Compounds for the treatment of coronavirus infection

Abstract

The present invention generally relates to inhibitors of SARS-CoV-2-related 3C-like protease (Mpro) having formula (A), which are useful for the treatment of coronavirus infections. Further provided is a method for inhibiting the replication of coronaviruses, which comprises administering to a subject a compound of formula (A) or a pharmaceutical composition comprising the compound. JPEG2025520541000945.jpg33170

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the priority and benefit of U.S. Provisional Patent Application No. 63 / 353,354, entitled "Compound for the Treatment of Coronavirus Infections", filed on June 17, 2022, and U.S. Provisional Patent Application No. 63 / 414,287, entitled "Compound for the Treatment of Coronavirus Infections", filed on October 7, 2022, the disclosure of which is hereby incorporated by reference in its entirety for all purposes.

[0002] (Field of the Invention) The present invention relates to inhibitors of coronavirus replication activity. The inhibitors described herein may be useful for the treatment of diseases caused by coronavirus infections, including COVID - 19 caused by SARS - CoV - 2 infection. In particular, the present invention relates to compounds and pharmaceutical compositions that inhibit SARS - CoV - 2 - related 3C - like proteases, methods of treating coronavirus infections, and methods of synthesizing these compounds.

Background Art

[0003] (Background) Coronaviruses are a large family of viruses that typically cause mild to moderate upper respiratory tract diseases in humans. However, three coronaviruses have caused more severe and fatal illnesses in people: the Severe Acute Respiratory Syndrome Coronavirus (SARS - CoV) that emerged in November 2002 and caused Severe Acute Respiratory Syndrome (SARS); the Middle East Respiratory Syndrome Coronavirus (MERS - CoV) that emerged in 2012 and caused Middle East Respiratory Syndrome (MERS); and SARS - CoV - 2 that emerged in 2019 and caused Coronavirus Disease 2019 (COVID - 19).

[0004] Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS - CoV - 2) causes Coronavirus Disease 2019 (COVID - 19).

[0005] The virus that causes COVID-19 spreads easily among people. According to data, the COVID-19 virus mainly spreads from person to person through close contact (within about 6 feet (2 meters)). The COVID-19 virus can also spread from people who are infected but have no symptoms. This is called asymptomatic infection. The COVID-19 virus can also spread from people who are infected but have not yet shown symptoms. This is called pre-symptomatic infection. It is possible to be infected with COVID-19 if one is reinfected with SARS-CoV-2, and this can occur multiple times.

[0006] Whole genome sequence analysis revealed that SARS-CoV-2 has 79.6% sequence identity with SARS-CoV. SARS-CoV-2 seems to have a relatively high infection rate among humans, causing severe and fatal pneumonia and other disorders, threatening people of all ages, especially the elderly and those with pre-existing conditions such as immunodeficiency, lung diseases, and metabolic diseases. With the rapid increase in the number of infected and dead, the development of therapeutic drugs for COVID-19 has become an urgent task.

[0007] SARS-CoV-2 is a complex virus consisting of three open reading frames that express polyproteins. The polyproteins undergo proteolytic processing to become their mature active forms. The spike glycoprotein is cleaved by cathepsin L and TMPRSS2, which are host proteases, while the remaining proteolytic processing steps are mediated by one of two virus-encoded proteases called main protease (Mpro or 3C-like protease (3CLpro)) and papain-like protease PLpro. Mpro plays an important role in the maturation of viral proteins required for RNA replication and is a suitable target for the development of direct-acting antiviral drugs that can inhibit SARS-CoV-2 infection. The Mpro enzyme of SARS-CoV-2 is approximately 96% similar to that of SARS-CoV.

[0008] Considering the ongoing spread of SARS-CoV-2, which is causing the COVID-19 pandemic worldwide, it is desirable to have a new method for inhibiting the replication of the SARS-CoV-2 virus and treating COVID-19 in patients.

[0009] (Summary) A first aspect of the present invention relates to a compound of formula (A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, wherein, each R N is independently selected from H, C1-C6 alkyl, cycloalkyl; Q is CR 5 R Q or NR Q ; R q is H; R Q is R N ; or R q and R Q together form a bond; R M is [Chemical formula] selected from; M is selected from 5- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, and the heterocyclyl or heteroaryl is optionally substituted with one or more R 16 ; R 1 is hydrogen, halogen, -OH, -CN, -NO2, -NR 14 R 15, selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 ; R 2 is hydrogen, halogen, -OH, -CN, -NO2, -NR 14 R 15 , selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 ; or R 1 and R 2 are both oxo; or R 2 and R 3 together form a double bond; R 3 is selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 ; R 4 is hydrogen, halogen, -OH, -CN, -NO2, -NR 14 R 15 , selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 ; or, R1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 3- to 10-membered cycloalkyl, 6- to 10-membered aryl, 3- to 14-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle or heteroaryl is optionally substituted with one or more R 16 ; R 5 is hydrogen, halogen, -OH, -CN, -NO2, -NR 14 R 15 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, -C(O)OR 14 , -C(O)N-NR 14 R 15 , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 ; each R 6 is independently selected from H, C1-C6 alkyl, cycloalkyl, -CH2-aryl, and the alkyl, cycloalkyl, or aryl is optionally substituted with one or more R 16 ; R 7 is -(CH2) n aryl, and the aryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO2, -NR 14 R 15 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; R 8 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; alternatively, R 7 and R 8together with the atoms to which they are attached and any intervening atoms form one or more R 13 optionally substituted 5- to 7-membered monocyclic or bicyclic heterocyclyl formed with 13 ; R 9 R 10 R 11 are each independently selected from C1-C6 alkyl, cycloalkyl, halogen, -CN; R 12 is selected from R 6 -S(O)2-, R 6 -C(O)-, R 6 -O-C(O)-, heteroaryl, and heteroaryl is optionally substituted with one or more R 16 ; each R 13 is independently selected from halogen, -OH, -CN, -C1-C6 alkyl, -C1-C6 haloalkyl; two R 13 together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C1-C6 alkyl, C1-C6 haloalkyl; R 14 and R 15 are each independently selected from H, C1-C6 alkyl, cycloalkyl; alternatively R 14 and R 15 together with the atoms to which they are attached and any intervening atoms form a heterocyclyl optionally substituted with one or more of halogen, -OH, -CN, C1-C6 alkyl; each R 16 is halogen, -OH, -CN, -NO2, -NR 14 R 15 R 14 -C(O)OR14 、 -C(O)N-NR 14 R 15 is independently selected from cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and said alkyl, alkoxy, cycloalkyl, heterocyclyl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C1-C6 alkyl, C1-C6 haloalkyl; or Two Rs 16 together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C1-C6 alkyl, C1-C6 haloalkyl; X is selected from hydrogen, halogen, OH, CN, NO2, CONH2, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-C1-C6 alkoxy, C1-C6 alkyl-NHC1-C6 alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, and the alkyl is optionally substituted with cycloalkyl, heterocyclyl, aryl, and heteroaryl; n is an integer selected from 0, 1, 2; m is an integer selected from 0 and 1; provided that when R q is H, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 3- to 10-membered cycloalkyl, 6- to 10-membered aryl, 3- to 14-membered heterocycle, or 5- to 6-membered heteroaryl; Cycloalkyl is a monocyclic or polycyclic saturated carbon ring containing 3 to 18 carbon atoms; Aryl is a cyclic aromatic hydrocarbon group having 1 to 3 aromatic rings; A heterocyclic ring is a saturated or partially unsaturated monocyclic ring of 3 to 10 members, bicyclic ring of 7 to 12 members (fused ring, bridged ring, or spiro ring), or tricyclic ring system of 11 to 14 members (fused ring, bridged ring, or spiro ring) having one or more heteroatoms selected from O, N, S, P, Se, or B; A heteroaryl is a monovalent monocyclic or polycyclic aromatic radical having 5 to 24 ring atoms, containing one or more ring heteroatoms selected from N, O, S, P, or B, and the remaining ring atoms being C.

[0010] In another aspect, the present invention relates to a compound of formula (I):

Chemical formula

[0011] In another aspect, the present invention relates to a compound of formula (II):

Chemical formula

[0012] Another aspect of the present invention relates to a pharmaceutical composition comprising a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier can further comprise an excipient, a diluent, or a surfactant.

[0013] Another aspect of the present invention relates to a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier can further comprise an excipient, a diluent, or a surfactant.

[0014] Another aspect of the present invention relates to a pharmaceutical composition comprising a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier can further comprise an excipient, a diluent, or a surfactant.

[0015] Another aspect of the present invention relates to a method for treating a coronavirus infection such as COVID-19. The method comprises administering to a patient in need of treatment for a coronavirus infection such as COVID-19 an effective amount of a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0016] Another aspect of the present invention relates to a method for treating a coronavirus infection such as COVID-19. The method comprises administering to a patient in need of treatment for a coronavirus infection such as COVID-19 an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0017] Another aspect of the present invention relates to a method for treating a coronavirus infection such as COVID-19. The method comprises administering to a patient in need of treatment for a coronavirus infection such as COVID-19 an effective amount of a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0018] Another aspect of the present invention relates to a method of inhibiting or preventing the replication of the SARS-CoV-2 virus. The method comprises administering to a patient in need thereof an effective amount of a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0019] Another aspect of the present invention relates to a method of inhibiting or preventing the replication of the SARS-CoV-2 virus. The method comprises administering to a patient in need thereof an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0020] Another aspect of the present invention relates to a method of inhibiting or preventing the replication of the SARS-CoV-2 virus. The method comprises administering to a patient in need thereof an effective amount of a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0021] Another aspect of the present invention relates to a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof, for use in the manufacture of a medicament for inhibiting or preventing the replication of the SARS-CoV-2 virus.

[0022] Another aspect of the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof, for use in the manufacture of a medicament for inhibiting or preventing the replication of the SARS-CoV-2 virus.

[0023] Another aspect of the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof, for use in the manufacture of a medicament for inhibiting or preventing the replication of the SARS-CoV-2 virus.

[0024] Another aspect of the present invention relates to the use of a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition, in the treatment of a disease or disorder associated with SARS-CoV-2 virus infection.

[0025] Another aspect of the present invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition, in the treatment of a disease or disorder associated with SARS-CoV-2 virus infection.

[0026] Another aspect of the present invention relates to the use of a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition, in the treatment of a disease or disorder associated with SARS-CoV-2 virus infection.

[0027] Another aspect of the present invention relates to a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition, for use in the manufacture of a medicament for treating or preventing a viral infection disclosed herein.

[0028] Another aspect of the present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition, for use in the manufacture of a medicament for treating or preventing a viral infection disclosed herein.

[0029] Another aspect of the present invention relates to a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition, for use in the manufacture of a medicament for treating or preventing a viral infection disclosed herein.

[0030] Another aspect of the present invention relates to a method for treating or preventing a coronavirus infection such as COVID-19 in a subject in need thereof. The method comprises administering to a patient in need of treatment an effective amount of a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0031] Another aspect of the present invention relates to a method for treating or preventing a coronavirus infection such as COVID-19 in a subject in need thereof. The method comprises administering to a patient in need of treatment an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0032] Another aspect of the present invention relates to a method for treating or preventing a coronavirus infection such as COVID-19 in a subject in need thereof. The method comprises administering to a patient in need of treatment an effective amount of a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0033] Another aspect of the present invention relates to the use of a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof, in the treatment of coronavirus infections.

[0034] Another aspect of the present invention relates to the use of a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof, in the treatment of coronavirus infections.

[0035] Another aspect of the present invention relates to the use of a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition, in the treatment of coronavirus infection.

[0036] The present invention further provides a method for treating coronavirus infection, comprising administering to a patient suffering from coronavirus infection a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition.

[0037] The present invention further provides a method for treating coronavirus infection, comprising administering to a patient suffering from coronavirus infection a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition.

[0038] The present invention further provides a method for treating coronavirus infection, comprising administering to a patient suffering from coronavirus infection a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer thereof, or a pharmaceutical composition.

[0039] The present invention provides an inhibitor of viral replication activity, which is a therapeutic agent for the treatment of coronavirus infection.

[0040] The present invention provides an SARS-CoV-2 related 3C-like protease inhibitor, which is a therapeutic agent for the treatment of coronavirus infection.

[0041] The present invention provides an SARS-CoV-2 related Mpro protease inhibitor, which is a therapeutic agent for the treatment of coronavirus infection.

[0042] The present invention further provides compounds and compositions having an improved efficacy and safety profile compared to known SARS-CoV-2 related 3C-like protease inhibitors.

[0043] The present invention further provides a method for treating a disease or disorder related to a coronavirus infection, the method comprising administering to a patient suffering from a coronavirus infection a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0044] The present invention further provides a method for treating a disease or disorder related to a coronavirus infection, the method comprising administering to a patient suffering from a coronavirus infection a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0045] The present invention further provides a method for treating a disease or disorder related to a coronavirus infection, the method comprising administering to a patient suffering from a coronavirus infection a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0046] The present invention provides a SARS-CoV-2 related 3C-like protease inhibitor which is a therapeutic agent in the treatment of coronavirus infections.

[0047] The present invention provides a SARS-CoV-2 related Mpro protease inhibitor which is a therapeutic agent in the treatment of coronavirus infections.

[0048] The present invention further provides compounds and compositions having an improved efficacy and safety profile compared to known SARS-CoV-2 related 3C-like protease inhibitors. The present invention also provides agents having a novel mechanism of action against SARS-CoV-2 related 3C-like protease in the treatment of coronavirus infections.

[0049] The present invention further provides compounds and compositions having an improved efficacy and safety profile compared to known SARS-CoV-2 related Mpro protease inhibitors. The present disclosure also provides agents having a novel mechanism of action against SARS-CoV-2 related Mpro protease in the treatment of coronavirus infections.

[0050] The present invention further provides a method for preventing, treating, or ameliorating coronavirus infections.

[0051] The present invention further provides a method for treating a disease, disorder, or symptom selected from the group consisting of cold; pneumonia (direct viral pneumonia or secondary bacterial pneumonia); bronchitis (direct viral bronchitis or secondary bacterial bronchitis); severe acute respiratory syndrome (SARS); Middle East respiratory syndrome (MERS); coronavirus disease 2019 (COVID-19); coronavirus HuPn-2018, the method comprising administering to a patient suffering from at least one of said disease or disorder a compound of formula (A), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0052] The present invention further provides a method for treating a disease, disorder, or symptom selected from the group consisting of cold; pneumonia (direct viral pneumonia or secondary bacterial pneumonia); bronchitis (direct viral bronchitis or secondary bacterial bronchitis); severe acute respiratory syndrome (SARS); Middle East respiratory syndrome (MERS); coronavirus disease 2019 (COVID-19); and coronavirus HuPn-2018, the method comprising administering to a patient suffering from at least one of the diseases or disorders a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0053] The present invention further provides a method for treating a disease, disorder, or symptom selected from the group consisting of cold; pneumonia (direct viral pneumonia or secondary bacterial pneumonia); bronchitis (direct viral bronchitis or secondary bacterial bronchitis); severe acute respiratory syndrome (SARS); Middle East respiratory syndrome (MERS); coronavirus disease 2019 (COVID-19); and coronavirus HuPn-2018, the method comprising administering to a patient suffering from at least one of the diseases or disorders a compound of formula (II), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, tautomer, or pharmaceutical composition thereof.

[0054] In some embodiments, the present disclosure provides a compound obtainable by, or obtained by, a method for preparing a compound described herein (e.g., a method comprising one or more steps described in the general procedures).

[0055] In some embodiments, the present disclosure provides an intermediate described herein that is suitable for use in a method for preparing a compound described herein (e.g., the intermediate is selected from the intermediates described in Preparation Part - Preparation 1 to 278).

[0056] In some embodiments, the present disclosure provides a method for preparing a compound of the present disclosure.

[0057] In some embodiments, the present disclosure provides a method for preparing a compound of the present disclosure, comprising one or more steps described herein.

[0058] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In this specification, the singular forms also include the plural forms unless the context clearly dictates otherwise. Methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, but suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference. The references cited herein are not admitted to be prior art to the claimed invention. In case of conflict, this specification, including definitions, will control. Further, the materials, methods, and examples are illustrative only and not intended to be limiting. In case of conflict between the chemical structure and the name of a compound disclosed herein, the chemical structure shall prevail.

[0059] Other features and advantages of the present disclosure will become apparent from the following detailed description and claims.

Mode for Carrying Out the Invention

[0060] (Detailed Description) The present disclosure provides a method for treating, preventing, or alleviating a viral infection associated with a coronavirus by administering to a subject in need thereof a therapeutically effective amount of a compound disclosed herein.

[0061] Details of the present disclosure are set forth in the following appended description. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, exemplary methods and materials are described herein. Other features, objects, and advantages of the present disclosure will be apparent from the specification and claims. In the specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited herein are incorporated by reference in their entirety. Definitions

[0062] The articles “a” and “an” are used in the present disclosure to refer to one or more (i.e., at least one) of the grammatical objects of the articles. By way of example, “an element” means one element or a plurality of elements.

[0063] In the present disclosure, the term “and / or” means either “and” or “or” unless otherwise specified.

[0064] The term "optionally substituted" is understood to mean that a given chemical moiety (e.g., an alkyl group) can (but need not) be bonded to another substituent (e.g., a heteroatom). For example, an optionally substituted alkyl group can be a fully saturated alkyl chain (i.e., a pure hydrocarbon). Alternatively, the same optionally substituted alkyl group can have one or more substituents different from hydrogen. For example, at any point along the chain, it can be bonded to a halogen atom, a hydroxyl group, or another substituent described herein. Thus, the term "optionally substituted" means that a given chemical moiety has the potential to contain other functional groups, but does not necessarily have any additional functional groups. Suitable substituents for any substitution of the described groups include, but are not limited to, halogen, oxo, -OH, -CN, -NH2, -NO2, -COOH, -CH2CN, -O-(C1-C6)alkyl, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C1-C6) haloalkoxy, -O-(C2-C6)alkenyl, -O-(C2-C6)alkynyl, (C2-C6)alkenyl, (C2-C6)alkynyl, -OP(O)(OH)2, -OC(O)(C1-C6)alkyl, -C(O)(C1-C6)alkyl, -OC(O)O(C1-C6)alkyl, -NH((C1-C6)alkyl), -N((C1-C6)alkyl)2, -NHC(O)(C1-C6)alkyl, -C(O)NH(C1-C6)alkyl, -S(O)2(C1-C6)alkyl, -S(O)NH(C1-C6)alkyl, and -S(O)N((C1-C6)alkyl)2. The substituents can themselves be optionally substituted. As used herein, "optionally substituted" means substituted or unsubstituted, and its meaning is described below.

[0065] As used herein, the term "substituted" means that a particular group or moiety has one or more suitable substituents, and the substituents may be attached to the particular group or moiety at one or more positions. For example, an aryl substituted with cycloalkyl indicates whether the cycloalkyl is attached by bonding to one atom of the aryl or is fused to the aryl to share two or more common atoms.

[0066] As used herein, the term "unsubstituted" means that a particular group has no substituents.

[0067] Unless otherwise defined, the term "aryl" refers to a cyclic aromatic hydrocarbon group having 1 to 3 aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl. When containing two aromatic rings (such as bicyclic), the aromatic rings of the aryl group can be bonded at one point (e.g., biphenyl) or fused (e.g., naphthyl). The aryl group can be optionally substituted at any bonding point by one or more substituents, e.g., 1 to 5 substituents. Exemplary substituents include, but are not limited to, -H, -halogen, -O-(C1-C6)alkyl, (C1-C6)alkyl, -O-(C2-C6)alkenyl, -O-(C2-C6)alkynyl, (C2-C6)alkenyl, (C2-C6)alkynyl, -OH, -OP(O)(OH)2, -OC(O)(C1-C6)alkyl, -C(O)(C1-C6)alkyl, -OC(O)O(C1-C6)alkyl, -NH2, -NH((C1-C6)alkyl), N((C1-C6)alkyl)2, -S(O)2-(C1-C6)alkyl, -S(O)NH(C1-C6)alkyl, and -S(O)N((C1-C6)alkyl)2. The substituents can themselves be optionally substituted. Further, when containing two fused rings, the aryl group as defined herein may have one or more saturated or partially unsaturated rings fused to a completely unsaturated aromatic ring. Examples of the ring systems of these aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, anthracenyl, phenalenyl, phenanthrenyl, indanyl, indenyl, tetrahydronaphthalenyl, tetrahydrobenzoannulenyl, etc.

[0068] Unless otherwise defined, "heteroaryl" means a monocyclic or polycyclic aromatic radical of 5 to 24 ring atoms containing one or more ring heteroatoms selected from N, O, S, P, or B, with the remaining ring atoms being C. The polycyclic aromatic radical contains two or more fused rings and can further contain two or more spiro-fused rings, such as bicyclic, tricyclic, tetracyclic, etc. Unless otherwise specified, "fused" means two rings sharing two ring atoms. Unless otherwise specified, "spiro-fused" means two rings sharing one ring atom. As defined herein, heteroaryl also means a bicyclic heteroaromatic group in which the heteroatom is selected from N, O, S, P, or B. As defined herein, heteroaryl also means a tricyclic heteroaromatic group containing one or more ring heteroatoms selected from N, O, S, P, or B. As defined herein, heteroaryl also means a tetracyclic heteroaromatic group containing one or more ring heteroatoms selected from N, O, S, P, or B. The aromatic radical may be independently substituted with one or more of the substituents described herein. Examples include furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolyl, benzopyranyl, isothiazolyl, thiazolyl, thiadiazole, indazole, benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl, imidazo[1,2-b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl, indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-b]pyridinyl, benzothiazolyl, indolyl, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuranyl, benzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, quinolinyl, isoquinolinyl, 1,6-naphthyridinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][1,6]naphthyridinyl, thieno[2,3-b]pyrazinyl, quinazolinyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, isoindolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[1,2-a]pyrimidinyl, tetrahydropyrrolo[1,2-a]pyrimidinyl, 3,4-dihydro-2H-1-pyrrolo[2,1-b]pyrimidine, dibenzo[b,d]thiophene, pyridin-2-one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, 1H-pyrido[3,4-b][1,4]thiazinyl, benzoxazolyl, benzoisoxazolyl, furo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl, furo[3,2-b]pyridine, [1,2,4]triazolo[1,5-a]pyridinyl, benzo[1,2,3]triazolyl, imidazo[1,2-a]pyrimidinyl, [1,2,4]triazolo[4,3-b]pyridazinyl, benzo[c][1,2,5]thiadiazolyl, benzo[c][1,2,5]oxadiazole, 1,3-dihydro-2H-benzo[d]imidazol-2-one, 3,4-dihydro-2H-pyrazolo[1,5-b][1,2]oxazinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, thiazolo[5,4-d]thiazolyl, imidazo[2,1-b][1,3,4]thiadiazolyl, thieno[2,3-b] including, but not limited to, pyrrolyl, 3H-indolyl, and derivatives thereof. Further, when containing two or more fused rings, the heteroaryl group as defined herein may have one or more saturated or partially unsaturated rings fused to one or more fully unsaturated aromatic rings. In a heteroaryl ring system containing more than two fused rings, the saturated or partially unsaturated ring may be further fused to the saturated or partially unsaturated ring described herein. Further, when containing three or more fused rings, the heteroaryl group as defined herein may be spiro-fused with one or more saturated or partially unsaturated rings. Any saturated or partially unsaturated ring described herein may be optionally substituted with one or more oxo. Exemplary ring systems of these heteroaryl groups are, for example, indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, 3,4-dihydro-1H-isoquinolinyl, 2,3-dihydrobenzofuranyl, benzofuranonyl, indolinyl, oxyindolyl, indolyl, 1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-onyl, 7,8-dihydro-6H-pyrido[3,2-b]pyrrolidinyl, 8H-pyrido[3,2-b]pyrrolidinyl, 1,5,6,7-tetrahydrocyclopenta[b]pyrazolo[4,3-e]pyridinyl, 7,8-dihydro-6H-pyrido[3,2-b]pyrrolidine, pyrazolo[1,5-a]pyrimidin-7(4H)-onyl, 3,4-dihydropyrazino[1,2-a]indol-1(2H)-onyl, or benzo[c][1,2]oxaborol-1(3H)-onyl, 6,6a,7,8-tetrahydro-9H-pyrido[2,3-b]pyrrolo[1,2-d][1,4]oxazin-9-onyl, or 6a’,7’-dihydro-6’H,9’H-spiro[cyclopropane-1,8’-pyrido[2,3-b]pyrrolo[1,2-d][1,4]oxazine]-9’-onyl.

[0069] Halogen or "halo" refers to fluorine, chlorine, bromine, or iodine.

[0070] "Alkyl" refers to a straight-chain or branched-chain saturated hydrocarbon containing 1 to 12 carbon atoms. Examples of (C1-C6) alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, and isohexyl.

[0071] "Alkoxy" refers to a straight-chain or branched-chain saturated hydrocarbon containing 1 to 12 carbon atoms and having a terminal "O" in the chain, i.e., -O(alkyl). Examples of alkoxy groups include, but are not limited to, methoxy group, ethoxy group, propoxy group, butoxy group, tert-butoxy group, or pentyloxy group.

[0072] "Alkenyl" refers to a straight-chain or branched-chain unsaturated hydrocarbon containing 2 to 12 carbon atoms. The "alkenyl" group contains at least one double bond in the chain. The double bond of the alkenyl group may be non-conjugated or conjugated with another unsaturated group. Examples of alkenyl groups include ethenyl, propenyl, n-butenyl, iso-butenyl, pentenyl, or hexenyl. The alkenyl group may be unsubstituted or substituted. The alkenyl defined herein may be straight-chain or branched.

[0073] "Alkynyl" refers to a straight-chain or branched-chain unsaturated hydrocarbon containing 2 to 12 carbon atoms. The "alkynyl" group contains at least one triple bond in the chain. Examples of alkynyl groups include ethynyl, propargyl, n-butynyl, iso-butynyl, pentynyl or hexynyl. The alkynyl group may be unsubstituted or substituted.

[0074] The term "alkylene" or "alkenyl" refers to a divalent alkyl radical. Any of the above monovalent alkyl groups can be alkylene by extraction of a second hydrogen atom from the alkyl. As defined herein, alkylene can be C1-C6 alkylene. Alkylene can further be C1-C4 alkylene. Typical alkylene groups include, but are not limited to, -CH2-, -CH(CH3)-, -C(CH3)2-, -CH2CH2-, -CH2CH(CH3)-, -CH2C(CH3)2-, -CH2CH2CH2-, and -CH2CH2CH2CH2-.

[0075] "Cycloalkyl" means a monocyclic or polycyclic saturated carbon ring containing 3 to 18 carbon atoms. The polycyclic cycloalkyl may be a fused bicyclic cycloalkyl, a bridged bicyclic cycloalkyl, or a spiro-fused bicyclic cycloalkyl. The polycyclic cycloalkyl contains at least one non-aromatic ring. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, norbornyl, norbornenyl, 1,2,3,4-tetrahydronaphthyl, 2,3-dihydro-1H-indenyl, spiro[3.5]nonyl, spiro[5.5]undecyl, bicyclo[1.1.1]pentanyl, bicyclo[2.2.2]octanyl, or bicyclo[2.2.2]octenyl.

[0076] "Heterocyclyl", "heterocyclic", or "heterocycloalkyl" containing 3 to 24 atoms including carbon and one or more heteroatoms selected from N, O, S, P, or B is monocyclic or polycyclic, where the ring is not aromatic. The heterocycloalkyl ring structure may be substituted by one or more substituents. The substituents may themselves be optionally substituted. Examples of heterocyclyl rings include, but are not limited to, oxetanyl, azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl, oxazolidinonyl, and homotropanyl.

[0077] The term "aromatic" means a planar ring having 4n + 2 electrons in a conjugated system. As used herein, the term "conjugated system" means a system in which p-orbitals having delocalized electrons are connected, and this system can include lone electron pairs.

[0078] As used herein, the term "haloalkyl" refers to an alkyl group as defined herein that is substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, pentafluoroethyl, trichloromethyl, etc.

[0079] As used herein, the term "haloalkoxy" refers to an alkoxy group as defined herein that is substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethoxy, difluoromethoxy, pentafluoroethoxy, trichloromethoxy, etc.

[0080] As used herein, the term "cyano" means a substituent having a carbon atom bonded to a nitrogen atom by a triple bond, i.e., C≡N.

[0081] "Spirocycloalkyl" or "spirocyclic" means a bicyclic carbon system in which the two rings are linked through a single atom. The rings may differ in size and nature, or may be the same in size and nature. Examples include spiropentane, spirohexane, spiroheptane, spirooctane, spirononane, spirodecane. One or both of the spiro rings may be fused to another carbocyclic, heterocyclic, aromatic, or heteroaromatic ring. One or more carbon atoms in the spiro ring may be substituted with a heteroatom (e.g., O, N, S, or P). (C3-C 12 ) Spirocycloalkyl is a spiro ring containing from 3 to 12 carbon atoms. One or more carbon atoms may be substituted with a heteroatom.

[0082] The terms "spiroheterocycloalkyl", "spiroheterocyclic" or "spiroheterocyclic" are understood to mean a spiro ring in which at least one of the rings is a heterocyclic ring (e.g., at least one of the rings is furanyl, morpholinyl or piperidinyl).

[0083] The term "solvate" refers to various stoichiometric complexes formed by a solute and a solvent. Such solvents for the purposes of the present disclosure should not be those that can interfere with the biological activity of the solute. Examples of suitable solvents include, but are not limited to, water, MeOH, EtOH, and AcOH. Solvates in which the solvent molecule is water are usually called hydrates. Hydrates include compositions containing a stoichiometric amount of water, as well as compositions containing a variable amount of water.

[0084] The term "isomer" refers to compounds that have the same composition and molecular weight but different physical and / or chemical properties. The structural differences can be in the constitution (geometric isomers) or the ability to rotate the plane of polarization (stereoisomers). With respect to stereoisomers, the compounds of formula (A) may have one or more asymmetric carbon atoms and can occur as racemates, racemic mixtures, and individual enantiomers or diastereomers.

[0085] The present disclosure also contemplates isotopically labeled compounds of formula (A) (e.g., 2 H and 14 C labeled ones). Deuterium (i.e., 2 H or D) isotopes and carbon-14 (i.e., 14 C) isotopes are particularly preferred in terms of ease of preparation and detectability. Furthermore, substitution with heavier isotopes such as deuterium can provide certain therapeutic advantages resulting from higher metabolic stability (e.g., increased in vivo half-life or reduced required dose) and may thus be preferred in some situations. The isotopically labeled compounds of formula (I) can generally be prepared according to procedures similar to those disclosed in the following schemes and / or examples by replacing the non-isotopically labeled reagents with appropriate isotopically labeled reagents.

[0086] The present disclosure also includes pharmaceutical compositions comprising a therapeutically effective amount of the disclosed compounds and a pharmaceutically acceptable carrier. Representative "pharmaceutically acceptable salts" include, for example, water-soluble and water-insoluble salts such as acetate, amsonate (4,4-diaminostilbene-2,2-disulfonate), benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, butyrate, calcium, calcium edetate, camsylate, carbonate, chloride, citrate, clavulariate, dihydrochloride, edetate, edisylic acid salt, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexafluorophosphate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, magnesium, malate, maleate, mandelate, mesylate, methyl bromide, methyl nitrate, methyl sulfate, mucate, napsylate, nitrate, N-methylglucamine ammonium salt, 3-hydroxy-2-naphthoate, oleate, oxalate, palmitate, pamoate, pantothenate, phosphate / diphosphate, picrate, polygalacturonate, propionate, p-toluenesulfonate, salicylate, stearate, basic acetate, succinate, sulfate, sulfosalicylate, tannate, tartrate, theocurate, tosylate, triethiodide, and valerate.

[0087] "Patient" or "subject" is a mammal such as a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or non-human primate such as a monkey, chimpanzee, baboon, or macaque.

[0088] "Effective amount", when used in connection with a compound, is an amount effective to treat or prevent a disease in a subject as described herein.

[0089] As used herein, the term "carrier" includes carriers, excipients and diluents, and refers to a liquid or solid filler, diluent, excipient, solvent or encapsulating material, composition or vehicle that is involved in the transport or conveyance of a pharmaceutical from one organ or part of the body to another organ or part of the body.

[0090] As used herein, the term "treating" with respect to a subject refers to ameliorating at least one symptom of a disorder in the subject. Treating includes curing, ameliorating, or at least partially ameliorating a disorder.

[0091] As used herein, the term "disorder" is used to mean, and is used interchangeably with, the term disease, condition, or illness, unless otherwise specified.

[0092] As used herein, the term "administer", "administering", or "administration" refers to either directly administering to a subject the disclosed compound or a pharmaceutically acceptable salt or composition of the disclosed compound, or administering to a subject a prodrug derivative or analog of the compound or a pharmaceutically acceptable salt or composition of the compound, which can form an equivalent amount of the active compound in the subject's body.

[0093] As used herein, the term "prodrug" refers to a compound that is convertible in vivo to the disclosed compound by metabolic means (e.g., hydrolysis).

[0094] The term "salt" means a pharmaceutically acceptable salt.

[0095] The term "pharmaceutically acceptable salt" also refers to salts of the compositions of the present disclosure that have acidic functional groups such as carboxylic acid functional groups and bases.

[0096] As used herein, the term "SARS-CoV-2 related 3C-like protease inhibitor" refers to a compound of formula (A), formula (I), or formula (II) that inhibits SARS-CoV-2 related 3C-like protease, and / or a composition comprising a compound of formula (A), formula (I), or formula (II).

[0097] As used herein, the term "SARS-CoV-2 virus replication inhibitor" refers to a compound of formula (A), formula (I), or formula (II) that inhibits the replication of SARS-CoV-2 virus and / or a composition comprising a compound of formula (A), formula (I), or formula (II).

[0098] The term "SARS-CoV-2 inhibitor" means a SARS-CoV-2 related coronavirus 3C-like protease inhibitor compound described herein, or a pharmaceutically acceptable salt, hydrate, prodrug, active metabolite, or solvate thereof, or a compound that inhibits the replication of SARS-CoV-2 in some way.

[0099] The amount of the compound of the composition described herein required to achieve a therapeutic effect can be determined empirically according to conventional procedures for a particular purpose. Generally, when administering a therapeutic agent (e.g., a compound or composition (and / or additional agent) of the disclosure described herein) for a therapeutic purpose, the therapeutic agent is administered in a pharmacologically effective dose.

[0100] "Pharmacologically effective amount", "pharmacologically effective dosage", "therapeutically effective amount", or "effective amount" means an amount sufficient to produce a desired physiological effect, or an amount capable of achieving a desired result, particularly for treating coronavirus infections. The effective amount as used herein includes, for example, an amount sufficient to delay the onset of symptoms of a disorder or disease, alter the course of symptoms of a disorder or disease (e.g., slow the progression of symptoms of a disease), reduce or eliminate one or more symptoms or signs of a disorder or disease, and reverse the symptoms of a disorder or disease. Therapeutic benefit also includes arresting or slowing the progression of the underlying disease or disorder, whether or not improvement is obtained. The compounds of the present disclosure

[0101] In one aspect, the present disclosure provides compounds of formula (A) and pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs, isotope derivatives, and tautomers thereof.

Chemical formula

[0102] For the compounds of formula (A), R N , R q , R M , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , Q, and X can each be selected, where applicable, from the groups described herein, and R N , R q , R M , R 1 , R 2, R 3 , R 4 , R 6 , R 7 , R 8 For any of R, Q, and X, any group described herein, where applicable, is R N , R q , R M , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 It is understood that it can be combined with any of the remaining one or more of Q and X with any group described herein.

[0103] In another aspect, the disclosure provides a compound of formula (I) and its pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs, isotope derivatives, and tautomers. [Chemical formula] Here, R N , R q , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , Q, and X are as described herein.

[0104] For the compound of formula (I), R N , R q , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12, Q, and X can each, when applicable, be selected from the groups described herein, and R N , R q , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , Q, and any of the groups described herein for X can, when applicable, be R N , R q , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , Q, and the remaining one or more of X can be combined with any of the groups described herein, it is understood.

[0105] In another aspect, the disclosure provides a compound of formula (II) and its pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs, isotope derivatives, and tautomers.

Chemical formula

[0106] For the compound of formula (I), R N , R q , R 1, R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , Q, M, m, and X can each, if applicable, be selected from the groups described herein, R N , R q , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , any of the groups described herein for any of Q, M, m, and X can, if applicable, be R N , R q , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , it is understood that any of the groups described herein for the remaining one or more of Q, M, m, and X can be combined therewith.

[0107] In some embodiments, each R N is independently selected from H, C1-C6 alkyl, cycloalkyl; Q is CR 5 R Q or NR Q ; R q is H; R Q is R N ; or R q and R Q together form a bond; R M is

Chemical formula

[0108] In some embodiments, Q is CR 5 R Q and NR Q is selected from.

[0109] In some embodiments, Q is CR 5 R Q is.

[0110] In some embodiments, Q is NR Q is.

[0111] In some embodiments, R Q is R N is.

[0112] In some embodiments, R Q is H.

[0113] In some embodiments, R q is H.

[0114] In some embodiments, R q and R Q together form a bond.

[0115] In some embodiments, R q and R Q together form an additional bond between C(R q ) and Q.

[0116] In some embodiments, R q and R Q together form a second bond between C(R q ) and Q.

[0117] In some embodiments, R N is selected from H, C1-C6 alkyl, cycloalkyl.

[0118] In some embodiments, R N is H.

[0119] In some embodiments, R N is C1-C6 alkyl.

[0120] In some embodiments, R N is CH3.

[0121] In some embodiments, R N is cycloalkyl.

[0122] In some embodiments, R N is cyclopropyl.

[0123] In some embodiments, R 1 is hydrogen, halogen, -OH, -CN, -NO2, -NR 14 R 15 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 .

[0124] In some embodiments, R 1 is hydrogen.

[0125] In some embodiments, R 1 and R 2 are both oxo.

[0126] In some embodiments, R 1 and R 4 together with the atom to which they are attached and any intervening atoms form a 3- to 10-membered cycloalkyl, 6- to 10-membered aryl, 3- to 14-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more R 16 .

[0127] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 3- to 10-membered cycloalkyl, which is optionally substituted with one or more R 16 .

[0128] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered cycloalkyl, which is optionally substituted with one or more R 16 .

[0129] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 3- to 10-membered cycloalkyl, which is optionally substituted with one or more R 16 , and R 2 and R 3 together form a double bond.

[0130] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 3- to 10-membered unsubstituted cycloalkyl, and R 2 and R 3 together form a double bond.

[0131] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered cycloalkyl, which is optionally substituted with one or more R 16 , and R 2 and R 3 together form a double bond.

[0132] In some embodiments, R 1 and R 4together with the atoms to which they are attached and any intervening atoms form a 6-membered unsubstituted cycloalkyl, and R 2 and R 3 form a double bond together.

[0133] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered cycloalkyl, and R 2 and R 3 form a double bond together, and the 6-membered cycloalkyl is substituted with two C1-C6 alkyls.

[0134] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered cycloalkyl, and R 2 and R 3 form a double bond together, and the 6-membered cycloalkyl is substituted with two methyls.

[0135] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered cycloalkyl, and R 2 and R 3 form a double bond together, and the 6-membered cycloalkyl is substituted with two halogens.

[0136] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered cycloalkyl, and R 2 and R 3 form a double bond together, and the 6-membered cycloalkyl is substituted with two fluorines.

[0137] In some embodiments, R 1 and R 4together with the atoms to which they are attached and any intervening atoms, form a 6-membered aryl optionally substituted with one or more R 16 groups.

[0138] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms, form a 6-membered unsubstituted aryl.

[0139] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms, form a 6-membered aryl substituted with one R 16 group.

[0140] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms, form a 6-membered aryl which is substituted with two R 16 groups.

[0141] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms, form a 6-membered aryl which is substituted with three R 16 groups.

[0142] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms, form a 6-membered aryl which is substituted with four R 16 groups.

[0143] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms, form a 6-membered aryl which is substituted with one or more halogens.

[0144] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one or more Fs.

[0145] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one F.

[0146] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one or more Cls.

[0147] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one Cl.

[0148] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is optionally substituted with one or more C1-C6 alkyls.

[0149] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one or more methyls.

[0150] In some embodiments, R 1 and R 4Together with the atoms to which they are attached and any intervening atoms, they form a 6-membered aryl which is substituted with one methyl.

[0151] In some embodiments, R 1 and R 4 Together with the atoms to which they are attached and any intervening atoms, they form a 6-membered aryl which is substituted with two methyls.

[0152] In some embodiments, R 1 and R 4 Together with the atoms to which they are attached and any intervening atoms, they form a 6-membered aryl which is optionally substituted with one or more C1-C6 alkoxys.

[0153] In some embodiments, R 1 and R 4 Together with the atoms to which they are attached and any intervening atoms, they form a 6-membered aryl which is substituted with one or more methoxys.

[0154] In some embodiments, R 1 and R 4 Together with the atoms to which they are attached and any intervening atoms, they form a 6-membered aryl which is substituted with one methoxy.

[0155] In some embodiments, R 1 and R 4 Together with the atoms to which they are attached and any intervening atoms, they form a 3- to 14-membered heterocyclic ring optionally substituted with one or more R 16 s.

[0156] In some embodiments, R 1 and R 4 Together with the atoms to which they are attached and any intervening atoms, they form a 6-membered heterocyclic ring optionally substituted with one or more R 16 s.

[0157] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered heterocyclic ring containing nitrogen as a heteroatom, optionally substituted with one or more R 16 .

[0158] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered heterocyclic ring containing oxygen as a heteroatom, optionally substituted with one or more R 16 .

[0159] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered heterocyclic ring containing sulfur as a heteroatom, optionally substituted with one or more R 16 .

[0160] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 5- to 6-membered heteroaryl optionally substituted with one or more R 16 .

[0161] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered heteroaryl optionally substituted with one or more R 16 .

[0162] In some embodiments, R 1 and R 4 together with the atoms to which they are attached and any intervening atoms form a 6-membered heteroaryl optionally substituted with one or more R 16Optionally substituted, it forms a 6-membered heteroaryl containing nitrogen as a heteroatom.

[0163] In some embodiments, R 2 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NR 14 R 15 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 .

[0164] In some embodiments, R 2 is H.

[0165] In some embodiments, R 2 and R 1 are both oxo.

[0166] In some embodiments, R 2 and R 3 form a double bond together.

[0167] In some embodiments, R 3 is selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 .

[0168] In some embodiments, R 3 and R 2 form a double bond together.

[0169] In some embodiments, R 3 is H.

[0170] In some embodiments, R 4 is selected from hydrogen, halogen, -OH, -CN, -NO2, -NR 13 R 14 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 .

[0171] In some embodiments, R 4 is H.

[0172] In some embodiments, R 4 is -OH.

[0173] In some embodiments, R 4 is halogen.

[0174] In some embodiments, R 4 is F.

[0175] In some embodiments, R 4 is C1-C6 alkyl.

[0176] In some embodiments, R 4 is methyl. In some embodiments, R 4 is ethyl. In some embodiments, R 4 is propyl. In some embodiments, R 4 is n-propyl. In some embodiments, R 4 is iso-propyl. In some embodiments, R 4 is butyl. In some embodiments, R 4 is n-butyl. In some embodiments, R 4 is iso-butyl. In some embodiments, R4 is n-butyl. In some embodiments, R 4 is sec-butyl. In some embodiments, R 4 is tert-butyl. In some embodiments, R 4 is pentyl. In some embodiments, R 4 is n-pentyl. In some embodiments, R 4 is n-hexyl.

[0177] In some embodiments, R 4 is CH3.

[0178] In some embodiments, R 4 is C1-C6 alkoxy.

[0179] In some embodiments, R 4 is methoxy. In some embodiments, R 4 is ethoxy. In some embodiments, R 4 is propoxy. In some embodiments, R 4 is -OCH2CH2CH3. In some embodiments, R 4 is -OCH(CH3)2. In some embodiments, R 4 is butoxy. In some embodiments, R 4 is -OCH2CH2CH2CH3 。 In some embodiments, R 4 is -OCH2CH(CH3)2. In some embodiments, R 4 is -OC(CH3)3. In some embodiments, R 4 is pentyloxy. In some embodiments, R 4 is hexyloxy.

[0180] In some embodiments, R 4 is -OCH3.

[0181] In some embodiments, R 4is -OC2H5.

[0182] In some embodiments, R 4 is -O-CH2CH2CH3.

[0183] In some embodiments, R 4 is

Chemical formula

[0184] In some embodiments, R 4 is

Chemical formula

[0185] In some embodiments, R 4 is -NR 6 R 7 as follows.

[0186] In some embodiments, R 4 is -NH2.

[0187] In some embodiments, R 4 is -NHCH3.

[0188] In some embodiments, R 4 is -N(CH3)2.

[0189] In some embodiments, R 4 is

Chemical formula

[0190] In some embodiments, R 4 is

Chemical formula

[0191] In some embodiments, R 4 is [Chemical formula] .

[0192] In some embodiments, R 4 is [Chemical formula] .

[0193] In some embodiments, R 4 is -N(CH3)2.

[0194] In some embodiments, R 4 is [Chemical formula] .

[0195] In some embodiments, R 4 is [Chemical formula] .

[0196] In some embodiments, R 4 is heterocyclyl.

[0197] In some embodiments, R 4 is [Chemical formula] .

[0198] In some embodiments, R 4 is [Chemical formula] .

[0199] In some embodiments, R 4 is a C1-C6 alkoxy substituted with one group R 5 .

[0200] In some embodiments, R 4 is a C1-C6 alkoxy substituted with one cycloalkyl.

[0201] In some embodiments, R 4 is

Chemical formula

[0202] In some embodiments, R 4 and R 1 , together with the atoms to which they are attached and any intervening atoms, form a 3- to 10-membered cycloalkyl, a 6- to 10-membered aryl, a 3- to 14-membered heterocycle, or a 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle or heteroaryl is optionally substituted with one or more R 16 .

[0203] In some embodiments, R 4 and R 1 , together with the atoms to which they are attached and any intervening atoms, form a 6-membered aryl, which is optionally substituted with one or more R 16 .

[0204] In some embodiments, R 4 and R 1 , together with the atoms to which they are attached and any intervening atoms, form an unsubstituted 6-membered aryl.

[0205] In some embodiments, R 4 and R 1 , together with the atoms to which they are attached and any intervening atoms, form a 6-membered aryl, which is substituted with one or more halogens.

[0206] In some embodiments, R 4 and R 1 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one or more Fs.

[0207] In some embodiments, R 4 and R 1 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one F.

[0208] In some embodiments, R 4 and R 1 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one or more Cls.

[0209] In some embodiments, R 4 and R 1 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one Cl.

[0210] In some embodiments, R 4 and R 1 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is optionally substituted with one or more C1-C6 alkyls.

[0211] In some embodiments, R 4 and R 1 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one or more methyls.

[0212] In some embodiments, R 4 and R 1together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one methyl.

[0213] In some embodiments, R 4 and R 1 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is optionally substituted with one or more C1-C6 alkoxys.

[0214] In some embodiments, R 4 and R 1 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one or more methoxys.

[0215] In some embodiments, R 4 and R 1 together with the atoms to which they are attached and any intervening atoms form a 6-membered aryl which is substituted with one methoxy.

[0216] In some embodiments, R 5 is selected from hydrogen, deuterium, halogen, -OH, -CN, -NO2, -NR 14 R 15 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, -C(O)OR 13 , -C(O)N-NR 14 R 15 , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R 16 .

[0217] In some embodiments, R 5 is hydrogen.

[0218] In some embodiments, R 5 is C1-C6 alkyl.

[0219] In some embodiments, R 6 is selected from H, C1-C6 alkyl, cycloalkyl, -CH2-aryl.

[0220] In some embodiments, R 6 is H.

[0221] In some embodiments, R 6 is C1-C6 alkyl.

[0222] In some embodiments, R 6 is methyl.

[0223] In some embodiments, R 6 is ethyl.

[0224] In some embodiments, R 6 is propyl.

[0225] In some embodiments, R 6 is n-propyl.

[0226] In some embodiments, R 6 is iso-propyl.

[0227] In some embodiments, R 6 is cycloalkyl.

[0228] In some embodiments, R 7 is -(CH2) n aryl selected, and aryl is halogen, -OH, -CN, -NO2, -NR 13 R 14Optionally substituted with one or more substituents independently selected from C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl.

[0229] In some embodiments, n is an integer selected from 0, 1, 2.

[0230] In some embodiments, n is 2.

[0231] In some embodiments, n is 1.

[0232] In some embodiments, n is 0.

[0233] In some embodiments, R 7 is -(CH2) n aryl, and the aryl is halogen, -OH, -CN, -NO2, -NR 13 R 14 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, optionally substituted with one or more substituents independently selected therefrom.

[0234] In some embodiments, R 7 is -CH2-aryl, and the aryl is halogen, -OH, -CN, -NO2, -NR 13 R 14 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, optionally substituted with one or more substituents independently selected therefrom.

[0235] In some embodiments, R 7 is -CH2-phenyl.

[0236] In some embodiments, R 7is -CH2-aryl, where the aryl is optionally substituted with one or more halogens.

[0237] In some embodiments, R 7 is

Chemical formula

[0238] In some embodiments, R 8 is selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl.

[0239] In some embodiments, R 8 is hydrogen.

[0240] In some embodiments, R 8 is C1-C6 alkyl.

[0241] In some embodiments, R 8 is methyl.

[0242] In some embodiments, R 7 and R 8 together with the atom to which they are attached and any intervening atoms form a 5- to 7-membered monocyclic or bicyclic heterocyclyl optionally substituted with one or more R 13 s.

[0243] In some embodiments, R 7 and R 8 together with the atom to which they are attached and any intervening atoms form a 5-membered monocyclic heterocyclyl, which is optionally substituted with one or more R 13 s.

[0244] In some embodiments, R 7 and R 8together with the atoms to which they are attached and any intervening atoms form a 6-membered monocyclic heterocyclyl which is optionally substituted with one or more R 13 In some embodiments, R

[0245] and R 7 and R 8 together with the atoms to which they are attached and any intervening atoms form a 7-membered monocyclic heterocyclyl which is optionally substituted with one or more R 13 In some embodiments, R

[0246] and R 7 and R 8 together with the atoms to which they are attached and any intervening atoms form a 6-membered bicyclic heterocyclyl which is optionally substituted with one or more R 13 In some embodiments, R

[0247] and R 7 and R 8 together with the atoms to which they are attached and any intervening atoms form a 7-membered bicyclic heterocyclyl which is optionally substituted with one or more R 13 In some embodiments, R

[0248] and R 7 and R 8 together with the atoms to which they are attached and any intervening atoms form

Chemical formula

[0249] and R 7 and R 8 together with the atoms to which they are attached and any intervening atoms form

Chemical formula

[0250] ​ In some embodiments, R 9 , R 10 , R 11 are each independently selected from C1-C6 alkyl, cycloalkyl, halogen, -CN.

[0251] In some embodiments, R 9 , R 10 , R 11 are each C1-C6 alkyl.

[0252] In some embodiments, R 9 , R 10 , R 11 are each methyl.

[0253] In some embodiments, R 9 , R 10 , R 11 are each halogen.

[0254] In some embodiments, R 9 , R 10 , R 11 are each F.

[0255] In some embodiments, R 9 is methyl and R 10 and R 11 are each F.

[0256] In some embodiments, R 9 is F and R 10 and R 11 are each methyl.

[0257] In some embodiments, R 12 is selected from R 6 -S(O)2-, R 6 -C(O)-, R 6 -O-C(O)-, heteroaryl, and heteroaryl is optionally substituted with one or more R 16 .

[0258] In some embodiments, R 12 is C1-C6 alkyl-S(O)2-, and the alkyl is optionally substituted with one or more R 16 .

[0259] In some embodiments, R 12 is CH3S(O)2-.

[0260] In some embodiments, R 12 is CF3S(O)2-.

[0261] In some embodiments, R 12 is CF3CH2S(O)2-.

[0262] In some embodiments, R 12 is cycloalkyl-S(O)2-, and the alkyl is optionally substituted with one or more R 16 .

[0263] In some embodiments, R 12 is [Chemical formula] .

[0264] In some embodiments, R 12 is C1-C6 alkyl-C(O)-, and the alkyl is optionally substituted with one or more R 16 .

[0265] In some embodiments, R 12 is CF3C(O)-.

[0266] In some embodiments, R 12 is (CH3)2CHC(O)-.

[0267] In some embodiments, R 12 is C1-C6 alkyl-O-C(O)-, and the alkyl is optionally substituted with one or more R 16is optionally replaced.

[0268] In some embodiments, R 12 is (CH3)3C - O - C(O)-.

[0269] In some embodiments, R 12 is CH3OC(O)-.

[0270] In some embodiments, R 12 is CH3CH2OC(O)-.

[0271] In some embodiments, R 12 is (CH3)2CH - OC(O)-.

[0272] In some embodiments, R 12 is heteroaryl.

[0273] In some embodiments, R 12 is 5 - membered heteroaryl.

[0274] In some embodiments, R 12 is 6 - membered heteroaryl.

[0275] In some embodiments, R 12 is 5 - membered heteroaryl containing one heteroatom.

[0276] In some embodiments, R 12 is 5 - membered heteroaryl containing two heteroatoms.

[0277] In some embodiments, R 12 is 5 - membered heteroaryl containing three heteroatoms.

[0278] In some embodiments, R 12 is 6 - membered heteroaryl containing one heteroatom.

[0279] In some embodiments, R 12 is a 6-membered heteroaryl containing two heteroatoms.

[0280] In some embodiments, R 12 is a 6-membered heteroaryl containing three heteroatoms.

[0281] In some embodiments, R 12 is a 5-membered heteroaryl containing one heteroatom selected from N, O, and S.

[0282] In some embodiments, R 12 is a 5-membered heteroaryl containing two heteroatoms independently selected from N, O, and S.

[0283] In some embodiments, R 12 is a 5-membered heteroaryl containing three heteroatoms independently selected from N, O, and S.

[0284] In some embodiments, R 12 is a 6-membered heteroaryl containing one heteroatom selected from N, O, and S.

[0285] In some embodiments, R 12 is a 6-membered heteroaryl containing two heteroatoms independently selected from N, O, and S.

[0286] In some embodiments, R 12 is a 6-membered heteroaryl containing three heteroatoms independently selected from N, O, and S.

[0287] In some embodiments, R 12 is a 5-membered heteroaryl containing one heteroatom selected from N, O, and S and substituted with one R 16 .

[0288] In some embodiments, R 12 is a 5-membered heteroaryl containing one heteroatom selected from N, O, and S and substituted with one R 16A 5-membered heteroaryl containing two heteroatoms independently selected from N, O, and S, which is substituted with

[0289] In some embodiments, R12 is a 5-membered heteroaryl containing three heteroatoms independently selected from N, O, and S, which is substituted with one R16.

[0290] In some embodiments, R 12 is a 6-membered heteroaryl containing one heteroatom selected from N, O, and S, which is substituted with one R 16

[0291] In some embodiments, R 12 is a 6-membered heteroaryl containing two heteroatoms independently selected from N, O, and S, which is substituted with one R 16

[0292] In some embodiments, R 12 is a 6-membered heteroaryl containing three heteroatoms independently selected from N, O, and S, which is substituted with one R 16

[0293] In some embodiments, R 12 is [Chemical formula]

[0294] In some embodiments, R 12 is [Chemical formula]

[0295] In some embodiments, R 12 is [Chemical formula]

[0296] ​​​​​​ In some embodiments, R 12 is

Chem.

[0297] In some embodiments, R 12 is

Chem.

[0298] In some embodiments, R 12 is

Chem.

[0299] In some embodiments, R 12 is

Chem.

[0300] In some embodiments, R 12 is

Chem.

[0301] In some embodiments, R 12 is

Chem.

[0302] In some embodiments, R 12 is

Chem.

[0303] In some embodiments, each R13 is independently selected from halogen, -OH, -CN, -C1-C6 alkyl, -C1-C6 haloalkyl.

[0304] In some embodiments, R 13 is -C1-C6 alkyl.

[0305] In some embodiments, the compound of formula (I) contains two Rs that are -C1-C6 alkyl. 13

[0306] In some embodiments, the compound of formula (I) contains two Rs that are methyl. 13

[0307] In some embodiments, two Rs 13 together with the atom to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C1-C6 alkyl, C1-C6 haloalkyl.

[0308] In some embodiments, two Rs 13 together with the atom to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, and the cycloalkyl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C1-C6 alkyl, C1-C6 haloalkyl.

[0309] In some embodiments, two Rs 13 together with the atom to which they are attached and any intervening atoms form a 6-membered aryl, and the aryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C1-C6 alkyl, C1-C6 haloalkyl.

[0310] ​​In some embodiments, two Rs 13 together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered heterocyclic ring, which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C1-C6 alkyl, C1-C6 haloalkyl.

[0311] In some embodiments, two Rs 13 together with the atoms to which they are attached and any intervening atoms form a 5- to 6-membered heteroaryl, which is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C1-C6 alkyl, C1-C6 haloalkyl.

[0312] In some embodiments, two Rs 13 together with the atoms to which they are attached and any intervening atoms form

Chemical formula

[0313] In some embodiments, R 14 and R 15 are each independently selected from H, C1-C6 alkyl, cycloalkyl.

[0314] In some embodiments, R 14 and R 15 are each H.

[0315] In some embodiments, R 14 and R 15 are each methyl.

[0316] In some embodiments, R 14 and R 15 together with the atoms to which they are attached and any intervening atoms form a heterocyclyl optionally substituted with one or more of halogen, -OH, -CN, C1-C6 alkyl.

[0317] In some embodiments, each R 16 is independently selected from halogen, -OH, -CN, -NO2, -NR 14 R 15 , C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, -C(O)OR 14 , -C(O)R 14 , -C(O)N-NR 14 R 15 , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C1-C6 alkyl, and C1-C6 haloalkyl.

[0318] In some embodiments, R 16 is halogen.

[0319] In some embodiments, R 16 is F.

[0320] In some embodiments, R 16 is Cl.

[0321] In some embodiments, R 16 is C1-C6 alkyl.

[0322] In some embodiments, R 16 is methyl.

[0323] In some embodiments, R 16 is ethyl.

[0324] In some embodiments, R 16 is propyl.

[0325] In some embodiments, R 16 is n-propyl.

[0326] In some embodiments, R 16 is iso-propyl.

[0327] In some embodiments, R 16 is C1-C6 alkoxy.

[0328] In some embodiments, R 16 is methoxy.

[0329] In some embodiments, R 16 is -C(O)R 14 is.

[0330] In some embodiments, R 16 is -C(O)CH3.

[0331] In some embodiments, X is hydrogen, deuterium, halogen, OH, CN, NO2, CONR 14 R 15 , C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkyl-C1-C6 alkoxy, C1-C6 alkyl-NHC1-C6 alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, and the alkyl is optionally substituted with cycloalkyl, heterocyclyl, aryl, and heteroaryl.

[0332] In some embodiments, X is -CN.

[0333] In some embodiments, X is CONR 14 R 15 is.

[0334] In some embodiments, X is CONH2.

[0335] In some embodiments, X is selected from C1-C6 alkyl optionally substituted with cycloalkyl, heterocyclyl, aryl, and heteroaryl.

[0336] In some embodiments, X is selected from C1-C6 alkyl substituted with heterocyclyl.

[0337] In some embodiments, X is

Chemical formula

[0338] In some embodiments, X is

Chemical formula

[0339] In some embodiments, R M is

Chemical formula

[0340] In some embodiments, R M is

Chemical formula

[0341] In some embodiments, R M is

Chemical formula

[0342] In some embodiments, M is selected from 5- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, and the heterocyclyl or heteroaryl is optionally substituted with one or more R 16 s.

[0343] In some embodiments, M is a 5- to 10-membered heterocyclyl optionally substituted with one or more R 16 s.

[0344] In some embodiments, M is a 5- to 10-membered heteroaryl optionally substituted with one or more Rs 16 and is optionally substituted with one or more Rs

[0345] In some embodiments, M is

Chemical formula

[0346] In some embodiments, M is

Chemical formula

[0347] In some embodiments, M is

Chemical formula

[0348] In some embodiments, M is

Chemical formula

[0349] In some embodiments, M is

Chemical formula

[0350] In some embodiments, M is

Chemical formula

[0351] In some embodiments, M is

Chemical formula

[0352] In some embodiments, M is

Chemical formula

[0353] In some embodiments, M is

Chemical formula

[0354] In some embodiments, M is

Chemical formula

[0355] In some embodiments, M is

Chemical formula

[0356] In some embodiments, M is

Chemical formula

[0357] In some embodiments, M is

Chemical formula

[0358] In some embodiments, M is

Chemical formula

[0359] In some embodiments, M is

Chemical formula

[0360] In some embodiments, M is

Chem.

[0361] In some embodiments, M is

Chem.

[0362] In some embodiments, M is

Chem.

[0363] In some embodiments, m is an integer selected from 0 and 1.

[0364] In some embodiments, m is 0.

[0365] In some embodiments, m is 1.

[0366] In some embodiments, the compound is of formula (I-I):

Chem.

[0367] In some embodiments, the compound is of formula (I-II):

Chem.

[0368] In some embodiments, the compound is of formula (I-I-I):

Chemical formula

[0369] In some embodiments, the compound is of formula (I-I-II):

Chemical formula

[0370] In some embodiments, the compound is of formula (I-II-I):

Chemical formula

[0371] In some embodiments, the compound is of formula (I-II-II):

Chemical formula

[0372] In some embodiments, the compound is of formula (I-I-I-A):

Chemical formula

[0373] In some embodiments, the compound is of formula (I-I-I-A-I):

Chemical formula

[0374] In some embodiments, the compound is of formula (I-I-I-A-I-a):

Chemical formula

[0375] In some embodiments, the compound is of formula (I-I-I-A-I-1):

Chemical formula

[0376] In some embodiments, the compound is of formula (I-I-I-A-I-1-a):

Chemical formula

[0377] In some embodiments, the compound is of formula (I-I-I-A-I-1-A-I):

Chemical formula

[0378] In some embodiments, the compound is of formula (I-I-I-A-I-1-A*):

Chemical formula

[0379] In some embodiments, the compound is of formula (I-I-I-A-I-1-A**):

Chemical formula

[0380] In some embodiments, the compound is of formula (I-A-I-1-A***):

Chemical formula

[0381] In some embodiments, the compound is of formula (I-I-I-A-I-1-A****): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, where x is an integer selected from 0, 1, 2, 3, 4, and all other variables are as defined herein.

[0382] In some embodiments, the compound is of formula (I-I-I-A-I-1-A-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0383] In some embodiments, the compound is of formula (I-I-I-A-I-1-A-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, and all variables are as defined herein.

[0384] In some embodiments, the compound is of formula (I-I-I-A-I-1-A-a**): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, and all variables are as defined herein.

[0385] In some embodiments, the compound is of formula (I-I-I-A-I-1-A-a***): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0386] In some embodiments, the compound is of formula (I-I-I-A-I-1-A-a****):

Chemical formula

[0387] In some embodiments, the compound is of formula (I-I-I-A-I-a-1-A-1):

Chemical formula

[0388] In some embodiments, the compound is of formula (I-I-I-A-I-a-1-A-1-a):

Chemical formula

[0389] In some embodiments, the compound is of formula (I-I-I-A-I-a-1-A-1-H):

Chemical formula

[0390] In some embodiments, the compound is of formula (I-A-I-a-1-A-1-H-a):

Chemical formula

[0391] In some embodiments, the compound is of formula (I-I-II):

Chemical formula

[0392] In some embodiments, the compound is of formula (I-I-II-I):

Chemical formula

[0393] In some embodiments, the compound is of formula (I-I-II-I-a):

Chemical formula

[0394] In some embodiments, the compound is of formula (I-I-II-I-a-1):

Chemical formula

[0395] In some embodiments, the compound is of formula (I-I-II-I-a-1-A):

Chemical formula

[0396] In some embodiments, the compound is of formula (I-I-II-I-a-1-A-I):

Chemical formula

[0397] In some embodiments, the compound is of formula (I-I-II-I-a-1-A-I-a):

Chemical formula

[0398] In some embodiments, the compound is of formula (I-I-II-I-a-1-A-I-a*):

Chemical formula

[0399] In some embodiments, the compound is of formula (I-I-II-II):

Chemical formula

[0400] In some embodiments, the compound is of formula (I-I-II-II-a):

Chemical formula

[0401] In some embodiments, the compound is of formula (I-I-II-II-a-1):

Chemical formula

[0402] In some embodiments, the compound is of formula (I-I-II-II-a-2):

Chemical formula

[0403] In some embodiments, the compound is of formula (I-I-II-II-a-1-A):

Chem.

[0404] In some embodiments, the compound is of formula (I-I-II-II-a-1-B):

Chem.

[0405] In some embodiments, the compound is of formula (I-I-II-II-a-2-A):

Chem.

[0406] In some embodiments, the compound is of formula (I-I-II-II-a-2-B):

Chem.

[0407] In some embodiments, the compound is of formula (I-I-II-II-a-1-A-I):

Chem.

[0408] In some embodiments, the compound is of formula (I-I-II-II-a-2-A-I):

Chem.

[0409] In some embodiments, the compound is of formula (I-I-II-II-a-1-B-I):

Chem.

[0410] In some embodiments, the compound is of formula (I-I-II-II-a-2-B-I):

Chem.

[0411] In some embodiments, the compound is of formula (I-I-II-II-a-1-A-II):

Chem.

[0412] In some embodiments, the compound is of formula (I-I-II-II-a-2-A-II): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0413] In some embodiments, the compound is of formula (I-I-II-II-a-1-B-II): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0414] In some embodiments, the compound is of formula (I-I-II-II-a-2-B-II): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0415] In some embodiments, the compound is of formula (I-I-II-II-a-1-A-III): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0416] In some embodiments, the compound is of formula (I-I-II-II-a-2-A-III): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0417] In some embodiments, the compound is of formula (I-I-II-II-a-1-B-III): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0418] In some embodiments, the compound is of formula (I-I-II-II-a-2-B-III): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0419] In some embodiments, the compound is of formula (I-I-II-II-a-1-A-IV): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0420] In some embodiments, the compound is of formula (I-I-II-II-a-2-A-IV): [Chemical formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0421] In some embodiments, the compound is of formula (I-I-II-II-a-1-B-IV): [Chemical formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0422] In some embodiments, the compound is of formula (I-I-II-II-a-2-B-IV): [Chemical formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0423] In some embodiments, the compound is of formula (I-I-II-II-a-1-A-I-a): [Chemical formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0424] In some embodiments, the compound is of formula (I-I-II-II-a-1-A-I-a*): [Chemical formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0425] In some embodiments, the compound is of formula (I-I-II-II-b):

Chemical formula

[0426] In some embodiments, the compound is of formula (I-I-II-II-b-1):

Chemical formula

[0427] In some embodiments, the compound is of formula (I-I-II-II-b-1-A):

Chemical formula

[0428] In some embodiments, the compound is of formula (I-I-II-II-b-1-A-I):

Chemical formula

[0429] In some embodiments, the compound is of formula (I-I-II-II-b-1-A-I-a):

Chemical formula

[0430] In some embodiments, the compound is of formula (I-I-II-II-b-1-A-I-a*):

Chemical formula

[0431] In some embodiments, the compound is of formula (I-I-II-II-c):

Chemical formula

[0432] In some embodiments, the compound is of formula (I-I-II-II-c-1):

Chemical formula

[0433] In some embodiments, the compound is of formula (I-I-II-II-c-1-A):

Chemical formula

[0434] In some embodiments, the compound is of formula (I-I-II-II-c-1-A-I): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0435] In some embodiments, the compound is of formula (I-I-II-II-c-1-A-I-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0436] In some embodiments, the compound is of formula (I-I-II-II-c-1-A-I-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0437] In some embodiments, the compound is of formula (I-I-II-III): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein x is an integer selected from 0, 1, 2, 3, 4, 5, and W is O, S, S(O), S(O)2, NR 16 ’, and R 16’ is selected from H, C1-C6 alkyl, C3-C7 cycloalkyl, -C(O)C1-C6 alkyl, and the other variables are as defined herein.

[0438] In some embodiments, the compound is of formula (I-I-II-III-a):

Chemical formula

[0439] In some embodiments, the compound is of formula (I-I-II-III-a-1):

Chemical formula

[0440] In some embodiments, the compound is of formula (I-I-II-III-a-1-A):

Chemical formula

[0441] In some embodiments, the compound is of formula (I-I-II-III-a-1-A-I):

Chemical formula

[0442] In some embodiments, the compound is of formula (I-I-II-III-a-1-A-I-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0443] In some embodiments, the compound is of formula (I-I-II-III-a-1-A-I-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0444] In some embodiments, the compound is of formula (I-I-II-III-b): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0445] In some embodiments, the compound is of formula (I-I-II-III-b-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0446] In some embodiments, the compound is of formula (I-I-II-III-b-1-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0447] In some embodiments, the compound is of formula (I-I-II-III-b-1-A-I):

Chemical formula

[0448] In some embodiments, the compound is of formula (I-I-II-III-b-1-A-I-a):

Chemical formula

[0449] In some embodiments, the compound is of formula (I-I-II-III-b-1-A-I-a*):

Chemical formula

[0450] In some embodiments, the compound is of formula (I-I-II-III-c):

Chemical formula

[0451] In some embodiments, the compound is of formula (I-I-II-III-c-1):

Chem.

[0452] In some embodiments, the compound is of formula (I-I-II-III-c-1-A):

Chem.

[0453] In some embodiments, the compound is of formula (I-I-II-III-c-1-A-I):

Chem.

[0454] In some embodiments, the compound is of formula (I-I-II-III-c-1-A-I-a):

Chem.

[0455] In some embodiments, the compound is of formula (I-I-II-III-c-1-A-I-a*):

Chem.

[0456] In some embodiments, the compound is of formula (I-I-II-III-d):

Chemical formula

[0457] In some embodiments, the compound is of formula (I-I-II-III-d-1):

Chemical formula

[0458] In some embodiments, the compound is of formula (I-I-II-III-d-1-A):

Chemical formula

[0459] In some embodiments, the compound is of formula (I-I-II-III-d-1-A-I):

Chemical formula

[0460] In some embodiments, the compound is of formula (I-I-II-III-d-1-A-I-a):

Chemical formula

[0461] In some embodiments, the compound is of formula (I-I-II-III-d-1-A-I-a*):

Chemical formula

[0462] In some embodiments, the compound is of formula (I-I-II-IV):

Chemical formula

[0463] In some embodiments, the compound is of formula (I-I-II-IV-a):

Chemical formula

[0464] In some embodiments, the compound is of formula (I-I-II-IV-a-1):

Chem.

[0465] In some embodiments, the compound is of formula (I-I-II-IV-a-1-A):

Chem.

[0466] In some embodiments, the compound is of formula (I-I-II-IV-a-1-A-I):

Chem.

[0467] In some embodiments, the compound is of formula (I-I-II-IV-a-1-A-I-a):

Chem.

[0468] In some embodiments, the compound is of formula (I-I-II-IV-a-1-A-I-a*): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0469] In some embodiments, the compound is of formula (I-I-II-III-b): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0470] In some embodiments, the compound is of formula (I-I-II-III-b-1): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0471] In some embodiments, the compound is of formula (I-I-II-III-b-1-A): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0472] In some embodiments, the compound is of formula (I-I-II-III-b-1-A-I): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0473] In some embodiments, the compound is of formula (I-I-II-III-b-1-A-I-a):

Chemical formula

[0474] In some embodiments, the compound is of formula (I-I-II-III-b-1-A-I-a*):

Chemical formula

[0475] In some embodiments, the compound is of formula (I-I-II-III-c):

Chemical formula

[0476] In some embodiments, the compound is of formula (I-I-II-III-c-1):

Chemical formula

[0477] In some embodiments, the compound is of formula (I-I-II-III-c-1-A):

Chemical formula

[0478] In some embodiments, the compound is of formula (I-I-II-III-c-1-A-I):

Chemical formula

[0479] In some embodiments, the compound is of formula (I-I-II-III-c-1-A-I-a):

Chemical formula

[0480] In some embodiments, the compound is of formula (I-I-II-III-c-1-A-I-a*):

Chemical formula

[0481] In some embodiments, the compound is of formula (I-I-II-III-d):

Chemical formula

[0482] In some embodiments, the compound is of formula (I-I-II-III-d-1):

Chemical formula

[0483] In some embodiments, the compound is of formula (I-I-II-III-d-1-A):

Chemical formula

[0484] In some embodiments, the compound is of formula (I-I-II-III-d-1-A-I):

Chemical formula

[0485] In some embodiments, the compound is of formula (I-I-II-III-d-1-A-I-a):

Chemical formula

[0486] In some embodiments, the compound is of formula (I-I-II-III-d-1-A-I-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0487] In some embodiments, the compound is of formula (I-I-II-V): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0488] In some embodiments, the compound is of formula (I-I-II-V-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0489] In some embodiments, the compound is of formula (I-I-II-V-a-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0490] In some embodiments, the compound is of formula (I-I-II-V-a-1-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0491] In some embodiments, the compound is of formula (I-I-II-V-a-1-A-I): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0492] In some embodiments, the compound is of formula (I-I-II-V-a-1-A-I-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0493] In some embodiments, the compound is of formula (I-I-II-V-a-1-A-I-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0494] In some embodiments, the compound is of formula (I-I-II-VI): [Chemical formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, x is an integer selected from 0, 1, 2, 3, 4, and all other variables are as defined herein.

[0495] In some embodiments, the compound is of formula (I-I-II-VI-a):

Chemical formula

[0496] In some embodiments, the compound is of formula (I-I-II-VI-a-1):

Chemical formula

[0497] In some embodiments, the compound is of formula (I-I-II-VI-a-1-A):

Chemical formula

[0498] In some embodiments, the compound is of formula (I-I-II-VI-a-1-B):

Chemical formula

[0499] In some embodiments, the compound is of formula (I-I-II-VI-a-1-A-I): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0500] In some embodiments, the compound is of formula (I-I-II-VI-a-1-A-II): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0501] In some embodiments, the compound is of formula (I-I-II-VI-a-1-A-III): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0502] In some embodiments, the compound is of formula (I-I-II-VI-a-1-A-IV): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0503] In some embodiments, the compound is of formula (I-I-II-VI-a-1-A-I-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0504] In some embodiments, the compound is of formula (I-I-II-VI-a-1-A-I-a*):

Chem.

[0505] In some embodiments, the compound is of formula (I-I-II-VI-b):

Chem.

[0506] In some embodiments, the compound is of formula (I-I-II-VI-b-1):

Chem.

[0507] In some embodiments, the compound is of formula (I-I-II-VI-b-1-A):

Chem.

[0508] In some embodiments, the compound is of formula (I-I-II-VI-b-1-A-I):

Chem.

[0509] In some embodiments, the compound is of formula (I-I-II-VI-b-1-A-I-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0510] In some embodiments, the compound is of formula (I-I-II-VI-b-1-A-I-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0511] In some embodiments, the compound is of formula (I-I-II-VI-c): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0512] In some embodiments, the compound is of formula (I-I-II-VI-c-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0513] In some embodiments, the compound is of formula (I-I-II-VI-c-1-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0514] In some embodiments, the compound is of formula (I-I-II-VI-c-1-A-I):

Chemical formula

[0515] In some embodiments, the compound is of formula (I-I-II-VI-c-1-A-I-a):

Chemical formula

[0516] In some embodiments, the compound is of formula (I-I-II-VI-c-1-A-I-a*):

Chemical formula

[0517] In some embodiments, the compound is of formula (I-I-II-VI-d):

Chemical formula

[0518] In some embodiments, the compound is of formula (I-I-II-VI-d-1):

Chemical formula

[0519] In some embodiments, the compound is of formula (I-I-II-VI-d-1-A):

Chem.

[0520] In some embodiments, the compound is of formula (I-I-II-VI-d-1-A-I):

Chem.

[0521] In some embodiments, the compound is of formula (I-I-II-VI-d-1-A-I-a):

Chem.

[0522] In some embodiments, the compound is of formula (I-I-II-VI-d-1-A-I-a*):

Chem.

[0523] In some embodiments, the compound is of formula (I-I-II-VI-e):

Chem.

[0524] In some embodiments, the compound is of formula (I-I-II-VI-e-1):

Chemical formula

[0525] In some embodiments, the compound is of formula (I-I-II-VI-e-1-A):

Chemical formula

[0526] In some embodiments, the compound is of formula (I-I-II-VI-e-1-A-I):

Chemical formula

[0527] In some embodiments, the compound is of formula (I-I-II-VI-e-1-A-I-a):

Chemical formula

[0528] In some embodiments, the compound is of formula (I-I-II-VI-e-1-A-I-a*):

Chemical formula

[0529] In some embodiments, the compound is of formula (I-I-II-VI-f):

Chem.

[0530] In some embodiments, the compound is of formula (I-I-II-VI-f-1):

Chem.

[0531] In some embodiments, the compound is of formula (I-I-II-VI-f-1-A):

Chem.

[0532] In some embodiments, the compound is of formula (I-I-II-VI-f-1-A-I):

Chem.

[0533] In some embodiments, the compound is of formula (I-I-II-VI-f-1-A-I-a):

Chem.

[0534] In some embodiments, the compound is of formula (I-I-II-VI-f-1-A-I-a*):

Chem.

[0535] In some embodiments, the compound is of formula (I-I-II-VI-g):

Chem.

[0536] In some embodiments, the compound is of formula (I-I-II-VI-g-1):

Chem.

[0537] In some embodiments, the compound is of formula (I-I-II-VI-g-1-A):

Chem.

[0538] In some embodiments, the compound is of formula (I-I-II-VI-g-1-A-I):

Chem.

[0539] In some embodiments, the compound is of formula (I-I-II-VI-g-1-A-I-a):

Chem.

[0540] In some embodiments, the compound is of formula (I-I-II-VI-g-1-A-I-a*):

Chem.

[0541] In some embodiments, the compound is of formula (I-I-II-VI-h):

Chem.

[0542] In some embodiments, the compound is of formula (I-I-II-VI-h-1):

Chem.

[0543] In some embodiments, the compound is of formula (I-I-II-VI-h-1-A):

Chem.

[0544] In some embodiments, the compound is of formula (I-I-II-VI-h-1-A-I): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0545] In some embodiments, the compound is of formula (I-I-II-VI-h-1-A-I-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0546] In some embodiments, the compound is of formula (I-I-II-VI-h-1-A-I-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0547] In some embodiments, the compound is of formula (I-I-II-VI-i): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0548] In some embodiments, the compound is of formula (I-I-II-VI-i-1): [Chemical formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0549] In some embodiments, the compound is of formula (I-I-II-VI-i-1-A):

Chemical formula

[0550] In some embodiments, the compound is of formula (I-I-II-VI-i-1-A-I):

Chemical formula

[0551] In some embodiments, the compound is of formula (I-I-II-VI-i-1-A-I-a):

Chemical formula

[0552] In some embodiments, the compound is of formula (I-I-II-VI-i-1-A-I-a*):

Chemical formula

[0553] In some embodiments, the compound is of formula (I-I-II-VI-j):

Chemical formula

[0554] In some embodiments, the compound is of formula (I-I-II-VI-j-1):

Chemical formula

[0555] In some embodiments, the compound is of formula (I-I-II-VI-j-1-A):

Chemical formula

[0556] In some embodiments, the compound is of formula (I-I-II-VI-j-1-A-I):

Chemical formula

[0557] In some embodiments, the compound is of formula (I-I-II-VI-j-1-A-I-a):

Chemical formula

[0558] In some embodiments, the compound is of formula (I-I-II-VI-j-1-A-I-a*):

Chemical formula

[0559] In some embodiments, the compound is of formula (I-I-II-VI-k): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0560] In some embodiments, the compound is of formula (I-I-II-VI-k-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0561] In some embodiments, the compound is of formula (I-I-II-VI-k-1-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0562] In some embodiments, the compound is of formula (I-I-II-VI-k-1-A-I): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0563] In some embodiments, the compound is of formula (I-I-II-VI-k-1-A-I-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0564] In some embodiments, the compound is of formula (I-I-II-VI-k-1-A-I-a*):

Chem.

[0565] In some embodiments, the compound is of formula (I-I-II-VI-l):

Chem.

[0566] In some embodiments, the compound is of formula (I-I-II-VI-l-1):

Chem.

[0567] In some embodiments, the compound is of formula (I-I-II-VI-l-1-A):

Chem.

[0568] In some embodiments, the compound is of formula (I-I-II-VI-l-1-A-I):

Chem.

[0569] In some embodiments, the compound is of formula (I-I-II-VI-l-1-A-I-a):

Chemical formula

[0570] In some embodiments, the compound is of formula (I-I-II-VI-l-1-A-I-a*):

Chemical formula

[0571] In some embodiments, the compound is of formula (I-I-II-VII):

Chemical formula

[0572] In some embodiments, the compound is of formula (I-I-II-VII-a):

Chemical formula

[0573] In some embodiments, the compound is of formula (I-I-II-VII-a-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0574] In some embodiments, the compound is of formula (I-I-II-VII-a-1-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0575] In some embodiments, the compound is of formula (I-I-II-VII-a-1-A-I): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0576] In some embodiments, the compound is of formula (I-I-II-VII-a-1-A-I-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0577] In some embodiments, the compound is of formula (I-I-II-VII-a-1-A-I-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0578] In some embodiments, the compound is of formula (I-I-II-VIII): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, where x is an integer selected from 0, 1, 2, 3, and all other variables are as defined herein.

[0579] In some embodiments, the compound is of formula (I-I-II-VIII-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0580] In some embodiments, the compound is of formula (I-I-II-VIII-a-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0581] In some embodiments, the compound is of formula (I-I-II-VIII-a-1-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0582] In some embodiments, the compound is of formula (I-I-II-VIII-a-1-A-I): [Chemical formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0583] In some embodiments, the compound is of formula (I-I-II-VIII-a-1-A-I-a):

Chemical formula

[0584] In some embodiments, the compound is of formula (I-I-II-VIII-a-1-A-I-a*):

Chemical formula

[0585] In some embodiments, the compound is of formula (I-A-A):

Chemical formula

[0586] In some embodiments, the compound is of formula (I-A-A-1):

Chemical formula

[0587] In some embodiments, the compound is of formula (I-A-A-2):

Chemical formula

[0588] In some embodiments, the compound is of formula (I-A-A-3):

Chemical formula

[0589] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0590] In some embodiments, the compound is of formula (I-A-A-1-1):

Chemical formula

[0591] In some embodiments, the compound is of formula (I-A-A-2-1):

Chemical formula

[0592] In some embodiments, the compound is of formula (I-A-A-3-1):

Chemical formula

[0593] In some embodiments, the compound is of formula (I-A-A-1-1-a):

Chemical formula

[0594] In some embodiments, the compound is of formula (I-A-A-2-1-a):

Chemical formula

[0595] In some embodiments, the compound is of formula (I-A-A-3-1-a):

Chemical formula

[0596] In some embodiments, the compound is of formula (I-A-A-1-1-a*):

Chemical formula

[0597] In some embodiments, the compound is of formula (I-A-A-2-1-a*):

Chem.

[0598] In some embodiments, the compound is of formula (I-A-A-3-1-a*):

Chem.

[0599] In some embodiments, the compound is of formula (I-A-A-1-2):

Chem.

[0600] In some embodiments, the compound is of formula (I-A-A-2-2):

Chem.

[0601] In some embodiments, the compound is of formula (I-A-A-3-2):

Chem.

[0602] In some embodiments, the compound is of formula (I-A-A-1-2-a):

Chemical formula

[0603] In some embodiments, the compound is of formula (I-A-A-2-2-a):

Chemical formula

[0604] In some embodiments, the compound is of formula (I-A-A-3-2-a):

Chemical formula

[0605] In some embodiments, the compound is of formula (I-A-A-1-2-a*):

Chemical formula

[0606] In some embodiments, the compound is of formula (I-A-A-2-2-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0607] In some embodiments, the compound is of formula (I-A-A-3-2-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0608] In some embodiments, the compound is of formula (I-A-A-1-3): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0609] In some embodiments, the compound is of formula (I-A-A-2-3): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0610] In some embodiments, the compound is of formula (I-A-A-3-3): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0611] In some embodiments, the compound is of formula (I-A-A-1-3-a):

Chemical formula

[0612] In some embodiments, the compound is of formula (I-A-A-2-3-a):

Chemical formula

[0613] In some embodiments, the compound is of formula (I-A-A-3-3-a):

Chemical formula

[0614] In some embodiments, the compound is of formula (I-A-A-1-3-a*):

Chemical formula

[0615] In some embodiments, the compound is of formula (I-A-A-2-3-a*):

Chem.

[0616] In some embodiments, the compound is of formula (I-A-A-3-3-a*):

Chem.

[0617] In some embodiments, the compound is of formula (I-A-A-1-4):

Chem.

[0618] In some embodiments, the compound is of formula (I-A-A-2-4):

Chem.

[0619] In some embodiments, the compound is of formula (I-A-A-3-4):

Chem.

[0620] In some embodiments, the compound is of formula (I-A-A-1-4-a):

Chemical formula

[0621] In some embodiments, the compound is of formula (I-A-A-2-4-a):

Chemical formula

[0622] In some embodiments, the compound is of formula (I-A-A-3-4-a):

Chemical formula

[0623] In some embodiments, the compound is of formula (I-A-A-1-4-a*):

Chemical formula

[0624] In some embodiments, the compound is of formula (I-A-A-2-4-a*):

Chem.

[0625] In some embodiments, the compound is of formula (I-A-A-3-4-a*):

Chem.

[0626] In some embodiments, the compound is of formula (I-A-B):

Chem.

[0627] In some embodiments, the compound is of formula (I-A-B-1):

Chem.

[0628] In some embodiments, the compound is of formula (I-A-B-2):

Chem.

[0629] In some embodiments, the compound is of formula (I-A-B-3):

Chemical formula

[0630] In some embodiments, the compound is of formula (I-A-B-1-1):

Chemical formula

[0631] In some embodiments, the compound is of formula (I-A-B-2-1):

Chemical formula

[0632] In some embodiments, the compound is of formula (I-A-B-3-1):

Chemical formula

[0633] In some embodiments, the compound is of formula (I-A-B-1-1-a):

Chemical formula

[0634] In some embodiments, the compound is of formula (I-A-B-2-1-a):

Chemical formula

[0635] In some embodiments, the compound is of formula (I-A-B-3-1-a):

Chemical formula

[0636] In some embodiments, the compound is of formula (I-A-B-1-1-a*):

Chemical formula

[0637] In some embodiments, the compound is of formula (I-A-B-2-1-a*):

Chemical formula

[0638] In some embodiments, the compound is of formula (I-A-B-3-1-a*):

Chemical formula

[0639] In some embodiments, the compound is of formula (I-A-B-1-2):

Chemical formula

[0640] In some embodiments, the compound is of formula (I-A-B-2-2):

Chemical formula

[0641] In some embodiments, the compound is of formula (I-A-B-3-2):

Chemical formula

[0642] In some embodiments, the compound is of formula (I-A-B-1-2-a):

Chemical formula

[0643] In some embodiments, the compound is of formula (I-A-B-2-2-a):

Chemical formula

[0644] In some embodiments, the compound is of formula (I-A-B-3-2-a):

Chemical formula

[0645] In some embodiments, the compound is of formula (I-A-B-1-2-a*):

Chemical formula

[0646] In some embodiments, the compound is of formula (I-A-B-2-2-a*):

Chemical formula

[0647] In some embodiments, the compound is of formula (I-A-B-3-2-a*):

Chemical formula

[0648] In some embodiments, the compound is of formula (I-A-B-1-3):

Chemical formula

[0649] In some embodiments, the compound is of formula (I-A-B-2-3):

Chemical formula

[0650] In some embodiments, the compound is of formula (I-A-B-3-3):

Chemical formula

[0651] In some embodiments, the compound is of formula (I-A-B-1-3-a):

Chem.

[0652] In some embodiments, the compound is of formula (I-A-B-2-3-a):

Chem.

[0653] In some embodiments, the compound is of formula (I-A-B-3-3-a):

Chem.

[0654] In some embodiments, the compound is of formula (I-A-B-1-3-a*):

Chem.

[0655] In some embodiments, the compound is of formula (I-A-B-2-3-a*):

Chem.

[0656] In some embodiments, the compound is of formula (I-A-B-3-3-a*):

Chemical formula

[0657] In some embodiments, the compound is of formula (I-A-B-1-4):

Chemical formula

[0658] In some embodiments, the compound is of formula (I-A-B-2-4):

Chemical formula

[0659] In some embodiments, the compound is of formula (I-A-B-3-4):

Chemical formula

[0660] In some embodiments, the compound is of formula (I-A-B-1-4-a):

Chemical formula

[0661] In some embodiments, the compound is of formula (I-A-B-2-4-a):

Chemical formula

[0662] In some embodiments, the compound is of formula (I-A-B-3-4-a):

Chemical formula

[0663] In some embodiments, the compound is of formula (I-A-B-1-4-a*):

Chemical formula

[0664] In some embodiments, the compound is of formula (I-A-B-2-4-a*):

Chemical formula

[0665] In some embodiments, the compound is of formula (I-A-B-3-4-a*):

Chemical formula

[0666] In some embodiments, the compound is of formula (I-I-I-A):

Chemical formula

[0667] In some embodiments, the compound is of formula (I-I-I-A-1):

Chemical formula

[0668] In some embodiments, the compound is of formula (I-I-I-A-2):

Chemical formula

[0669] In some embodiments, the compound is of formula (I-I-I-A-1-1):

Chemical formula

[0670] In some embodiments, the compound is of formula (I-I-I-A-2-1):

Chemical formula

[0671] In some embodiments, the compound is of formula (I-I-I-A-1-1-a):

Chemical formula

[0672] In some embodiments, the compound is of formula (I-I-I-A-2-1-a):

Chemical formula

[0673] In some embodiments, the compound is of formula (I-I-I-A-1-1-a*):

Chemical formula

[0674] In some embodiments, the compound is of formula (I-I-I-A-2-1-a*):

Chemical formula

[0675] In some embodiments, the compound is of formula (I-I-I-A-1-2):

Chemical formula

[0676] In some embodiments, the compound is of formula (I-I-I-A-2-2):

Chemical formula

[0677] In some embodiments, the compound is of formula (I-I-I-A-1-2-a):

Chemical formula

[0678] In some embodiments, the compound is of formula (I-I-I-A-2-2-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0679] In some embodiments, the compound is of formula (I-I-I-A-1-2-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0680] In some embodiments, the compound is of formula (I-I-I-A-2-2-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0681] In some embodiments, the compound is of formula (I-I-I-A-1-3): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0682] In some embodiments, the compound is of formula (I-I-I-A-2-3): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0683] In some embodiments, the compound is of formula (I-I-I-A-1-3-a):

Chemical formula

[0684] In some embodiments, the compound is of formula (I-I-I-A-2-3-a):

Chemical formula

[0685] In some embodiments, the compound is of formula (I-I-I-A-1-3-a*):

Chemical formula

[0686] In some embodiments, the compound is of formula (I-I-I-A-2-3-a*):

Chemical formula

[0687] In some embodiments, the compound is of formula (I-I-I-A-1-4):

Chemical formula

[0688] In some embodiments, the compound is of formula (I-I-I-A-2-4):

Chemical formula

[0689] In some embodiments, the compound is of formula (I-I-I-A-1-4-a):

Chemical formula

[0690] In some embodiments, the compound is of formula (I-I-I-A-2-4-a):

Chemical formula

[0691] In some embodiments, the compound is of formula (I-I-I-A-1-4-a*):

Chemical formula

[0692] In some embodiments, the compound is of formula (I-I-I-A-2-4-a*):

Chemical formula

[0693] In some embodiments, the compound is of formula (I-I-II-A):

Chemical formula

[0694] In some embodiments, the compound is of formula (I-I-II-A-1):

Chemical formula

[0695] In some embodiments, the compound is of formula (I-I-II-A-2):

Chemical formula

[0696] In some embodiments, the compound is of formula (I-A-A-1-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0697] In some embodiments, the compound is of formula (I-A-A-2-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0698] In some embodiments, the compound is of formula (I-I-II-A-1-1-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0699] In some embodiments, the compound is of formula (I-I-II-A-2-1-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0700] In some embodiments, the compound is of formula (I-I-II-A-1-1-a*): [Chemical formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, and all variables are as defined herein.

[0701] In some embodiments, the compound is of formula (I-I-II-A-2-1-a*):

Chemical formula

[0702] In some embodiments, the compound is of formula (I-I-II-A-1-2):

Chemical formula

[0703] In some embodiments, the compound is of formula (I-I-II-A-2-2):

Chemical formula

[0704] In some embodiments, the compound is of formula (I-I-II-A-1-2-a):

Chemical formula

[0705] In some embodiments, the compound is of formula (I-I-II-A-2-2-a): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0706] In some embodiments, the compound is of formula (I-I-II-A-1-2-a*): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0707] In some embodiments, the compound is of formula (I-I-II-A-2-2-a*): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0708] In some embodiments, the compound is of formula (I-I-II-A-1-3): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0709] In some embodiments, the compound is of formula (I-I-II-A-2-3): [Chemical Formula] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, and all variables are as defined herein.

[0710] In some embodiments, the compound is of formula (I-I-II-A-1-3-a):

Chemical formula

[0711] In some embodiments, the compound is of formula (I-I-II-A-2-3-a):

Chemical formula

[0712] In some embodiments, the compound is of formula (I-I-II-A-1-3-a*):

Chemical formula

[0713] In some embodiments, the compound is of formula (I-I-II-A-2-3-a*):

Chemical formula

[0714] In some embodiments, the compound is of formula (I-I-II-A-1-4):

Chem.

[0715] In some embodiments, the compound is of formula (I-I-II-A-2-4):

Chem.

[0716] In some embodiments, the compound is of formula (I-I-II-A-1-4-a):

Chem.

[0717] In some embodiments, the compound is of formula (I-I-II-A-2-4-a):

Chem.

[0718] In some embodiments, the compound is of formula (I-I-II-A-1-4-a*):

Chem.

[0719] In some embodiments, the compound is of formula (I-I-II-A-2-4-a*):

Chemical formula

[0720] In some embodiments, the compound is of formula (I-II-I-A):

Chemical formula

[0721] In some embodiments, the compound is of formula (I-II-I-A-1):

Chemical formula

[0722] In some embodiments, the compound is of formula (I-II-I-A-2):

Chemical formula

[0723] In some embodiments, the compound is of formula (I-II-I-A-1-1):

Chem.

[0724] In some embodiments, the compound is of formula (I-II-I-A-2-1):

Chem.

[0725] In some embodiments, the compound is of formula (I-II-I-A-1-1-a):

Chem.

[0726] In some embodiments, the compound is of formula (I-II-I-A-2-1-a):

Chem.

[0727] In some embodiments, the compound is of formula (I-II-I-A-1-1-a*):

Chem.

[0728] In some embodiments, the compound is of formula (I-II-I-A-2-1-a*):

Chemical formula

[0729] In some embodiments, the compound is of formula (I-II-I-A-1-2):

Chemical formula

[0730] In some embodiments, the compound is of formula (I-II-I-A-2-2):

Chemical formula

[0731] In some embodiments, the compound is of formula (I-II-I-A-1-2-a):

Chemical formula

[0732] In some embodiments, the compound is of formula (I-II-I-A-2-2-a):

Chem.

[0733] In some embodiments, the compound is of formula (I-II-I-A-1-2-a*):

Chem.

[0734] In some embodiments, the compound is of formula (I-II-I-A-2-2-a*):

Chem.

[0735] In some embodiments, the compound is of formula (I-II-I-A-1-3):

Chem.

[0736] In some embodiments, the compound is of formula (I-II-I-A-2-3):

Chem.

[0737] In some embodiments, the compound is of formula (I-II-I-A-1-3-a):

Chemical formula

[0738] In some embodiments, the compound is of formula (I-II-I-A-2-3-a):

Chemical formula

[0739] In some embodiments, the compound is of formula (I-II-I-A-1-3-a*):

Chemical formula

[0740] In some embodiments, the compound is of formula (I-II-I-A-2-3-a*):

Chemical formula

[0741] In some embodiments, the compound is of formula (I-II-I-A-1-4):

Chem.

[0742] In some embodiments, the compound is of formula (I-II-I-A-2-4):

Chem.

[0743] In some embodiments, the compound is of formula (I-II-I-A-1-4-a):

Chem.

[0744] In some embodiments, the compound is of formula (I-II-I-A-2-4-a):

Chem.

[0745] In some embodiments, the compound is of formula (I-II-I-A-1-4-a*):

Chem.

[0746] In some embodiments, the compound is of formula (I-II-I-A-2-4-a*):

Chemical formula

[0747] In some embodiments, the compound is of formula (I-II-II-A):

Chemical formula

[0748] In some embodiments, the compound is of formula (I-II-II-A-1):

Chemical formula

[0749] In some embodiments, the compound is of formula (I-II-II-A-2):

Chemical formula

[0750] In some embodiments, the compound is of formula (I-II-II-A-A): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, where x is an integer selected from 0, 1, 2, 3, and 4, and all other variables are as defined herein.

[0751] In some embodiments, the compound is of formula (I-II-II-A-1-1): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, and all variables are as defined herein.

[0752] In some embodiments, the compound is of formula (I-II-II-A-2-1): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, and all variables are as defined herein.

[0753] In some embodiments, the compound is of formula (I-II-II-A-1-1-a): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, and all variables are as defined herein.

[0754] In some embodiments, the compound is of formula (I-II-II-A-2-1-a): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0755] In some embodiments, the compound is of formula (I-II-II-A-1-1-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0756] In some embodiments, the compound is of formula (I-II-II-A-2-1-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0757] In some embodiments, the compound is of formula (I-II-II-A-1-2): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0758] In some embodiments, the compound is of formula (I-II-II-A-2-2): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0759] In some embodiments, the compound is of formula (I-II-II-A-1-2-a):

Chemical formula

[0760] In some embodiments, the compound is of formula (I-II-II-A-2-2-a):

Chemical formula

[0761] In some embodiments, the compound is of formula (I-II-II-A-1-2-a*):

Chemical formula

[0762] In some embodiments, the compound is of formula (I-II-II-A-2-2-a*):

Chemical formula

[0763] In some embodiments, the compound is of formula (I-II-II-A-1-3):

Chemical formula

[0764] In some embodiments, the compound is of formula (I-II-II-A-2-3):

Chem.

[0765] In some embodiments, the compound is of formula (I-II-II-A-1-3-a):

Chem.

[0766] In some embodiments, the compound is of formula (I-II-II-A-2-3-a):

Chem.

[0767] In some embodiments, the compound is of formula (I-II-II-A-1-3-a*):

Chem.

[0768] In some embodiments, the compound is of formula (I-II-II-A-2-3-a*): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0769] In some embodiments, the compound is of formula (I-II-II-A-1-4): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0770] In some embodiments, the compound is of formula (I-II-II-A-2-4): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0771] In some embodiments, the compound is of formula (I-II-II-A-1-4-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0772] In some embodiments, the compound is of formula (I-II-II-A-2-4-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0773] In some embodiments, the compound is of formula (I-II-II-A-1-4-a*):

Chemical formula

[0774] In some embodiments, the compound is of formula (I-II-II-A-2-4-a*):

Chemical formula

[0775] In some embodiments, the compound is of formula (I-I-II-B):

Chemical formula

[0776] In some embodiments, the compound is of formula (I-I-II-B-1):

Chemical formula

[0777] In some embodiments, the compound is of formula (I-I-II-B-2):

Chem.

[0778] In some embodiments, the compound is of formula (I-I-II-B-1-1):

Chem.

[0779] In some embodiments, the compound is of formula (I-I-II-B-2-1):

Chem.

[0780] In some embodiments, the compound is of formula (I-I-II-B-1-1-a):

Chem.

[0781] In some embodiments, the compound is of formula (I-I-II-B-2-1-a):

Chem.

[0782] In some embodiments, the compound is of formula (I-I-II-B-1-1-a*):

Chemical formula

[0783] In some embodiments, the compound is of formula (I-I-II-B-2-1-a*):

Chemical formula

[0784] In some embodiments, the compound is of formula (I-I-II-B-1-2):

Chemical formula

[0785] In some embodiments, the compound is of formula (I-I-II-B-2-2):

Chemical formula

[0786] In some embodiments, the compound is of formula (I-I-II-B-1-2-a):

Chem.

[0787] In some embodiments, the compound is of formula (I-I-II-B-2-2-a):

Chem.

[0788] In some embodiments, the compound is of formula (I-I-II-B-1-2-a*):

Chem.

[0789] In some embodiments, the compound is of formula (I-I-II-B-2-2-a*):

Chem.

[0790] In some embodiments, the compound is of formula (I-I-II-B-1-3):

Chem.

[0791] In some embodiments, the compound is of formula (I-I-II-B-2-3):

Chemical formula

[0792] In some embodiments, the compound is of formula (I-I-II-B-1-3-a):

Chemical formula

[0793] In some embodiments, the compound is of formula (I-I-II-B-2-3-a):

Chemical formula

[0794] In some embodiments, the compound is of formula (I-I-II-B-1-3-a*):

Chemical formula

[0795] In some embodiments, the compound is of formula (I-I-II-B-2-3-a*):

Chem.

[0796] In some embodiments, the compound is of formula (I-I-II-B-1-4):

Chem.

[0797] In some embodiments, the compound is of formula (I-I-II-B-2-4):

Chem.

[0798] In some embodiments, the compound is of formula (I-I-II-B-1-4-a):

Chem.

[0799] In some embodiments, the compound is of formula (I-I-II-B-2-4-a):

Chem.

[0800] In some embodiments, the compound is of formula (I-I-II-B-1-4-a*):

Chemical formula

[0801] In some embodiments, the compound is of formula (I-I-II-B-2-4-a*):

Chemical formula

[0802] In some embodiments, the compound is of formula (I-G-A):

Chemical formula

[0803] In some embodiments, the compound is of formula (I-G-B-G):

Chemical formula

[0804] In some embodiments, the compound is of formula (I-G-B):

Chem.

[0805] In some embodiments, the compound is of formula (I-G-C):

Chem.

[0806] In some embodiments, the compound is of formula (I-A-A-D-G):

Chem.

[0807] In some embodiments, the compound is of formula (I-G-D):

Chem.

[0808] In some embodiments, the compound is of formula (I-G-E):

Chem.

[0809] In some embodiments, the compound is of formula (I-G-F):

Chemical formula

[0810] In some embodiments, the compound is of formula (I-G-G):

Chemical formula

[0811] In some embodiments, the compound is of formula (I-G-H):

Chemical formula

[0812] In some embodiments, the compound is of formula (I-G-J):

Chemical formula

[0813] In some embodiments, the compound is of formula (I-G-K):

Chemical formula

[0814] In some embodiments, the compound is of formula (I-A-A-A):

Chem.

[0815] In some embodiments, the compound is of formula (I-A-A-B-G):

Chem.

[0816] In some embodiments, the compound is of formula (I-A-A-B):

Chem.

[0817] In some embodiments, the compound is of formula (I-A-A-C):

Chem.

[0818] In some embodiments, the compound is of formula (I-A-A-D-G):

Chem.

[0819] In some embodiments, the compound is of formula (I-A-A-D):

Chemical formula

[0820] In some embodiments, the compound is of formula (I-A-A-E):

Chemical formula

[0821] In some embodiments, the compound is of formula (I-A-A-F):

Chemical formula

[0822] In some embodiments, the compound is of formula (I-A-A-G):

Chemical formula

[0823] In some embodiments, the compound is of formula (I-A-A-H):

Chemical formula

[0824] In some embodiments, the compound is of formula (I-A-A-J):

Chemical formula

[0825] In some embodiments, the compound is of formula (I-A-A-K):

Chemical formula

[0826] In some embodiments, the compound is of formula (I-I-II-A-A):

Chemical formula

[0827] In some embodiments, the compound is of formula (I-I-II-A-B-G):

Chemical formula

[0828] In some embodiments, the compound is of formula (I-I-II-A-B-G-1): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein R s is C1-C6 alkyl, which is optionally substituted with one or more halogens.

[0829] In some embodiments, the compound is of formula (I-I-II-A-B-G-2): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein R s is C1-C6 alkyl, which is optionally substituted with one or more halogens.

[0830] In some embodiments, the compound is of formula (I-I-II-A-B-G-3): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein R s is C1-C6 alkyl, which is optionally substituted with one or more halogens.

[0831] In some embodiments, the compound is of formula (I-I-II-A-B-G-4): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein R s is C1-C6 alkyl, which is optionally substituted with one or more halogens.

[0832] In some embodiments, the compound is of formula (I-I-II-A-B-G-5):

Chemical formula

[0833] In some embodiments, the compound is of formula (I-I-II-A-B-G-6):

Chemical formula

[0834] In some embodiments, the compound is of formula (I-I-II-A-B-G-7):

Chemical formula

[0835] In some embodiments, the compound is of formula (I-I-II-A-B-G-8):

Chemical formula

[0836] In some embodiments, the compound is of formula (I-I-II-A-B-1):

Chemical formula

[0837] In some embodiments, the compound is of formula (I-I-II-A-C):

Chemical formula

[0838] In some embodiments, the compound is of formula (I-I-II-A-C-1):

Chemical formula

[0839] In some embodiments, the compound is of formula (I-I-II-A-D-G):

Chemical formula

[0840] In some embodiments, the compound is of formula (I-I-II-A-D-G-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein H contains 1 to 3 heteroatoms selected from O, N, and S, and one or more R 16 is a 5- to 6-membered heteroaryl optionally substituted with.

[0841] In some embodiments, the compound is of formula (I-I-II-A-D): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0842] In some embodiments, the compound is of formula (I-I-II-A-D-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0843] In some embodiments, the compound is of formula (I-I-II-A-E): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0844] In some embodiments, the compound is of formula (I-I-II-A-E-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof.

[0845] In some embodiments, the compound is of formula (I-I-II-A-F):

Chemical formula

[0846] In some embodiments, the compound is of formula (I-I-II-A-F-1):

Chemical formula

[0847] In some embodiments, the compound is of formula (I-I-II-A-G):

Chemical formula

[0848] In some embodiments, the compound is of formula (I-I-II-A-G-1):

Chemical formula

[0849] In some embodiments, the compound is of formula (I-I-II-A-H):

Chemical formula

[0850] In some embodiments, the compound is of formula (I-I-II-A-H-1):

Chemical formula

[0851] In some embodiments, the compound is of formula (I-I-II-A-J):

Chemical formula

[0852] In some embodiments, the compound is of formula (I-I-II-A-J-1):

Chemical formula

[0853] In some embodiments, the compound is of formula (I-I-II-A-K):

Chemical formula

[0854] In some embodiments, the compound is of formula (I-I-II-A-K-1):

Chemical formula

[0855] In some embodiments, the compound of formula (I) is any combination of fragments (1), (2), and (3) shown in Table 1.

[0856] Table 1. List of fragments (1), (2), and (3) that give the structure of the compound of formula (I) by combining any of fragments (1), (2), and (3). JPEG2025520541000547.jpg120170JPEG2025520541000548.jpg232170JPEG2025520541000549.jpg235170JPEG2025520541000550.jpg246170JPEG2025520541000551.jpg221170JPEG2025520541000552.jpg240170JPEG2025520541000553.jpg129170

[0857] In some embodiments, the compound is of formula (II-I):

Chemical formula

[0858] In some embodiments, the compound is of formula (II-II):

Chemical formula

[0859] In some embodiments, the compound is of formula (II-I-I):

Chem.

[0860] In some embodiments, the compound is of formula (II-I-II):

Chem.

[0861] In some embodiments, the compound is of formula (II-II-I):

Chem.

[0862] In some embodiments, the compound is of formula (II-II-II):

Chem.

[0863] In some embodiments, the compound is of formula (II-I-I-A):

Chem.

[0864] In some embodiments, the compound is of formula (II-I-I-B):

Chemical formula

[0865] In some embodiments, the compound is of formula (II-I-II-A):

Chemical formula

[0866] In some embodiments, the compound is of formula (II-I-II-B):

Chemical formula

[0867] In some embodiments, the compound is of formula (II-II-I-A):

Chemical formula

[0868] In some embodiments, the compound is of formula (II-II-I-B): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0869] In some embodiments, the compound is of formula (II-II-II-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0870] In some embodiments, the compound is of formula (II-II-II-B): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0871] In some embodiments, the compound is of formula (II-I-I-A-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0872] In some embodiments, the compound is of formula (II-I-I-B-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, wherein all variables are as defined herein.

[0873] In some embodiments, the compound is of formula (II-I-II-A-1):

Chemical formula

[0874] In some embodiments, the compound is of formula (II-I-II-B-1):

Chemical formula

[0875] In some embodiments, the compound is of formula (II-II-I-A-1):

Chemical formula

[0876] In some embodiments, the compound is of formula (II-II-I-B-1):

Chemical formula

[0877] In some embodiments, the compound is of formula (II-II-II-A-1):

Chem.

[0878] In some embodiments, the compound is of formula (II-II-II-B-1):

Chem.

[0879] In some embodiments, the compound is of formula (II-I-I-A-1-a):

Chem.

[0880] In some embodiments, the compound is of formula (II-I-I-B-1-a):

Chem.

[0881] In some embodiments, the compound is of formula (II-I-II-A-1-a):

Chem.

[0882] In some embodiments, the compound is of formula (II-I-II-B-1-a):

Chemical formula

[0883] In some embodiments, the compound is of formula (II-II-I-A-1-a):

Chemical formula

[0884] In some embodiments, the compound is of formula (II-II-I-B-1-a):

Chemical formula

[0885] In some embodiments, the compound is of formula (II-II-II-A-1-a):

Chemical formula

[0886] In some embodiments, the compound is of formula (II-II-II-B-1-a):

Chemical formula

[0887] In some embodiments, the compound is of formula (II-I-I-A-1-a-I):

Chemical formula

[0888] In some embodiments, the compound is of formula (II-I-I-B-1-a-I):

Chemical formula

[0889] In some embodiments, the compound is of formula (II-I-II-A-1-a-I):

Chemical formula

[0890] In some embodiments, the compound is of formula (II-I-II-B-1-a-I):

Chemical formula

[0891] In some embodiments, the compound is of formula (II-II-I-A-1-a-I):

Chemical formula

[0892] In some embodiments, the compound is of formula (II-II-I-B-1-a-I):

Chemical formula

[0893] In some embodiments, the compound is of formula (II-II-II-A-1-a-I):

Chemical formula

[0894] In some embodiments, the compound is of formula (II-II-II-B-1-a-I):

Chemical formula

[0895] In some embodiments, the compound is of formula (II-I-I-A-1-a-I-A):

Chem.

[0896] In some embodiments, the compound is of formula (II-I-I-B-1-a-I-A):

Chem.

[0897] In some embodiments, the compound is of formula (II-I-II-A-1-a-I-A):

Chem.

[0898] In some embodiments, the compound is of formula (II-I-II-B-1-a-I-A):

Chem.

[0899] In some embodiments, the compound is of formula (II-II-I-A-1-a-I-A):

Chem.

[0900] In some embodiments, the compound is of formula (II-II-I-B-1-a-I-A):

Chem.

[0901] In some embodiments, the compound is of formula (II-II-II-A-1-a-I-A):

Chem.

[0902] In some embodiments, the compound is of formula (II-II-II-B-1-a-I-A):

Chem.

[0903] In some embodiments, the compound is of formula (II-I-I-A-1-a-I-A-1):

Chem.

[0904] In some embodiments, the compound is of formula (II-I-I-B-1-a-I-A-1):

Chemical formula

[0905] In some embodiments, the compound is of formula (II-I-II-A-1-a-I-A-1):

Chemical formula

[0906] In some embodiments, the compound is of formula (II-I-II-B-1-a-I-A-1):

Chemical formula

[0907] In some embodiments, the compound is of formula (II-II-I-A-1-a-I-A-1):

Chemical formula

[0908] In some embodiments, the compound is of formula (II-II-I-B-1-a-I-A-1):

Chemical formula

[0909] In some embodiments, the compound is of formula (II-II-II-A-1-a-I-A-1):

Chem.

[0910] In some embodiments, the compound is of formula (II-II-II-B-1-a-I-A-1):

Chem.

[0911] In some embodiments, the compound is of formula (II-I-I-A-1-a-I-B):

Chem.

[0912] In some embodiments, the compound is of formula (II-I-I-B-1-a-I-B):

Chem.

[0913] In some embodiments, the compound is of formula (II-I-II-A-1-a-I-B):

Chemical formula

[0914] In some embodiments, the compound is of formula (II-I-II-B-1-a-I-B):

Chemical formula

[0915] In some embodiments, the compound is of formula (II-II-I-A-1-a-I-B):

Chemical formula

[0916] In some embodiments, the compound is of formula (II-II-I-B-1-a-I-B): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, K is selected from O, NH, S, y is an integer selected from 0, 1, and 2, and all other variables are as defined herein.

[0917] In some embodiments, the compound is of formula (II-II-II-A-1-a-I-B): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, x is an integer selected from 0, 1, 2, 3, and 4, and all other variables are as defined herein.

[0918] In some embodiments, the compound is of formula (II-II-II-B-1-a-I-B): [Chemistry] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative or tautomer thereof, and all variables are as defined herein.

[0919] In some embodiments, the compound of formula (II) is any combination of fragments (1), (2), and (3) shown in Table 2.

[0920] Table 2. List of fragments (1), (2), and (3) that give the structure of the compound of formula (II) by combining any of fragment (1) with any of fragment (2) and any of fragment (3). JPEG2025520541000616.jpg 237 170 JPEG2025520541000617.jpg 210 170 JPEG2025520541000618.jpg 218 170 JPEG2025520541000619.jpg 230 170 JPEG2025520541000620.jpg 243 170 JPEG2025520541000621.jpg 143 170

[0921] In some embodiments, the compound is of formula (A’):

Chemical formula

Chemical formula

[0922] In some embodiments, the compound is of formula (I’):

Chemical formula

[0923] In some embodiments, the compound is of formula (II’):

Chemical formula

[0924] In some embodiments, the compound is of formula (A’-I):

Chemical formula

[0925] In some embodiments, the compound is of formula (A’-I-a):

Chemical formula

[0926] In some embodiments, the compound is of formula (A’-I-b):

Chemical formula

[0927] In some embodiments, the compound is of formula (A’-I-a-1):

Chemical formula

[0928] In some embodiments, the compound is of formula (A’-I-a-1-A):

Chemical formula

[0929] In some embodiments, the compound is of formula (A’-I-a-1-B):

Chemical formula

[0930] In some embodiments, the compound is of formula (A’-I-a-2):

Chemical formula

[0931] In some embodiments, the compound is of formula (A’-I-a-3):

Chemical formula

[0932] In some embodiments, the compound is of formula (A’-I-a-3-A):

Chemical formula

[0933] In some embodiments, the compound is of formula (A’-I-a-3-B):

Chemical formula

[0934] In some embodiments, the compound is of formula (A’-I-a-4):

Chemical formula

[0935] In some embodiments, the compound is of formula (A’-I-a-4-A):

Chemical formula

[0936] In some embodiments, the compound is of formula (A’-I-a-4-B):

Chemical formula

[0937] In some embodiments, the compound is of formula (A’-I-a-5):

Chemical formula

[0938] In some embodiments, the compound is of formula (A’-I-a-5-A):

Chemical formula

[0939] In some embodiments, the compound is of formula (A’-I-a-5-B):

Chemical formula

[0940] In some embodiments, the compound is of formula (A’-I-a-5-C):

Chemical formula

[0941] In some embodiments, the compound is of formula (A’-I-a-5-D):

Chemical formula

[0942] In some embodiments, the compound is of formula (A’-I-b-1):

Chemical formula

[0943] In some embodiments, the compound is of formula (A’-I-b-1-A):

Chemical formula

[0944] In some embodiments, the compound is of formula (A’-I-b-1-B):

Chemical formula

[0945] In some embodiments, the compound is of formula (A’-I-b-2): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[0946] In some embodiments, the compound is of formula (A’-I-b-3): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, wherein W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0947] In some embodiments, the compound is of formula (A’-I-b-3-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, wherein W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0948] In some embodiments, the compound is of formula (A’-I-b-3-B): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, wherein W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0949] In some embodiments, the compound is of formula (A’-I-b-4): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, wherein W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0950] In some embodiments, the compound is of formula (A’-I-b-4-A):

Chemical formula

[0951] In some embodiments, the compound is of formula (A’-I-b-4-B):

Chemical formula

[0952] In some embodiments, the compound is of formula (A’-I-b-5):

Chemical formula

[0953] In some embodiments, the compound is of formula (A’-I-b-5-A):

Chemical formula

[0954] In some embodiments, the compound is of formula (A’-I-b-5-B):

Chemical formula

[0955] In some embodiments, the compound is of formula (A’-I-b-5-C):

Chemical formula

[0956] In some embodiments, the compound is of formula (A’-I-b-5-D):

Chemical formula

[0957] In some embodiments, the compound is of formula (A’-II):

Chemical formula

[0958] In some embodiments, the compound is of formula (A’-II-a):

Chem.

[0959] In some embodiments, the compound is of formula (A’-II-b):

Chem.

[0960] In some embodiments, the compound is of formula (A’-II-a-1):

Chem.

[0961] In some embodiments, the compound is of formula (A’-II-a-1-A):

Chem.

[0962] In some embodiments, the compound is of formula (A’-II-a-1-B):

Chem.

[0963] In some embodiments, the compound is of formula (A’-II-a-2):

Chemical formula

[0964] In some embodiments, the compound is of formula (A’-II-a-3):

Chemical formula

[0965] In some embodiments, the compound is of formula (A’-II-a-3-A):

Chemical formula

[0966] In some embodiments, the compound is of formula (A’-II-a-3-B):

Chemical formula

[0967] In some embodiments, the compound is of formula (A’-II-a-4): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0968] In some embodiments, the compound is of formula (A’-II-a-4-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0969] In some embodiments, the compound is of formula (A’-II-a-4-B): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0970] In some embodiments, the compound is of formula (A’-II-a-5): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, each U is independently selected from CH and N, at least one U is N, x is an integer selected from 0 to (the number of 4 - N), and all other variables are as defined herein.

[0971] In some embodiments, the compound is of formula (A’-II-a-5-A):

Chem.

[0972] In some embodiments, the compound is of formula (A’-II-a-5-B):

Chem.

[0973] In some embodiments, the compound is of formula (A’-II-a-5-C):

Chem.

[0974] In some embodiments, the compound is of formula (A’-II-a-5-D):

Chem.

[0975] In some embodiments, the compound is of formula (A’-II-b-1):

Chemical formula

[0976] In some embodiments, the compound is of formula (A’-II-b-1-A):

Chemical formula

[0977] In some embodiments, the compound is of formula (A’-II-b-1-B):

Chemical formula

[0978] In some embodiments, the compound is of formula (A’-II-b-2):

Chemical formula

[0979] In some embodiments, the compound is of formula (A’-II-b-3):

Chemical formula

[0980] In some embodiments, the compound is of formula (A’-II-b-3-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0981] In some embodiments, the compound is of formula (A’-II-b-3-B): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0982] In some embodiments, the compound is of formula (A’-II-b-4): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0983] In some embodiments, the compound is of formula (A’-II-b-4-A): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0984] In some embodiments, the compound is of formula (A’-II-b-4-B): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein W is selected from O, NH, S, S(O), S(O)2, and all other variables are as defined herein.

[0985] In some embodiments, the compound is of formula (A’-II-b-5): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, isotope derivative, or tautomer thereof, wherein each U is independently selected from CH and N, at least one U is N, x is an integer selected from 0 to (the number 4 - N), and all other variables are as defined herein.

[0986] In some embodiments, the compound is of formula (A’-II-b-5-A): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, wherein x is an integer selected from 0, 1, 2, and 3, and all other variables are as defined herein.

[0987] In some embodiments, the compound is of formula (A’-II-b-5-B): [Chemical Formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, wherein x is an integer selected from 0, 1, 2, and 3, and all other variables are as defined herein.

[0988] In some embodiments, the compound is of formula (A’-II-b-5-C):

Chem.

[0989] In some embodiments, the compound is of formula (A’-II-b-5-D):

Chem.

[0990] In some embodiments, the compound is of formula (I’-I):

Chem.

[0991] In some embodiments, the compound is of formula (I’-II):

Chem.

[0992] In some embodiments, the compound is of formula (I’-I-a):

Chem.

[0993] In some embodiments, the compound is of formula (I’-I-b):

Chemical formula

[0994] In some embodiments, the compound is of formula (I’-II-a):

Chemical formula

[0995] In some embodiments, the compound is of formula (I’-II-b):

Chemical formula

[0996] In some embodiments, the compound is of formula (II’-I):

Chemical formula

[0997] In some embodiments, the compound is of formula (II’-II):

Chemical formula

[0998] In some embodiments, the compound is of formula (II’-I-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[0999] In some embodiments, the compound is of formula (II’-I-b): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1000] In some embodiments, the compound is of formula (II’-II-a): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1001] In some embodiments, the compound is of formula (II’-II-b): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1002] In some embodiments, the compound is of formula (II’-I-a-1): [Chemical formula] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1003] In some embodiments, the compound is of formula (II’-I-a-2): [Chemical] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1004] In some embodiments, the compound is of formula (II’-I-b-1): [Chemical] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1005] In some embodiments, the compound is of formula (II’-I-b-2): [Chemical] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1006] In some embodiments, the compound is of formula (II’-II-a-1): [Chemical] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1007] In some embodiments, the compound is of formula (II’-II-a-2): [Chemical] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1008] In some embodiments, the compound is of formula (II’-II-b-1): [Chemical] Or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof.

[1009] In some embodiments, the compound is of formula (II’-II-b-2):

Chemical formula

[1010] In some embodiments, the compound of formula (A) is the compound of formula (I).

[1011] In some embodiments, the compound of formula (A) is the compound of formula (II).

[1012] Suitable pharmaceutically acceptable salts of the compounds of the present disclosure are, for example, acid addition salts of the compounds of the present disclosure that are sufficiently basic, for example, acid addition salts with inorganic acids or organic acids, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, formic acid, citric acid, methanesulfonic acid or maleic acid. Further, suitable pharmaceutically acceptable salts of the compounds of the present disclosure that are sufficiently acidic are alkali metal salts, for example sodium or potassium salts, alkaline earth metal salts, for example calcium or magnesium salts, ammonium salts or salts with organic bases that give pharmaceutically acceptable cations, for example salts with methylamine, dimethylamine, diethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxyethyl)amine.

[1013] It will be understood that any one of the compounds of the formulas disclosed herein and any of its pharmaceutically acceptable salts include stereoisomers, mixtures of stereoisomers, and polymorphs of all isomeric forms of said compounds.

[1014] In some embodiments, the compound is selected from the compounds described in Table 3, and pharmaceutically acceptable salts, stereoisomers, solvates, prodrugs, isotope derivatives, or tautomers thereof.

[1015] In some embodiments, the compound is selected from the compounds described in Table 3, as well as prodrugs and pharmaceutically acceptable salts thereof.

[1016] In some embodiments, the compound is selected from the compounds described in Table 3 and pharmaceutically acceptable salts thereof.

[1017] In some embodiments, the compound is selected from prodrugs of the compounds described in Table 3 and pharmaceutically acceptable salts thereof.

[1018] In some embodiments, the compound is selected from the compounds described in Table 3.

[1019] Table 3. Specific examples of compounds of formula (A) JPEG2025520541000712.jpg198170JPEG2025520541000713.jpg218170JPEG2025520541000714.jpg208170JPEG2025520541000715.jpg218170JPEG2025520541000716.jpg218170JPEG2025520541000717.jpg218170JPEG2025520541000718.jpg218170JPEG2025520541000719.jpg208170JPEG2025520541000720.jpg218170JPEG2025520541000721.jpg208170JPEG2025520541000722.jpg218170JPEG2025520541000723.jpg239170JPEG2025520541000724.jpg218170JPEG2025520541000725.jpg218170JPEG2025520541000726.jpg218170JPEG2025520541000727.jpg198170JPEG2025520541000728.jpg208170JPEG2025520541000729.jpg218170JPEG2025520541000730.jpg218170JPEG2025520541000731.jpg218170JPEG2025520541000732.jpg198170JPEG2025520541000733.jpg239170JPEG2025520541000734.jpg208170JPEG2025520541000735.jpg208170JPEG2025520541000736.jpg239170JPEG2025520541000737.jpg239170JPEG2025520541000738.jpg63170

[1020] In some embodiments, the compound is a pharmaceutically acceptable salt of any one of the compounds described in Table 3.

[1021] In some embodiments, the compound is a lithium salt, sodium salt, potassium salt, calcium salt, or magnesium salt of any one of the compounds described in Table 3.

[1022] In some embodiments, the compound is a sodium salt or potassium salt of any one of the compounds described in Table 3.

[1023] In some embodiments, the compound is a salt of any acid described in Table 4 and any one of the compounds described in Table 3.

[1024] Table 4. Compounds of formula (A) form pharmaceutically acceptable acid addition salts. JPEG2025520541000739.jpg209170

[1025] In some embodiments, the compound is a salt of acetic acid and any one of the compounds described in Table 3.

[1026] In some embodiments, the compound is a salt of adipic acid and any one of the compounds described in Table 3.

[1027] In some embodiments, the compound is a salt of ascorbic acid (L) and any one of the compounds described in Table 3.

[1028] In some embodiments, the compound is a salt of hydrobromic acid and any one of the compounds described in Table 3.

[1029] In some embodiments, the compound is a salt of hydrochloric acid and any one of the compounds described in Table 3.

[1030] In some embodiments, the compound is a salt of citric acid and any one of the compounds described in Table 3.

[1031] In some embodiments, the compound is a salt of glutamic acid and any one of the compounds described in Table 3.

[1032] In some embodiments, the compound is a salt of oxalic acid and any one of the compounds described in Table 3.

[1033] In some embodiments, the compound is a salt of formic acid and any one of the compounds described in Table 3.

[1034] In some embodiments, the compound is a salt of sulfuric acid and any one of the compounds described in Table 3.

[1035] In some aspects, the present disclosure provides a compound that is an isotope derivative (e.g., an isotope-labeled compound) of any one of the compounds of the formula disclosed herein.

[1036] In some embodiments, the compound is an isotope derivative of any one of the compounds described in Table 3, as well as its prodrug and pharmaceutically acceptable salts.

[1037] In some embodiments, the compound is an isotope derivative of any one of the compounds described in Table 3 and its pharmaceutically acceptable salts.

[1038] In some embodiments, the compound is an isotope derivative of any one of the prodrugs of the compounds described in Table 3 and its pharmaceutically acceptable salts.

[1039] In some embodiments, the compound is an isotope derivative of any one of the compounds described in Table 3.

[1040] It is understood that the isotope derivatives can be prepared using any of the various techniques recognized in the art. For example, isotope derivatives can generally be prepared by using isotope-labeled reagents instead of non-isotope-labeled reagents and by carrying out the schemes and / or procedures disclosed in the examples described herein.

[1041] In some embodiments, the isotope derivative is a deuterium-labeled compound.

[1042] In some embodiments, the isotope derivative is a deuterium-labeled compound of any one of the compounds of the formulas disclosed herein.

[1043] The term "isotope derivative", as used herein, refers to a derivative of a compound in which one or more atoms are isotopically enriched or labeled. For example, an isotope derivative of a compound of formula (A) is isotopically enriched or labeled with respect to one or more isotopes as compared to the corresponding compound of formula (A). In some embodiments, the isotope derivative is 2 H, 13 C, 14 C, 15 N, 18 O, 29 Si, 31 P, and 34 S. In some embodiments, the isotope derivative is a deuterium-labeled compound (i.e., enriched with 2 H with respect to one or more of its atoms).

[1044] In some embodiments, the compound is a deuterium-labeled compound of any one of the compounds listed in Table 3, as well as prodrugs and pharmaceutically acceptable salts thereof.

[1045] In some embodiments, the compound is a deuterium-labeled compound of any one of the compounds listed in Table 3 and pharmaceutically acceptable salts thereof.

[1046] In some embodiments, the compound is a deuterium-labeled compound of any one of the prodrugs of the compounds listed in Table 3 and pharmaceutically acceptable salts thereof.

[1047] In some embodiments, the compound is a deuterium-labeled compound of any one of the compounds listed in Table 3.

[1048] The deuterium-labeled compound is understood to contain deuterium atoms having an abundance of deuterium that is substantially greater than the natural abundance of deuterium, which is 0.015%.

[1049] In some embodiments, the deuterium-labeled compound has a deuterium enrichment factor of at least 3500 (52.5% deuterium incorporation in each deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium), 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 deuterium atom. As used herein, the term "deuterium enrichment factor" means the ratio of the deuterium abundance to the natural abundance of deuterium.

[1050] It is understood that the deuterium-labeled compound can be prepared using any of a variety of techniques recognized in the art. For example, the deuterium-labeled compound can generally be prepared by using deuterium-labeled reagents instead of non-deuterium-labeled reagents and by carrying out the procedures disclosed in the schemes and / or examples described herein.

[1051] The compounds of the disclosure containing the above deuterium atom(s), or pharmaceutically acceptable salts or solvates thereof, are within the scope of the disclosure. Further, substitution with deuterium (i.e., 2 H) can provide certain therapeutic advantages resulting from greater metabolic stability, such as an increase in in vivo half-life or a decrease in the required dose.

[1052] In some embodiments, the compound is 18 an F-labeled compound.

[1053] In some embodiments, the compound is 33S-labeled compound, 34 S-labeled compound, 35 S-labeled compound, 36 S-labeled compound, or any combination thereof.

[1054] 18 F, 33 S, 34 S, 35 S, and / or 36 It is understood that the S-labeled compound can be prepared using any of the various techniques recognized in the art. For example, a deuterium-labeled compound is generally prepared by performing the procedures disclosed in the schemes and / or examples described herein and using 18 F, 33 S, 34 S, 35 S, and / or 36 S-labeled reagent.

[1055] The above 18 F, 33 S, 34 S, 35 S, and 36 The disclosed compounds containing one or more of the S atom(s), or a pharmaceutically acceptable salt or solvate thereof, are within the scope of the present disclosure. Further, substitution with an isotope (e.g., 18 F, 33 S, 34 S, 35 S and / or 36 S) can provide certain therapeutic advantages resulting from greater metabolic stability, e.g., an increase in in vivo half-life or a decrease in the required dose.

[1056] To avoid doubt, it is understood that when a group is limited by "described herein", the group encompasses the broadest definition at its first occurrence, as well as each and every specific definition of that group.

[1057] The various functional groups and substituents that make up the compound of formula (A) are typically selected such that the molecular weight of the compound does not exceed 1000 Daltons. More usually, the molecular weight of the compound is less than 1000, for example less than 900, or less than 800, or less than 700, or less than 600, or less than 500.

[1058] As used herein, the term "isomerism" means compounds that have the same molecular formula but differ in the order of their atomic bonds or the arrangement of those atoms in space. Isomers that differ in the arrangement of atoms in space are called "stereoisomers". Stereoisomers that are not mirror images of each other are called "diastereoisomers", and stereoisomers that cannot be superimposed on their mirror images are called "enantiomers" or sometimes optical isomers. A mixture containing equal amounts of the individual enantiomeric forms of opposite chirality is designated a "racemic mixture".

[1059] As used herein, the term "chiral center" refers to a carbon atom bonded to four different substituents.

[1060] As used herein, the term "chiral isomer" means a compound having at least one chiral center. Compounds having multiple chiral centers can exist as individual diastereomers or as a mixture of diastereomers called a "mixture of diastereomers". When there is one chiral center, the stereoisomers are characterized by the absolute configuration (R or S) of that chiral center. The absolute configuration refers to the spatial arrangement of the substituents attached to the chiral center. The substituents attached to the chiral center are ranked according to the Cahn, Ingold, and Prelog sequence rules. (Cahn et al., Angew. Chem. Inter. Edit. 1966, 5, 385; errata 511; Cahn et al., Angew. Chem. 1966, 78, 413; Cahn and Ingold, J. Chem. Soc. 1951 (London), 612; Cahn et al., Experientia 1956, 12, 81; Cahn, J. Chem. Educ. 1964, 41, 116).

[1061] As used herein, the term "geometric isomer" means diastereomers that exist due to restricted rotation around a double bond or a cycloalkyl linker (e.g., 1,3-cyclobutyl). These configurations are distinguished by their names with the prefixes cis and trans, or Z and E, indicating that the groups are on the same or opposite sides of the double bond within the molecule according to the Cahn-Ingold-Prelog rules.

[1062] It should be understood that the compounds of the present disclosure can be presented as different chiral isomers or geometric isomers. Also, when a compound has chiral isomer or geometric isomer forms, it is intended that all isomeric forms are included within the scope of the present disclosure, and it is understood that the naming of the compound does not exclude all isomeric forms and that not all isomers have the same level of activity.

[1063] It should be understood that the structures and other compounds discussed in this disclosure include all atropic isomers thereof. It should also be understood that not all atropic isomers have the same level of activity.

[1064] As used herein, the term "atropic isomer" is a type of stereoisomer in which the atoms of two isomers are spatially differently arranged. Atropic isomers exist because the rotation of large groups around the central bond is hindered and the rotation is restricted. Such atropic isomers typically exist as a mixture, but as a result of recent advances in chromatography techniques, it has become possible to separate the mixture of two atropic isomers when selected.

[1065] As used herein, the term "tautomer" is one of two or more structural isomers that exist in equilibrium and are readily convertible from one isomeric form to another. This conversion results in a formal transfer of a hydrogen atom accompanied by the switching of adjacent conjugated double bonds. Tautomers exist as a mixture of tautomers in solution. In a solution where tautomerization is possible, a chemical equilibrium of tautomers is reached. The exact ratio of tautomers depends on several factors such as temperature, solvent, and pH. The concept of tautomers that can be interconverted by tautomerization is called tautomerism. Of the various types of tautomerism possible, two are commonly observed. In keto-enol tautomerism, a simultaneous shift of electrons and hydrogen atoms occurs. Ring-chain tautomerism results from the reaction of the aldehyde group (-CHO) of a sugar molecule with one of the hydroxy groups (-OH) of the same molecule, giving a cyclic (ring-shaped) form as shown by glucose.

[1066] It should be understood that the compounds of the present disclosure may be shown as different tautomers. When a compound has tautomeric forms, it is intended that all tautomeric forms are included within the scope of the present disclosure, and it should also be understood that the naming of the compound does not exclude any tautomeric form. It will be understood that a particular tautomer may have a higher level of activity than other tautomers.

[1067] Compounds that have the same molecular formula but differ in the nature or order of bonding of their atoms, or in the arrangement of those atoms in space, are called "isomers". Isomers that differ in the arrangement of atoms in space are called "stereoisomers". Stereoisomers that are not mirror images of each other are called diastereomers, and stereoisomers that cannot be superimposed on their mirror images are called enantiomers. If a compound has an asymmetric center, for example, if it is bonded to four different groups, a pair of enantiomers may exist. Enantiomers are characterized by the absolute configuration of their asymmetric center and are described by the Cahn and Prelog R- and S-configuration rules, or by the way the molecule rotates the plane of polarization of light, and are called dextrorotatory or levorotatory (i.e., as the (+) or (-)-isomers, respectively). Chiral compounds can exist as either individual enantiomers or mixtures thereof. A mixture containing equal ratios of enantiomers is called a "racemic mixture".

[1068] The compounds of the present disclosure can have one or more asymmetric centers; such compounds can be produced as individual (R)- or (S)-stereoisomers or mixtures thereof. Unless otherwise stated, the description or naming of a particular compound in this specification and the claims is intended to include both the individual enantiomers and mixtures thereof, racemates or other mixtures. Methods for the determination of stereochemistry and the separation of stereoisomers are well known in the art, for example, by synthesis from optically active starting materials or by resolution of racemates (see the discussion in Chapter 4 of “Advanced Organic Chemistry”, 4th edition J. March, John Wiley and Sons, New York, 2001). Some of the compounds of the present disclosure can have geometric isomerism centers (E-isomers and Z-isomers). It should be understood that the present disclosure encompasses all optical isomers, diastereoisomers and geometric isomers having inflammasome inhibitory activity and mixtures thereof.

[1069] The present disclosure also encompasses the disclosed compounds as defined herein, including one or more isotope substitutions.

[1070] It should be understood that any of the compounds of the formulas described herein, where applicable, include the compounds themselves, as well as their salts and their solvates. For example, salts can be formed between an anion on a substituted compound disclosed herein and a positively charged group (e.g., amino). Suitable anions include chloride, bromide, iodide, sulfate, bisulfate, sulfamate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, glutamate, glucuronate, glutarate, malate, maleate, succinate, fumarate, tartrate, tosylate, salicylate, lactate, naphthalenesulfonate, and acetate (e.g., trifluoroacetate).

[1071] As used herein, the term "pharmaceutically acceptable anion" refers to an anion suitable for forming a pharmaceutically acceptable salt. Similarly, salts can also be formed between a cation on a substituted compound disclosed herein and a negatively charged group (e.g., carboxylate). Suitable cations include sodium ion, potassium ion, magnesium ion, calcium ion, and ammonium cations such as tetramethylammonium ion or diethylamine ion. The substituted compounds disclosed herein also include salts containing a quaternary nitrogen atom.

[1072] It should be understood that the compounds of the present disclosure, such as salts of the compounds, can exist in hydrated or non-hydrated (anhydrous) forms, or as solvates with other solvent molecules. Non-limiting examples of hydrates include monohydrates, dihydrates, etc., and non-limiting examples of solvates include ethanol solvates, acetone solvates, etc.

[1073] As used herein, the term "solvate" means a solvate form containing a solvent, either in stoichiometric or non-stoichiometric amounts. Some compounds have a tendency to capture solvent molecules in a certain molar ratio in the crystalline solid state and form solvates. When the solvent is water, the resulting solvate is a hydrate; when the solvent is an alcohol, the resulting solvate is an alcoholate. A hydrate is formed by the combination of one molecule of a substance in which water retains its molecular state as H2O and one or more molecules of water.

[1074] As used herein, the term "analogue" refers to a compound that is structurally similar to another but has a slightly different composition (e.g., substitution of one atom by an atom of a different element, or substitution of one atom in the presence of a particular functional group, or substitution of one functional group by another functional group). Thus, an analogue is a compound that is similar or equivalent in function and appearance but different from the reference compound in structure or origin.

[1075] As used herein, the term "derivative" refers to a compound having a common core structure and substituted with various groups as described herein.

[1076] As used herein, the term "biological equivalent" refers to a compound resulting from the exchange of an atom or group of atoms with another, broadly similar atom or group of atoms. The purpose of a bioequivalent substitution is to produce a new compound having biological properties similar to those of the parent compound. Bioequivalent substitutions can be based on physicochemistry or topology. Examples of carboxylic acid biological equivalents include, but are not limited to, acylsulfonamides, tetrazoles, sulfonates, and phosphonates. See, for example, Patani and LaVoie, Chem. Rev. 96, 3147-3176, 1996.

[1077] It should also be understood that any particular compound of the formulas disclosed herein may exist in solvated and unsolvated forms, such as hydrated forms. Suitable pharmaceutically acceptable solvates are, for example, hydrates such as hemihydrate, monohydrate, dihydrate or trihydrate. It is to be understood that this disclosure encompasses all such solvated forms having inflammasome inhibitory activity.

[1078] Moreover, it should also be understood that any particular compound of the formulas disclosed herein may exhibit polymorphism, and that this disclosure encompasses all such forms or mixtures thereof having inflammasome inhibitory activity. Crystalline materials are generally known to be analyzable using conventional techniques such as X-ray powder diffraction analysis, differential scanning calorimetry, thermogravimetric analysis, diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, near infrared (NIR) spectroscopy, solution and / or solid nuclear magnetic resonance spectroscopy. The water content of such crystalline substances can be measured by Karl Fischer analysis.

[1079] Any compound of the formulas disclosed herein can exist in many different tautomeric forms, and reference to a compound of formula (A) includes all such forms. To avoid doubt, if a compound can exist in one of several tautomeric forms and only one is specifically described or illustrated, nevertheless all others are encompassed by formula (A). Examples of tautomeric forms include, for example, the following tautomeric pairs: keto / enol (shown below), imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enthiole, and keto-, enol-, and enolate-forms such as nitro / acid-nitro.

Chem.

[1080] Any one of the compounds of the formula disclosed herein containing an amine functional group can also form an N-oxide. As used herein, reference to a compound of formula (A) containing an amine functional group also includes the N-oxide. When a compound contains several amine functional groups, one or more nitrogen atoms can be oxidized to form an N-oxide. Specific examples of N-oxides are the N-oxides of tertiary amines or the nitrogen atoms of nitrogen-containing heterocycles. N-oxides can be produced by treating the corresponding amine with an oxidizing agent such as hydrogen peroxide or a peracid (e.g., peroxycarboxylic acid), see, for example, Jerry March, 4th Edition, Wiley Interscience, pages Advanced Organic Chemistry. More specifically, N-oxides can be prepared by the method of L.W. Deady (Syn. Comm. 1977, 7, 509-514), where the amine compound reacts with meta-chloroperoxybenzoic acid (mCPBA) in an inert solvent such as dichloromethane.

[1081] Any one of the compounds of the formula disclosed herein can be administered in the form of a prodrug that is decomposed in the human or animal body to release the disclosed compound. The prodrug can be used to change the physical properties and / or pharmacokinetic properties of the compounds of the present disclosure. When the compounds of the present disclosure contain suitable groups or substituents to which a property-modifying group can be attached, a prodrug can be formed. Examples of prodrugs include derivatives containing an alkyl or acyl substituent cleavable in vivo on any one of the ester or amide groups of the formula disclosed herein.

[1082] Accordingly, the present ...

Claims

1. A compound of formula (A): 【Chemical Formula 1】 or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof. [Wherein,[[]]END]] Each R Ｎ is independently selected from H, C １ -C ６ alkyl, cycloalkyl; Q is CR ５ R Ｑ or NR Ｑ and; R ｑ is H; R Ｑ is R Ｎ or R ｑ and R Ｑ form a bond together; R Ｍ is [Chemical 2] is selected from; M is selected from 5- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, said heterocyclyl or heteroaryl being optionally substituted with one or more R １６ ; R １ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; R ２ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Alternatively, R １ and R ２ are both oxo; Alternatively, R ２ and R ３ form a bond together; R ３ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein said alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; R ４ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Alternatively, R １ and R ４ together with the atoms to which they are attached and any intervening atoms form a 3- to 10-membered cycloalkyl, 6- to 10-membered aryl, 3- to 14-membered heterocycle, or 5- to 6-membered heteroaryl, wherein the cycloalkyl, aryl, heterocycle or heteroaryl is optionally substituted with one or more R １６ ; R ５ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Each R ６ is independently selected from H, C １ -C ６ alkyl, cycloalkyl, -CH ２ -aryl, and the alkyl, cycloalkyl, or aryl is optionally substituted with one or more R １６ ; R ７ is -(CH ２ ) ｎ aryl, and the aryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; R ８ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, C １ -C ６ -alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; Alternatively, R ７ and R ８ together with the atoms to which they are attached and any intervening atoms form a 5- to 7-membered monocyclic or bicyclic heterocyclyl optionally substituted with one or more R １３ ; R ９ 、R １０ 、R １１ are each independently selected from C １ -C ６ -alkyl, cycloalkyl, halogen, -CN; R １２ is selected from R ６ -S(O)-, R ２ -, R ６ -C(O)-, R ６ -O-C(O)-, heteroaryl, wherein said heteroaryl is optionally substituted with one or more R １６ ; Each R １３ is independently selected from halogen, -OH, -CN, -C １ -C ６ alkyl, -C １ -C ６ haloalkyl; Two Rs １３ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; R １４ and R １５ are each independently selected from H, C １ -C ６ alkyl, cycloalkyl; Alternatively, R １４ and R １５ together with the atoms to which they are attached and any intervening atoms form one or more halogens, —OH, —CN, C １ —C ６ heterocyclyl optionally substituted with alkyl; Each R １６ is independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)R １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkoxy, cycloalkyl, heterocyclyl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; or Two Rs １６ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; X is hydrogen, halogen, OH, CN, NO ２ , CONH ２ , C １ -C ６ alkyl, C １ -C ６ alkoxy, C １ -C ６ alkyl-C １ -C ６ alkoxy, C １ -C ６ alkyl-NHC １ -C ６ selected from alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl is optionally substituted with cycloalkyl, heterocyclyl, aryl, and heteroaryl; n is an integer selected from 0, 1 and 2; m is an integer selected from 0 and 1; However, when R ｑ is H, R １ and R ４ together with the atoms to which they are attached and any intervening atoms form a 3- to 10-membered cycloalkyl, 6- to 10-membered aryl, 3- to 14-membered heterocycle, or 5- to 6-membered heteroaryl; Cycloalkyl is a monocyclic or polycyclic saturated carbon ring containing 3 to 18 carbon atoms; Aryl is a cyclic aromatic hydrocarbon group having 1 to 3 aromatic rings; Heterocyclyl is a saturated or partially unsaturated 3- to 10-membered monocyclic, 7- to 12-membered bicyclic (fused ring, bridged ring, or spiro ring), or 11- to 14-membered tricyclic ring system (fused ring, bridged ring, or spiro ring) having one or more heteroatoms selected from O, N, S, P, Se, or B; Heteroaryl is a monovalent monocyclic or polycyclic aromatic radical having 5 to 24 ring atoms containing one or more ring heteroatoms selected from N, O, S, P, or B, and the remaining ring atoms are C.]

2. The compound is of formula (I): 【Chemical Formula 3】 or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, the compound according to claim 1. [Wherein,[[]]END]] Each R Ｎ is independently selected from H, C １ -C ６ alkyl, cycloalkyl; Q is CR ５ R Ｑ or NR Ｑ and; R ｑ is H; R Ｑ is R Ｎ ; or R ｑ and R Ｑ form a bond together; R １ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; R ２ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Alternatively, R １ and R ２ are both oxo; Alternatively, R ２ and R ３ form a double bond together; R ３ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; R ４ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Alternatively, R １ and R ４ together with the atoms to which they are attached and any intervening atoms form a 3- to 10-membered cycloalkyl, 6- to 10-membered aryl, 3- to 14-membered heterocycle, or 5- to 6-membered heteroaryl, wherein the cycloalkyl, aryl, heterocycle or heteroaryl is optionally substituted with one or more R １６ ; R ５ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Each R ６ is independently selected from H, C １ -C ６ alkyl, cycloalkyl, -CH ２ -aryl, and said alkyl, cycloalkyl, or aryl is optionally substituted with one or more R １６ ; R ７ is -(CH ２ ) ｎ aryl, and the aryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; R ８ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, C １ -C ６ -alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; Alternatively, R ７ and R ８ together with the atoms to which they are attached and any intervening atoms form a 5- to 7-membered monocyclic or bicyclic heterocyclyl optionally substituted with one or more R １３ ; R ９ 、R １０ 、R １１ are each independently selected from C １ -C ６ alkyl, cycloalkyl, halogen, -CN; R １２ is selected from R ６ -S(O) ２ -, R ６ -C(O)-, R ６ -O-C(O)-, heteroaryl, wherein the heteroaryl is optionally substituted with one or more R １６ ; Each R １３ is independently selected from halogen, -OH, -CN, -C １ -C ６ alkyl, -C １ -C ６ haloalkyl; Two Rs １３ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; R １４ and R １５ are each independently selected from H, C １ -C ６ alkyl, cycloalkyl; Alternatively R １４ and R １５ together with the atoms to which they are attached and any intervening atoms form one or more halogens, -OH, -CN, C １ -C ６ heterocyclyl optionally substituted with alkyl; Each R １６ is independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)R １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkoxy, cycloalkyl, heterocyclyl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; or Two Rs １６ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; X is hydrogen, halogen, OH, CN, NO ２ , CONH ２ , C １ -C ６ alkyl, C １ -C ６ alkoxy, C １ -C ６ alkyl-C １ -C ６ alkoxy, C １ -C ６ alkyl-NHC １ -C ６ selected from alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl is optionally substituted with cycloalkyl, heterocyclyl, aryl, and heteroaryl; n is an integer selected from 0, 1 and 2.]

3. The compound is of formula (II): 【Chemical Formula 4】 or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, the compound according to claim 1. [Wherein,[[]]END]] Each R Ｎ is independently selected from H, C １ -C ６ alkyl, cycloalkyl; Q is CR ５ R Ｑ or NR Ｑ and; R ｑ is H; R Ｑ is R Ｎ ; or R ｑ and R Ｑ form a bond together; M is selected from 5- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, said heterocyclyl or heteroaryl being optionally substituted with one or more R １６ ; and R １ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; R ２ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Alternatively, R １ and R ２ are both oxo; Alternatively, R ２ and R ３ form a double bond together; R ３ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein said alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; R ４ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Alternatively, R １ and R ４ together with the atoms to which they are attached and any intervening atoms form a 3- to 10-membered cycloalkyl, 6- to 10-membered aryl, 3- to 14-membered heterocycle, or 5- to 6-membered heteroaryl, wherein the cycloalkyl, aryl, heterocycle or heteroaryl is optionally substituted with one or more R １６ ; R ５ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Each R ６ is independently selected from H, C １ -C ６ alkyl, cycloalkyl, -CH ２ -aryl, and the alkyl, cycloalkyl, or aryl is optionally substituted with one or more R １６ ; R ７ is -(CH ２ ) ｎ aryl, and the aryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; R ８ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, C １ -C ６ -alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; Alternatively, R ７ and R ８ together with the atoms to which they are attached and any intervening atoms form a 5- to 7-membered monocyclic or bicyclic heterocyclyl optionally substituted with one or more R １３ ; Each R １３ is independently selected from halogen, -OH, -CN, -C １ -C ６ alkyl, -C １ -C ６ haloalkyl; Two Rs １３ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; R １４ and R １５ are each independently selected from H, C １ -C ６ alkyl, cycloalkyl; Alternatively, R １４ and R １５ together with the atoms to which they are attached and any intervening atoms form one or more halogens, -OH, -CN, C １ -C ６ heterocyclyl optionally substituted with alkyl; Each R １６ is independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)R １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and said alkyl, alkoxy, cycloalkyl, heterocyclyl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; or Two Rs １６ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; X is hydrogen, halogen, OH, CN, NO ２ , CONH ２ , C １ -C ６ alkyl, C １ -C ６ alkoxy, C １ -C ６ alkyl-C １ -C ６ alkoxy, C １ -C ６ alkyl-NHC １ -C ６ selected from alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl is optionally substituted with cycloalkyl, heterocyclyl, aryl, and heteroaryl; m is an integer selected from 0 and 1; n is an integer selected from 0, 1, 2.]

4. The compound is of formula (A'): 【Chemical Formula 5】 or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, the compound according to claim 1. [Wherein,[[]]END]] Each R Ｎ is independently selected from H, C １ -C ６ alkyl, cycloalkyl; Q is CR ５ R Ｑ or NR Ｑ and; R ｑ is H; R Ｑ is R Ｎ or R ｑ and R Ｑ form a bond together; R Ｍ is [[Chemical Formula 6]] is selected from; M is selected from 5- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, said heterocyclyl or heteroaryl being optionally substituted with one or more R １６ ; C is a ring selected from 3- to 10-membered cycloalkyl, 6- to 10-membered aryl, 3- to 14-membered heterocycle, or 5- to 6-membered heteroaryl; R ２ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; R ３ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and said alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Alternatively, R ２ and R ３ form a bond together; R ５ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Each R ６ is independently selected from H, C １ -C ６ alkyl, cycloalkyl, -CH ２ -aryl, and said alkyl, cycloalkyl, or aryl is optionally substituted with one or more R １６ ; R ７ is -(CH ２ ) ｎ aryl, and the aryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; R ８ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, C １ -C ６ -alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; Alternatively, R ７ and R ８ together with the atoms to which they are attached and any intervening atoms form a 5- to 7-membered monocyclic or bicyclic heterocyclyl optionally substituted with one or more R １３ ; R ９ 、R １０ 、R １１ are each independently selected from C １ -C ６ alkyl, cycloalkyl, halogen, -CN; R １２ is selected from R ６ -S(O)- ２ -, R ６ -C(O)-, R ６ -O-C(O)-, heteroaryl, wherein the heteroaryl is optionally substituted with one or more R １６ ; and is optionally substituted with; Each R １３ is independently selected from halogen, -OH, -CN, -C １ -C ６ alkyl, -C １ -C ６ haloalkyl; Two Rs １３ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; R １４ and R １５ are each independently selected from H, C １ -C ６ alkyl, cycloalkyl; Alternatively R １４ and R １５ together with the atoms to which they are attached and any intervening atoms form one or more halogens, -OH, -CN, C １ -C ６ optionally substituted with alkyl to form a heterocyclyl; Each R １６ is independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)R １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkoxy, cycloalkyl, heterocyclyl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; or Two Rs １６ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; X is hydrogen, halogen, OH, CN, NO ２ , CONH ２ , C １ -C ６ alkyl, C １ -C ６ alkoxy, C １ -C ６ alkyl-C １ -C ６ alkoxy, C １ -C ６ alkyl-NHC １ -C ６ selected from alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl is optionally substituted with cycloalkyl, heterocyclyl, aryl, and heteroaryl; n is an integer selected from 0, 1, 2; m is an integer selected from 0 and 1; x is an integer selected from 0, 1, 2, 3, and 4.]

5. The compound is of formula (I') 【Chemical Formula 7】 or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, the compound according to claim 2. [Wherein,[[]]END]] Each R Ｎ is independently selected from H, C １ -C ６ alkyl, cycloalkyl; Q is CR ５ R Ｑ or NR Ｑ and; R ｑ is H; R Ｑ is R Ｎ or R ｑ and R Ｑ form a bond together; C is a ring selected from 3- to 10-membered cycloalkyl, 6- to 10-membered aryl, 3- to 14-membered heterocyclic ring, or 5- to 6-membered heteroaryl; R ２ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; R ３ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, wherein said alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Alternatively, R ２ and R ３ form a double bond together; R ５ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Each R ６ is independently selected from H, C １ -C ６ alkyl, cycloalkyl, -CH ２ -aryl, and the alkyl, cycloalkyl, or aryl is optionally substituted with one or more R １６ ; R ７ is selected from -(CH ２ ) ｎ aryl, and the aryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; R ８ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, C １ -C ６ -alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; Alternatively, R ７ and R ８ together with the atoms to which they are attached and any intervening atoms form a 5- to 7-membered monocyclic or bicyclic heterocyclyl optionally substituted with one or more R １３ ; R ９ 、 R １０ 、 R １１ are each independently selected from C １ -C ６ alkyl, cycloalkyl, halogen, -CN; R １２ is selected from R ６ -S(O)-, R ２ -, R ６ -C(O)-, R ６ -O-C(O)-, heteroaryl, wherein said heteroaryl is optionally substituted with one or more R １６ ; Each R １３ is independently selected from halogen, -OH, -CN, -C １ -C ６ alkyl, -C １ -C ６ haloalkyl; Two Rs １３ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; R １４ and R １５ are each independently selected from H, C １ -C ６ alkyl, cycloalkyl; Alternatively, R １４ and R １５ together with the atoms to which they are attached and any intervening atoms form one or more halogens, —OH, —CN, C １ —C ６ heterocyclyl optionally substituted with alkyl; Each R １６ is independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)R １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkoxy, cycloalkyl, heterocyclyl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; or Two Rs １６ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; X is hydrogen, halogen, OH, CN, NO ２ , CONH ２ , C １ -C ６ alkyl, C １ -C ６ alkoxy, C １ -C ６ alkyl-C １ -C ６ alkoxy, C １ -C ６ alkyl-NHC １ -C ６ selected from alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl is optionally substituted with cycloalkyl, heterocyclyl, aryl, and heteroaryl; n is an integer selected from 0, 1, and 2; x is an integer selected from 0, 1, 2, 3, and 4. ]

6. The compound is of formula (II’): [Chemical Formula 8] or a pharmaceutically acceptable salt, stereoisomer, solvate, prodrug, or tautomer thereof, the compound according to claim 3. [Wherein, Each R Ｎ is independently selected from H, C １ -C ６ alkyl, cycloalkyl; Q is CR ５ R Ｑ or NR Ｑ and; R ｑ is H; R Ｑ is R Ｎ or R ｑ and R Ｑ form a bond together; M is selected from 5- to 10-membered heterocyclyl or 5- to 10-membered heteroaryl, said heterocyclyl or heteroaryl being optionally substituted with one or more R １６ ; C is a ring selected from cycloalkyl, aryl, heterocyclyl or heteroaryl; R ２ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; R ３ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Alternatively, R ２ and R ３ form a bond together; R ５ is selected from hydrogen, halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heterocyclyl, or heteroaryl is optionally substituted with one or more R １６ ; Each R ６ is independently selected from H, C １ -C ６ alkyl, cycloalkyl, -CH ２ -aryl, and said alkyl, cycloalkyl, or aryl is optionally substituted with one or more R １６ ; R ７ is selected from -(CH ２ ) ｎ aryl, and the aryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; R ８ is selected from hydrogen, C １ -C ６ -alkyl, C ２ -C ６ -alkenyl, C ２ -C ６ -alkynyl, C １ -C ６ -alkoxy, cycloalkyl, aryl, heterocyclyl, and heteroaryl; Alternatively, R ７ and R ８ together with the atoms to which they are attached and any intervening atoms form a 5- to 7-membered monocyclic or bicyclic heterocyclyl optionally substituted with one or more R １３ ; Each R １３ is independently selected from halogen, -OH, -CN, -C １ -C ６ alkyl, -C １ -C ６ haloalkyl; Two Rs １３ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; R １４ and R １５ are each independently selected from H, C １ -C ６ alkyl, cycloalkyl; Alternatively R １４ and R １５ together with the atoms to which they are attached and any intervening atoms form one or more halogens, -OH, -CN, C １ -C ６ heterocyclyl optionally substituted with alkyl; Each R １６ is independently selected from halogen, -OH, -CN, -NO ２ , -NR １４ R １５ , C １ -C ６ alkyl, C ２ -C ６ alkenyl, C ２ -C ６ alkynyl, C １ -C ６ alkoxy, -C(O)OR １４ , -C(O)R １４ , -C(O)N-NR １４ R １５ , cycloalkyl, -O-cycloalkyl, aryl, heterocyclyl, and heteroaryl, and the alkyl, alkoxy, cycloalkyl, heterocyclyl, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; or Two Rs １６ together with the atoms to which they are attached and any intervening atoms form a 5- to 8-membered cycloalkyl, 6-membered aryl, 5- to 8-membered heterocycle, or 5- to 6-membered heteroaryl, and the cycloalkyl, aryl, heterocycle, or heteroaryl is optionally substituted with one or more substituents independently selected from halogen, -OH, -CN, C １ -C ６ alkyl, C １ -C ６ haloalkyl; X is hydrogen, halogen, OH, CN, NO ２ , CONH ２ , C １ -C ６ alkyl, C １ -C ６ alkoxy, C １ -C ６ alkyl-C １ -C ６ alkoxy, C １ -C ６ alkyl-NHC １ -C ６ selected from alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl is optionally substituted with cycloalkyl, heterocyclyl, aryl, and heteroaryl; m is an integer selected from 0 and 1; n is an integer selected from 0, 1, and 2; x is an integer selected from 0, 1, 2, 3, and 4. ]

7. The compound is of formula (I-II-III-VI): 【Chemical Formula 9】 or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof, the compound according to claim 5.

8. The compound is of formula (I-II-II-A-A): 【Chemical Formula 10】 or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof, the compound according to claim 5.

9. A compound selected from the following: or a pharmaceutically acceptable salt, stereoisomer, solvate or tautomer thereof.

10. A pharmaceutical composition comprising the compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer or tautomer thereof, and a pharmaceutically acceptable carrier.

11. The pharmaceutical composition according to claim 10, further comprising an additional pharmaceutically active agent.

12. A method for inhibiting the replication of coronavirus, comprising administering the compound according to any one of claims 1 to 9, or the pharmaceutical composition according to any one of claims 10 or 11, to a subject.

13. A method for treating a disease or disorder associated with coronavirus infection, comprising administering the compound according to any one of claims 1 to 9, or the pharmaceutical composition according to any one of claims 10 or 11, to a subject.

14. A method for treating coronavirus infection, comprising administering the compound according to any one of claims 1 to 9, or the pharmaceutical composition according to any one of claims 10 or 11, to a subject in need of treatment.

15. The method according to claim 14, wherein the coronavirus infection is COVID-19.

16. The method according to any one of claims 12 to 15, wherein the subject is a human.

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