable salt thereof, [ka] During the ceremony, W is -SO2R 10 or -SO2NR 14 R 10 It is a cyclopropyl substituted with; R 10 R is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, cyclopropyl, and pyridinyl; where R 10 It is optionally substituted with one or two groups independently selected from methyl, -OH, -NH2, -CH2OH, and -CH2NH2; L is -CH2-; R 1 , R 2 , and R 14 Each of these is H; t is 0, and R 3 It does not exist; R 4 H, C 1~ C3 alkyl, or C substituted with 1-2 groups independently selected from -OH and methyl 1~ It is a C3 alkyl group; Furthermore, R B This is one R 5 Phenyl is optionally substituted with a group; and, R 5is a compound of formula (I) having the structure of formula (II), or a pharmaceutically acceptable salt thereof, which is a halo or -CN. Embodiment 151. A compound of formula (I), selected from any one of the compounds described in Examples 1 to 242 or a pharmaceutically acceptable salt thereof. This embodiment includes each of the examples shown in the table of bioactivity data provided herein. Embodiment 152. A compound of formula (I) or a pharmaceutically acceptable salt thereof, the following: N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-N-(4-fluorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-N,1-dimethyl-7-oxo-4,5,6,7-tetrahydro-1H -Pyrazolo[3,4-c]pyridine-3-carboxamide; N-((6-chloropyridine-3-yl)methyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-N-(4-methylbenzyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyano-3-fluorobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-((5-chlorothiophen-2-yl)methyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyano-3-methylbenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyano-2-methylbenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyano-2-fluorobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-((5-cyanopyridine-2-yl)methyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyano-3-methoxybenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(1-(4-cyanophenyl)ethyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(1-(4-cyanophenyl)ethyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(1-(4-chlorophenyl)-2-hydroxyethyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(1-(4-chlorophenyl)-2-hydroxyethyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(ethylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-1-methyl-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3 ,4-c]pyridine-3-carboxamide; N-(4-cyano-3-fluorobenzyl)-1-methyl-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 4-Cyanobenzyl 6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate; 4-(2-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-2-oxoethoxy)benzonitrile; 4-((5-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-1,3,4-oxadiazole-2-yl)methyl)benzonitrile; 4-((5-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-1,2,4-oxadiazole-3-yl)methyl)benzonitrile; 4-((3-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-1,2,4-oxadiazole-5-yl)methyl)benzonitrile; 4-((5-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-2H-tetrazole-2-yl)methyl)benzonitrile; 4-((5-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-1H-tetrazole-1-yl)methyl)benzonitrile; 4-(3-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-4,5-dihydroisoxazole-5-yl)benzonitrile; (R)-4-(3-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-4,5-dihydroisoxazole-5-yl)benzonitrile; (S)-4-(3-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-4,5-dihydroisoxazole-5-yl)benzonitrile; 4-((3-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)isoxazole-5-yl)methyl)benzonitrile; 4-((4-(6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-1H-1,2,3-triazole-1-yl)methyl)benzonitrile; 6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-3-(1-((4,4-difluorocyclohexyl)methyl)-1H-1,2,3-triazole-4-yl)-1-methyl-5,6-dihydro-1H-pyrazolo[3,4-c]pyridine-7 (4H)-on; N-(4-chlorophenoxy)-1-methyl-6-((1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((difluoromethyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-((difluoromethyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1,5-dimethyl-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-1,5-dimethyl-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-1,5-dimethyl-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-cyclopropyl-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 4-((8-((1-(methylsulfonyl)cyclopropyl)methyl)-1,7-dioxo-3,4,7,8,9,10-hexahydropyrido[3',4':3,4]pyrazolo[1,5-a]pyrazine-2(1H)-yl)methyl)benzonitrile; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-((1-(hydroxymethyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-((1-(hydroxymethyl)cyclopropyl)methyl)-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-hydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-((6-chloropyridine-3-yl)methyl)-6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-fluorobenzyl)-6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(1-(4-cyanophenyl)ethyl)-6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(1-(4-cyanophenyl)ethyl)-6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-hydroxy-2-methylpropan-2-yl-1,1-d2)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 2-((1-((3-((4-cyanobenzyl)carbamoyl)-1-methyl-7-oxo-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine-6(7H)-yl)methyl)cyclopropyl)sulfonyl)-2-methylpropylacetate; N-(4-cyanobenzyl)-6-((1-((1-(difluoromethoxy)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((2-cyanopropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(3-fluoroazetidine-1-yl)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-((2-methyl-1-morpholinopropan-2-yl)sulfonyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((1-(3-methoxypyrrolidine-1-yl)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(3-hydroxyazetidine-1-yl)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(3-methoxyazetidine-1-yl)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-((2-methyl-1-(2-oxa-6-azaspiro[3,3]heptan-6-yl)propan-2-yl)sulfonyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(3-hydroxypyrrolidine-1-yl)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-((2-hydroxyethyl)amino)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-amino-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-formamido-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-acetamido-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; Methyl(2-((1-((3-((4-cyanobenzyl)carbamoyl)-1-methyl-7-oxo-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine-6-yl)methyl)cyclopropyl)sulfonyl)-2-methylpropyl)carbamate; 6-((1-((1-(2-aminoacetamide)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((1-(2-aminopropanamide)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((1-(2-aminopropanamide)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-(2-amino-2-methylpropanamide)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c Pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(2-(dimethylamino)acetamide)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(1-fluoro-2-hydroxyethoxy)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((1-(1-fluoro-2-hydroxyethoxy)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-((1-(1-fluoro-2-hydroxyethoxy)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((1-(2-amino-1-fluoroethoxy)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((1-(2-amino-1-fluoroethoxy)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(1,1-difluoro-2-hydroxyethoxy)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-(2-amino-1,1-difluoroethoxy)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(2-hydroxy-2-methylpropyl)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(2-hydroxyethoxy)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-((1-(2-hydroxyethoxy)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(2-hydroxypropyl)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((1-(2-hydroxyprop (L)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-((1-(2-hydroxypropyl)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-(2-aminoethoxy)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-(2-aminoethoxy)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-(2-aminoethoxy)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-fluorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-((2-aminoethoxymethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-((2-aminoethoxy)methyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((1-(2-aminopropyl)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((1-(2-aminopropyl)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((1-(2-aminopropyl)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((1-(2-aminopropyl)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-((2-methyl-1-(2-(methylamino)ethoxy)propan-2-yl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-((azetidine-3-yloxy)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine -3-carboxamide; 6-((1-((1-(2-amino-2-methylpropyl)-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(2-(dimethylamino)ethoxy)-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 4-((4-(6-((1-((1-hydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-1H-1,2,3-triazole-1-yl)methyl)benzonitrile; 4-(3-(6-((1-((1-hydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-4,5-dihydroisoxazole-5-yl)benzonitrile; (R)-4-(3-(6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-4,5-dihydroisoxazole-5-yl)benzonitrile; (S)-4-(3-(6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-yl)-4,5-dihydroisoxazole-5-yl)benzonitrile; 6-((1-((1-amino-2-methyl-1-oxopropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-1-methyl-6-((1-((2-methyl-1-(methylamino)-1-oxopropan-2-yl)sulfonyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-1-methyl-6-((1-((2-(3-methyl-4,5-dihydroisoxazole-5-yl)propan-2-yl)sulfonyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-1-methyl-6-((1-((2-(3-methyl-4,5-dihydroisoxazole-5-yl)propan-2-yl)sulfonyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((4-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((4-hydroxy-2-methylpentan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((4-hydroxy-2-methylpentan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo -4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-((4-hydroxy-2-methylpentan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-(2-hydroxyethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((2-hydroxy-2-methylpropyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(((1s,3s)-3-hydroxycyclobutyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(((1r,3r)-3-hydroxycyclobutyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-1-methyl-7-oxo-6-((1-sulfamoylcyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (E)-N-(4-chlorobenzyl)-6-((1-(N-((dimethylamino)methylene)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(N-methylsulfamoyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(morpholinosulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((4-hydroxypiperidine-1-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((3-hydroxypyrrolidine-1-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-((3-hydroxypyrrolidine-1-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((3-hydroxyazetidine-1-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-cyclopropylsulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-((3-hydroxy-3-methylpyrrolidine-1-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((3-hydroxy-3-methyl Pyrrolidine-1-yl)sulfonyl)cyclopropyl)methyl)1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(N-(oxetan-3-yl)sulfamoyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(piperazine-1-ylsulfonyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-(N-(3-aminopropyl)sulfamoyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-(N-(2-aminoethyl)sulfamoyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-((4-methylpiperazine-1-yl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(N-(piperidine-4-yl)sulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((4-aminopiperidine-1-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-(((3R,4R)-3-amino-4-hydroxypyrrolidine-1-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-(((3S,4S)-3-amino-4-hydroxypyrrolidine-1-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((3-aminopyrrolidine-1-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((3-aminopyrrolidine-1-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(N-(2-hydroxyethyl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(N-(2-hydroxyethyl)-N-methylsulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(2-hydroxyethyl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(2-hydroxyethyl)-N-methylsulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(1,3-dihydroxypropan-2-yl)-N-methylsulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(N-(1-hydroxy-2-methylpropan-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(1-hydroxy-2-methylpropan-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-((3-hydroxyazetidine-1-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-1-methyl-6-((1-(N-methylsulfamoyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(N-(2-hydroxy-2-methylpropyl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(N-(1,3-dihydroxy-2-methylpropan-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(N-(1,3-dihydroxy-2-methylpropan-2-yl)-N-methylsulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(N-(pyridine-2-yl)sulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(N-(1-methyl-1H-pyrazole-3-yl)sulfamoyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(N-(6-methylpyridine-2-yl)sulfamoyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-1-methyl-7-oxo-6-((1-(N-(pyridine-2-yl)sulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(3-methoxypyridine-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(3-methoxy-6-methylpyridine-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(N-(2-methylpyridine -3-yl)sulfamoyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(2-methoxypyridine-3-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(6-methoxypyridine-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(N-(3-methylpyridine-2-yl)sulfamoyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(N-(5-methylisoxazole-3-yl)sulfamoyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-1-methyl-6-((1-(N-(5-methylisoxazole-3-yl)sulfamoyl)cyclopropyl)methyl)7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(5-cyclopropylisoxazole-3-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-(oxetane-3-ylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-((tetrahydro-2H-pyran-4-yl)sulfonyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-((tetrahydrofuran-3-yl)sulfonyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-((tetrahydrofuran-3-yl)sulfonyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-6-((1-((3-methyloxetan-3-yl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((3-(hydroxymethyl)oxetan-3-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((3-(aminomethyl)oxetan-3-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-((1,3-dihydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1,3-dihydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboc Samido; (S)-N-(1-(4-chlorophenyl)ethyl)-6-((1-((1,3-dihydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(1-(4-chlorophenyl)ethyl)-6-((1-((1,3-dihydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1,3-dimethoxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-hydroxy-3-methoxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((1-hydroxy-3-methoxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-((1-hydroxy-3-methoxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-amino-3-hydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((1-amino-3-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((1-amino-3-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-amino-3-hydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((1-amino-3-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((1-amino-3-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-((3,4-dihydroxy-2-methyl b Tan-2-yl)sulfonyl)cyclopropyl)methyl)1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-chlorobenzyl)-6-((1-((3,4-dihydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-chlorobenzyl)-6-((1-((3,4-dihydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-((3,4-dihydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((3,4-dihydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-((1-(1,2-dihydroxyethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((1-(1,2-dihydroxyethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-chlorobenzyl)-6-((1-((1-(1,2-dihydroxyethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-chlorobenzyl)-6-((1-((1-(1,2-dihydroxyethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((4-amino-3-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((4-amino-3-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((4-amino-3-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((4-amino-3-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine- 3-Carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((3-hydroxy-2-methyl-4-(methylamino)butan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-((3-hydroxy-2-methyl-4-(methylamino)butan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide, (R)-N-(4-chlorobenzyl)-6-((1-((3-hydroxy-2-methyl-4-(methylamino)butan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-chlorobenzyl)-6-((1-((3-hydroxy-2-methyl-4-(methylamino)butan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-chlorobenzyl)-6-((1-((4-(dimethylamino)-3-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-chlorobenzyl)-6-((1-((4-(dimethylamino)-3-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-(2-amino-1-hydroxyethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((1-(2-amino-1-hydroxyethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-((4-amino-3-hydroxy-2,4-dimethylpentan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((4-amino-3-hydroxy-2,4-dimethylpentan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-6-((1-((4-amino-3-hydroxy-2,4-dimethylpentan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((3-amino-4-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((3-amino-4-hydroxy-2-methylbutan-2-yl (Sulfonyl)cyclopropyl)methyl)-N-(4-chlorobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide hydrochloride ((1-((3-((4-chlorobenzyl)carbamoyl)-1-methyl-7-oxo-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine-6-yl)methyl)cyclopropyl)sulfonyl)-D-valine; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxyethyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-(2-hydroxyethyl)-6-((1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxyethyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-1-(2-hydroxyethyl)-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-hydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-(2-hydroxyethyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-(2-hydroxyethyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-1-(2-(2-hydroxyethoxy)ethyl)-6-((1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 1-(2-(2-aminoethoxy)ethyl)-N-(4-chlorobenzyl)-6-((1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxypropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxypropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxypropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-7-oxo-1-(2-oxobutyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-((1-hydroxycyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxy-2-methylpropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxy-2-methylpropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-1-(2-hydroxy-2-methylpropyl)-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-(2-hydroxy-2-methylpropyl)-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(ethylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxy-2-methylpropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-(2-hydroxy-2-methylpropyl)-6-((1-((1-(hydroxymethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-hydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-(2-hydroxy-2-methylpropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(3-hydroxypropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-(3-hydroxypropyl)-6-((1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; Macrocyclic N-(4-cyanobenzyl)carboxamide ethylene glycol; Macrocyclic N-(4-chlorobenzyl)carboxamide ethylene glycol; Lactam macrocyclic N-(4-cyanobenzyl)carboxamide, and A compound of formula (I) or a pharmaceutically acceptable salt thereof, selected from macrocyclic N-(4-cyanobenzyl)carboxamides of amines. Embodiment 153. A compound of formula (I) or a pharmaceutically acceptable salt thereof, the following: N-(4-chlorobenzyl)-6-((1-((1,3-dihydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxyethyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1,3-dihydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-6-((1-((4-amino-3-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine- 3-Carboxamide; (S)-6-((1-((4-amino-3-hydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-(2-hydroxyethyl)-6-((1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-(2-hydroxy-2-methylpropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((1-hydroxy-2-methylpropane-2-yl)sulfonyl)cyclopropyl)methyl)-1-(2-hydroxy-2-methylpropyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chlorobenzyl)-6-((1-((1-hydroxy-2-methylpropan-2-yl)sulfonyl)cyclopropyl)methyl)-1-(2-hydroxyethyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-cyanobenzyl)-6-((1-((3,4-dihydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-(2-hydroxy-2-methylpropyl)-6-((1-((1-(hydroxymethyl)cyclopropyl)sulfonyl)cyclopropyl)methyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; and A compound of formula (I) or a pharmaceutically acceptable salt thereof, selected from N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(N-(pyridine-2-yl)sulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide. Embodiment 154. [ka] In the formula, L, R 1 , R 2 , R B , R 4 , R 10 , R 11 , and R 12 However, as defined for equation (I); Or, L, R 1 , R 2 , R B , R 4 , R 10 , R 11 , and R 12 However, as defined in Embodiment 21; Or, L, R 1 , R 2 , R B , R 4 , R 10 , R 11 , and R 12 However, as defined in Embodiment 22; Or, L, R 1 , R 2, R B , R 4 , R 10 , R 11 , and R 12 However, a compound of formula (II) or a pharmaceutically acceptable salt thereof as described in any one of embodiments 21 to 23, having the structure of formula (IIa) as defined in Embodiment 23. Embodiment 155. [ka] In the formula, L, R 1 , R 4 , R 5 , R 10 , R 11 , and R 12 However, as defined for equation (I); Or, L, R 1 , R 4 , R 5 , R 10 , R 11 , and R 12 However, as defined in Embodiment 21; Or, L, R 1 , R 4 , R 5 , R 10 , R 11 , and R 12 However, as defined in Embodiment 22; Or, L, R 1 , R 4 , R 5 , R 10 , R 11 , and R 12 However, a compound of formula (II) or a pharmaceutically acceptable salt thereof as described in any one of embodiments 21 to 23, having the structure of formula (IIb) as defined in Embodiment 23. Embodiment 156.R 5 The compound described in Embodiment 155 or a pharmaceutically acceptable salt thereof, wherein the compound is -CN or a halo. Embodiment 157.R 4 The compound described in any one of embodiments 154 to 156, or a pharmaceutically acceptable salt thereof, wherein the compound is methyl. Embodiment 158. A compound of formula (IVa) having the structure of formula (IVd), [ka] In the formula, L, R 1 , R 5 , and R 10 This is defined for equation (I); Or, L, R 1 , R 5 , and R 10 This is as defined in Embodiment 22; Or, L, R 1 , R 4 , R 5 , R 10 , R 11 , and R 12 However, a compound of formula (IVa) having the structure of formula (IVd), as defined in Embodiment 23. Embodiment 159.R 5 The compound described in Embodiment 158 ​​or a pharmaceutically acceptable salt thereof, wherein the compound is -CN or a halo. Embodiment 160. Each R 5 However, it is Haro, R 10 However, two -L 3 C substituted with OH 1~ It is a C5 alkyl group, and here L 3 However, the compound of formula (Vc) described in Embodiment 30 or a pharmaceutically acceptable salt thereof, as defined in formula (I). Embodiment 161.R 5 However, it is Haro, R 10 However, two -L 3 C substituted with OH 1~ It is a C5 alkyl group, and here L 3 However, the compound of formula (Va) described in Embodiment 30 or a pharmaceutically acceptable salt thereof, as defined in formula (I). Embodiment 162.R 5 However, it is -CN, and R 10 However, two -L 3 C substituted with OH 1~ It is a C5 alkyl group, and here L 3However, the compound of formula (Va) described in Embodiment 30 or a pharmaceutically acceptable salt thereof, as defined in formula (I). Embodiment 163. A compound of formula (I) having the structure of formula (VIII) or a pharmaceutically acceptable salt thereof, [ka] In the formula, R 10 The following: Phenyl, unsubstituted, or substituted with one -CN; A 6-membered heteroaryl having 1-2 heteroatoms (each heteroatom is N, unsubstituted, or -L) 3 Halo, -L 3 OH, or -L 3 NHC(=O)R 13 It is replaced by one base selected from, where L 3 However, it is a bond, or a linear or branched C1-C3 alkylene, R 13 However, it is a C1-C4 alkyl group; and, 1 piece -L 3 C(=O)NR13R14, or two or three -L 3 C1-C5 alkyl groups substituted with OH (where L 3 R is a bond, or a linear or branched C1-C3 alkylene, 13 is H or C1-C4 alkyl, R 14 (is selected from H or C1-C4 alkyl) A compound of formula (I) having the structure of formula (VIII), or a pharmaceutically acceptable salt thereof. Embodiment 164.L 3 However, the compound described in Embodiment 163 or a pharmaceutically acceptable salt thereof is a bond. Embodiment 165.R 10 The compound according to Embodiment 163 or 164 or a pharmaceutically acceptable salt thereof, wherein the compound is an unsubstituted 6-membered heteroaryl having 1 to 2 heteroatoms, and each heteroatom is N. Embodiment 166. The compound is N-(4-cyanobenzyl)-6-((1-(N-(6-(hydroxymethyl)pyridine-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-(N-(6-acetamidopyridine-2-yl)sulfamoyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(N-(pyrazine-2-yl)sulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(N-phenylsulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(3-fluoropyridine-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(2-cyanophenyl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-chloro-3-fluorobenzyl)-6-((1-((3,4-dihydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (R)-N-(4-chloro-3-fluorobenzyl)-6-((1-((3,4-dihydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; (S)-N-(4-chloro-3-fluorobenzyl)-6-((1-((3,4-dihydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-((3,4-dihydroxy-2-methylbutan-2-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; 6-((1-(N-(4-amino-2-methyl-4-oxobutan-2-yl)sulfamoyl)cyclopropyl)methyl)-N-(4-cyanobenzyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(3-(dimethylamino)-3-oxopropyl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(((3S,4S)-3,4-dihydroxypyrrolidine-1-yl)sulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(N-(1-(pyridazin-3-yl)cyclopropyl)sulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(1,3-dihydroxy-2-methylpropan-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(N-(pyrimidine-2-ylmethyl)sulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(N-(1-(pyrazine-2-yl)ethyl)sulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-(N-(pyrazine-2-ylmethyl)sulfamoyl)cyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; N-(4-cyanobenzyl)-6-((1-(N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)sulfamoyl)cyclopropyl)methyl)-1-methyl-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide; and N-(4-cyanobenzyl)-1-methyl-7-oxo-6-((1-sulfamoylcyclopropyl)methyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide A compound or a pharmaceutically acceptable salt thereof, selected from any one of embodiments 163 to 165. Embodiment 167.R 4 However, -OH and R 10 A compound according to any one of Embodiments 1 to 150 or a pharmaceutically acceptable salt thereof, which is a C2-C3 alkyl group substituted with one or two groups independently selected from the above. Embodiment 168.R 4However, it is substituted with -OH and optionally substituted with methyl, A compound or a pharmaceutically acceptable salt thereof, as described in any one of the requests 1-150 and 167. Embodiment 169.W is L 2 SO2R 10 The compound according to any one of claims 1 to 150 and 167 to 168, or a pharmaceutically acceptable salt thereof. Embodiment 170.L 2 However, it is a bond, R 10 The compound according to any one of claims 1 to 150 and 167 to 169 or a pharmaceutically acceptable salt thereof, wherein the compound is a C1 to C4 alkyl group substituted with 1 to 3 groups selected from C1 to C4 alkyl groups and -OH groups.

[0062] The compound of formula (VII) is novel and is useful as an intermediate for the preparation of the compounds of formulas (I) to (VI) described herein.

[0063] The compound of formula (VII) is novel and useful as an intermediate for the preparation of the compound of formula (VIII) described herein. General synthesis procedure

[0064] The compounds of the present invention can be prepared by organic synthesis methods known to those skilled in the art, as described in more detail in the examples below, with reference to the following general reaction synthesis scheme.

[0065] All starting materials, components, reagents, acids, bases, dehydrating agents, solvents, and catalysts used to synthesize the compounds of the present invention are either commercially available or can be produced by organic synthesis methods known to those skilled in the art ("Houben-Weyl," 4th edition (1952), "Methods of Organic Synthesis," Thieme, Vol. 21).

[0066] Within the scope of this specification, only readily removable groups that are not components of a particular desired final product of the compounds of the present invention are referred to as “protecting groups” unless otherwise indicated in the context. The protection of functional groups by such protecting groups, the protecting groups themselves, and their cleavage reactions are discussed in standard references, e.g., "Science of Synthesis: Houben-Weyl Methods of Molecular Transformation," Georg Thieme Verlag (Stuttgart, Germany, 2005), p. 41627 (URL: http: / / www.science-of-synthesis.com (electronic edition, Vol. 48)); JFWMcOmie, "Protective Groups in Organic Chemistry," Plenum Press (London and New York, 1973); TW Greene and PGMWuts, "Protective Groups in Organic Synthesis," 3rd edition, Wiley (New York, 1999); "The Peptides"; Vol. 3 (edited by E. Gross and J. Meienhofer), Academic Press (London and New York, 1981); "Methoden der Organischen Chemie" ("Methods of Organic Chemistry"). Houben Weyl, 4th edition, Volume 15 / I, Georg Thieme Verlag (Stuttgart, 1974), H.-D. Jakubke and H. Jeschkeit, tides, Proteins), Verlag Chemie (Weinheim, Deerfield Beach, and Basel, 1982), and Jochen This is described in Lehmann, "Chemie der Kohlenhydrate: Monosaccharide und Derivate" ("Chemistry of Carbohydrates: Monosaccharides and Derivatives"), and Georg Thieme Verlag (Stuttgart, 1974), among others. The characteristics of protecting groups include, for example, solvolysis, reduction, photolysis, and Alternatively, it can be easily removed under physiological conditions (e.g., by enzymatic cleavage) (i.e., without the occurrence of unwanted secondary reactions).

[0067] A general method for synthesizing the compound of formula (I) is provided in the following schemes I to VI. In particular, schemes I to III show general methods 1 to 14 for synthesizing the compound of formula (I) where Z is W and LMC is absent, where R 1 , R 2 , R 3 , R 4 , R 15 , R B t, L, and W are as defined herein for the compound of formula (I). [ka]

[0068] Scheme I is when X is [ka] And Y is a combination, [ka] General methods 1-7 for synthesizing the compound of formula (I) are shown. The bicyclic intermediate (e.g., intermediate I-1) can be N-alkylated to bond the desired WL- moiety, for example, if L is bonded via -CH2-. WL-X1 represents a suitable alkylating agent for such a reaction, where X1 is a halo (e.g., Br or I), etc. The leaving group is a sulfonate leaving group such as a mesylate, tosylate, or triflate. The WL- portion may, of course, contain a functional group such as a hydroxyl group or an amine group that can be further modified in a protected form that can be deprotected and further derivatized in the product of formula (I).

[0069] R C This can be a simple alkyl ester such as methyl, ethyl, propyl, isopropyl, t-butyl, or n-butyl, and if WL- contains an ester, R C Since R can be a different ester such as benzyl, which can be easily differentiated from one of the WL- C R can be selectively hydrolyzed for coupling reactions in scheme I. In some examples, R C This is an ester that hydrolyzes under alkylation conditions, likely due to the presence of incidental moisture or hydroxides. In other examples, separate hydrolysis steps are used, such as the addition of lithium hydroxide, sodium hydroxide, or potassium hydroxide and water. The resulting free carboxylate compound is then subjected to the desired R using standard amide bond formation conditions and appropriate reagents. B The carboxylic acid can be readily coupled to a suitable amine containing the group. This may be by direct amidation of the carboxylate salt (Methods 1 and 2), or by converting the carboxylic acid to an activated intermediate (acyl chloride, acyl anhydride, etc.), as is known in the art and illustrated by the accompanying examples (Method 4). Examples of amide coupling reagents used in Methods 1, 2, 4, and 5 include, but are not limited to, EDCI, HATU, HBTU, TBTU, and T3P. Furthermore, the carboxylic acid can be converted to an activated intermediate (Method 5) and subsequently etherified. Typical etherification occurs using an alkyl (Cl,Br,I) halogen in the presence of a base such as KCO3 or KOH.

[0070] Alternatively, the carboxylic acid may undergo esterification using a Lewis acid catalyst or Brønsted acid catalyst with an alcohol (Method 6), but examples of other esterification reagents include diethyl azodicarboxylate (DEAD ) or diisopropyl azodicarboxylate (DI AD), di-tert-butyl azodicarboxylate (DTBAD), dicyclohexylcarbodiimide (DTBAD) CC) / 4-N,N-dimethylaminopyridine(4-N,N-dimethylaminopyridine:DMA Examples include P) and 2,4,6-trichlorobenzoyl chloride / 4-N,N-dimethylaminopyridine (DMAP).

[0071] Finally, for the compound of formula (I), R 4 is, R 15 It contains an alkyl halide moiety, and the secondary amine on the pyrazolyl ring can be alkylated (Method 7), thereby forming a third condensed ring. Alternatively, hydroamination and amine alkylation with alcohol are performed. 15 It can be used if it contains the appropriate reactive group. [ka]

[0072] Scheme II shows a general method for synthesizing the compound of formula (I), where X is a 5-6 member heteroaryl and Y is [ka] The compounds of formula (I) containing oxadiazole can be easily obtained using the carboxylic acid intermediate described in scheme (I). In method 8, oxadiazole synthesis is carried out by condensation with a carboxylic acid, followed by dehydration and cyclization of the resulting diacylhydrazide intermediate. Alternatively, in method 9, oxadiazole synthesis occurs by condensation of a carboxylic acid with an amidooxime, followed by cyclization. Finally, in method 10, the carboxylic acid intermediate is converted to an amide, followed by nitrile formation, which is then used to form an amidooxime intermediate. Oxadiazole formation is then carried out by condensation of a carboxylic acid with an amidooxime, followed by cyclization. Reagents used in such methods are known in the art and are illustrated by the attached examples. [ka]

[0073] Scheme III shows a general method for synthesizing the compound of formula (I), where X is a 5-6 member heteroaryl or 5-6 member heterocyclyl, and Y is a bond or [ka] The carboxylic acid intermediate or the corresponding ester intermediate described in scheme (I) can be used to obtain compounds of formula (I) containing triazole, tetrazole, isoxazole, or dihydroisoxazole. In method 11, an aldehyde intermediate formed from an ester is used to form a nitrile intermediate. Subsequent copper-catalyzed "click" chemistry using the nitrile and azide intermediates results in triazole formation. In addition, in method 12, an aldehyde intermediate formed from an ester is used to form an oxime intermediate, which is later converted to a carbimidoyl chloride derivative. Dihydroisoxazole is obtained by the reaction of a doyl derivative with an alkene. Alternatively, isoxazole is obtained by the reaction of a carbimidoyl chloride derivative with a nitrile intermediate (Method 13). Finally, in Method 14, the carboxylic acid intermediate is converted to an amide, followed by nitrile formation, then tetrazole intermediate formation, and then N-alkylation using an alkyl halide.

[0074] Scheme IV shows a general method for the synthesis of compounds of formula (I) in which LMC exists, where R 1 , R 2 , R 3 , R 4 , R 15 , R B , t, and L are as defined herein for the compound of formula (I). [ka]

[0075] In scheme (IV), the macrocyclic compound of formula (I) is obtained using the amine-protected bicyclic intermediate described in scheme (I) (e.g., intermediate I-1). Herein, the bicyclic intermediate can be N-alkylated as described in scheme I to attach the desired OH-ZL- moiety, for example, L is attached via -CH2-. The hydroxyl of the OH-ZL group is alkylated, thereby attaching a linker moiety that is further attached by N-alkylation of the deprotected amine after deprotection. The ester is converted to the corresponding carboxylic acid and then amidated with the desired amine intermediate.

[0076] Scheme V shows a general method for the synthesis of compounds of formula (I) in which LMC exists, where R 1 , R 2 , R 3 , R 4 , R 15 , R B , t, and L are as defined herein for the compound of formula (I). [ka]

[0077] In scheme (V), the macrocyclic compound of formula (I) is obtained using the amine-protected bicyclic intermediate described in scheme (I) (e.g., intermediate I-1). Herein, the bicyclic intermediate can be N-alkylated as described in scheme I to attach the desired OH-ZL- moiety, in particular, L is attached via -CH2-. The ester is then converted to the corresponding carboxylic acid and subsequently amidated with the desired amine intermediate. After deprotection, the amine is alkylated to attach to the linker and subsequently activated at the azide moiety. The hydroxyl of the OH-ZL group is converted to the carboxylic acid and subsequently amidated via the azide moiety, thereby attaching the linker and completing the macrocyclic formation.

[0078] Scheme VI shows a general method for the synthesis of compounds of formula (I) in which LMC exists, where R 1 , R 2 , R 3 , R 4 , R 15 , R B , t, and L are as defined herein for the compound of formula (I). [ka]

[0079] In scheme (VI), the macrocyclic compound of formula (I) is obtained using the amine-protected bicyclic intermediate described in scheme (I) (e.g., intermediate I-1). Herein, the bicyclic intermediate can be N-alkylated as described in scheme I to attach the desired OH-ZL- moiety, for example, L is attached via -CH2-. The ester is then converted to the corresponding carboxylic acid and subsequently amidated with the desired amine intermediate. After deprotection, the amine is alkylated to attach to the linker and subsequently activated at the azide moiety. The hydroxyl of the OH-ZL group is converted to an aldehyde and subsequently amidated via the azide moiety, thereby attaching the linker and completing the macrocyclic formation.

[0080] Schemes IV to VI are such that X [ka] And Y is combined, [ka] This describes a general method for synthesizing the macrocyclic compound of formula (I), where X is [ka] It is a 5-6 member heteroaryl, 5-6 member heterocycloalkyl, or 5-6 member heterocyclyl, where Y is bonded. [ka] It can be used in embodiments that are as follows.

[0081] Using these methods described above, along with additional extensions, modifications, and variations illustrated by the following examples, those skilled in the art can easily prepare a variety of compounds of formulas (I) to (VI).

[0082] The intermediates and final products can be work-up and / or purified according to a preferred method, such as chromatography, partitioning, and (re)crystallization.

[0083] Depending on the selection of starting materials and procedures, compounds may exist in one form of one of the possible isomers, or as a mixture thereof, depending on the number of chiral carbon atoms, for example, as a pure optical isomer, or as an isomer mixture such as a racemic mixture and a diastereoisomer mixture. The present invention is intended to include all such possible stereoisomers, including racemic mixtures, diastereomer mixtures, and optically pure forms. Optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents, or can be divided using the prior art. If the compound contains a double bond, the substituent may be in an E configuration or a Z configuration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis configuration or a trans configuration. All tautomer forms are also intended to be included.

[0084] Any resulting mixture of isomers can be separated into pure or substantially pure geometric isomers, optical isomers, or diastereomers based on the physicochemical differences of their components, for example, by chromatography and / or fractional crystallization.

[0085] A mixture of isomers that can be obtained according to the present invention can be separated into individual isomers in ways known to themselves. Diastereoisomers can be separated, for example, by partitioning between multiphase solvent mixtures, recrystallization, and / or by chromatographic separation, for example, on silica gel, or by medium-pressure liquid chromatography, for example, on a reversed-phase column, and racemates can be separated, for example, by salt formation with an optically pure salt-forming reagent and separation of the mixture of diastereoisomers thus obtained, for example, by fractional crystallization, or by chromatography on an optically active column material.

[0086] Any resulting racemic mixture of the final product or intermediate can be obtained by known methods, for example, light The diastereomer salts obtained using a chemically active acid or base can be separated and the optically active acidic or basic compound liberated, thereby separating them into optical counterparts. In particular, the compounds of the present invention can be separated into their optical counterparts by fractional crystals of salts formed with an optically active acid, such as tartaric acid, dibenzoyl tartaric acid, diacetyl tartaric acid, di-O,O'-p-thuloyl tartaric acid, mandelic acid, malic acid, or camphor-10-sulfonic acid, using the basic moiety. The racemic products can also be separated by chiral chromatography, such as high-pressure liquid chromatography (HPLC) using a chiral adsorbent.

[0087] Many of the compounds of the present invention contain one or more chiral centers. These compounds can be prepared and used as single isomers or as mixtures of isomers. Methods for separating isomers, including diastereomers and enantiomers, are known in the art, and examples of preferred methods are described herein. In certain embodiments, the compounds of the present invention are used as a single, substantially pure isomer, meaning that at least 90% of a sample of the compound is a specific isomer, and less than 10% of the sample is any other isomer or a mixture of isomers. For example, at least 95% of the sample is a single isomer. In consideration of this disclosure, the selection of a suitable isomer is within the realm of the art for those skilled in the art. For example, one isomer may be more active in the in vitro assay of herpesvirus DNA polymerase described herein. If the difference in in vitro activity between isomers is relatively small, e.g., less than about 4 times, the single isomer may be selected based on its activity level for viral replication in cell cultures using methods such as those described herein: e.g., a lower IC 50 or EC 50 You may select an isomer that has the characteristic.

[0088] Furthermore, the compounds of the present invention, including those salts, may be obtained in the form of their hydrates or may include other solvents used for their crystallization. The compounds of the present invention may, essentially or by design, form solvates with pharmaceutically acceptable solvents (including water). Thus, the present invention is intended to encompass both solvated and non-solvated forms. The term "solvate" refers to a molecular complex of the compound of the present invention (including its pharmaceutically acceptable salts) with one or more solvent molecules. Such solvent molecules are known to be harmless to recipients, such as water and ethanol, and are commonly used in the pharmaceutical art. The term "hydrate" refers to a complex in which the solvent molecule is water.

[0089] The compounds of the present invention (including their salts, hydrates, and solvates) may be polymorphic in nature or by design.

[0090] As used herein, the terms "salt" or "salts" are used in accordance with the foregoing. This refers to an acid addition salt or base addition salt of the compound of the present invention. "Salt" specifically includes "pharmaceutically acceptable salts." The term "pharmaceutically acceptable salt" refers to a salt that retains the biological efficacy and properties of the compound of the present invention and is not typically biologically or otherwise undesirable. In many cases, the compounds of the present invention can form acid salts and / or base salts in the presence of an amino group and / or a carboxyl group or similar group.

[0091] Pharmacologically acceptable acid addition salts, such as acetate, aspartate, benzoate, besylate, bromide / hydrobromide, bicarbonate / carbonate, bisulfate / sulfate, camphor sulfonate, chloride / hydrochloride, chlortheophyllonate, citrate Salts, ethandisulfonate, fumarate, gluceptate, gluconate, glucuronate, hippurate, hydroiodide / iodide, isethionate, lactate, lactobionate, lauryl sulfate, malate, maleate, malonate, mandelate, mesylate, methyl sulfate, naphthoate, napsylate, Nicotinates, nitrates, octadecanoates, oleates, oxalates, palmitates, pamoates, phosphates / hydrogen phosphates / dihydrogen phosphates, phosphates, polygalactuloses, propionates, stearates, succinates, sulfosalicylates, tartrates, tosylates, and trifluoroacetates can be formed from inorganic and organic acids.

[0092] Examples of inorganic acids that can induce salt formation include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid.

[0093] Examples of organic acids that can induce salt formation include acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, and sulfosalicylic acid. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases.

[0094] Examples of inorganic bases that can be used to derive salts include ammonium salts and metals from columns I to XII of the periodic table. In certain embodiments, salts are derived from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper, with particularly preferred salts being ammonium salts, potassium salts, sodium salts, calcium salts, and magnesium salts.

[0095] Examples of organic bases that can induce salt formation include primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins. Specific organic amines include isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, and pipette. Examples include radin and tromethamine.

[0096] The pharmaceutically acceptable salts of the present invention can be synthesized from the basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acidic form of these compounds with a stoichiometric amount of a suitable base (such as Na, Ca, Mg, or K hydroxide, carbonate, or bicarbonate), or by reacting the free basic form of these compounds with a stoichiometric amount of a suitable acid. Such reactions are typically carried out in water, an organic solvent, or a mixture of the two. Generally, the use of non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile is preferred when feasible. A list of additional suitable salts can be found, for example, in Remington's Pharmaceutical Sciences, 20th edition, Mack. This information can be found in Publishing Company (Easton, Pa., 1985) and "Handbook of Pharmaceutical Salts: Properties, Selection, and Use," and in Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002).

[0097] Salts of the compounds of the present invention having at least one salt-forming group can be prepared in known ways. For example, salts of the compounds of the present invention having an acid group can be formed by treating the compound with a metal compound such as an alkali metal salt of a suitable organic carboxylic acid, e.g., the sodium salt of 2-ethylhexanoic acid, the corresponding hydroxide, carbonate or bicarbonate, e.g., an organic alkali metal or alkaline earth metal compound such as sodium hydroxide or potassium hydroxide, carbonate or bicarbonate, e.g., the corresponding calcium compound, or ammonia or a suitable organic amine, and a stoichiometric amount or a slightly excess of the salt-forming agent may be used. Acid addition salts of the compounds of the present invention can be obtained in a conventional way, for example, by treating the compound with an acid or a suitable anion exchange reagent. Intramolecular salts of the compounds of the present invention containing acidic and basic salt-forming groups, e.g., free carboxyl groups and free amino groups, For example, it can be formed by neutralization to the isoelectric point of a salt, such as an acid addition salt, through treatment with a weak base or an ion exchanger.

[0098] Salts can be converted to free compounds in the usual manner. Metal salts and ammonium salts can be converted, for example, by treatment with suitable acids and acid addition salts, or by treatment with suitable basic agents.

[0099] Any formula shown herein represents an unlabeled form of the compound of the present invention, as well as up to three atoms having a non-natural isotopic distribution, for example, deuterium or 13 C or 15 This is intended to represent an isotopically labeled form having a nitrogen-enriched region. The isotopically labeled compound has the structure represented by the formula shown herein, except that one or more atoms are replaced by atoms having a selected atomic mass or mass number other than that of its naturally occurring mass distribution. Examples of isotopes that may be usefully and in excess incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, for example, 2 H, 3 H, 11 C, 13 C, 14C, 15 N, 18 F, 31 P, 32 P, 35 S, 36 Cl, 125 I can be cited. The present invention relates to various isotope-labeled compounds, for example, 3 H and 14 Radioactive isotopes such as C, or 2 H and 13 This includes compounds in which non-radioactive isotopes such as 13C are present at levels substantially exceeding the normal isotopic distribution. Such isotope-labeled compounds are used in metabolic studies (e.g., 14 (by C), reaction kinetic studies (for example, 2 H or 3 In detection or imaging techniques such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug or substrate tissue distribution assays, or in patients' radiation It is useful in radiation therapy. In particular, the present invention 18 Fluorine-labeled compounds may be particularly desirable for PET or SPECT studies. The isotope-labeled compounds of the present invention can generally be prepared by processes similar to those described in the accompanying examples and preparations, using conventional techniques known to those skilled in the art, or by using appropriate isotope-labeling reagents instead of typically used unlabeled reagents. Labeled samples may be useful in cases of very low isotope uptake, such as when radiolabeling is used to detect trace amounts of compounds.

[0100] Furthermore, heavier isotopes, especially deuterium (i.e., 2More broad substitutions with H or D may result in certain therapeutic benefits due to greater metabolic stability, such as extended half-life in vivo, reduced drug dose requirements, or improved therapeutic index. In this context, deuterium is considered a substituent of the compounds of the present invention, and typically, a sample of a compound having deuterium as a substituent is understood to have at least 50% deuterium incorporation at the labeled position(s). The concentration of such heavier isotopes, specifically deuterium, may be defined by the isotopic enrichment factor. The term "isotopic enrichment factor," as used herein, means the ratio of the isotopic abundance to the natural abundance of a particular isotope. When the substituent in the compound of the present invention is deuterium, such compound has an isotopic enrichment factor of at least 3500 (52.5% deuterium incorporation in each designated deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation) for each designated deuterium atom.

[0101] The pharmaceutically acceptable solvates according to the present invention are those in which the crystallization solvent is isotope-substituted, for example, D2O, d 6 -acetone, d 6 -Includes those that may be DMSO.

[0102] Compounds of the present invention containing groups capable of acting as hydrogen bond donors and / or acceptors may be capable of forming cocrystals with suitable cocrystal-forming agents. These cocrystals can be prepared from the compounds of the present invention by known cocrystal-forming procedures. Such procedures include grinding, heating, co-sublimation, co-melting, or contact in solution of the compounds of the present invention and the cocrystal-forming agent under crystallization conditions, and isolation of the cocrystals formed thereby. Suitable cocrystal-forming agents include those described in International Publication No. 2004 / 078163. Accordingly, the present invention further provides cocrystals comprising the compounds of the present invention.

[0103] All methods described herein may be carried out in any preferred order, unless otherwise specified herein or unless the context clearly contradicts it. The use of any and all examples or exemplary phrases (e.g., "etc.") provided herein is intended solely to further illustrate the invention and not to limit the scope of the claimed invention.

[0104] The present invention also provides a method for producing compounds of formula I as described herein, and intermediates useful for the preparation of compounds of formula (I). Therefore, the present invention also includes a method for producing compounds of formula (I), the method being: This involves contacting the compound of formula (A), [ka] During the ceremony: X1 represents an -OH group or a leaving group; t is 0, 1, or 2; Each R 3 If present, -LW is a substituent on the ring to which it is directly bonded, where each R 3 However, Hello, CN, C 1~ C3 alkoxy, C 1~ C3alkyl, C(=O)OR 10 , and C(=O)NR 13 R 14 Selected independently of; R 4H, C 1~ C3 alkyl, C 3~ C6 cycloalkyl, or -OH, -C(=O)R 15 , and R 10 C substituted with 1-2 groups independently selected from 1~ It is a C3 alkyl group; L is a C1-C4 linear or branched alkylene linker, or bond; W is H, -OH, -OR 10 -C(=O)NR 13 R 14 , -C(=O)OR 13 , -NR 13 R 14 , -NR 13 C(=O)OR 10 , -NR 13 C(=O)R 10 , -SO2R 10 -SO2NR 13 R 14 , -NR 13 SO2R 10 , -P(=O)(OR 13 )2, -S(=O)R 10 -S(=O)(=NR 13 )R 10 ,-CR 11 R 12 C(=O)NR 13 R 14 ,-CR 11 R 12 C(=O)OR 13 ,-CR 11 R 12 NR 13 R 14 ,-CR 11 R 12 NR 13 C(=O)OR 10 ,-CR 11 R 12 NR 13 C(=O)R 10 ,-CR 11 R 12 SO2R 10 ,-CR 11 R 12 SO2NR 13 R 14 ,-CR 11 R12 NR 13 SO2R 10 ,-CR 11 R 12 P(=O)(OR 13 )2, -CR 11 R 12 S(=O)R 10 ,-CR 11 R 12 S(=O)(=NR 13 )R 10 , 3-6 member cycloalkyl, phenyl, N, NH, NR 17 5-6 member heterocycloalkyl, N, NH, NR, containing one or two ring members independently selected from O, or S. 17 A 5-6 member heterocycline containing one or two ring members independently selected from O or S, or a 5-member heteroaryl having 1-4 heteroatoms selected as ring members from N, O, and S, which can be optionally condensed with phenyl. Here, W consists of 3-6 member cycloalkyls, phenyls, 5-6 member heterocycloalkyls, 5-6 member heterocyclines, and 5 member heteroaryls, respectively, C 1~ C3 alkyl, oxo, halo, C 1~ C3 haloalkyl, -L 2 OH, -L 2 Ure 10 , -L 2 OC(=O)NR 13 R 14 , -L 2 SO2R 10 , -L 2 SO2NR 14 R 10 , -L 2 SO2NR 13 R 14 , -L 2 SO2N=CR 13 NR 13 R 14 , -L 2 SO2NR 13 C(=O)R 10 , -L 2 C(=O)NR 13 SO2R 10 , -L 2 S(=O)R 10 , -L2 S(=O)(=NR 13 )R 10 , -L 2 NR 13 SO2NR 13 R 14 , -L 2 NR 13 SO2R 10 , -L 2 NR 13 R 14 , -L 2 NR 13 C(=O)R 13 , -L 2 NR 13 C(=O)OR 10 , -L 2 C(=O)NR 13 R 14 , and -L 2 C(=O)OR 13 It is arbitrarily replaced by 1 to 3 elements selected independently of it; R in each appearance 10 C 1~ C4 alkyl, C 1~ C3 haloalkyl, 3-6 membered cycloalkyl, phenyl, N, O, and S, having 1-4 heteroatoms independently selected as ring members, 5-6 membered heteroaryl, N, NH, NR 17 4-6 member heterocycloalkyls containing one or two ring members independently selected from O or S, and N, NH, NR 17 Independently selected from 4-6 membered heterocyclines containing 1-2 ring members independently selected from O, or S; Here, each R 10 C 1~ C4alkyl, deuterium, C 1~ C4 haloalkoxy, -L 3 OH, -L 3 CN, -L 3 OC(=O)R 14 , -L 3 Ure 13 , C 1~ C2-haloalkyl, oxo, -L 3 Halo, -L 3 C 1~ C3 alkoxy, -L 3 OC(=O)NR13 R 14 , -L 3 SO2R 13 , -L 3 SO2NR 13 R 14 , -L 3 SO2NR 13 C(=O)R 13 , -L 3 C(=O)NR 13 SO2R 13 , -L 3 S(=O)R 13 , -L 3 S(=O)(=NR 14 )R 13 , -L 3 NR 13 SO2NR 13 R 14 , -L 3 NR 13 SO2R 13 , -L 3 NR 13 R 14 , -L 3 NR 14 C(=O)R 13 , -L 3 NR 14 C(=O)OR 13 , -L 3 C(=O)NR 13 R 14 , -L 3 C(=O)OR 13 , -L 3 -(N, NH, NR 17 A 4-7 member heterocycloalkyl group containing 1-2 ring members independently selected from O, or S, (O or S), -L 3 -(N, NH, NR 17 (4-7 member heterocycline containing 1-2 ring members independently selected from O, or S), -L 3 -C 3~ C5 cycloalkyl, and -L 3 -Optionally substituted with 1 to 5 groups independently selected from (a 5-6 membered heteroaryl ring having 1 to 4 heteroatoms, containing 1 to 4 nitrogen atoms, 0 or 1 oxygen atom, and 0 or 1 sulfur atom as ring members), where C 1~C4 alkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocyclyl, C 3~ C5 cycloalkyl and 5-6 membered heteroaryl rings are, respectively, halo and C 1~ C3 alkyl, C 1~ C3 haloalkyl, -L 4 Ure 13 , -L 4 CN, and -L 4 NR 13 R 14 It is further optionally replaced by 1 to 3 bases, which are independently selected from; R 11 and R 12 H and C, respectively. 1~ Selected independently from C4 alkyl; Each R 13 H, C 1~ C4 alkyl, N, NH, NR 17 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S. 17 A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C 3~ Independently selected from C6 cycloalkyl groups, where C 1~ C4 alkyl, heterocyclyl, and C 3~ C6 cycloalkyl is C 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , -C(=O)OR 15 , C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group; R 14 H, C 1~ C4 alkyl, and C 3~ Selected from C6 cycloalkyl, where C 1~ C4 alkyl and C 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , C 1~C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group; Or, R 13 and R 14 Both, together with the nitrogen atom to which they are directly bonded, optionally contain additional N, O, or S as ring members, and C 1~ C2 alkyl, C 1~ 4-6 molecules optionally substituted with 1-3 groups selected from C2 alkoxy, oxo, and hydroxyl groups. It can form a member ring; Each L 2 and L 3 and L 4 These are independently linked, or linear or branched C 1~ It is a C3 alkylene, and [ka] However, this represents a single bond or a double bond; This includes contact with the compound of formula (I-2): [ka] During the ceremony: R B R is phenyl, pyridinyl, thiophenyl, pyrimidinyl, or a 5-8 membered cycloalkyl, where R B However, 1 to 3 R 5 It can be arbitrarily substituted in the base; R 1 H, C 1~ C3 alkyl and C substituted with 1-3 -OH groups 1~ Selected from C3 alkyl groups; R2 is H, C 1~ C3 alkyl and C substituted with 1-3 -OH groups 1~ Selected from C3 alkyl groups; Or, R 1 and R 2 These can, together with the carbon atoms to which they are bonded, form a 3- to 6-membered cycloalkyl ring; Each R5 These are halo, -CN, hydroxy, and -NR. 13 R 14 , C 3~ C6 cycloalkyl, C 1~ C3 alkoxy, C 1~ C3 haloalkyl and 1-3 R 6 C arbitrarily substituted in R 1~ Independently selected from C3 alkyl groups, where R B This is two R 5 Replaced by each R 5 This is 1 to 3 R 6 A C arbitrarily substituted in the base 1~ It is a C3 alkyl group, and when directly bonded to the same carbon atom, both atoms together form 1 to 3 R atoms. 6 It can form a 3- to 5-membered cycloalkyl ring optionally substituted with a group; Each R 6 is halo, hydroxy, CN, C 1~ C3 alkoxy, C 1~ C3 alkyl, and C 3~ Independently selected from C5 cycloalkyl groups, Alternatively, two R 6 The group contains O, N, or S as ring members, together with the carbon atoms to which both are directly bonded, and is oxo and C 1~ They can form a 3- to 5-membered cycloalkyl ring or a 4- to 6-membered heterocycle, optionally substituted with 1-2 groups independently selected from the C3 alkyl group; Each R 13 H, C 1~ C4 alkyl, N, NH, NR 17 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S. 17 A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C 3~ Independently selected from C6 cycloalkyl groups, where C 1~ C4 alkyl, heterocyclyl, and C 3~ C6 cycloalkyl is C 1~ C4 alkyl, halo, -OH, -NR 15 R16 , -C(=O)OR 15 , C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group; R 14 H, C 1~ C4 alkyl, and C 3~ Selected from C6 cycloalkyl, where C 1~ C4 alkyl and C 3~ C6 cycloalkyl, 1~ C4 alkyl, halo, -OH, -NR 15 R 16 , C 1~ C2 alkoxy and C substituted with 1-2 hydroxyl groups 1~ Optionally substituted with 1 to 3 groups independently selected from the C4 alkyl group; Or, R 13 and R 14 Both, together with the nitrogen atom to which they are directly bonded, optionally contain additional N, O, or S as ring members, and C 1~ C2 alkyl, C 1~ 4-6 molecules optionally substituted with 1-3 groups selected from C2 alkoxy, oxo, and hydroxyl groups. It can form a member ring; R 15 and R 16 H and C, respectively. 1~ Selected independently from C4 alkyl, and Each R 17 H, C 1~ It is independently selected from C4 alkyl and C3-C8 cycloalkyl groups. Typically, these methods involve combining or mixing the compounds of formula (A) and formula (I-2) in the presence of an inert solvent under conditions suitable for amide bond formation, including known methods used in peptide synthesis. For example, when X represents -OH, any of the broad range of dehydrating agents suitable for amide bond formation from amines and carboxylic acids can be used. Some of these are exemplified by the examples herein and include carbodiimides (e.g., dicyclohexylcarbodiimide; diisopropylcarbodiimide; and EDC, etc.). Optionally, the reaction with carbodiimide can be accelerated by the presence of an activator such as HOBt, HOAt, or N-hydroxysuccinimide. Alternatively, the acid of formula (A) or its salt can be activated before contact with the amine compound of formula (I-2) by reaction with an activator such as HATU, HBTU, BOP, PyBOP, PyBrOP, TBTU, COMU, or TFFH, optionally in the presence of a base such as triethylamine, DIPEA, DMAP, and pyridine. If X represents a leaving group, it is a halo (e.g., Cl) or -OC(O)-OR * These could be acyl groups, and here, R * This refers to a maximum of 3 halos or C 1~3 This represents alkyl C1-C6 alkyl groups that are optionally substituted with alkoxy groups.

[0105] In a particular embodiment, the compound of formula (A) is the compound of formula (VII): [ka] In the formula, R C H is H; L is -CH2-; and W is -SO2R 10 -SO2NR 14 R 10 , or -SO2NR 13 R 14 It is a cyclopropyl substituted with, where t, R 10 , R 13 , and R 14 This is defined for equation (A).

[0106] The compounds of formulas (A) and (I-2) described above, as well as methods for producing the compounds of the present invention using them, are also embodiments of the present invention.

[0107] The present invention further includes any variation of the process in which an intermediate product that can be obtained at any stage is used as a starting material and the remaining steps are carried out, or the starting material is formed in situ under reaction conditions, or the reactants are used in the form of their salts or optically pure materials.

[0108] The present invention also relates to a form of process in which a compound that can be obtained as an intermediate at any stage of the process is used as a starting material and the remaining process steps are carried out, or a form of process in which the starting material is formed under reaction conditions or used in the form of a derivative, such as a protected form or a salt form, or a form of process in which a compound that can be obtained by the process according to the present invention is produced under process conditions and further processed in situ. Pharmaceutical composition and route of administration

[0109] The scope of the present invention includes pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0110] According to a further embodiment of this embodiment, the pharmaceutical composition according to the present invention further comprises a therapeutically effective amount of at least one other antiviral agent.

[0111] The compounds of the present invention can be administered by known methods, including oral, parenteral, and inhalation. In certain embodiments, the compounds of the present invention are administered orally as pills, lozenges, troches, capsules, liquids, or suspensions. In other embodiments, the compounds of the present invention are administered by injection or infusion. Infusion is typically, often, performed intravenously over a period of about 15 minutes to 4 hours. In other embodiments, the compounds of the present invention are administered intranasally or by inhalation. Inhalation is particularly useful for the treatment of respiratory infections. The compounds of the present invention exhibit oral bioavailability and can be administered orally.

[0112] The term "pharmaceutical composition" includes preparations suitable for administration to mammals, such as humans. When the compounds of the present invention are administered as pharmaceuticals to mammals, such as humans, they can be administered either on their own or as pharmaceutical compositions containing, for example, 0.1 to 99.5% (e.g., 0.5 to 90%) of at least one compound of formula (I), or any subgenus thereof, as an active ingredient in combination with a pharmaceutically acceptable carrier, or optionally two or more pharmaceutically acceptable carriers.

[0113] The term "pharmaceutically acceptable carrier" is recognized in the art and includes pharmaceutically acceptable materials, compositions, or vehicles suitable for administering the compounds of the present invention to mammals. The carrier includes liquid or solid fillers, diluents, excipients, solvents, or encapsulating materials and is involved in transporting or delivering the drug of interest from one organ or part of the body to another, or to a part of the body. Each carrier must be compatible with the other components of the formulation and "acceptable" in the sense that it is not harmful to the patient. Some examples of materials that can function as pharmaceutically acceptable carriers include, but are not limited to, sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose, and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; tragacanth powder; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols such as propylene glycol; polyols such as glycerin, sorbitol, mannitol, and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffers such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer, and other non-toxic, suitable substances used in pharmaceutical formulations. Typically, pharmaceutically acceptable carriers are sterile and / or substantially free of pyrogens.

[0114] Wetting agents, emulsifiers, and lubricants such as sodium lauryl sulfate and magnesium stearate, as well as colorants, release agents, coating agents, sweeteners, flavoring agents, fragrances, preservatives, and antioxidants, may also be present in the composition.

[0115] Examples of pharmaceutically acceptable antioxidants include: water-soluble antioxidants such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, and sodium sulfite; ascorbyl palmitate; butylated hydroxyanisole (BHA); and butylated hydroxytoluene. Oil-soluble antioxidants such as ne:BHT, lecithin, propyl gallate, and α-tocopherol; and metal chelating agents such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, and phosphoric acid.

[0116] The formulations of the present invention include those suitable for oral, nasal, inhalation, topical, transdermal, buccal, sublingual, rectal, vaginal, and / or parenteral administration. The formulations may be conveniently presented in unit dosage forms and may be prepared by preferred methods. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form is generally the amount of the compound that produces the therapeutic effect. Generally, out of 100 percent, this amount is in the range of about 1 percent to about 99 percent, for example, about 5 percent to about 70 percent, or about 10 percent to about 30 percent of the active ingredient.

[0117] Methods for preparing these formulations or compositions include the step of associating the compounds of the present invention with a carrier and optionally one or more minor components. Generally, formulations are prepared by homogeneously and closely associating the compounds of the present invention with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product.

[0118] Formulations of the present invention suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored base, for example, usually sucrose and acacia or tragacanth), powders, granules, or as liquids or suspensions in aqueous or non-aqueous liquids, or as oil-in-water or water-in-oil emulsions, or as elixirs or syrups, or as lozenges (using an inert base such as gelatin and glycerin, or sucrose and acacia), and / or as mouthwashes, each containing a predetermined amount of the compound of the present invention as an active ingredient. The compound of the present invention may also be administered as a bolus, lick, or paste.

[0119] In the solid dosage forms of the present invention for oral administration (such as capsules, tablets, pills, sugar-coated tablets, powders, and granules), the active ingredient is mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and / or any of the following: fillers or bulking agents such as starch, lactose, sucrose, glucose, mannitol, and / or silicic acid; binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and / or acacia; humectants such as glycerol; disintegrants such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; solution retarders such as paraffin; absorption enhancers such as quaternary ammonium compounds; humectants such as cetyl alcohol and glycerol monostearate; absorbents such as kaolin and bentonite clay; lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate, and mixtures thereof; and colorants. In the case of capsules, tablets, and pills, the pharmaceutical composition may also contain a buffer. Similar types of solid compositions may also be used as fillers for soft and hard-filled gelatin capsules, using excipients such as lactose or milk sugar, as well as high molecular weight polyethylene glycol, etc.

[0120] Tablets may be prepared by compressing or molding with one or more adjuncts as desired. Compressed tablets may be prepared using a binder (e.g., gelatin or hydroxypropyl methylcellulose), a lubricant, an inert diluent, a preservative, a disintegrant (e.g., sodium starch glycolate or cross-linked carboxymethylcellulose sodium), a surfactant, or a dispersant. Molded tablets may be prepared by molding a mixture of powder compounds moistened with an inert liquid diluent using a suitable machine.

[0121] Tablets, as well as other pharmaceutical compositions of the present invention such as sugar-coated tablets, capsules, pills, and granules. Solid dosage forms may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings. They may also be formulated to provide sustained or controlled release of the active ingredient therein, for example, using various proportions of hydroxypropyl methylcellulose, other polymer matrices, liposomes, and / or microspheres to provide a desired release profile. They may be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating a sterilizer in the form of a sterile solid composition that can be dissolved in sterile water, or by some other sterile injection medium immediately before use. These compositions may also optionally contain an opacifier and may release the active ingredient(s) only in specific parts of the gastrointestinal tract, or preferentially in specific parts, optionally in a delayed manner. Examples of implantable compositions that may be used include polymer substances and waxes. The active ingredient may also be in microencapsulated form having one or more of the above excipients, as needed.

[0122] Liquid dosage forms for oral administration of the compounds of the present invention include pharmaceutically acceptable emulsions, microemulsion formulations, solutions, suspensions, syrups, and elixirs. In addition to the active ingredient, the liquid dosage forms may contain, for example, water or other solvents, solubilizers, and emulsifiers, such as inert diluents commonly used in the art, including ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (particularly cottonseed oil, peanut oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan, and mixtures thereof.

[0123] In addition to inert diluents, oral compositions may also contain adjuvants such as humectants, emulsifiers and suspending agents, sweeteners, flavoring agents, colorants, fragrances, and preservatives.

[0124] In addition to the active compound, the suspension may contain a suspending agent, such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol, and sorbitan esters, microcrystalline cellulose, aluminum methhydroxyoxide, bentonite, agar, and tragacanth, or mixtures thereof.

[0125] Formulations of the pharmaceutical compositions of the present invention for rectal or vaginal administration may also be presented as suppositories that can be prepared by mixing one or more compounds of the present invention with one or more suitable non-irritating excipients or carriers, such as cocoa butter, polyethylene glycol, suppository wax, or salicylate, which are solid at room temperature but liquid at body temperature, and therefore melt in the rectum or vaginal cavity to release the active compound.

[0126] Formulations of the present invention suitable for intravaginal administration also include pessaries, tampons, creams, gels, pastes, foams, or sprays containing such carriers, which are known to be suitable in the art.

[0127] Dosage forms for topical or transdermal administration of the compounds of the present invention include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically acceptable carrier and any preservatives, buffers, or propellants as needed.

[0128] The ointments, pastes, creams, and gels may contain, in addition to the active compounds of the present invention, excipients such as animal and vegetable fats, oils, waxes, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicic acid, talc, and zinc oxide, or mixtures thereof.

[0129] The powders and sprays may contain, in addition to the compounds of the present invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicate, and polyamide powder, or mixtures thereof. The sprays may further contain conventional propellants such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons such as butane and propane.

[0130] Transdermal patches offer the additional advantage of providing controlled delivery of the compounds of the present invention into the body. Such dosage forms can be prepared by dissolving or dispersing the compounds in a suitable medium. Absorption enhancers can also be used to increase the flow of the compounds across the skin. The rate of such flow can be controlled by providing a rate-controlling membrane or by dispersing the active compounds in a polymer matrix or gel.

[0131] Ophthalmic preparations, eye ointments, powders, and liquids are also conceived as being within the scope of the present invention.

[0132] The pharmaceutical compositions of the present invention, suitable for parenteral administration, may contain one or more compounds of the present invention in combination with one or more pharmaceutically acceptable carriers, such as a sterile isotonic aqueous solution or nonaqueous solution, dispersion, suspension, emulsion, or sterile powder, which can be reconstituted into a sterile injectable solution or dispersion immediately before use, and which may contain antioxidants, buffers, bacteriostatic agents, solutes that make the preparation isotonic with the blood of the intended recipient, or suspending agents or thickeners.

[0133] Suitable aqueous and non-aqueous carriers that can be used in the pharmaceutical compositions of the present invention include water, ethanol, glycol ethers, polyols (e.g., glycerol, propylene glycol, and polyethylene glycol), and suitable mixtures thereof, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate. Appropriate fluidity can be maintained, for example, by using a coating material such as lecithin, maintaining the required particle size in the case of a dispersion, and using a surfactant.

[0134] These compositions may also contain adjuvants such as preservatives, humectants, emulsifiers, and dispersants. Prevention of microbial action can be ensured by including various antimicrobial and antifungal agents, such as parabens, chlorobutanol, and phenolsorbic acid. It may also be desirable to include isotonic agents such as sugars and sodium chloride in the composition. In addition, long-term absorption in injectable forms can be achieved by including absorption-delaying agents such as aluminum monostearate and gelatin.

[0135] In some cases, it is desirable to delay the absorption of a drug from subcutaneous or intramuscular injection in order to prolong its effects. This can be achieved by using a liquid suspension of a crystalline or amorphous material with poor water solubility. The absorption rate of the drug then depends on its dissolution rate, and subsequently on the crystal size and morphology. Alternatively, delayed absorption of a parenterally administered drug form can be achieved by dissolving or suspending the drug in an oily vehicle.

[0136] Injectable depot formulations are prepared by forming a microcapsule matrix of the target compound in a biodegradable polymer such as polylactide-polyglycolide. The drug release rate can be controlled depending on the drug-to-polymer ratio and the properties of the specific polymer used. Other examples of biodegradable polymers include poly(orthoester) and poly(anhydride). Injectable depot formulations can also be prepared by encapsulating the drug in liposomes or microemulsion formulations compatible with body tissues.

[0137] The preparations of the present invention may be administered orally, parenterally, topically, or rectally. These may, of course, be administered in a form suitable for each route of administration. For example, they may be administered by injection, infusion, or inhalation in the form of tablets or capsules, by injection, inhalation, eye drops, ointment, or suppository; topically as a lotion or ointment; and rectally as a suppository.

[0138] As used herein, the terms “parenteral administration” and “administered parenterally” mean a mode of administration other than enteral and topical administration, usually by injection, and include, but are not limited to, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subepidermal, intra-articular, subcapsular, subarachnoid, intraspinal, and substernal injections and infusions. In some embodiments, the compounds of the present invention are administered by intravenous infusion. The infusion may be used to deliver a single daily dose or multiple doses. In some embodiments, the compounds of the present invention are administered by infusion over intervals of 15 minutes to 4 hours, typically 0.5 to 3 hours. Such infusions may be used once daily, twice daily, or up to three times per day.

[0139] When used herein, the terms “systemic administration,” “administered systemically,” “peripheral administration,” and “administered peripherally” mean the administration of a compound, drug, or other material that enters the patient’s system and is therefore administered in a manner other than directly to the central nervous system, such as through metabolism and other similar processes, such as subcutaneous administration.

[0140] These compounds may be administered to humans and other animals for therapeutic purposes by any suitable route of administration, including orally and nasally, for example, by spray, rectally, vaginally, parenterally, intracisionally, and topically, in the form of powder, ointment, or drops (including oral and sublingual).

[0141] Regardless of the selected route of administration, the compounds of the present invention, and / or the pharmaceutical compositions of the present invention, which can be used in a preferred hydrated form, are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those skilled in the art.

[0142] The actual drug dose level of the active ingredient in the pharmaceutical composition of the present invention may be varied to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient.

[0143] The selected drug dose level depends on a variety of factors, including the activity of the specific compound of the present invention used, or its ester, salt, or amide; the route of administration; the time of administration; the excretion rate of the specific compound used; the duration of treatment; other drugs, compounds, and / or materials used in combination with the specific compound used; and the age, sex, weight, condition, overall health, and prior medical history of the patient being treated.

[0144] A physician or veterinarian skilled in the art can determine and prescribe the effective amount of the required pharmaceutical composition. For example, a physician or veterinarian can start the dose of the compound of the present invention used in the pharmaceutical composition at a lower level than necessary to achieve the desired therapeutic effect and to gradually increase the drug dose until the desired effect is achieved.

[0145] Generally, the preferred daily dose of the compound of the present invention is the amount of the compound that is the minimum effective dose to produce a therapeutic effect. Such an effective dose generally depends on the factors mentioned above. Generally, the intravenous and subcutaneous doses of the compound of the present invention for a patient, when used for the indicated effect, are in the range of about 0.0001 to about 100 mg / kg body weight per day, and further, for example, about 0.01 to about 50 mg / kg per day, or about 0.1 to about 20 mg / kg per day. The effective dose is the prevention of viral infections such as CMV or another herpes virus. This is the amount to treat.

[0146] If necessary, the effective daily dose of the active compound may be administered in unit dosage form as a single daily dose or as two, three, four, five, or six or more secondary doses administered separately at appropriate intervals throughout the day. Compounds delivered orally or by inhalation are generally administered in doses of one to four times per day. Compounds delivered by injection are typically administered once daily or every other day. Compounds delivered by infusion are typically administered in doses of one to three times per day. If multiple doses are administered within a day, the doses may be administered at intervals of approximately four hours, six hours, eight hours, or twelve hours.

[0147] While the compounds of the present invention can be administered individually, they are generally administered as part of a pharmaceutical composition, such as those described herein. Therefore, a method of using the compounds of the present invention involves administering the compounds as part of a pharmaceutical composition, where at least one of the compounds of the present invention is mixed with a pharmaceutically acceptable carrier before administration.

[0148] Various embodiments of the pharmaceutical compositions of the present invention are described herein. It will be recognized that certain features in each embodiment may be combined with other specific features to provide further embodiments. The embodiments listed below are representative examples of the pharmaceutical compositions of the present invention. Embodiment 171. A pharmaceutical composition comprising a compound of formula (I), or a compound described in any one of Embodiments 1 to 153, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. Embodiment 172. The pharmaceutical composition according to Embodiment 154, further comprising at least one other antiviral agent. Embodiment 173. At least one other antiviral agent is a herpesvirus entry inhibitor; a herpesvirus initial transcription inhibitor; a herpesvirus helicase / primase inhibitor; Ganciclovir (Cytovene®), Valganciclovir (Valcyte®), Cymeval®, Cidofovir (Vistide®), Foscarnet (Foscavir®), CMX001, cyclopropavir (MBX-400), and Valaciclovir (Valt A pharmaceutical composition according to Embodiment 155, selected from herpesvirus DNA polymerase inhibitors such as rex(registered trademark); Zelitrex(registered trademark); UL97 kinase inhibitors such as Maribavir; herpesvirus protease inhibitors; herpesvirus terminase inhibitors such as AIC246(Letermovir); herpesvirus maturation inhibitors; other inhibitors such as Artesunate; CMV vaccines such as TransVax; and herpesvirus biological agents such as Cytogam(Cytotect(registered trademark)). Embodiment 174. A pharmaceutical composition comprising a compound of formula (I), or a compound described in any one of Embodiments 154 to 170, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. Embodiment 175. The pharmaceutical composition according to Embodiment 174, further comprising at least one other antiviral agent. Embodiment 176. At least one other antiviral agent is a herpesvirus entry inhibitor; a herpesvirus initial transcription inhibitor; a herpesvirus helicase / primase inhibitor; a herpesvirus DNA polymerase inhibitor such as Ganciclovir (Cytovene®), Valganciclovir (Valcyte®), Cymeval®, Cidofovir (Vistide®), Foscarnet (Foscavir®), CMX001, cyclopropavir (MBX-400), and Valaciclovir (Valtrex®; Zelitrex®); or a UL97 kinase such as Maribavir. A pharmaceutical composition according to Embodiment 175, selected from herpesvirus inhibitors; herpesvirus protease inhibitors; herpesvirus terminase inhibitors such as AIC246 (Letermovir); herpesvirus maturation inhibitors; other inhibitors such as artesunate; CMV vaccines such as TransVax; and herpesvirus biological agents such as Cytogam (Cytotect®). Pharmacology and utility

[0149] Another aspect of the present invention relates to a method for treating or preventing herpesvirus disease and / or infection in humans, comprising administering to a human being, either together or separately, an effective amount of the compound of the present invention, a pharmaceutically acceptable salt thereof, or the composition described above, either alone or in combination with at least one other antiviral agent.

[0150] A further aspect of the present invention relates to a method for inhibiting the replication of CMV or another herpesvirus, comprising exposing the virus to an effective amount of a compound of formula (I) or a salt thereof under conditions that inhibit viral replication. This method can be carried out in vitro or in vivo.

[0151] The use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical product for the treatment or prevention of herpesvirus disease and / or infection in humans, including CMV, is also within the scope of the present invention.

[0152] Another embodiment of the present invention provides, as a pharmaceutical product, the above-mentioned compound or a pharmaceutically acceptable salt thereof.

[0153] The present invention also provides the use of the pharmaceutical compositions described herein for the treatment of CMV infection or other herpesviruses in humans who have CMV infection or are at risk of CMV infection.

[0154] The present invention also provides the use of the pharmaceutical compositions described herein for the treatment of CMV disease or other herpesvirus infections in humans who have or are at risk of CMV disease.

[0155] An additional aspect of the present invention refers to a product comprising a composition effective for treating herpesvirus diseases and / or infections, and packaging material including a label indicating that the composition may be used to treat herpesvirus diseases and / or infections such as CMV, wherein the composition comprises a compound of formula (I) according to the present invention or a pharmaceutically acceptable salt thereof.

[0156] The use of a compound of formula (I) or a salt thereof to inhibit CMV replication is further included within the scope of the present invention.

[0157] The applicable daily dose range of the compound of the present invention is typically 0.01 to 100 mg / kg body weight, for example, 0.1 to 50 mg / kg body weight. Each drug dose unit may conveniently contain 5% to 95% (w / w) of the active compound. For example, such preparations may contain 20% to 80% of the active compound.

[0158] The actual pharmacokinetic or therapeutic dose will naturally depend on factors known to those skilled in the art, such as the patient's age and weight, route of administration, and severity of the disease. In any case, the combination is administered in a dosage and manner that allows for the delivery of a pharmacokinetic dose based on the patient's specific condition.

[0159] The “effective amount” of a compound is the amount necessary or sufficient to treat or prevent a viral infection and / or disease or condition described herein. For example, the effective amount of a herpesvirus or CMV DNA polymerase inhibitor of formula I is sufficient to treat a viral infection in a subject. In another example, the effective amount of a DNA polymerase inhibitor is sufficient to treat a viral infection, such as but not limited to CMV, VZV, or EBV, in a subject requiring such treatment. The effective amount may vary depending on factors such as the size and weight of the subject, the type of disease, or the specific compound of the present invention. For example, the selection of the compound of the present invention may affect what constitutes the “effective amount.” Those skilled in the art will be able to study the factors described herein and make a determination regarding the effective amount of the compound of the present invention without excessive experimentation.

[0160] The administration regimen may affect what constitutes the effective dose. The compounds of the present invention can be administered to subjects either before or after the onset of a viral infection. Furthermore, several divided doses and staggered dosages may be administered daily or sequentially, or the dose may be administered by continuous infusion or bolus injection. Furthermore, the dosage of the compound(s) of the present invention may be increased or decreased proportionally, as indicated by the urgency of the therapeutic or preventive situation.

[0161] The compounds of the present invention may be used for the treatment of conditions, disorders, or diseases described herein, or for the manufacture of pharmaceutical compositions for use in the treatment of these diseases. The present invention provides the use of the compounds of the present invention in the treatment of these diseases, or a method for preparing pharmaceutical compositions having the compounds of the present invention for the treatment of these diseases.

[0162] Another aspect of the present invention relates to a method for treating a viral disease and / or infection in a human, comprising administering to a human, either together or separately, an antiviral effective amount of the compound of the present invention, a pharmaceutically acceptable salt thereof, or the composition described above, either alone or in combination with at least one other antiviral agent, wherein the viral disease or infection is selected from CMV infection, congenital CMV, genital herpes, oral herpes (herpes simplex), herpetic keratitis, neonatal herpes, herpes encephalitis, varicella (chickenpox), herpes zoster (herpes zoster), infectious mononucleosis, post-transplant lymphoproliferative disorder (PTLD), Castelman's disease, and hemophagocytic lymphohistiocytosis in an immunocompromised patient (e.g., a transplant recipient).

[0163] Another aspect of the present invention relates to a method for treating a disorder that may be induced / exacerbated / promoted by a herpesvirus infection in humans, comprising administering to a human, either together or separately, an effective amount of the compound of the present invention, a pharmaceutically acceptable salt thereof, or the composition described above, either alone or in combination with at least one other antiviral agent, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes mellitus.

[0164] Another aspect of the present invention relates to a method for treating a disorder that may be induced / exacerbated / promoted by a herpesvirus infection in humans, comprising administering to a human, either together or separately, an effective amount of the compound of the present invention, a pharmaceutically acceptable salt thereof, or the composition described above, either alone or in combination with at least one other antiviral agent, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), atherosclerosis (AS), celiac disease, and type 1 diabetes mellitus.

[0165] Another aspect of the present invention is the use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical product for treating or preventing a disorder that may be induced / exacerbated / promoted by a herpesvirus infection, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes.

[0166] Another aspect of the present invention is the use of the compound of the present invention or a pharmaceutically acceptable salt thereof in the manufacture of a pharmaceutical product for treating or preventing a disorder that may be induced / exacerbated / promoted by a herpesvirus infection, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), atherosclerosis (AS), celiac disease, and type 1 diabetes.

[0167] Another aspect of the present invention is the use of the pharmaceutical compositions described herein for the treatment of viral diseases and / or infections in humans, wherein the viral disease or infection is selected from CMV infection, congenital CMV, genital herpes, oral herpes (herpes simplex), herpetic keratitis, neonatal herpes, herpes encephalitis, varicella (chickenpox), herpes zoster (herpes zoster), infectious mononucleosis, post-transplant lymphoproliferative disorder (PTLD), Castelman's disease, and hemophagocytic lymphohistiocytosis in immunocompromised patients (e.g., transplant recipients).

[0168] Another aspect of the present invention is the use of the pharmaceutical compositions described herein for the treatment of disorders that may be induced / exacerbated / promoted by herpesvirus infection, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes.

[0169] Another aspect of the present invention is the use of the pharmaceutical compositions described herein for the treatment of disorders that may be induced / exacerbated / promoted by herpesvirus infection, wherein the disorder is selected from Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), atherosclerosis (AS), celiac disease, and type 1 diabetes.

[0170] Various embodiments of therapeutic and use methods for the compounds of the present invention are described herein. It will be recognized that specific features in each embodiment may be combined with other specific features to provide further embodiments. The embodiments listed below are representative examples of therapeutic and use methods for the compounds of the present invention. Embodiment 177. A method for treating a herpes virus infection, comprising administering to a patient having a herpes virus infection a compound of formula (I) described in any one of Embodiments 1 to 153, or a pharmaceutical composition containing a compound of formula (I) or any one of Embodiments 1 to 153. Embodiment 178. The method according to Embodiment 177, wherein the herpesvirus is selected from cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), herpes simplex viruses including HSV-1 and HSV-2, herpesvirus 6, human herpesvirus 7, and Kaposi's sarcoma-associated herpesvirus. Embodiment 179. A method for treating herpesvirus infection, comprising: a patient having a herpesvirus infection; a compound of formula (I) described in any one of Embodiments 154 to 170, or a pharmaceutical compound comprising a compound of formula (I) or any one of Embodiments 154 to 170. A method including administering a substance. Embodiment 180. The method according to Embodiment 179, wherein the herpesvirus is selected from cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), herpes simplex viruses including HSV-1 and HSV-2, herpesvirus 6, human herpesvirus 7, and Kaposi's sarcoma-associated herpesvirus. Embodiment 181. Use of a compound according to any one of Embodiments 1 to 170, or a pharmaceutically acceptable salt thereof, for the preparation of a pharmaceutical for the treatment of a viral infection. Embodiment 182. A compound for use in the treatment of a viral infection in a patient requiring it, comprising any one of the compounds described in Embodiments 1 to 170. Embodiment 183. Compounds disclosed in Examples 1 to 262. Embodiment 184. Use of any one of the compounds described in Embodiments 1 to 170 and 183 in the treatment of a viral infection. Combination therapy

[0171] In some embodiments, the compound of formula (I) is co-administered with at least one additional agent selected from herpesvirus entry inhibitors, herpesvirus early transcription phenomenon inhibitors, herpesvirus helicase / primase inhibitors, other herpesvirus DNA polymerase inhibitors, UL97 kinase inhibitors, herpesvirus protease inhibitors, herpesvirus terminase inhibitors, herpesvirus maturation inhibitors, inhibitors of other targets in the herpesvirus life cycle, herpesvirus vaccines, and herpesvirus biological agents. In some embodiments, the herpesvirus is CMV.

[0172] These additional agents may be combined with the compound of the present invention to create a single pharmaceutical dosage form. Alternatively, these additional agents may be administered separately to the patient as part of multiple dosage forms, for example, using a kit. Such additional agents may be administered to the patient before, simultaneously with, or after administration of the compound of the present invention or a pharmaceutically acceptable salt thereof.

[0173] If the composition of the present invention comprises a combination of the compound of the present invention and one or more additional therapeutic or prophylactic agents, both the compound and the additional agents should be present at a drug dose level of about 10-100% of the drug dose typically administered in a monotherapy regimen, for example, about 10-80%.

[0174] Antiviral agents intended for use in such combination therapies include, but are not limited to, agents (compounds or biologics) that are effective in inhibiting the formation and / or replication of viruses in humans, by interfering with either the host or viral mechanism necessary for the formation and / or replication of viruses in humans. Such drugs may be selected from herpesvirus entry inhibitors; herpesvirus early transcription inhibitors; herpesvirus helicase and primase inhibitors; herpesvirus DNA polymerase inhibitors such as Ganciclovir (Cytovene®), Valganciclovir (Valcyte®), Cymeval®, Cidofovir (Vistide®), Foscarnet (Foscavir®), CMX001, cyclopropavir (MBX-400), and Valaciclovir (Valtrex®; Zelitrex®); UL97 kinase inhibitors such as Maribavir; herpesvirus protease inhibitors; herpesvirus terminase inhibitors such as AIC246 (Letermovir); herpesvirus maturation inhibitors; other inhibitors such as Artesunate; CMV vaccines such as TransVax; and herpesvirus biological agents such as Cytogam (Cytotect®).

[0175] The compounds of the present invention may also be used in combination with other agents (combination partners), such as additional antiviral agents of formula I or not of formula I, for the treatment of viral infections in subjects.

[0176] The term "combination / combination" means any combination fixed in a single unit dosage form, either as separate dosage forms suitable for use together, either simultaneously or sequentially, or as a kit of components for combination administration, in particular, within a time interval that allows the combination partner to exhibit cooperative, for example, synergistic, effective, or any combination thereof.

[0177] In certain embodiments of the present invention, the compounds of the present invention are used in combination with a second antiviral agent, such as those named herein.

[0178] A second antiviral agent may be administered in combination with the compound of the present invention, where the second antiviral agent is administered before, simultaneously with, or after one or more compounds of the present invention. If simultaneous administration of the compound of the present invention and the second agent is desired and the administration route is the same, the compound of the present invention may be formulated in the same dosage form together with the second agent. Examples of dosage forms containing the compound of the present invention and the second agent are tablets or capsules.

[0179] In some embodiments, the combination of the compound of the present invention and a second antiviral agent may provide synergistic activity. The compound of the present invention and the second antiviral agent may be administered together, separately but simultaneously, or sequentially. Use of the compound of the present invention in combination with an immunomodulator

[0180] The compounds and compositions described herein may be used or administered in combination with one or more therapeutic agents acting as immunomodulators, such as activators of costimulatory molecules, inhibitors of immunosuppressive molecules, or vaccines. Programmed Death 1 (PD-1) protein is an inhibitory member of the extended CD28 / CTLA4 family of T cell regulators (Okazaki et al. (2002) "Curr Opin Immunol" Vol. 14, pp. 391779-82; Bennett et al. (2003) "J. Immunol." Vol. 170, pp. 711-718). PD-1 is expressed on activated B cells, T cells, and monocytes. PD-1 is an immunosuppressive protein that negatively regulates TCR signaling (Ishida, Y. et al. (1992) "EMBO J." Vol. 11 pp. 3887-3895; Blank, C. et al. (Epub, December 29, 2006) "Immunol.Immunother." Vol. 56 No. 5 pp. 739-745), and is upregulated in chronic infections. The interaction between PD-1 and PD-L1 can act as an immune checkpoint, potentially leading to a decrease in infiltrating lymphocytes, reduced T cell receptor-mediated proliferation, and / or immune evasion by cancerous or infected cells (Dong et al. (2003) "J.Mol.Med." Vol. 81 pp. 281-287; Blank et al. (2005) "Cancer Immunol.Immunother." Vol. 54 pp. 307-314; Konishi et al. (2004) "Clin.Cancer Res." Vol. 10 pp. 5094-50100). Immunosuppression can be reversed by inhibiting the local interaction between PD-1 and PD-L1 or PD-L2. If the interaction between PD-1 and PD-L2 is also blocked, the effect is additive (Iwai et al. (2002) "Proc. Nat'l. Acad. Sci. USA" Vol. 99, pp. 12293-12297; Brown et al. (2003) "J. Immunol." Vol. 170, pp. 1257-1256). Immunomodulation can be achieved by binding to either an immunosuppressive protein (e.g., PD-1) or a binding protein that modulates inhibitory proteins (e.g., PD-L1, PD-L2).

[0181] In one embodiment, the combination therapy of the present invention comprises an immunomodulator, which is an inhibitor or antagonist of an inhibitory molecule of an immune checkpoint molecule. In another embodiment, the immunomodulator binds to a protein that naturally inhibits an immunoinhibitory checkpoint molecule. When used in combination with an antiviral compound, these immunomodulators can enhance the antiviral response and thus enhance the efficacy compared to treatment with the antiviral compound alone.

[0182] The term "immune checkpoint" refers to a group of molecules on the cell surface of CD4 and CD8 T cells. These molecules can effectively function as "brakes" to downmodulate or inhibit adaptive immune responses. Examples of immune checkpoint molecules include programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (Cytotoxic T-Lymphocyte Antigen 4). 4:CTLA-4), B7H1, B7H4, OX-40, CD137, CD40, and LAG3 is one example, but is not limited to it, as it directly inhibits immune cells. Immunotherapy agents that can act as useful immune checkpoint inhibitors in the methods of the present invention include, but are not limited to, inhibitors of PD-L1, PD-L2, CTLA4, TIM3, LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, and / or TGFR beta. Inhibition of inhibitory molecules can be carried out by inhibition at the DNA, RNA, or protein level. In some embodiments, inhibitory nucleic acids (e.g., dsRNA, siRNA, or shRNA) can be used to inhibit the expression of inhibitory molecules. In other embodiments, the inhibitor of the inhibitory signal is a polypeptide that binds to the inhibitory molecule, such as a soluble ligand or an antibody or antigen-binding fragment thereof.

[0183] The phrase "in combination with" is not intended to mean that the therapies or therapeutic agents must be administered simultaneously and / or formulated to be delivered together, although these delivery methods are within the scope described herein. Immunomodulators may be administered simultaneously, before, or after one or more compounds of the present invention and optionally one or more additional therapies or therapeutic agents. The therapeutic agents in the combination may be administered in any order. Generally, each agent is administered in the dose and / or time schedule determined for that agent. It will be further understood that the therapeutic agents used in this combination may be administered together in a single composition or separately in different compositions. Generally, each therapeutic agent used in combination is expected to be used at a level not exceeding the level at which they are used individually. In some embodiments, the level at which they are used in combination is lower than that at which they are used individually.

[0184] In certain embodiments, the antiviral compounds described herein are administered in combination with one or more immunomodulators, which are inhibitors of PD-1, PD-L1, and / or PD-L2. Each such inhibitor may be an antibody, its antigen-binding fragment, an immunoadhesin, a fusion protein, or an oligopeptide. Examples of such immunomodulators are known in the art.

[0185] In some embodiments, the immunomodulator is an anti-PD-1 antibody selected from MDX-1106, Merck 3475, or CT-011.

[0186] In some embodiments, the immunomodulator is an immunoadhesin (for example, an immunoadhesin containing an extracellular or PD-1 binding moiety of PD-L1 or PD-L2 fused to a constant region (e.g., the Fc region of an immunoglobulin sequence)).

[0187] In some embodiments, the immunomodulator is a PD-1 inhibitor such as AMP-224.

[0188] In some embodiments, the immunomodulator is a PD-Ll inhibitor, such as an anti-PD-Ll antibody.

[0189] In some embodiments, the immunomodulator is an anti-PD-Ll conjugating antagonist selected from YW243.55.S70, MPDL3280A, MEDI-4736, MSB-0010718C, or MDX-1105. MDX-1105, also known as BMS-936559, is an anti-PD-Ll antibody described in International Publication No. 2007 / 005874. Antibody YW243.55.S70 is an anti-PD-Ll antibody described in International Publication No. 2010 / 077634.

[0190] In some embodiments, the immunomodulator is nivolumab (CAS Registry No.: 946414-94-4). Alternative names for nivolumab include MDX-1106, MDX-1106-04, ONO-4538, or BMS-936558. Nivolumab is a fully human IgG4 monoclonal antibody that specifically blocks PD-1. Nivolumab (clone 5C4) and other human monoclonal antibodies that specifically bind to PD-1 are disclosed in U.S. Patent No. 8,008,449, European Patent No. 2161336, and International Publication No. 2006 / 121168.

[0191] In some embodiments, the immunomodulator is the anti-PD-1 antibody pembrolizumab. Pembrolizumab (also known as lambrolizumab, MK-3475, MK03475, SCH-900475, or KEYTRUDA® (Merck)) is a humanized IgG4 monoclonal antibody that binds to PD-1. Pembrolizumab and other humanized anti-PD-1 antibodies are disclosed in Hamid, O. et al. (2013) "New England Journal of Medicine" Vol. 369 No. 2 pp. 134-44, U.S. Patent No. 8,354,509, International Publication No. 2009 / 114335 and International Publication No. 2013 / 079174.

[0192] In some embodiments, the immunomodulator is pidilizumab (CT-011; CureTech), a humanized IgG1k monoclonal antibody that binds to PD1. Pidilizumab and other humanized anti-PD-1 monoclonal antibodies are disclosed in International Publication No. 2009 / 101611.

[0193] Other anti-PD1 antibodies useful as immunomodulators for use in the methods disclosed herein include AMP 514 (Amplimmune) and anti-PD1 antibodies disclosed in U.S. Patent No. 8,609,089, U.S. Patent Application Publication No. 2010028330, and / or U.S. Patent Application Publication No. 20120114649. In some embodiments, the anti-PD-L1 antibody is MSB0010718C. MSB0010718C (also known as A09-246-2 (Merck Serono)) is a monoclonal antibody that binds to PD-L1.

[0194] In some embodiments, the immunomodulator is MDPL3280A (Genentech / Roche), a human Fc-optimized IgG1 monoclonal antibody that binds to PD-L1. MDPL3280A and other human monoclonal antibodies against PD-L1 are disclosed in U.S. Patent No. 7,943,743 and U.S. Patent Application Publication No. 20120039906. Other anti-PD-L1 conjugates useful as immunomodulators for the methods of the present invention include YW243.55.S70 (see International Publication No. 2010 / 077634), MDX-1105 (also known as BMS-936559), and anti-PD-L1 conjugates disclosed in International Publication No. 2007 / 005874.

[0195] In some embodiments, the immunomodulator is AMP-224 (B7-DCIg; Amplimmune; for example, disclosed in International Publication Nos. 2010 / 027827 and 2011 / 066342), which is a PD-L2Fc fusion soluble receptor that blocks the interaction between PD1 and B7-H1.

[0196] In some embodiments, the immunomodulator is an anti-LAG-3 antibody such as BMS-986016. BMS-986016 (also referred to as BMS986016) is a monoclonal antibody that binds to LAG-3. BMS-986016 and other humanized anti-LAG-3 antibodies are disclosed in U.S. Patent Application Publication 2011 / 0150892, International Publication 2010 / 019570, and International Publication 2014 / 008218.

[0197] In certain embodiments, the combination therapies disclosed herein include a co-stimulatory molecule or an inhibitory molecule, such as a modulator of a co-inhibitory ligand or receptor.

[0198] In one embodiment, the co-stimulatory modulator of the co-stimulatory molecule, for example, the agonist, is selected from agonists of OX40, CD2, CD27, CDS, ICAM-1, LFA-1 (CD11a / CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, or CD83 ligands (for example, an agonist antibody or its antigen-binding fragment, or a soluble fusion).

[0199] In another embodiment, the combination therapy disclosed herein includes an immunomodulator, which is a positive signal-related agonist containing a co-stimulatory molecule, such as CD28, CD27, ICOS, and / or GITR's co-stimulatory domain.

[0200] Examples of GITR agonists include, for example, GITR fusion proteins and anti-GITR antibodies (e.g., bivalent anti-GITR antibodies), such as the GITR fusion proteins described in U.S. Patent No. 6,111,090, European Patent No. 090505(B1), U.S. Patent No. 8,586,023, International Publication No. 2010 / 003118, and International Publication No. 2011 / 090754, or, for example, U.S. Patent No. 7,025,962, European Patent No. 1947183(B1), U.S. Patent No. 7,812,135, U.S. Patent No. 8,388,967, U.S. Patent No. 8,591, Examples include anti-GITR antibodies described in Patent No. 886, European Patent No. 1866339, International Publication No. 2011 / 028683, International Publication No. 2013 / 039954, International Publication No. 2005 / 007190, International Publication No. 2007 / 133822, International Publication No. 2005 / 055808, International Publication No. 99 / 40196, International Publication No. 2001 / 03720, International Publication No. 99 / 20758, International Publication No. 2006 / 083289, International Publication No. 2005 / 115451, U.S. Patent No. 7,618,632, and International Publication No. 2011 / 051726.

[0201] In one embodiment, the immunomodulator used is a soluble ligand (e.g., CTLA-4-Ig), or an antibody or antibody fragment that binds to PD-L1, PD-L2, or CTLA4. For example, an anti-PD-1 antibody molecule can be administered in combination with, for example, an anti-CTLA-4 antibody, such as ipilimumab. Exemplary anti-CTLA4 antibodies include tremelimumab (an IgG2 monoclonal antibody available from Pfizer, formerly known as tisilimubab, CP-675,206) and ipilimumab (a CTLA-4 antibody, also known as MDX-010, CAS number 477202-00-9).

[0202] In one embodiment, an anti-PD-1 antibody molecule is administered after treatment with the compound of the present invention as described herein.

[0203] In another embodiment, an anti-PD-1 or PD-L1 antibody molecule is administered in combination with an anti-LAG-3 antibody or its antigen-binding fragment. In yet another embodiment, an anti-PD-1 or PD-L1 antibody molecule is administered in combination with an anti-TIM-3 antibody or its antigen-binding fragment. In yet another embodiment, an anti-PD-1 or PD-L1 antibody molecule is administered in combination with an anti-LAG-3 antibody and an anti-TIM-3 antibody, or their antigen-binding fragments. The antibody combinations listed herein may be administered separately, for example, as distinct antibodies, or linked together, for example, as bispecific or trispecific antibody molecules. In one embodiment, a bispecific antibody comprising an anti-PD-1 or PD-L1 antibody molecule and an anti-TIM-3 or anti-LAG-3 antibody, or its antigen-binding fragment, is administered. In certain embodiments, the antibody combinations listed herein are used to treat cancer, for example, the cancers described herein (e.g., solid tumors). The efficacy of the aforementioned combinations can be tested in animal models known in the art. For example, an animal model for testing the synergistic effects of anti-PD-1 and anti-LAG-3 is described, for instance, by Woo et al. (2012), "Cancer Res. Vol. 72, No. 4, pp. 917-927."

[0204] Examples of immunomodulatory agents that can be used in combination therapy include, but are not limited to, aftuzumab (available from Roche®); pegfilgrastim (Neulasta®); lenalidomide (CC-5013, Revlimid®); thalidomide (Thalomid®), actimide (CC4047); and cytokines, such as IL-21 or IRX-2 (a mixture of human cytokines containing interleukin-1, interleukin-2, and interferon-γ, CAS 951209-71-5, available from IRX Therapeutics).

[0205] Exemplary doses of such immunomodulators that can be used in combination with the antiviral compounds of the present invention include an anti-PD-1 antibody molecule at a dose of about 1 to 10 mg / kg, for example, 3 mg / kg, and an anti-CTLA-4 antibody, for example, ipilimumab, at a dose of about 3 mg / kg.

[0206] Examples of embodiments of methods for using the antiviral compounds of the present invention in combination with immunomodulators include those which may be used with the compounds of formula I disclosed herein or any subgenus or species thereof: i. A method for treating a viral infection in a subject, comprising administering to the subject a compound of formula (I) and an immunomodulator described herein. ii. The method according to embodiment i, wherein the immunomodulator is an activator of a costimulatory molecule or an inhibitor of an immune checkpoint molecule. iii. The method according to any one of Embodiments i and ii, wherein the activator of the co-stimulatory molecule is one or more agonists from among OX40, CD2, CD27, CDS, ICAM-1, LFA-1 (CD11a / CD18), ICOS (CD278), 4-1BB (CD137), GITR, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, and CD83 ligands. iv. The method according to any one of embodiments i to iii above, wherein the inhibitor of an immune checkpoint molecule is selected from PD-1, PD-L1, PD-L2, CTLA4, TIM3, LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4, and TGFR beta. v. The method according to any one of embodiments i to iii, wherein the inhibitor of the immune checkpoint molecule is selected from inhibitors of PD-1, PD-L1, LAG-3, TIM-3, or CTLA4, or any combination thereof. vi. Inhibitors of immune checkpoint molecules can bind to immune checkpoint molecules. The method according to any one of embodiments i to v, wherein the ligand is soluble, or an antibody or antigen-binding fragment thereof. vii. The method according to any one of embodiments i to vi, wherein the antibody or its antigen-binding fragment is derived from IgG1 or IgG4 (e.g., human IgG1 or IgG4). viii. The method according to any one of embodiments i to vii, wherein the antibody or its antigen-binding fragment is modified, for example, mutated, to increase or decrease one or more of the following: Fc receptor binding, antibody glycosylation, number of cysteine ​​residues, effector cell function, or complement function. ix. The method according to any one of embodiments i to viiii, wherein the antibody molecule is a bispecific or multispecific antibody molecule having a first binding specificity to PD-1 or PD-L1 and a second binding specificity to TIM-3, LAG-3, or PD-L2. x. The method according to any one of embodiments i to ix, wherein the immunomodulator is an anti-PD-1 antibody selected from nivolumab, pembrolizumab, or pidilizumab. xi. The method according to any one of embodiments i to x, wherein the immunomodulator is an anti-PD-L1 antibody selected from YW243.55.S70, MPDL3280A, MEDI-4736, MSB-0010718C, or MDX-1105. xii. The method according to any one of embodiments i to x, wherein the immunomodulator is an anti-LAG-3 antibody molecule. xiii. The method according to embodiment xii, wherein the anti-LAG-3 antibody molecule is BMS-986016. xiv. The method according to any one of embodiments i to x, wherein the immunomodulator is an anti-PD-1 antibody molecule administered by injection (e.g., subcutaneously or intravenously) at a dose of approximately 1 to 30 mg / kg, for example, approximately 5 to 25 mg / kg, approximately 10 to 20 mg / kg, approximately 1 to 5 mg / kg, or approximately 3 mg / kg, for example, once a week to once every 2, 3, or 4 weeks. xv. The method according to embodiment xiv, wherein an anti-PD-1 antibody molecule is administered every other week at a dose of approximately 10-20 mg / kg. xvi. The method according to embodiment xv, wherein an anti-PD-1 antibody molecule, such as nivolumab, is administered intravenously every two weeks at a dose of approximately 1 mg / kg to 3 mg / kg, for example, approximately 1 mg / kg, 2 mg / kg, or 3 mg / kg. xvii. The method according to embodiment xv, wherein an anti-PD-1 antibody molecule, such as nivolumab, is administered intravenously at a dose of approximately 2 mg / kg at intervals of 3 weeks. [Examples]

[0207] The present invention is further illustrated by the following embodiments, which should not be construed as limiting. The assays used throughout the embodiments are well established in the art. Demonstrations of efficacy in these assays are generally considered to be predictive of efficacy in the subject. [Table 1-1] [Table 1-2] Preparation of important intermediates Intermediate 1 1-(bromomethyl)-1-(cyclopropylsulfonyl)cyclopropane(int-1) [ka]

[0208] Step 1: Benzyl 2-bromoacetate (5.97 mL, 37.7 mmol, 1.0 equivalent) was added to a slurry of sodium cyclopropanesulfinate (5.79 g, 45.2 mmol, 1.2 equivalents) in DMF (30 mL). The resulting mixture was stirred overnight at room temperature and then diluted with H2O and Et2O. The layers were separated, and the aqueous layer was extracted with Et2O. The combined organic extracts were washed with brine, dried over Na2SO4, and filtered. The solution was concentrated to obtain benzyl 2-(cyclopropylsulfonyl) acetate (i1-a). 1 H NMR (400MHz, CDCl3) δ7.44-7.34(m,5H),5.26(s,2H),4.09-4.03(m,2H),2.76-2.67(m,1H),1.31-1.24(m,2H),1.09-1.02(m,2H).

[0209] Step 2: To a solution of benzyl 2-(cyclopropylsulfonyl)acetate (i1-a) (9.37 g, 36.8 mmol, 2.0 equivalents) in DMF (350 mL), K2CO3 (10.18 g, 73.7 mmol, 1.0 equivalent) and 1,2-dibromoethane (3.81 mL, 44.2 mmol, 1.2 equivalents) were added. The resulting mixture was stirred at 60°C for 12 hours, then cooled to room temperature and diluted with Et2O. The solid was removed by filtration, the filtrate was washed with water, and the aqueous layer was extracted with Et2O. The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The oily substance was purified by column chromatography (SiO2, 0-100% DCM / heptane) to obtain benzyl 1-(cyclopropylsulfonyl)cyclopropanecarboxylate (i1-b). 1 H NMR(400MHz,CDCl3)δ7.41-7.32(m,5H),5.26-5.22(m,2H),3.00(tt,J=8.09,4.90H z,1H),1.78-1.72(m,2H),1.68-1.63(m,2H),1.25-1.20(m,2H),1.01-0.95(m,2H).

[0210] Step 3: To a solution of benzyl 1-(cyclopropylsulfonyl)cyclopropanecarboxylate (i1-b) (6.53 g, 23.29 mmol) in THF (50 mL), LiBH4 (2.0 M in THF, 11.65 mL, 23.29 mmol) was added. After stirring the resulting solution overnight at room temperature, the reaction mixture was added to a 2 M HCl / ice mixture. The two-phase mixture was extracted by DCM, and the combined organic extract was then dried over Na2SO4, filtered, and concentrated. The oily substance was purified by column chromatography (SiO2, 0-100% siRNA / heptane) to obtain (1-(cyclopropylsulfonyl)cyclopropyl)methanol (i1-c). TLC R f = 0.2 (1:3 HCl / petroleum ether). 1H NMR (400MHz, CDCl3) δ3.92(d,J=6.11Hz,2H),2.59-2.50(m,2H),1.52-1.47(m,2H),1.29-1.23(m,2H),1.10-1.01(m,4H).MS(ESI):m / z177.1[M+H]+.

[0211] Step 4: A solution of (1-(cyclopropylsulfonyl)cyclopropyl)methanol (i1-c) (10.0 g, 56.7 mmol, 1.0 equivalent) and DPPE (16.0 g, 39.7 mmol, 0.7 equivalents) in THF (100 mL) was cooled to 0°C. Then, a solution of CBr4 (38.0 g, 113.5 mmol, 2.0 equivalents) in THF (20 mL) was added over 0.5 hours. After 90 minutes at 25°C, the solid was removed by filtration, and the filtrate was concentrated. The residue was purified by column chromatography (SiO2, 10-25% SiO2 / petroleum ether) to obtain 1-(bromomethyl)-1-(cyclopropylsulfonyl)cyclopropane (int-1). TLC R f = 0.5 (25% HCl / petroleum ether). 1 H NMR (400MHz, CDCl3) δ3.89(s,2H),2.66(m,1H),1.78-1.69(m,2H),1.33-1.26(m,2H),1.23-1.18(m,2H),1.16-1.09(m,2H). Intermediate 2 1-(bromomethyl)-1-((1-methylcyclopropyl)sulfonyl)cyclopropane(int-2) [ka]

[0212] Step 1: A solution of (1-(cyclopropylsulfonyl)cyclopropyl)methanol (30 g, 170 mmol, 1.0 equivalent) in DMF (300 mL) was cooled to 0°C, and NaH (60% of mineral oil, 13.6 g, 341 mmol, 2.0 equivalents) was gradually added (gas generation). The reaction mixture was stirred at 0°C for 0.5 hours, and then NaI (1.7 g, 17.0 mmol, 0.1 equivalent) and BnBr (29 g, 170 mmol, 1.0 equivalent) were added at 0°C. The reaction mixture was stirred at 0°C for 3 hours, then poured into saturated NH4Cl (300 mL) and extracted with SiO2 (3 × 100 mL). The combined organic extract was dried over Na2SO4, filtered, and concentrated. The material was purified from SiO / petroleum ether by grinding to obtain (((1-(cyclopropylsulfonyl)cyclopropyl)methoxymethyl)benzene (i2-a). 1 H NMR (400MHz, CDCl3) δ7.38-7.32(m,5H),4.59(s,2H),3.82(s,2H),2.70(m,1H),1.51-1.49(m,2H),1.22-1.20(m,2H),1.03-0.98(m,4H).

[0213] Step 2: n-BuLi (2.16 mL, 5.40 mmol, 1.2 equivalents, 2.5 M in hexane) was added dropwise at -60°C to a solution of (((1-(cyclopropylsulfonyl)cyclopropyl)methoxy)methyl)benzene (i2-a) (1.2 g, 4.50 mmol, 1.0 equivalent) in THF (20 mL). The reaction mixture was stirred at 0°C for 30 minutes, and then MeI (0.84 mL, 13.5 mmol, 3.0 equivalents) was added at 0°C. The reaction mixture was stirred at 25°C for 1 hour, then quenched with water (20 mL) and extracted with RINKAN (3 × 10 mL). The combined organic extract was washed with brine (20 mL), dried over Na₂SO₄, filtered, and concentrated. The residue was purified by RP-HPLC to obtain (((1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methoxy)methyl)benzene (i2-b). TLC R f =0.4(1:5 HCl / petroleum ether).MS(ESI):m / z281.0[M+H] + .

[0214] Step 3: A mixture of (((1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methoxy)methyl)benzene (i2-b) ​​(900 mg, 2.71 mmol, 1.0 equivalent) and Pd / C (200 mg) in MeOH (10 mL) and AcOH (10 mL) was stirred at 20°C for 12 hours under a hydrogen atmosphere. The solid was removed by filtration, and the filtrate was concentrated. The residue was diluted with water (10 mL), neutralized with saturated Na2CO3, and extracted with ELISA (3 × 5 mL). The combined organic extract was dried over Na2SO4, filtered, and concentrated to obtain (1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methanol (i2-c). TLC R f = 0.1 (1:5 ¼ / petroleum ether). 1 H NMR(400MHz,MeOH-d4)δ3.78(s,2H),1.43(s,3H),1.30-1.29(m,2H),1.24-1.22(m,2H),1.00-0.98(m,2H),0.78-0.76(m,2H).

[0215] Step 4: A solution of (1-((1-methylcyclopropyl)sulfonyl)cyclopropyl)methanol)(i2-c) (220 mg, 1.16 mmol, 1.0 equivalent) in THF (4 mL) was cooled to -40°C, and Et3N (234 mg, 2.32 mmol, 2.0 equivalent) and MsCl (199 mg, 1.73 mmol, 1.5 equivalent) were added. The mixture was stirred at -40°C for 1 hour, then placed in an ice bath, and LiBr (502 mg, 5.78 mmol, 5.0 equivalent) was added all at once. The mixture was stirred at 25°C for 1 hour, then diluted with water (20 mL) and extracted with SiO (3 × 20 mL). The combined organic extract was washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (SiO2, 10-25% SiO2 / petroleum ether) to obtain 1-(bromomethyl)-1-((1-methylcyclopropyl)sulfonyl)cyclopropane (int-2). TLC R f = 0.8 (25% HCl / petroleum ether). 1H NMR (400MHz, MeOH-d4) δ3.95(s,2H), 1.70-1.65(m,2H), 1.58(s,3H), 1.51-1.46(m,2H), 1.33-1.27(m,3H), 1.01-0.95(m,2H). Intermediate 3 1-(bromomethyl)-1-(ethylsulfonyl)cyclopropane(int-3) [ka]

[0216] Step 1: Ethyl 1-(ethylsulfonyl)cyclopropanecarboxylate (i3-a) was obtained using the method described for the synthesis of intermediate (i1-b), except that benzyl 2-(cyclopropylsulfonyl)acetate (i1-a) was replaced with ethyl 2-(ethylsulfonyl)acetate. TLC R f = 0.5 (33% Â / petroleum ether). 1 H NMR(400MHz,CDCl3)δ4.23(q,J=7.2Hz,2H),3.45(q,J=7.5Hz,2H),2.02(s,1H),1 .78-1.72(m,2H),1.66-1.60(m,2H),1.38(t,J=7.5Hz,3H),1.28(t,J=7.2Hz,3H).

[0217] Step 2: A solution of ethyl 1-(ethylsulfonyl)cyclopropanecarboxylate (i3-a) (15 g, 72.7 mmol, 1.0 equivalent) in THF (150 mL) was cooled to 0°C, and LiAlH4 (3.3 g, 87.2 mmol, 1.2 equivalents) was gradually added. The mixture was warmed to room temperature and stirred at that temperature for 3 hours, then quenched with a solution of sodium hydroxide (3.3 g) in water (10 mL). The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, 15-50% siRNA / petroleum ether) to obtain 1-(ethylsulfonyl)cyclopropyl)methanol (i3-b). TLC R f = 0.1 (33% HCl / petroleum ether). 1H NMR (400MHz, CDCl3) δ3.82(s,2H),3.15(q,J=7.6Hz,2H),2.56(s,1H),1.44-1.40(m,2H),1.34(t,J=7.6Hz,3H),0.97-0.93(m,2H).

[0218] Step 3: 1-(bromomethyl)-1-(ethylsulfonyl)cyclopropane (int-3) was obtained using the method described in Step 4 for the synthesis of intermediate (int-1), except that (1-(cyclopropylsulfonyl)cyclopropyl)methanol (i1-c) was replaced with (1-(ethylsulfonyl)cyclopropyl)methanol (i3-b). 1 H NMR (400MHz, CDCl3) δ3.79(s,2H),3.28-3.16(m,2H),1.74-1.66(m,2H),1.36(t,J=7.5Hz,3H),1.16-1.08(m,2H). Intermediate 4 1-(bromomethyl)-1-(methylsulfonyl)cyclopropane(int-4) [ka]

[0219] Step 1: Methyl 1-(methylsulfonyl)cyclopropanecarboxylate (i4-a) was obtained using the method described for the synthesis of intermediate (i1-b), except that benzyl 2-(cyclopropylsulfonyl)acetate (i1-a) was replaced with methyl 2-(methylsulfonyl)acetate. 1 H NMR (400MHz, CDCl3) δ3.81(s,3H),3.20(s,3H),1.84-1.79(m,2H),1.70-1.65(m,2H).

[0220] Step 2: (1-(methylsulfonyl)cyclopropyl)methanol (i4-b) was obtained using the method described for the synthesis of intermediate (i1-c), except that benzyl 1-(cyclopropylsulfonyl)cyclopropanecarboxylate (i1-b) was replaced with methyl 1-(methylsulfonyl)cyclopropanecarboxylate (i4-a). 1 H NMR (400MHz, CDCl3) δ3.92(d,J=5.53Hz,2H),3.04(s,3H),2.48(t,J=5.45Hz,1H),1.54-1.48(m,2H),1.08-1.01(m,2H).

[0221] Step 3: 1-(bromomethyl)-1-(methylsulfonyl)cyclopropane (int-4) was obtained using the method described in Step 4 for the synthesis of intermediate (int-1), except that (1-(cyclopropylsulfonyl)cyclopropyl)methanol (i1-c) was replaced with (1-(methylsulfonyl)cyclopropyl)methanol (i4-b). 1 H NMR (400MHz, CDCl3) δ3.86(s,1H), 3.10(s,3H), 1.79-1.76(m,2H), 1.23-1.19(m,2H). Intermediate 5 Ethyl 1-methyl-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (int-5) [ka]

[0222] Step 1: To a solution of 3-iodo-1H-pyrazolo[3,4-c]pyridine (7.2 g, 29.4 mmol, 1.0 equivalent) in DMF (160 mL), NaH (60% in mineral oil, 2.4 g, 58.8 mmol, 2.0 equivalent) was gradually added at 0°C (gas generation). After stirring the mixture for 30 minutes, CH3I (8.7 g, 61.3 mmol, 2.1 equivalent) was added at 0°C. After stirring the reaction mixture at 0°C for 30 minutes and at 15°C for 1 hour, the mixture was diluted with H2O (300 mL) and neutralized to pH 7 with 1 M HCl. The aqueous layer was extracted with ELISA (3 × 200 mL), and the combined organic extract was dried over Na2SO4, filtered, and concentrated. The crude solid was purified by RP-HPLC to obtain 3-iodo-1-methyl-1H-pyrazolo[3,4-c]pyridine (i5-a). 1 H NMR(400MHz,CDCl3)δ8.86(s,1H),8.31(d,J=5.6Hz,1H),7.3 0(d,J=5.6Hz,1H),4.15(s,3H).MS(ESI):m / z260.1[M+H] + .

[0223] Step 2: To a solution of 3-iodo-1-methyl-1H-pyrazolo[3,4-c]pyridine (i5-a) (4.0 g, 15.4 mmol, 1.0 equivalent) in EtOH (150 mL), Pd(dppf)Cl2 (3.95 g, 5.41 mmol, 0.35 equivalent) and Et3N (6.44 mL, 46.3 mmol, 3.0 equivalent) were added. The mixture was stirred at 40°C for 24 hours under a CO atmosphere (50 psi), and then concentrated. The residue was loaded onto silica gel in a dry state and purified by column chromatography (SiO2, 20-75% Â / petroleum ether) to obtain ethyl 1-methyl-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (i5-b). 1 H NMR(400MHz,CDCl3)δ8.97(d,J=1.0Hz,1H),8.40(d,J=5.6Hz,1H),7.98(dd,J=1.2,5.6Hz ,1H),4.46(q,J=7.2Hz,2H),4.22(s,3H),1.42(t,J=7.2Hz,3H).MS(ESI):m / z206.3[M+H]+ .

[0224] Step 3: To a solution of N-oxide × (221 mg, 1.0 mmol, 1.0 equivalent) in DMF (3 mL), TFAA (1.5 mL) was added dropwise at 20°C. The reaction mixture was stirred for 18 hours and then diluted with ice water (10 mL). The mixture was neutralized with 10% Na₂CO₃ and extracted with SiO₂ (4 × 3 mL). The combined organic extract was dried over Na₂SO₄, filtered, and concentrated. The residue was purified by column chromatography (SiO₂, 50% SiO₂ / petroleum ether) to obtain ethyl 1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (int-5). 1 H NMR(400MHz,MeOH-d4)δ7.08(d,J=7.1Hz,1H),6.95(d,J=7.1Hz,1H),4.45(q,J=7.1Hz,2H),4.41(s,3H),1.45(t,J=7.2Hz,3H).MS(ESI):m / z222.1[M+H] + . Intermediate 6 Ethyl 6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate(int-6) [ka]

[0225] A mixture of ethyl 1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (int-5) (80 mg, 0.37 mmol, 1.0 equivalent), Cs2CO3 (620 mg, 1.9 mmol, 5.0 equivalents), and 1-(bromomethyl)-1-(cyclopropylsulfonyl)cyclopropane (int-1) (177 mg, 0.74 mmol, 2.0 equivalents) in DMF (2 mL) was stirred at 50°C for 12 hours, then diluted with water (2 mL) and extracted with ethyl phosphate (3 × 2 mL). The combined organic extract was washed with water (4 mL) and brine (2 × 4 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by preparative TLC (SiO2, 67% SiO / petroleum ether) to ethyl 6-((1-(cyclopropylsulfonyl)cyclopropyl)methyl)-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[3,4 -c]pyridine-3-carboxylate was obtained (int-6). TLC R f = 0.4 (67% HCl / petroleum ether). 1 H NMR(400MHz,MeOH-d4)δ7.39(brd,J=7.2Hz,1H),6.93(brd,J=7.3Hz,1H),4.63 (s,2H),4.47-4.42(m,2H),4.39(s,3H),1.43-1.39(m,3H),1.15-1.02(m,8H). Intermediate 7 Ethyl 1-methyl-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate(int-7) [ka]

[0226] Ethyl 1-methyl-6-((1-(methylsulfonyl)cyclopropyl)methyl)-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridine-3-carboxylate (int-7) was obtained using the method described for the synthesis of intermediate (int-6), except that 1-(bromomethyl)-1-(cyclopropylsulfonyl)cyclopropane (int-1) was replaced with 1-(bromomethyl)-1-(methylsulfonyl)cyclopropane (int-4). TLC R f = 0.2 (33% Â / petroleum ether). 1 H NMR(400MHz,MeOH-d4)δ7.38(d,J=7.4Hz,1H),6.93(d,J=7.3Hz,1H),4.57(s,2H),4.44(q,J=7. 2Hz,2H),4.40(s,3H),3.01(s,3H),1.49-1.46(m,2H),1.43(t,J=7.2Hz,3H),1.31-1.27(m,2H). Intermediate 8 (Z)-Ethyl 2-chloro-2-(2-cyclopropylhydrazono)acetate (int-8) [ka]

[0227] Step 1: To a solution of ethyl 2-oxoacetate (2.7 g, 13.2 mmol) in THF (20 mL), K2CO3 (6.1 g, 44.0 mmol) and cyclopropylhydrazine dihydrochloride (2.0 g, 13.8 mmol) were added at 0°C. The mixture was stirred at 25°C for 12 hours. The mixture ...

Claims

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof, 【Chemistry 1】 During the ceremony: X is, 【Chemistry 1-1】 And; Y is, 【Chemistry 1-2】 And; q is 1; L ＭＣ は、 ＊ -((CR １１ R １２ ) ｎ O) ｍ (CR １１ R １２ ) ｐ - ＊＊ 、 ＊ -C(=O)NR １５ ((CR １１ R １２ ) ｎ O) ｍ (CR １１ R １２ ) ｐ - ＊＊ 、 ＊ -(CR １１ R １２ ) ｎ NR １５ ((CR １１ R １２ ) ｎ O) ｍ (CR １１ R １２ ) ｐ - ＊＊ 、 ＊ -(CR １１ R １２ ) ｎ - ＊＊ 、 ＊ -((CR １１ R １２ ) ｎ NR １５ ) ｍ (CR １１ R １２ ) ｐ - ＊＊ 、 ＊ -(CR １１ R １２ )C(=O)NR １５ (CR １１ R １２ ) ｎ - ＊＊ 、 ＊ -C(=O)NR １５ (CR １１ R １２ ) ｎ - ＊＊ 、 ＊ -O(CR １１ R １２ ) ｎ - ＊＊ , or ＊ -NR １５ (CR １１ R １２ ) ｎ - ＊＊ And here, L ＭＣ of ＊ This indicates the connection point to Z, and L ＭＣ of ＊＊ This indicates the connection point to A; A is a combination; and Z is, [Chemistry 1-3] And in the formula, the above Z ＊ is, L ＭＣ It shows the connection point to the aforementioned Z ＊＊ This indicates the connection point to L; m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; Each n is independently selected from 1, 2, 3, 4, 5, 7, 8, 9, and 10; p is 1, 2, 3, 4, 5, or 6; R Ｂ is phenyl, and here, R Ｂ This is 1 to 3 R ５ It is arbitrarily substituted in the base; R １ H is; R ２ H is; t is 0, 1, or 2; Each R ３ is, when present, a substituent on the ring to which -L-Z is directly attached, where each R ３ is independently selected from halo, CN, C １～ C ３ alkoxy, C １～ C ３ alkyl, C(=O)OR １０ , and C(=O)NR １３ R １４ ; and is independently selected from Each R ５ is halo, -CN, hydroxy, -NR １３ R １４ , C ３～ C ６ cycloalkyl, C １～ C ３ alkoxy, C １～ C ３ haloalkyl, and 1 to 3 R ６ groups, and is independently selected from C １～ C ３ alkyl optionally substituted with R Ｂ where R ５ is substituted with two R ５ groups, and each R ６ is C １～ C ３ alkyl optionally substituted with 1 to 3 R ６ groups, and when directly bonded to the same carbon atom, together with said carbon to which both are directly bonded, can form a 3- to 5-membered cycloalkyl ring optionally substituted with 1 to 3 R Each R ６ is halo, hydroxy, CN, C １～ C ３ Alkoxy, C １～ C ３ Alkyl and C ３～ C ５ Selected independently from cycloalkyl, Or, two R ６ The group contains O, N, or S as ring members, together with the carbon atoms to which both are directly bonded, and is oxo and C １～ C ３ They can form 3- to 5-membered cycloalkyl rings or 4- to 6-membered heterocycles, which are optionally substituted with one or two groups independently selected from the alkyl group; L is C １ ~C ４ It is a linear or branched alkylene linker, or L is a ring in which W is optionally substituted, C １ ~C ４ It may be a linear or branched alkylene linker or linkage; R １０ C １～ C ５ Alkyl, C １～ C ３ Haloalkyl, 3-6 membered cycloalkyl, phenyl, N, O, and S, having 1-4 heteroatoms independently selected as ring members, 5-6 membered heteroaryl, N, NH, NR １７ A 4-6 member heterocycloalkyl group containing one or two ring members independently selected from O, or S, and N, NH, NR １７ Selected from a 4-6 membered heterocyclyl containing 1-2 ring members independently selected from O, or S; Here, each R １０ C １～ C ４ Alkyl, deuterium, C １～ C ４ Haloalkoxy, -L ３ OH, -L ３ CN, -L ３ OC(=O)R １４ , -L ３ OR １３ , C １～ C ２ Haloalkyl, oxo, -L ３ Halo, -L ３ C １～ C ３ Alkoxy, -L ３ OC(=O)NR １３ R １４ , -L ３ SO ２ R １３ , -L ３ SO ２ NR １３ R １４ , -L ３ SO ２ NR １３ C(=O)R １３ , -L ３ C(=O)NR １３ SO ２ R １３ , -L ３ S(=O)R １３ , -L ３ S (= O) (= NR １４ ) R １３ , -L ３ NR １３ SO ２ NR １３ R １４ , -L ３ NR １３ SO ２ R １３ , -L ３ NR １３ R １４ , -L ３ NR １４ C(=O)R １３ , -L ３ NR １４ C (=O) OR １３ , -L ３ C(=O)NR １３ R １４ , -L ３ C (=O) OR １３ , -L ３ - (N, NH, NR １７ (4-7 membered heterocycloalkyl) containing 1-2 ring members independently selected from O, or S, -L ３ - (N, NH, NR １７ (4-7 membered heterocyclyl containing 1-2 ring members independently selected from O, or S), -L ３ -C ３～ C ５ Cycloalkyl, and -L ３ - Optionally substituted with 1 to 5 groups independently selected from (a 5-6 membered heteroaryl ring having 1 to 4 heteroatoms, containing 1 to 4 nitrogen atoms, 0 or 1 oxygen atom, and 0 or 1 sulfur atom as ring members), where the C １～ C ４ Alkyl, 4-7 member heterocycloalkyl, 4-7 member heterocyclyl, C ３～ C ５ Cycloalkyl and 5-6 membered heteroaryl rings are, respectively, halo and C. １～ C ３ Alkyl, C １～ C ３ Haloalkyl, -L ４ OR １３ , -L ４ CN, and -L ４ NR １３ R １４ It is further optionally replaced by 1 to 3 elements, which are independently selected from; R １１ and R １２ H and C, respectively. １～ C ４ Selected independently of alkyl; Each R １３ H, C １～ C ４ alkyl, N, NH, NR １７ 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S １７ A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C ３～ C ６ Selected independently from cycloalkyl, where C １～ C ４ Alkyl, heterocyclyl, and C ３～ C ６ Cycloalkyl is C １～ C ４ Alkyl, Halo, -OH, -NR １５ R １６ , -C (=O) OR １５ , C １～ C ２ Alkoxy and C substituted with 1-2 hydroxyl groups １～ C ４ Optionally substituted with 1 to 3 groups independently selected from alkyl groups; Each R １４ H and C are independent of each other. １～ C ４ Alkyl and C ３～ C ６ Selected from cycloalkyl, where C １～ C ４ Alkyl and C ３～ C ６ Cycloalkyl is C １～ C ４ Alkyl, Halo, -OH, -NR １５ R １６ , C １～ C ２ Alkoxy and C substituted with 1-2 hydroxyl groups １～ C ４ Optionally substituted with 1 to 3 groups independently selected from alkyl groups; Or, R １３ and R １４ Both, together with the nitrogen atom to which they are directly bonded, optionally contain additional N, O, or S as ring members, and C １～ C ２ Alkyl, C １～ C ２ It can form a 4-6 membered ring, optionally substituted with 1-3 groups selected from alkoxy, oxo, and hydroxyl groups; R １５ and R １６ H and C, respectively. １～ C ４ Selected independently of alkyl; Each R １７ H, C １～ C ４ Alkyl and C ３ ~C ８ Selected independently from cycloalkyl, or R １７ C １～ C ４ It is alkyl, which, together with the nitrogen atom directly bonded to it and the nitrogen atom from the pyrazole ring, can form a 5- to 8-membered ring condensed on the pyrazole ring; Each L ２ and L ３ and L ４ These are independently linked, or linear or branched C １～ C ３ It is alkylene; and [Chemistry 1-4] This represents a single bond or a double bond. A compound or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1, wherein, t is 0, 1, or 2; Each R ３ However, if present, -L-W is a substituent on the ring to which it is directly bonded, where each R ３ However, Haro, CN, C １～ C ３ Alkoxy, C １～ C ３ Alkyl, C(=O)OR １０ , and C(=O)NR １３ R １４ Selected independently of; Each R ５ However, halo, -CN, hydroxy, -NR １３ R １４ , C ３～ C ６ Cycloalkyl, C １～ C ３ Alkoxy, C １～ C ３ Haloalkyl and 1 to 3 R ６ C arbitrarily substituted in the base １～ C ３ Selected independently of alkyl, where R Ｂ However, two R ５ Replaced by each R ５ However, 1 to 3 R ６ C arbitrarily substituted in the base １～ C ３ When an alkyl group is directly bonded to the same carbon atom, it forms 1 to 3 R atoms together with the carbon atom to which it is directly bonded. ６ It can form a 3- to 5-membered cycloalkyl ring optionally substituted with a group; Each R ６ However, halo, hydroxy, CN, C １～ C ３ Alkoxy, C １～ C ３ Alkyl and C ３～ C ５ From cycloalkyl groups, independently selected in each occurrence, Or, two R ６ The group contains O, N, or S as ring members, together with the carbon atoms to which both are directly bonded, and includes oxo and C １～ C ３ They can form 3- to 5-membered cycloalkyl rings or 4- to 6-membered heterocycles, which are optionally substituted with one or two groups independently selected from the alkyl group; L is C １ ~C ４ If it is a linear or branched alkylene linker, or if L is a ring in which W is optionally substituted, then C １ ~C ４ It may be a linear or branched alkylene linker or linkage; R １０ However, C １～ C ５ Alkyl, C １～ C ３ Haloalkyl, 3-6 membered cycloalkyl, phenyl, N, O, and S, having 1-4 heteroatoms independently selected as ring members, 5-6 membered heteroaryl, N, NH, NR １７ A 4-6 member heterocycloalkyl group containing one or two ring members independently selected from O, or S, and N, NH, NR １７ Selected from a 4-6 membered heterocyclyl containing 1-2 ring members independently selected from O, or S; Here, each R １０ However, C １～ C ４ Alkyl, deuterium, C １～ C ４ Haloalkoxy, -OH, -CN, -OC(=O)R １４ , -L ３ OR １３ , C １～ C ２ Haloalkyl, oxo, -halo, -C １～ C ３ Alkoxy, -OC(=O)NR １３ R １４ , -SO ２ R １３ , -SO ２ NR １３ R １４ , -SO ２ NR １３ C(=O)R １３ , -C(=O)NR １３ SO ２ R １３ , -S(=O)R １３ , -S(=O)(=NR １４ ) R １３ , -NR １３ SO ２ NR １３ R １４ , -NR １３ SO ２ R １３ , -NR １３ R １４ , -NR １４ C(=O)R １３ , -NR １４ C (=O) OR １３ , -C(=O)NR １３ R １４ , -C (=O) OR １３ (N, NH, NR １７ (4-7 membered heterocycloalkyl) containing 1-2 ring members independently selected from O, or S, (N, NH, NR １７ A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S), -C ３～ C ５ Optionally substituted with 1 to 5 groups independently selected from cycloalkyl and -- (a 5-6 membered heteroaryl ring having 1 to 4 heteroatoms, containing 1 to 4 nitrogen atoms, 0 or 1 oxygen atom, and 0 or 1 sulfur atom as ring members), where the C １ ~C ４ Alkyl, 4-7 member heterocycloalkyl, 4-7 member heterocyclyl, C ３ ~C ５ Cycloalkyl and 5-6 membered heteroaryl rings are, respectively, halo and C. １～ C ３ Alkyl, C １～ C ３ Haloalkyl, -OR １３ -CN, and -NR １３ R １４ It is further optionally replaced by 1 to 3 elements, which are independently selected from; R １１ and R １２ However, H and C respectively １～ C ４ Selected independently of alkyl; Each R １３ However, H, C １～ C ４ alkyl, N, NH, NR １７ 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S １７ A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C ３～ C ６ Selected independently from cycloalkyl, where C １～ C ４ Alkyl, heterocyclyl, and C ３～ C ６ Cycloalkyl, C １～ C ４ Alkyl, Halo, -OH, -NR １５ R １６ , -C (=O) OR １５ , C １～ C ２ Alkoxy and C substituted with 1-2 hydroxyl groups １～ C ４ Optionally substituted with 1 to 3 groups independently selected from alkyl groups; R １４ However, H, C １～ C ４ Alkyl and C ３～ C ６ Selected from cycloalkyl, where C １～ C ４ Alkyl and C ３～ C ６ Cycloalkyl, C １～ C ４ Alkyl, Halo, -OH, -NR １５ R １６ , C １～ C ２ Alkoxy and C substituted with 1-2 hydroxyl groups １～ C ４ Optionally substituted with 1 to 3 groups independently selected from alkyl groups; Or, R １３ and R １４ However, together with the nitrogen atom to which both are directly bonded, they optionally contain additional N, O, or S as ring members, and C １～ C ２ Alkyl, C １～ C ２ It can form a 4-6 membered ring, optionally substituted with 1-3 groups selected from alkoxy, oxo, and hydroxyl groups; R １５ and R １６ However, H and C respectively １～ C ４ Selected independently of alkyl; L ３ However, the bond, or the linear or branched chain C １～ C ３ It is alkylene; and 【Chemistry 2】 However, it represents a single bond or a double bond. compound.

3. A compound according to claim 1 or 2, wherein, t is 0, 1, or 2; Each R ３ However, if present, -L-W is a substituent on the ring to which it is directly bonded, where each R ３ However, C １～ C ３ Selected independently of alkyl; Each R ５ However, halo, -CN, C １～ C ３ Alkoxy, and C １～ C ３ Selected independently of alkyl; L is C １ ~C ４ If it is a linear or branched alkylene linker, or if L is a ring in which W is optionally substituted, then C １ ~C ４ It may be a linear or branched alkylene linker or linkage; R １０ However, C １～ C ５ Alkyl, C １～ C ３ Haloalkyl, 3-6 membered cycloalkyl, 5-6 membered heteroaryl having 1-4 heteroatoms independently selected as ring members from N, O, and S, N, NH, NR １７ A 4-6 member heterocycloalkyl group containing one or two ring members independently selected from O, or S, and N, NH, NR １７ Selected from a 4-6 membered heterocycline containing 1-2 ring members independently selected from O or S, Here, each R １０ However, C １～ C ４ Alkyl, deuterium, C １～ C ４ Haloalkoxy, -OH, -CN, -OC(=O)R １４ , -L ３ OR １３ , -NR １３ R １４ , -NR １４ C(=O)R １３ , -NR １４ C (=O) OR １３ , -C(=O)NR １３ R １４ , -C (=O) OR １３ (N, NH, NR １７ (4-7 membered heterocycloalkyls containing 1-2 ring members independently selected from O, or S), (N, NH, NR １７ (A 4-7 membered heterocycline containing 1-2 ring members, independently selected from O, or S), and -C ３～ C ５ It is optionally substituted with 1 to 5 groups independently selected from cycloalkyl groups, where the C １～ C ４ Alkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocyclyl, and C ３～ C ５ The cycloalkyl groups are, respectively, halo, -OR １３ , and -NR １３ R １４ It is further optionally replaced by 1 to 3 elements independently selected from; R １１ and R １２ However, H and C respectively １～ C ４ Selected independently of alkyl; Each R １３ However, H, C １～ C ４ alkyl, N, NH, NR １７ 4-7 member heterocycloalkyl, N, NH, NR containing 1-2 ring members independently selected from O, or S １７ A 4-7 membered heterocycline containing 1-2 ring members independently selected from O, or S, and C ３～ C ６ Selected independently from cycloalkyl, where C １～ C ４ Alkyl, heterocycloalkyl, heterocyclyl, and C ３～ C ６ Cycloalkyl, C １～ C ４ Alkyl, Halo, -OH, -NR １５ R １６ , -C (=O) OR １５ , C １～ C ２ Alkoxy and C substituted with 1-2 hydroxyl groups １～ C ４ Optionally substituted with 1 to 3 groups independently selected from alkyl groups; R １４ However, H and C １～ C ４ Selected from alkyl groups; R １５ and R １６ However, H and C respectively １～ C ４ Selected independently of alkyl; L ３ However, the bond, or the linear or branched chain C １～ C ３ It is alkylene; and 【Transformation 3】 However, it represents a single bond or a double bond. compound.

4. A compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof, wherein Each R ５ However, it is selected independently from Cl, F, and -CN; L is bonded, or CH ２ Or CH ２ CH ２ And; and R １０ However, it is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, cyclopropyl, cyclobutyl, pyridinyl, pyrazolyl, isoxazolyl, oxetanyl, tetrahydrofuranil, tetrahydropyranil, morpholinyl, piperidinyl, piperazinyl, pyrrolidinyl, and azetidinyl. Here, each R １０ However, methyl, ethyl, deuterium, -OCH ３ , -OH, -OCHF ２ -CN, -NH ２ , - NHCH ３ , -N(CH ３ ) ２ , - NHR １３ , -NHCH(=O), -NHC(=O)CH ３ , -NHC(=O)OCH ３ , -NHC(=O)CH ２ NH ２ , -NHC(=O)CH ２ N(CH ３ ) ２ , -NHC(=O)CH(CH ３ ) NH ２ , -NHC(=O)C(CH ３ ) ２ NH ２ , -OCH ２ CH ２ OH, -OCH ２ CH (CH ３ )OH, -OCH ２ CH (CH ３ ) ２ OH, -OCH(F)CH ２ OH, -OCF ２ CH ２ OH, -OCH ２ CH ２ NH ２ , -OCH ２ CH (CH ３ ) NH ２ , -OCH ２ C (CH ３ ) ２ NH ２ , -OCH ２ CH ２ NHCH ３ , -OCH ２ CH ２ N(CH ３ ) ２ , -OCH(F)CH ２ NH ２ , -OCF ２ CH ２ NH ２ ien-CH ２ OCH ２ CH ２ NH ２ ien-CH ２ CH ２ OH, -CH ２ OH, -CH ２ NH ２ -O-azetidinyl, -C(=O)NH ２ , -C(=O)NHCH ３ , -OC(=O)CH ３ , optionally substituted with 1 to 4 groups independently selected from cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl, Here, methyl, ethyl, cyclopropyl, azetidinyl, pyrrolidinyl, morpholinyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 2-oxa-6-azaspiro[3.3]heptanyl, and 4,5-dihydroisoxazolyl are, respectively, F, -OH, and -OCH ３ , -NH ２ It is further optionally substituted with 1 to 3 elements independently selected from the above. A compound or a pharmaceutically acceptable salt thereof.

5. A compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof, wherein R １０ However, the following: 【Chemistry 5-1】 【Chemistry 5-2】 【Chemistry 5-3】 Selected from, A compound or a pharmaceutically acceptable salt thereof.

6. Each R ５ However, Cl, F, -CN, -OCH ３ A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, independently selected from , and methyl.

7. Each R ５ However, a compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, independently selected from Cl and -CN.

8. L is -CH ２ - or -CH ２ CH ２ - The compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof.

9. L is -CH ２ - The compound according to any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof. [Request Item 10] [Chemistry 11] A compound or a pharmaceutically acceptable salt thereof, selected from the above.

11. A pharmaceutical composition comprising a compound according to any one of claims 1 to 10 and at least one pharmaceutically acceptable carrier.

12. A composition for treating a herpesvirus infection in a patient having a herpesvirus infection, comprising a compound according to any one of claims 1 to 10 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition according to claim 11.

13. The composition according to claim 12, wherein the herpesvirus is selected from cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), herpes simplex viruses including HSV-1 and HSV-2, herpesvirus 6, human herpesvirus 7, and Kaposi's sarcoma-associated herpesvirus.

14. A composition according to claim 12 for treating a disorder induced, aggravated, or exacerbated by the herpesvirus infection, wherein the disorder is selected from the group consisting of Alzheimer's disease, chronic fatigue syndrome (CFS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes mellitus.

15. A composition according to claim 12 for treating atherosclerosis (AS), wherein the AS is induced, aggravated, or promoted by the herpesvirus infection.

16. Use of a compound according to any one of claims 1 to 10 or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical for the treatment of a viral infection.

17. A composition for use in the treatment of a viral infection in a patient requiring the use thereof, comprising a compound according to any one of claims 1 to 10 or a pharmaceutically acceptable salt thereof.

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