TYK2 degrader and its use

Abstract

This invention provides compounds, compositions thereof, and methods of using them. The compounds and pharmaceutically acceptable compositions thereof of the present invention are useful for treating various diseases, disorders, or conditions associated with the regulation of TYK2. Such diseases, disorders, or conditions include those described herein. The compounds provided by the present invention are also useful for the study of TYK2 kinase in biological and pathological phenomena; for the study of intracellular signaling pathways occurring in body tissues; and for the comparative evaluation of novel TYK2 inhibitors or other regulators of kinase, signaling pathways, and cytokine levels in vitro or in vivo.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 497,504 filed on 21 April 2023, U.S. Provisional Patent Application No. 63 / 587,879 filed on 4 October 2023, U.S. Provisional Patent Application No. 63 / 596,205 filed on 3 November 2023, and U.S. Provisional Patent Application No. 63 / 617,188 filed on 3 January 2024 (the contents of which are incorporated herein by reference).

[0002] The present invention relates to compounds and methods useful for modulating tyrosine kinase 2 ("TYK2") protein by ubiquitination and / or degradation by compounds according to the present invention. The present invention also provides pharmaceutically acceptable compositions comprising the compounds of the present invention and methods for using said compositions in the treatment of various disorders. [Background technology]

[0003] The ubiquitin-proteasome pathway (UPP) or ubiquitin-proteasome system (UPS) is a crucial pathway that regulates key regulatory proteins and degrades misfolded or abnormal proteins. The UPP is central to multiple cellular processes, and deficiencies or imbalances can lead to the development of various diseases. The covalent binding of ubiquitin to specific protein substrates is activated through the action of E3 ubiquitin ligases.

[0004] UPPs are used to induce selective proteolysis, including the use of fusion proteins to artificially ubiquitinize target proteins and synthetic small molecule probes to induce proteasome-dependent degradation. Bifunctional compounds consist of a target protein-binding ligand and an E3 ubiquitin ligase ligand, inducing proteasome-mediated degradation of selected proteins via their recruitment to the E3 ubiquitin ligase, followed by ubiquitination. These drug-like molecules offer the potential for temporal control over protein expression. Such compounds can induce inactivation of proteins of interest upon addition to cells or administration to animals or humans, making them useful as biochemical reagents and potentially leading to a new paradigm for disease treatment by eliminating pathogenic or oncogenic proteins (Crews C, Chemistry & Biology, 2010, 17(6):551-555; Schnnekloth JS Jr., Chembiochem, 2005, 6(l):40-46).

[0005] TYK2 is an enzyme encoded by the human TYK2 gene and is a member of the Janus kinase (JAK) family of proteins. TYK2 is involved in IL-12, IL-23, and type I interferon (IFN) signaling (Morris R, et al., Protein Science, Volume: 27, Issue: 12, Pages: 1984-2009, 2018). Human genetic studies suggest that TYK2 inhibition may be broadly beneficial in treating autoimmune and inflammatory diseases (Dendrou C, et al., Science Translational Medicine, Vol 8, Issue 363, p. 363ra149 2016). There is a continuing need in the art for effective treatments of diseases mediated by pro-inflammatory molecules such as IFN-α / β, IL-12, and IL-23, particularly autoimmune and inflammatory diseases and disorders, that do not involve JAK1 / 2 inhibition that can cause on-target adverse events. Therefore, small molecule therapeutics that utilize E3 ligase-mediated proteolysis of pro-inflammatory-related proteins such as tyrosine kinase 2 (TYK2) while potentially preserving molecules such as IL-10 and IL-22, which are involved in wound healing and protection against microorganisms, are promising as therapeutic agents for conditions such as Crohn's disease and ulcerative colitis. Thus, the discovery of compounds that are useful TYK2 degraders as therapeutic agents remains necessary. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Crews C,Chemistry & Biology,2010,17(6):551-555 [Non-Patent Document 2] Schnnekloth JS Jr.,Chembiochem,2005,6(l):40-46 [Non-Patent Document 3] Morris R,et al.,Protein Science,Volume:27,Issue:12,Pages:1984-2009,2018 [Non-Patent Document 4] Dendrou C, et al.,Science Translational Medicine,Vol 8,Issue 363,p.363ra149 2016 [Overview of the project] [Means for solving the problem]

[0007] This study found that the heterobifunctional compounds and pharmaceutically acceptable compositions thereof of the present invention are effective in degrading TYK2. In certain embodiments, the present invention provides compounds of the formulas presented herein.

[0008] The compounds and pharmaceutically acceptable compositions thereof of the present invention are useful for treating various diseases, disorders, or conditions associated with the adjustment of TYK2. Such diseases, disorders, or conditions include those described herein.

[0009] The compounds provided by the present invention are also useful for studying TYK2 kinase in biological and pathological phenomena; studying intracellular signaling pathways occurring in body tissues; and for comparative evaluation of novel TYK2 inhibitors or other regulators of kinases, signaling pathways, and cytokine levels in vitro or in vivo. [Modes for carrying out the invention]

[0010] 1. General description of specific embodiments of the present invention: In a particular embodiment, the present invention relates to one compound of any of the following formulas: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each variable element is as defined and described herein, both individually and in combination.

[0011] In some embodiments, the present invention provides pharmaceutical compositions comprising a compound of formula Ia, Ic, or Ic, and a pharmaceutically acceptable carrier, adjuvant, or diluent.

[0012] In some embodiments, the present invention provides a method for treating a TYK2-mediated disease, disorder, or condition, comprising administering a compound of formula -a, Ic, or Ic, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof to a patient in need.

[0013] 2. Compounds and Definitions: The compounds of the present invention generally include those described herein, and are further illustrated by the classes, subclasses, and species disclosed herein. Where used herein, unless otherwise indicated, the following definitions shall apply. For the purposes of the present invention, Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75 th The chemical elements are identified according to Ed. Furthermore, the general principles of organic chemistry are incorporated herein by reference in their entirety by “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999 and “March's Advanced Organic Chemistry”, 5 th This information is found in Ed., Ed.: Smith, MB and March, J., John Wiley & Sons, New York: 2001.

[0014] The terms “aliphatic” or “aliphatic group,” as used herein, mean a linear (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is fully saturated or contains one or more unsaturated units, or a monocyclic, bicyclic, bridging bicyclic or spirocyclic hydrocarbon that is fully saturated or contains one or more unsaturated units but is not aromatic (also referred herein as “carbocyclic,” “alicyclic,” or “cycloalkyl”), and has a single linkage point to the rest of the molecule. Unless otherwise specified, an aliphatic group contains 1 to 6 aliphatic carbon atoms. In some embodiments, an aliphatic group contains 1 to 5 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1 to 4 aliphatic carbon atoms. In yet another embodiment, an aliphatic group contains 1 to 3 aliphatic carbon atoms, and in yet another embodiment, an aliphatic group contains 1 to 2 aliphatic carbon atoms. In some embodiments, “alicyclic” (or “carbocyclic” or “cycloalkyl”) refers to a monocyclic C3-C6 hydrocarbon that is fully saturated or contains one or more unsaturated units, is not aromatic, and has one linkage point with the rest of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups and their hybrids, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

[0015] As used herein, the term "bridged bicyclic" refers to any bicyclic ring system having at least one bridge, i.e., a carbocyclic or heterocyclic ring, saturated or partially unsaturated. As defined by IUPAC, a "bridge" is an unbranched chain of multiple or one atom or monovalent bond connecting two bridgeheads, and a "bridgehead" is any skeletal atom of a ring system that is bonded to three or more skeletal atoms (excluding hydrogen). In some embodiments, the bridged bicyclic group has 7 to 12 ring members and 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include the groups shown below, wherein each group is linked to the remainder of the molecule by any substitutable carbon or nitrogen atom. Unless otherwise specified, the bridged bicyclic group is optionally substituted with one or more substituents as shown for aliphatic groups. Additionally or alternatively, any substitutable nitrogen of the bridged bicyclic group is optionally substituted.

[0016] The term "alkyl" refers to a C 1-12 straight or branched saturated aliphatic group. In certain examples, alkyl is a C 1-8 straight or branched saturated aliphatic group, or a C 1-6 straight or branched saturated aliphatic group. The term "lower alkyl" refers to a C 1-4 straight or branched alkyl group. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl (also referred to interchangeably herein as iPr, i Pr, and i-Pr), butyl, isobutyl (also referred to interchangeably herein as iBu, i Bu, and i-Bu), and tert-butyl (also referred to interchangeably herein as tBu, t Bu, and t-Bu).

[0017] The term "alkenyl" refers to a C 2-12 straight or branched partially unsaturated aliphatic group containing at least one unsaturated carbon-carbon double bond. In certain examples, "alkenyl" refers to a C 2-8 or C 1-6This refers to a linear or branched partial unsaturated aliphatic group. The term "lower alkenyl" refers to a group containing at least one unsaturated carbon-carbon double bond. 2-4 This refers to linear or branched partially unsaturated aliphatic groups. Alkenyl groups include both cis (Z) and trans (E) positional isomers. Exemplary lower alkenyl groups are vinyl, allyl, 2-propenyl, and butenyl isomers (-CH2CH2CH=CH2, -CH2CH=CHCH3, and -CH=CH=CH2CH3).

[0018] The term "alkynyl" refers to a C2-12 linear or branched partially unsaturated aliphatic group containing at least one unsaturated carbon-carbon triple bond. In certain examples, "alkynyl" refers to a C2-8 or C1-6 linear or branched partially unsaturated aliphatic group containing at least one unsaturated carbon-carbon triple bond. The term "lower alkynyl" refers to a C2-4 linear or branched partially unsaturated aliphatic group containing at least one unsaturated carbon-carbon triple bond. Exemplary lower alkynyl groups are ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, and 3-butynyl.

[0019] The term "haloalkyl" refers to a linear or branched alkyl group substituted with one or more halogen atoms. The term "lower haloalkyl" refers to a C group substituted with one or more halogen atoms. 1-4 This refers to linear or branched alkyl groups.

[0020] The term "heteroatom" refers to one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (any oxidation form of nitrogen, sulfur, phosphorus, or silicon; any quaternation form of any basic nitrogen or; a substituteable nitrogen in a heterocycle, e.g., N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or NR) + This means (including those found in N-substituted pyrrolidinyls).

[0021] When used herein, the term "unsaturated" means that a part has one or more unsaturated units.

[0022] When used herein, "divalent C" 1-8 (or C 1-6 The term "saturated or unsaturated, linear or branched, hydrocarbon chain" refers to a divalent alkylene, alkenylene, and alkynylene chain that is linear or branched as defined herein.

[0023] The term "alkylene" refers to a divalent alkyl group. An "alkylene chain" is a polymethylene group, i.e., -(CH2) n - where n is a positive integer, preferably 1-6, 1-4, 1-3, 1-2, or 2-3. The substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms are replaced by substituents. Suitable substituents for the substituted aliphatic group are listed below.

[0024] The term "alkenylene" refers to a divalent alkenyl group. A substituted alkenylene chain is a polymethylene group containing at least one double bond in which one or more hydrogen atoms are replaced by substituents. Suitable substituents for the substituted aliphatic group are listed below.

[0025] As used herein, the term "cyclopropyrenyl" refers to the following structure: [ka] This refers to the divalent cyclopropyl group.

[0026] The term "halogen" refers to F, Cl, Br, or I.

[0027] The term “aryl,” used alone or as part of a larger phrase such as “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to a monocyclic or bicyclic ring system having a total of 5 to 14 ring members, wherein at least one ring in the system is aromatic, and each ring in the system contains 3 to 7 ring members. The term “aryl” may be used interchangeably with the term “aryl ring.” In particular embodiments of the present invention, “aryl” refers to an aromatic ring system, including but not limited to phenyl, biphenyl, naphthyl, anthranyl, and which may have one or more substituents. As used herein, groups in which an aromatic ring is condensed to one or more non-aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenantridinyl, or tetrahydronaphthyl, also fall within the scope of the term “aryl.”

[0028] When used alone or as part of a larger part, e.g., "heteroaryl" or "heteroal-", "heteroaryl-" refers to a group having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 π electrons shared in a cyclic array; or having 1 to 5 heteroatoms in addition to carbon atoms. The term "heteroatom" refers to nitrogen, oxygen, or sulfur, and includes all oxidation forms of nitrogen or sulfur and all quaternization forms of basic nitrogen. Examples of heteroaryl groups include, but are not limited to, pyrazinyl, pyrazolyl, pyridadinyl, pyridyl, pyrimidinyl, triazinyl, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl (i.e., 1,2,3-triazolyl), 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, indolidinyl, prinyl, naphthilidinyl, and pteridinyl. The terms "heteroaryl" and "hetero-" as used herein also include groups in which an aromatic heterocycle is condensed with one or more aryl, alicyclic, or heterocyclyl rings, and the radical or linkage is located on the aromatic heterocycle.Non-limiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, indolidinyl, isoindolin-1-only, 1,2-dihydro-3H-pyrrolo[3,4-c]pyridine-3-onyl, 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-1-onyl, imidazo[1,2-a]pyridyl, imidazo[1,5-a]pyridyl, and pyrazolo[1,5-a]pyridyl. Examples include pyrrolo[1,2-b]pyridazinyl, pyrrolo[1,2-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, imidazo[1,2-a]pyrimidinyl, benzimidazolyl, benzothiazolyl, quinolyl, isoquinolyl, cinolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolidinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxadinyl, tetrahydroquinolinyl, and tetrahydroisoquinolinyl. The heteroaryl group may be monocyclic, bicyclic, or tricyclic. The heteroaryl ring may contain one or more oxo (=O) or thioxo (=S) substituents. The term "heteroaryl" can be used interchangeably with the terms "heteroaryl ring," "heteroaryl group," or "aromatic heterocycle," any of which may include a ring that is optionally substituted. The term "heteroaralkyl" refers to an alkyl group that is substituted with a heteroaryl group, where the alkyl and heteroaryl moieties are optionally substituted independently.

[0029] As used herein, the terms “heterocyclic,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic” are interchangeable and refer to a stable 5-7 member monocyclic or 7-10 member bicyclic heterocyclic moiety that is either saturated or partially unsaturated and has one or more, preferably 1-4, heteroatoms in addition to the carbon atoms, as defined above. When used in reference to the ring atoms of a heterocyclic ring, the term “nitrogen” includes the substituted nitrogen. For example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur, or nitrogen, nitrogen may be N(3,4-dihydro-2H-pyrrolyl), NH(pyrrolidinyl), or+ It may be NR (in the case of N-substituted pyrrolidinyl).

[0030] The heterocycle may be linked to its pendant group by any heteroatom or carbon atom that can produce a stable structure, and any of the ring atoms may be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, but are not limited to, oxetanyl, azetidinyl, tetrahydrofuranyl, tetrahydrothiophenylpyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, 2-oxa-6-azaspiro[3.3]heptane, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical” are used interchangeably herein and include groups to which a heterocyclyl ring is condensed with one or more aryl, heteroaryl, or alicyclic rings, such as indolinyl, 3H-indolyl, chromanyl, phenantridinyl, or tetrahydroquinolinyl. The heterocyclyl group may be monocyclic, bicyclic, bridging bicyclic, spirocyclic, or a mixture thereof. The heterocycle may contain one or more oxo (=O) or thioxo (=S) substituents. The term “heterocyclylalkyl” refers to an alkyl group substituted with a heterocyclyl, where the alkyl and heterocyclyl moieties are independently and optionally substituted.

[0031] As used herein, the term “partially unsaturated” refers to a ring moiety containing at least one double or triple bond. As defined herein, the term “partially unsaturated” is intended to encompass rings having multiple unsaturated moies, but not to include aryl or heteroaryl moies.

[0032] As described herein, the compounds of the present invention may contain “optionally substituted” moieties. Generally, the term “substituted” means that one or more hydrogens of a given moiety are replaced with suitable substituents. Unless otherwise specified, an “optionally substituted” group may have suitable substituents at each substituted position of the group, and if multiple positions in a given structure can be replaced with multiple substituents selected from a given group, the substituents may be the same or different at all positions. The substituent combinations envisioned by the present invention preferably result in the formation of stable or chemically feasible compounds. The term “stable,” as used herein, means a compound that is substantially unchanged when subjected to conditions that enable their production, detection, and, in particular embodiments, their recovery, purification, and use for one or more purposes disclosed herein.

[0033] A suitable monovalent substituent on the replaceable carbon atom of the "optionally substituted" group is, independently, a halogen;-(CH2) 0-4 R°;-(CH2) 0-4 OR°;-O(CH2) 0-4 R o -O-(CH2) 0-4 C(O)OR°;-(CH2) 0-4 CH(OR°)2;-(CH2) 0-4 SR°;R° can be substituted -(CH2) 0-4 (CH2) can be substituted with Ph;R°. 0-4 O(CH2) 0-1 Can be substituted with Ph;R° -CH=CHPh;R° -(CH2) 0-4 O(CH2) 0-1 -Pyridyl;-NO2;-CN;-N3;-(CH2) 0-4 N(R°)2;-(CH2) 0-4 N(R°)C(O)R°;-N(R°)C(S)R°;-(CH2) 0-4 N(R°)C(O)NR°2;-N(R°)C(S)NR°2;-(CH2) 0-4N(R°)C(O)OR°;-N(R°)N(R°)C(O)R°;-N(R°)N(R°)C(O)NR°2;-N(R°)N(R°)C(O)OR°;-(CH2) 0-4 C(O)R°;-C(S)R°;-(CH2) 0-4 C(O)OR°;-(CH2) 0-4 C(O)SR°;-(CH2) 0-4 C(O)OSiR°3;-(CH2) 0-4 OC(O)R°;-OC(O)(CH2) 0-4 SR°;-(CH2) 0-4 SC(O)R°;-(CH2) 0-4 C(O)NR°2;-C(S)NR°2;-C(S)SR°;-SC(S)SR°,-(CH2) 0-4 OC(O)NR°2;-C(O)N(OR°)R°;-C(O)C(O)R°;-C(O)CH2C(O)R°;-C(NOR°)R°;-(CH2) 0-4 SSR°;-(CH2) 0-4 S(O)2R°;-(CH2) 0-4 S(O)2OR°;-(CH2) 0-4 OS(O)2R°;-S(O)2NR°2;-(CH2) 0-4 S(O)R°;-N(R°)S(O)2NR°2;-N(R°)S(O)2R°;-N(OR°)R°;-C(NH)NR°2;-(CH2) 0-4 P(O)2R°;-(CH2) 0-4 P(O)R°2;-(CH2) 0-4 P(O)(OR°)2;-(CH2) 0-4 OP(O)R°2;-(CH2) 0-4 OP(O)(OR°)2;SiR°3;-(C 1-4 Linear or branched alkylene) ON(R°)2; or -(C 1-4 The linear or branched alkylene is C(O)ON(R°)2, where each R° may be substituted as defined below, independently of hydrogen and C. 1-6 Aliphatic, -CH2Ph, -O(CH2) 0-1Ph, -CH2- (a 5-6 membered heteroaryl ring), or a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the foregoing, two independent occurrences of R° together with their intervening atoms to form a 3-12 membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.

[0034] A suitable monovalent substituent on R° (or the ring formed by two independent occurrences of R° and their intervening atoms) is, independently, a halogen, -(CH2) 0-2 R ● ,-(HaroR ● ), -(CH2) 0-2 OH, -(CH 2 ) 0-2 Ure ● ,-(CH2) 0-2 CH(OR ● )2, -O(HaroR ● ), -CN, -N3, -(CH2) 0-2 C(O)R ● ,-(CH2) 0-2 C(O)OH, -(CH2) 0-2 C(O)OR ● ,-(CH2) 0-2 SR ● ,-(CH2) 0-2 SH, -(CH2) 0-2 NH2, -(CH2) 0-2 NHR ● ,-(CH2) 0-2 NR ● 2, -NO2, -SiR ● 3. -OSiR ● 3, -C(O)SR ● ,-(C 1-4 Linear or branched alkylene)C(O)OR λ , or -SSR λ And here, each R λ It is either unsubstituted, or if preceded by "halo", it is substituted with only one or more halogens, C 1-4Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or independently selected from 0 to 4 heteroatoms selected from nitrogen, oxygen or sulfur, and independently selected from 5- to 6-membered saturated, partially unsaturated or aryl rings. Suitable divalent substituents on the saturated carbon atoms of R° include =O and =S.

[0035] Suitable divalent substituents on the saturated carbon atoms of the "optionally substituted" group are as follows: =O, =S, =NNR * 2, =NNHC(O)R * , =NNHC(O)OR * , =NNHS(O)2R * , =NR * , =NOR * , -O(C(R * 2)) 2-3 O- or -S(C(R * 2)) 2-3 S-, where each independent occurrence of R * is hydrogen, C 1-6 aliphatic which may be substituted as defined below, or selected from unsubstituted 5- to 6-membered saturated, partially unsaturated or aryl rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur. Suitable divalent substituents bonded to the adjacent replaceable carbon of the "optionally substituted" group include the following: -O(CR * 2) 2-3 O- (where each independent occurrence of R * is hydrogen, C 1-6 aliphatic or selected from unsubstituted 5- to 6-membered saturated, partially unsaturated or aryl rings having 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur).

[0036] R * Suitable substituents on the aliphatic group of are halogen, -R ● , -(haloR ● ), -OH, -OR ● , -O(haloR ● ), -CN, -C(O)OH, -C(O)OR ● , -NH2, -NHR● , -NR ● 2 or -NO2 are mentioned, where each R ● If it is unsubstituted, or if "halo" comes first, it is substituted by only one or more halogens, independently, C 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 The pH is a 5-6 member saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0037] Suitable substituents on the substituted nitrogen of the "optionally substituted" group include -R † , -NR † 2, -C(O)R † , -C(O)OR † ,-C(O)C(O)R † -C(O)CH2C(O)R † -S(O)2R † -S(O)2NR † 2, -C(S)NR † 2, -C(NH)NR † 2 or -N(R † )S(O)2R † These are listed; here, each R † Hydrogen and C are independent of each other. 1-6 Aliphatic (which may be substituted as defined below), unsubstituted -OPh, or an unsubstituted 5-6 member saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or notwithstanding the above definition, R † The two independent occurrences of these atoms, together with their intervening atoms, form an unsubstituted 3-12 member saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0038] R † Suitable substituents on the aliphatic group are, independently, halogens, -R ● ,-(HaroR ● ), -OH, -OR ● ,-O(HaroR ● ), -CN, -C(O)OH, -C(O)OR● -NH2, -NHR ● , -NR ● It is 2 or -NO2, where each R ● If it is unsubstituted, or if "halo" precedes it, it is substituted by only one or more halogens, and independently C 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 The pH is a 5-6 member saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0039] Unless otherwise specified, the structures shown herein refer to all isomers of the structure (e.g., enantiomers, diastereomers, and geometric (or stereostructural) forms); for example, the R and S stereoconfigurations for each chiral center, the Z and E double bond isomers, and the Z and E stereostructural isomers, and R a (or M) and S a This also means including (or P) atrop isomers. Therefore, single stereochemical isomers of the compound, as well as enantiomers, diastereomers, and geometric (or stereostructural) mixtures, are within the scope of the present invention. Unless otherwise specified, all tautomeric forms of the compounds of the present invention are within the scope of the present invention. Furthermore, unless otherwise specified, structures shown herein also mean compounds that differ only in the presence of one or more isotopically enriched atoms. For example, the substitution of hydrogen with deuterium or tritium or 13 C- or 14 Compounds having this structure, including carbon substitution with carbon-rich carbon, fall within the scope of the present invention. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents according to the present invention.

[0040] As used herein, the term “inhibitoryly active metabolite or its residue” means that the metabolite or its residue is also an inhibitor or variant of TYK2.

[0041] As used herein, the term “degradably active metabolite or its residue” means that the metabolite or its residue is also a degrader or variant of TYK2.

[0042] As used herein, the term “inhibitor” is defined as a compound that binds to and / or inhibits TYK2 having a measurable affinity. In certain embodiments, the inhibitor is an IC2 with an IC2 of less than about 50 μM, less than about 1 μM, less than about 500 nM, less than about 100 nM, less than about 10 nM, or less than about 1 nM. 50 It has and / or coupling constants.

[0043] As used herein, the term “degrader” is defined as a heterobifunctional compound that binds to and / or inhibits both TYK2 and E3 ligase with a measurable affinity that causes ubiquitination and subsequent degradation of TYK2. In certain embodiments, the degrader is a DC compound with a concentration of less than about 50 μM, less than about 1 μM, less than about 500 nM, less than about 100 nM, less than about 10 nM, or less than about 1 nM. 50 It holds.

[0044] When used herein, the terms “measurable affinity” and “measurable inhibition” mean a measurable change in TYK2 activity between a sample containing the compound or composition thereof and TYK2 of the present invention and an equivalent sample containing TYK2 in the absence of the compound or composition thereof.

[0045] As used herein, the term “patient” refers to an animal, preferably a mammal, most preferably a human.

[0046] As used herein, the term “pharmaceutically acceptable salt” refers to a salt that is within the bounds of sound medical judgment, free from unwanted toxicity, irritation, or allergic reactions, suitable for use in contact with human and lower animal tissues, and balanced by a reasonable benefit-risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, SMBerge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the present invention include those derived from appropriate inorganic and organic acids and bases. Examples of pharmaceutically acceptable, non-toxic acid addition salts are salts of amino groups formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or by other methods used in the art, such as ion exchange. Other pharmaceutically acceptable salts include adipine, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptone, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, and 2-hydroxyethane. Examples include sulfonates, lactobionates, lactates, laurates, lauryl sulfates, malic acid, maleates, malons, methanesulfonates, 2-naphthalenesulfonates, nicotinates, nitrates, oleic acid, oxalates, palmitates, pamoates, pectins, persulfates, 3-phenylpropionates, phosphates, pivalates, propions, stearates, succinates, sulfates, tartrates, thiocyanates, p-toluenesulfonates, undecanoates, and valersates.

[0047] Suitable base-derived salts include alkali metals, alkaline earth metals, ammonium, and N + (C 1-4Examples include alkyl)4 salts. Typical alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, and magnesium. Further pharmaceutically acceptable salts include, where appropriate, non-toxic ammonium, quaternary ammonium, and amine cations, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates formed using counterions such as halides. In some embodiments, the compounds provided are purified in salt form, for convenience and / or ease of purification, for example, using an acidic or basic mobile phase in chromatography. The salt forms of the compounds provided formed during chromatographic purification are intended herein and will be readily apparent to those skilled in the art.

[0048] As used herein, the term “pharmaceutically acceptable carrier, adjuvant, or vehicle” refers to a non-toxic carrier, adjuvant, or vehicle that does not impair the pharmacological activity of the compounds formulated together. Examples of pharmaceutically acceptable carriers, adjuvants, or vehicles that may be used in the compositions of the present invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffering substances such as phosphates, glycine, sorbic acid, potassium sorbate, partially glyceride mixtures of saturated vegetable fatty acids, water, salts, or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylate, wax, polyethylene-polyoxypropylene-block polymer, polyethylene glycol, and lanolin.

[0049] As used herein, “pharmaceutically acceptable derivative” means any non-toxic salt, ester, ester salt or other derivative of the compound of the present invention that, upon administration to a recipient, can directly or indirectly provide the compound of the present invention or a metabolite or residue thereof that is inhibitory or degradatively active.

[0050] As used herein, the term “Provided Compounds” refers to any genus, subgenus, and / or species shown herein.

[0051] 3. Description of a typical embodiment: As described above, in certain embodiments, the present invention relates to a compound of formula Ia: [ka] Or provide a pharmaceutically acceptable salt thereof, here, X is a divalent moiety selected from -CH2- or -C(O)-; X 1 Covalent bond, [ka] , or optionally substituted rings selected from 4-6 member saturated carbocycllenyl or heterocycllenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, phenylenyl, 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-8 member saturated bridged bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; X 2 is a covalent bond, -O-, or -NR-; Y is either N or CH; Y 1 is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Z 1 and Z 2 Independently, is either N or C, where Z 1 and Z2 One of them is N, and Z 1 and Z 2 The other is C; each [ka] These are, independently, single or double bonds; Ring A is phenylenyl, pyridinyl, [ka] It is a ring selected from; Ring B is a fused ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring C is a 9-10 member saturated or partially unsaturated bicyclic heterocyclinyl having 1-3 heteroatoms independently selected from phenylenyl, pyridylenyl, nitrogen, oxygen, and sulfur; an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 12-15 member saturated or partially unsaturated tricyclic spirocyclic heterocyclinyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R a These are hydrogen, halogen, -CN, -OR, oxo, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms a These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; R b is hydrogen, or: R b R 1 It binds to the nitrogen that is bonded, R 1It forms an optionally substituted 5-6 membered partially unsaturated or aromatic heterocycle having 0-2 heteroatoms selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom to which it is bonded; R 1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 It is a cycloalkyl; Each R 2 and R 5 These are independently hydrogen, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)2, - OP(O)(OR)NR2, -OP(O)(NR2)2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)P(O)R2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -N(R)P(O)(NR2)2, -N(R)S(O)2R, or R A and; m and n are independently 0, 1, 2, 3, or 4; R 3 is hydrogen, or halogen, -CN, C 1-6 Alkyl, C 1-6 C is optionally substituted with 1-2 substituents selected from haloalkyl and -OR. 1-6 Alkyl or C 3-6 It is a cycloalkyl; R 3 and R 5 This refers to divalent saturated or partially unsaturated linear or branched carbon atoms. 3-6 Linked by hydrocarbon chains, where 0-2 methylene units in the chain are independently -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-; R 4 Hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, -OC 1-6Alkyl, or -OC 1-6 It is a haloalkyl; L is a covalent bond, -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C 1-10 It is a hydrocarbon chain, where 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, and -C(O)-; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroaryrenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroaryrenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C 1-6 A group that is optionally substituted, selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings having 1-2 heteroatoms, or heterocycles and 5-6 member heteroaryl rings having 1-4 heteroatoms, or: Two R groups on the same carbon or nitrogen atom may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring, having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R A Independently, C 1-6 The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0052] As described above, in certain embodiments, the present invention relates to compounds of formula I-a': [ka] Or provide a pharmaceutically acceptable salt thereof, here, X is a divalent moiety selected from -CH2- or -C(O)-; X 1 Covalent bond, [ka] , or optionally substituted rings selected from 4-6 member saturated carbocyclilenyl or heterocyclilenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, phenylenyl, 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-8 member saturated bridged bicyclic carbocyclilenyl or heterocyclilenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; X 2 is a covalent bond, -O-, or -NR-; Y is either N or CH; Y 1 is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Z 1 and Z 2 Independently, is either N or C, where Z 1 and Z 2 One of them is N, and Z 1 and Z 2 The other is C; each [ka] These are, independently, single or double bonds; Ring A is phenylenyl, pyridinyl, [ka] It is a ring selected from; Ring B is a fused ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring C is a 9-10 member saturated or partially unsaturated bicyclic heterocyclinyl having 1-3 heteroatoms independently selected from phenylenyl, pyridylenyl, nitrogen, oxygen, and sulfur; an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 12-15 member saturated or partially unsaturated tricyclic spirocyclic heterocyclinyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R a These are hydrogen, halogen, -CN, -OR, oxo, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms a These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; R b is hydrogen, or: R b R 1 It binds to the nitrogen that is bonded, R 1 It forms an optionally substituted 5-6 membered partially unsaturated or aromatic heterocycle having 0-2 heteroatoms selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom to which it is bonded; R 1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 It is a cycloalkyl; Each R 2 and R 5 These are independently hydrogen, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)2, - OP(O)(OR)NR2, -OP(O)(NR2)2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)P(O)R2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -N(R)P(O)(NR2)2, -N(R)S(O)2R, or R A and; m and n are independently 0, 1, 2, 3, or 4; R 3 is hydrogen, or halogen, -CN, C 1-6 Alkyl, C 1-6 C 1-6 A 3- to 9-membered saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring having 0-3 heteroatoms independently selected from alkyl, nitrogen, oxygen, and sulfur; R 3 and R 5 This refers to divalent saturated or partially unsaturated linear or branched carbon atoms. 3-6Linked by hydrocarbon chains, where 0-2 methylene units in the chain are independently -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-; R 4 Hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl, or -OC 1-6 It is a haloalkyl; L is a covalent bond, -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C 1-10 It is a hydrocarbon chain, where 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, and -C(O)-; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroaryrenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroaryrenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C 1-6A optionally substituted group selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings, heterocycles, and 5-6 member heteroaryl rings having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same carbon or nitrogen atom may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring, having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R A Independently, C 1-6 The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0053] As described above, in certain embodiments, the present invention relates to compounds of formula I-a'': [ka] Or provide a pharmaceutically acceptable salt thereof, here, X is a divalent moiety selected from -CH2- or -C(O)-; X 1 Covalent bond, [ka] , or optionally substituted rings selected from 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic or spirocyclic carbocycllenyl or heterocyclenyl having 1-2 heteroatoms independently selected from phenylenyl, nitrogen, oxygen and sulfur, and 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur; X2 The bond is covalent, -CR2-, -O-, or -NR-; Y is either N or CH; Y 1 is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Z 1 , Z 2 , Z 4 , and Z 6 Independently, is either N or C, where Z 1 and Z 2 One of them is N, and Z 1 and Z 2 The other is C; Z 3 is N, O, or S; Z 5 is N or CR b and; each [ka] These are, independently, single or double bonds; Ring A is phenylenyl, naphthalenyl, pyridinyl, 4-7 member saturated or partially unsaturated carbocycllenyl, 4-7 member saturated or partially unsaturated heterocyclenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5-6 member heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 8-10 member bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 8-15 member saturated or partially unsaturated tricyclic heterocyclenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 8-15 member tricyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring C is an 8-15 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, spirocyclic, or tricyclic carbocyclinyl or heterocyclinyl having 1-3 heteroatoms independently selected from phenylenyl, pyridylenyl, nitrogen, oxygen, and sulfur, or an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R a These are hydrogen, halogen, -CN, -OR, oxo, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms a These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; R b is hydrogen, or: R b R 1 It binds to the nitrogen that is bonded, R 1 It forms an optionally substituted 5-6 membered partially unsaturated or aromatic heterocycle having 0-2 heteroatoms selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom to which it is bonded; R 1a R 1 NHR 1 , OR 1 , or SR 1 and; R 1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl, or C 1-6 Alkyl-OC 1-6 It is alkyl; Each R 2 and R 5These are independently hydrogen, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)2, -O P(O)(OR)NR2, -OP(O)(NR2)2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N (R)P(O)R2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -N(R)P(O)(NR2)2, -N(R)S(O)2R, or R A is; or: Two R's of ring A 2 The groups, together with their interfacing atoms, form optionally substituted rings selected from 3-10 member saturated or partially unsaturated carbocyclyl or heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; benzo; or 5-10 member heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; m and n are independently 0, 1, 2, 3, or 4; R 3 is either hydrogen or C 1-6 An optionally substituted group selected from 3-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic or spirocyclic carbocyclinyl or heterocyclinyl having 1-3 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and 5-10 member monocyclic or bicyclic heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: R 3 and R 5 This refers to divalent saturated or partially unsaturated linear or branched carbon atoms. 3-6 Linked by hydrocarbon chains, where 0-2 methylene units in the chain are independently -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-; R 4 Hydrogen, halogen, C1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl, or -OC 1-6 It is a haloalkyl; L is a covalent bond, -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C 1-10 A hydrocarbon chain in which 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, -C(O)-, or S(O)2; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroaryrenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroaryrenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C 1-6 A optionally substituted group selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings, heterocycles, and 5-6 member heteroaryl rings having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same carbon or nitrogen atom may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring, having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R A Independently, C 1-6 The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0054] In certain embodiments, the present invention relates to compounds of formula Ib: [ka] Or provide a pharmaceutically acceptable salt thereof, here, X is a divalent moiety selected from -CH2- or -C(O)-; X 2 and X 3 These are independently covalent, -O-, or -NR-; Y is either N or CH; Y 1 is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Ring A is phenylenyl, pyridinyl, [ka] It is a ring selected from; Ring B is a fused ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring D is a divalent ring selected from a 4-7 member saturated or partially unsaturated carbocyclenyl or heterocyclenyl ring having 1-2 heteroatoms independently selected from phenylenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroarylenyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring E is a divalent ring selected from a 4-7 member saturated or partially unsaturated carbocycllenyl or heterocyclenyl having 1-2 heteroatoms independently selected from phenylenyl, naphthylenyl, nitrogen, oxygen, and sulfur; a 5-6 member heteroaryrenyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 9-10 member saturated or partially unsaturated bicyclic heterocyclenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and an 8-10 member bicyclic heteroaryrenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring F is a 4-7 member saturated or partially unsaturated carbocyclyl or heterocyclyl having 1-2 heteroatoms independently selected from phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R a These are hydrogen, halogen, -CN, -OR, oxo, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms a These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; Each R 2 , R 5 , R 6 , and R 7These are independently hydrogen, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)2, - OP(O)(OR)NR2, -OP(O)(NR2)2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)P(O)R2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -N(R)P(O)(NR2)2, -N(R)S(O)2R, or R A and; Each of m, n, o, and p is independently 0, 1, 2, 3, or 4; R 4 Hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl, or -OC 1-6 It is a haloalkyl; L is a covalent bond, -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C 1-10 It is a hydrocarbon chain, where 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, and -C(O)-; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroaryrenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroaryrenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C 1-6 A optionally substituted group selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings, heterocycles, and 5-6 member heteroaryl rings having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same carbon or nitrogen atom may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring, having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R A Independently, C 1-6 The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0055] In certain embodiments, the present invention relates to compounds of formula Ic: [ka] Or provide a pharmaceutically acceptable salt thereof, here, X is a divalent moiety selected from -CH2- or -C(O)-; X 1 Covalent bond, [ka] , or optionally substituted rings selected from 4-6 member saturated carbocycllenyl or heterocycllenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, phenylenyl, 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-8 member saturated bridged bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Y is either N or CH; Y 1 is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Z 1 and Z 2 Independently, is either N or C, where Z 1 and Z 2 One of them is N, and Z 1 and Z 2 The other is C; each [ka] These are, independently, single or double bonds; Ring A is phenylenyl, pyridinyl, [ka] It is a ring selected from; Ring B is a fused ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring F is a 4-7 member saturated or partially unsaturated carbocyclyl or heterocyclyl having 1-2 heteroatoms independently selected from phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R a These are hydrogen, halogen, -CN, -OR, oxo, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms a These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; Each R 2 , R 5 , and R 6 These are independently hydrogen, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)2, -O P(O)(OR)NR2, -OP(O)(NR2)2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N (R)P(O)R2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -N(R)P(O)(NR2)2, -N(R)S(O)2R, or R A is or: Two Rs on adjacent atoms 6These link together to form an optionally substituted condensed 5-6 member partially saturated or aromatic heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; Each of m, n, and o is independently 0, 1, 2, 3, or 4; R 4 Hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl, or -OC 1-6 It is a haloalkyl; L is a covalent bond, -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C 1-10 It is a hydrocarbon chain, where 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, and -C(O)-; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroaryrenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroaryrenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C 1-6A optionally substituted group selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings, heterocycles, and 5-6 member heteroaryl rings having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same carbon or nitrogen atom may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring, having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R A Independently, C 1-6 The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0056] As defined herein and as described above, X is a divalent moiety selected from -CH2- or -C(O)-.

[0057] In some embodiments, X is -CH2-. In some embodiments, X is -C(O)-.

[0058] In some embodiments, X is as shown in the compounds in Table 1 below.

[0059] As defined herein and as described above, X 1 Covalent bond, [ka] or optionally substituted rings selected from phenylenyl, nitrogen, oxygen, and sulfur, or 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocycllenyl or heterocyclenyl having 1-2 heteroatoms independently selected from phenylenyl, nitrogen, oxygen, and sulfur, and 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0060] In some embodiments, X 1 X is an optionally substituted 5-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclirenyl. In some embodiments, X 1 X is an optionally substituted 5-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, X 1 This is an optionally substituted 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0061] In some embodiments, X 1 is an optionally substituted 5- to 8-membered saturated monocyclic or bridged bicyclic carbocyclirenyl. In some embodiments, X 1 is an optionally substituted 5-6 member saturated monocyclic carbocyclinyl. In some embodiments, X 1 This is an optionally substituted 7-8 member saturated crosslinked bicyclic carbocyclilenyl.

[0062] In some embodiments, X 1 X is an optionally substituted 5-8 member saturated monocyclic or bridging bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, X 1X is an optionally substituted 5-6 member saturated monocyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, X 1 This is an optionally substituted 6-8 member saturated bridged bicyclic heterocyclinyl having 1-2 heteroatoms independently selected from nitrogen and oxygen.

[0063] In some embodiments, X 1 X is an optionally substituted 9-11 member saturated spirocyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, X 1 This is an optionally substituted 9-11 member saturated spirocyclic heterocyclinyl having two nitrogen atoms.

[0064] As defined herein and as described above, X 1 Covalent bond, [ka] The rings are optionally substituted, selected from: 4-6 member saturated carbocyclilenyl or heterocyclilenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; phenylenyl; 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and 5-8 member saturated bridged bicyclic carbocyclilenyl or heterocyclilenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0065] In some embodiments, X 1 It is a covalent bond. In some embodiments, X 1 teeth, [ka] In some embodiments, X 1 is an optionally substituted 4- to 6-membered saturated carbocyclinyl. In some embodiments, X1 X is an optionally substituted 4-6 member saturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, X 1 is an optionally substituted phenylenyl. In some embodiments, X 1 X is an optionally substituted 5-6 member heteroaryrenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, X 1 is an optionally substituted 5- to 8-membered saturated crosslinked bicyclic carbocyclinyl. In some embodiments, X 1 This is an optionally substituted 5-8 member saturated bridged bicyclic heterocyclinyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0066] In some embodiments, X 1 X is an optionally substituted 6-membered heteroaryrenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, X 1 This is an optionally substituted 8-membered saturated bridged bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0067] In some embodiments, X 1 is non-substitutable. In some embodiments, X 1 is replaced. In some embodiments, X 1 is halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl, or -OC 1-6 It is substituted with a haloalkyl. In some embodiments, X 1 It is substituted with fluoro, chloro, or methyl.

[0068] In some embodiments, X 1 teeth, [ka] And here, each R ab These are, independently, halogen or C 1-3 It is an alkyl group; f is an integer between 0 and 2. In some embodiments, each R ab is a halogen. In some embodiments, each R ab f is fluoro. In some embodiments, f is 1. In some embodiments, f is 2. In some embodiments, f is 0.

[0069] In some embodiments, X 1 teeth, [ka] And here, R ab is halogen or C 1-3 It is alkyl. In some embodiments, R ab is a halogen. In some embodiments, R ab It is fluoro.

[0070] In some embodiments, X 1 These are 5-6 member heterocyclenyl having one or two ring nitrogens, 4-6 member saturated carbocyclenyl, 5-6 member heteroaryrenyl having one or two ring nitrogens, or 5-8 member saturated bridged bicyclic heterocyclenyl having one or two ring nitrogens, where each of the 5- or 6-member heterocyclenyl, 4-6 member saturated carbocyclenyl, 5- or 6-member heteroaryrenyl, and 5-8 member saturated bridged bicyclic heterocyclenyl is optionally substituted with one or two halogens.

[0071] In some embodiments, X 1 is a 5- to 6-membered heterocyclenyl having one or two ring nitrogens, where each 5 or 6-membered heterocyclenyl is optionally substituted with one or two appearing halogens. In some embodiments, X 1This is a 5- to 6-membered heteroaryrenyl having one or two ring nitrogens, where each 5 or 6-membered heteroaryrenyl is optionally substituted with one or two appearing halogens.

[0072] In some embodiments, X 1 Covalent bond, [ka] That is the case.

[0073] In some embodiments, X 1 These are as shown in the compounds in Table 1 below.

[0074] As defined herein and as described above, X 2 The bond is covalent, -CR2-, -O-, or -NR-.

[0075] In some embodiments, X 2 It is a covalent bond. In some embodiments, X 2 is -CR2-. In some embodiments, X 2 is -O-. In some embodiments, X 2 It is -NR-.

[0076] In some embodiments, X 2 is -NH-. In some embodiments, X 2 It is -CH2-.

[0077] As defined herein and as described above, X 3 The bond is covalent, -O-, or -NR-.

[0078] In some embodiments, X 3 It is a covalent bond. In some embodiments, X 3 is -O-. In some embodiments, X 3 It is -NR-.

[0079] In some embodiments, X 3 It is -NH-.

[0080] In some embodiments, X 2 It is -NH- and X 3 is -NH-. In some embodiments, X 2 It is -NH- and X 3 This is a covalent bond.

[0081] In some embodiments, X 2 and X 3 These are as shown in the compounds in Table 1 below.

[0082] As defined herein and as described above, Y is N or CH.

[0083] In some embodiments, Y is N. In some embodiments, Y is CH.

[0084] In some embodiments, Y is as shown in the compounds in Table 1 below.

[0085] As defined herein and as described above, Y 1 The bond is covalent, -O-, -S-, -NR-, or -C(O)NR-.

[0086] In some embodiments, Y 1 It is a covalent bond. In some embodiments, Y 1 is -O-. In some embodiments, Y 1 is -S-. In some embodiments, Y 1 is -NR-. In some embodiments, Y 1 It is -C(O)NR-.

[0087] In some embodiments, Y 1 is -NH-. In some embodiments, Y 1 It is -C(O)NH-.

[0088] In some embodiments, Y 1 The bond is covalent, -O-, -NR-, -S-, -CR2-, -NRC(O)-, or -C(O)NR-. In some embodiments, Y 1 is -O-, -NR-, -S-, -CR2-, -NRC(O)-, or -C(O)NR-. In some embodiments, Y 1 is -CR2-. In some embodiments, Y 1 is -CH2-. In some embodiments, Y 1 It is -NHC(O)-.

[0089] In some embodiments, Y 1 These are as shown in the compounds in Table 1 below.

[0090] As defined herein and as described above, R a These are hydrogen, halogen, -CN, -OR, oxo, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 It is either cycloalkyl, or has two R atoms on the same carbon atom or adjacent carbon atoms. a These link together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur.

[0091] In some embodiments, R a is hydrogen. In some embodiments, R a is a halogen. In some embodiments, R a is -CN. In some embodiments, R a is -OR. In some embodiments, R a is an oxo. In some embodiments, R a C 1-6 It is alkyl. In some embodiments, R a C 1-6 In some embodiments, R a C 3-6It is cycloalkyl. In some embodiments, two R atoms are located on the same carbon atom or adjacent carbon atoms. a These link together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, two R atoms on the same carbon atom a This forms geminal dimethyl. In some embodiments, two R on the same carbon atom a This forms a geminal difluoro. In some embodiments, two R on the same carbon atom a This forms cyclopropylene. In some embodiments, two R atoms on adjacent carbon atoms a This forms a condensed cyclopropyl. In some embodiments, two R atoms on adjacent carbon atoms a This forms a crosslinked methylene group (i.e., -CH2-). In some embodiments, two R groups on adjacent carbon atoms a This forms cross-linked ethylene (i.e., -CH2CH2-).

[0092] In some embodiments, R a These are as shown in the compounds in Table 1 below.

[0093] As defined herein and as described above, a is 0, 1, or 2.

[0094] In some embodiments, a is 0. In some embodiments, a is 1. In some embodiments, a is 2.

[0095] In some embodiments, a is as shown in the compounds in Table 1 below.

[0096] In some embodiments, [ka] teeth, [ka] That is the case.

[0097] As defined herein and as described above, Z 1 , Z 2 , Z 4 , and Z 6 Independently, is either N or C, where Z 1 and Z 2 One of them is N, and Z 1 and Z 2 The other is C.

[0098] As defined herein and as described above, Z 1 and Z 2 Independently, is either N or C, where Z 1 and Z 2 One of them is N, and Z 1 and Z 2 The other is C.

[0099] In some embodiments, Z 1 In some embodiments, Z 1 In some embodiments, Z 2 In some embodiments, Z 2 is C

[0100] In some embodiments, Z 1 C is Z 2 In some embodiments, Z 1 is N, and Z 2 It is C.

[0101] In some embodiments, Z 4 In some embodiments, Z 4 It is C.

[0102] In some embodiments, Z 6 In some embodiments, Z 6 It is C.

[0103] As defined herein and as described above, Z 3 It is N, O, or S.

[0104] In some embodiments, Z 3 In some embodiments, Z 3 In some embodiments, Z 3 S is.

[0105] As defined herein and as described above, Z 5 is N or CR b That is the case.

[0106] In some embodiments, Z 5 In some embodiments, Z 5 CR b That is the case.

[0107] In some embodiments, [ka] teeth, [ka] That is the case.

[0108] In some embodiments, Z 1 , Z 2 , Z 3 , Z 4 , Z 5 and Z 6 These are as shown in the compounds in Table 1 below.

[0109] As set forth herein and as described above, each [ka] These are, independently, single or double bonds.

[0110] In some embodiments, [ka] It is a single bond. In some embodiments, [ka] It is a double bond.

[0111] In some embodiments, [ka] These are as shown in the compounds in Table 1 below.

[0112] As set forth above and as described herein, ring A is phenylenyl, naphthalenyl, pyridinyl, 4-7 member saturated or partially unsaturated carbocycllenyl, 4-7 member saturated or partially unsaturated heterocyclenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 5-6 member heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 8-10 member bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, 8-15 member saturated or partially unsaturated tricyclic heterocyclenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 8-15 member tricyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0113] In some embodiments, ring A is phenylenyl. In some embodiments, ring A is naphthalenyl. In some embodiments, ring A is pyridinyl. In some embodiments, ring A is a 4-7 member saturated or partially unsaturated carbocycllenyl. In some embodiments, ring A is a 4-7 member saturated or partially unsaturated heterocyclenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an 8-10 member saturated or partially unsaturated bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 5-6 member heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an 8-10 member bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an 8-15 member saturated or partially unsaturated tricyclic heterocyclelenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an 8-15 member tricyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0114] In some embodiments, ring A is a 9-10 member saturated or partially unsaturated monocyclic or bicyclic heterocyclenyl or heteroarylenyl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0115] In some embodiments, ring A is an 8-10 member saturated or partially unsaturated bicyclic heterocyclenyl or heteroarylenyl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 9-10 member saturated or partially unsaturated bicyclic heterocyclenyl or heteroarylenyl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0116] In some embodiments, ring A is a nine-membered saturated or partially unsaturated bicyclic heterocyclenyl or heteroarylenyl containing one to four heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a nine-membered saturated or partially unsaturated bicyclic heterocyclenyl or heteroarylenyl containing one nitrogen and one oxygen heteroatom.

[0117] In some embodiments, ring A is a saturated or partially unsaturated 5,6-condensed bicyclic heterocyclenyl or heteroaryrenyl containing 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a saturated or partially unsaturated 5,6-condensed bicyclic heterocyclenyl or heteroaryrenyl containing one nitrogen and one oxygen heteroatom.

[0118] In some embodiments, ring A is a five-membered heteroarylenyl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a five-membered heteroarylenyl having 1 to 4 heteroatoms and a nitrogen heteroatom. In some embodiments, ring A is a five-membered heteroarylenyl having 1 to 2 heteroatoms and a nitrogen heteroatom. In some embodiments, ring A is a five-membered heteroarylenyl having 1 nitrogen heteroatom and 1 oxygen heteroatom. In some embodiments, ring A is a five-membered heteroarylenyl having 1 nitrogen heteroatom and 1 sulfur heteroatom. In some embodiments, ring A is pyrrolyl, pyrazolyl, imidazolyl, triazolyl, or tetrazolyl. In some embodiments, ring A is pyrrolyl. In some embodiments, ring A is pyrazolyl. In some embodiments, ring A is imidazolyl. In some embodiments, ring A is triazolyl. In some embodiments, ring A is tetrazolyl. In some embodiments, ring A is furanyl, oxazolyl, isoxazolyl, or oxadiazolyl. In some embodiments, ring A is furanyl. In some embodiments, ring A is oxazolyl. In some embodiments, ring A is isoxazolyl. In some embodiments, ring A is oxadiazolyl. In some embodiments, ring A is thiophenyl, thiazolyl, isothiazolyl, or thiadiazolyl. In some embodiments, ring A is thiophenyl. In some embodiments, ring A is thiazolyl. In some embodiments, ring A is isothiazolyl. In some embodiments, ring A is thiadiazolyl.

[0119] In some embodiments, ring A is a six-membered heteroaryrenyl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a six-membered heteroaryrenyl having 1 to 4 heteroatoms and a nitrogen heteroatom. In some embodiments, ring A is a six-membered heteroaryrenyl having 1 to 3 heteroatoms and a nitrogen heteroatom. In some embodiments, ring A is a pyridinyl, pyrimidinyl, or triazinyl. In some embodiments, ring A is a pyrimidinyl. In some embodiments, ring A is a triazinyl.

[0120] In some embodiments, ring A is a 4-membered saturated or partially unsaturated heterocycline having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 7-membered saturated or partially unsaturated heterocycline having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0121] In some embodiments, ring A is a 5-membered saturated or partially unsaturated heterocyclyl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is pyrrolidinyl, pyrrolidinyl, pyrazolidinyl, pyrazolinyl, imidazolidinyl, or imidazolinyl. In some embodiments, ring A is pyrrolidinyl. In some embodiments, ring A is pyrrolidinyl. In some embodiments, ring A is pyrazolidinyl. In some embodiments, ring A is pyrazolinyl. In some embodiments, ring A is imidazolidinyl. In some embodiments, ring A is imidazolinyl. In some embodiments, ring A is tetrahydrofuranyl, 1,3-dioxolanyl, tetrahydrothiophenyl, 1,2-oxathiolanyl, or 1,3-oxathiolanyl. In some embodiments, ring A is tetrahydrofuranyl. In some embodiments, ring A is 1,3-dioxolanyl. In some embodiments, ring A is tetrahydrothiophenyl. In some embodiments, ring A is 1,2-oxathiolanyl. In some embodiments, ring A is 1,3-oxathiolanyl.

[0122] In some embodiments, ring A is a 6-membered saturated or partially unsaturated heterocyclyl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is piperidinyl, piperazinyl, tetrahydropyranyl, 2H-pyranyl, 4H-pyranyl, 1,4-dioxanyl, 1,4-dioxynyl, thianyl, 2H-thiopyranyl, 4H-thiopyranyl, 1,3-ditanium, 1,4-ditanium, morpholinyl, or thiomorpholinyl. In some embodiments, ring A is piperidinyl. In some embodiments, ring A is piperazinyl. In some embodiments, ring A is tetrahydropyranyl. In some embodiments, ring A is 2H-pyranyl. In some embodiments, ring A is 4H-pyranyl. In some embodiments, ring A is 1,4-dioxanyl. In some embodiments, ring A is 1,4-dioxynyl. In some embodiments, ring A is thianyl. In some embodiments, ring A is 2H-thiopyranyl. In some embodiments, ring A is 4H-thiopyranyl. In some embodiments, ring A is 1,3-ditanyl. In some embodiments, ring A is 1,4-ditanyl. In some embodiments, ring A is morpholinyl. In some embodiments, ring A is thiomorpholinyl. In some embodiments, ring A is pyrimidonyl or pyridadinol. In some embodiments, ring A is pyrimidonyl. In some embodiments, ring A is pyridadinol.

[0123] In some embodiments, ring A is not phthalimide.

[0124] In some embodiments, ring A is [ka] or a pharmaceutically acceptable salt thereof, where each R 2 , Ring B, X A , and m are as defined above and described herein, either individually or in combination; XA It is CR2, NR, O, or S; Z A It is O, S, or NR.

[0125] As set forth above and as described herein, Z A is O, S, or NR. In some embodiments, Z A In some embodiments, Z A In some embodiments, Z A It is NR.

[0126] As set forth above and as described herein, X A is CR2, NR, O, or S. In some embodiments, X A This is CR2. In some embodiments, X A is NR. In some embodiments, X A In some embodiments, X A S is.

[0127] In some embodiments, ring A is [ka] or a pharmaceutically acceptable salt thereof, where each R 2 Rings B and m are as defined above and described herein, either individually or in combination; X B CR 2 Or it is N.

[0128] As set forth above and as described herein, X B CR 2 Or N. In some embodiments, X B CR 2 In some embodiments, X B It is N.

[0129] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] That is the case.

[0130] As defined herein and as described above, ring A is phenylenyl, naphthyrenyl, pyridinyl [ka] It is a ring selected from.

[0131] In some embodiments, ring A is phenylenyl. In some embodiments, ring A is pyridinyl. In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] That is the case.

[0132] In some embodiments, ring A is [ka] [ka] That is the case.

[0133] In some embodiments, ring A is [ka] [ka] That is the case.

[0134] In some embodiments, ring A is [ka] That is the case.

[0135] In some embodiments, ring A is a 10-15 member saturated or partially unsaturated tricyclic heterocyclenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0136] In some embodiments, ring A is a 12-membered saturated or partially unsaturated tricyclic heterocyclenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 12-membered saturated or partially unsaturated tricyclic heterocyclenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a 12-membered saturated or partially unsaturated tricyclic heterocyclenyl having 3 nitrogen heteroatoms.

[0137] In some embodiments, ring A is a saturated or partially unsaturated 5,6,5-condensed tricyclic heterocyclenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a saturated or partially unsaturated 5,6,5-condensed tricyclic heterocyclenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a saturated or partially unsaturated 5,6,5-condensed tricyclic heterocyclenyl having 3 nitrogen heteroatoms.

[0138] In some embodiments, ring A is a saturated or partially unsaturated 5,5,6-condensed tricyclic heterocyclenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a saturated or partially unsaturated 5,5,6-condensed tricyclic heterocyclenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a saturated or partially unsaturated 5,5,6-condensed tricyclic heterocyclenyl having 3 nitrogen heteroatoms.

[0139] In some embodiments, ring A is a 13-membered saturated or partially unsaturated tricyclic heterocyclenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 13-membered saturated or partially unsaturated tricyclic heterocyclenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a 13-membered saturated or partially unsaturated tricyclic heterocyclenyl having 3 nitrogen heteroatoms.

[0140] In some embodiments, ring A is a saturated or partially unsaturated 5,6,6-condensed tricyclic heterocyclenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a saturated or partially unsaturated 5,6,6-condensed tricyclic heterocyclenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a saturated or partially unsaturated 5,6,6-condensed tricyclic heterocyclenyl having 3 nitrogen heteroatoms.

[0141] In some embodiments, ring A is a saturated or partially unsaturated 6,5,6-condensed tricyclic heterocyclenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a saturated or partially unsaturated 6,5,6-condensed tricyclic heterocyclenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a saturated or partially unsaturated 6,5,6-condensed tricyclic heterocyclenyl having 3 nitrogen heteroatoms.

[0142] In some embodiments, ring A is a 14-membered saturated or partially unsaturated tricyclic heterocyclenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0143] In some embodiments, ring A is a 10-15 membered tricyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0144] In some embodiments, ring A is a 12-membered saturated or partially unsaturated tricyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 12-membered saturated or partially unsaturated tricyclic heteroarylenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a 12-membered saturated or partially unsaturated tricyclic heteroarylenyl having 3 nitrogen heteroatoms.

[0145] In some embodiments, ring A is a saturated or partially unsaturated 5,6,5-condensed tricyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a saturated or partially unsaturated 5,6,5-condensed tricyclic heteroarylenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a saturated or partially unsaturated 5,6,5-condensed tricyclic heteroarylenyl having 3 nitrogen heteroatoms.

[0146] In some embodiments, ring A is a saturated or partially unsaturated 5,5,6-condensed tricyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a saturated or partially unsaturated 5,5,6-condensed tricyclic heteroarylenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a saturated or partially unsaturated 5,5,6-condensed tricyclic heteroarylenyl having 3 nitrogen heteroatoms.

[0147] In some embodiments, ring A is a 13-membered saturated or partially unsaturated tricyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 13-membered saturated or partially unsaturated tricyclic heteroarylenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a 13-membered saturated or partially unsaturated tricyclic heteroarylenyl having 3 nitrogen heteroatoms.

[0148] In some embodiments, ring A is a saturated or partially unsaturated 5,6,6-condensed tricyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a saturated or partially unsaturated 5,6,6-condensed tricyclic heteroarylenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a saturated or partially unsaturated 5,6,6-condensed tricyclic heteroarylenyl having 3 nitrogen heteroatoms.

[0149] In some embodiments, ring A is a saturated or partially unsaturated 6,5,6-condensed tricyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a saturated or partially unsaturated 6,5,6-condensed tricyclic heteroarylenyl having 1 to 5 nitrogen heteroatoms. In some embodiments, ring A is a saturated or partially unsaturated 6,5,6-condensed tricyclic heteroarylenyl having 3 nitrogen heteroatoms.

[0150] In some embodiments, ring A is a 14-membered saturated or partially unsaturated tricyclic heteroarylenyl having 1 to 5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0151] In some embodiments, ring A is a ring of formula ABC-1 or ABC-2: [ka] or a pharmaceutically acceptable salt thereof, where each R1 R 2 m is as defined above and described herein, and can be either independent or in combination; Ring A 1 , ring B 1 , and ring C 1 Each of these is independently a fused ring selected from 4-7 member saturated or partially unsaturated carbocyclelenyl; benzo; 4-7 member saturated or partially unsaturated heterocyclelenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or 5-6 member heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0152] In some embodiments, ring A 1 This is a 4- to 7-membered saturated or partially unsaturated condensed carbocyclinyl. In some embodiments, ring A 1 is a benzo. In some embodiments, ring A 1 This is a 4-7 member saturated or partially unsaturated condensed tricyclic heterocyclenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A 1 This is a condensed 5-6 member heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0153] In some embodiments, ring B 1 This is a 4-7 member saturated or partially unsaturated condensed carbocyclinyl. In some embodiments, ring B 1 is a benzo. In some embodiments, ring B 1 This is a 4-7 member saturated or partially unsaturated condensed tricyclic heterocyclenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B 1 This is a condensed 5-6 member heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0154] In some embodiments, ring C 1This is a 4- to 7-membered saturated or partially unsaturated condensed carbocyclirenyl. In some embodiments, the ring C 1 is a benzo. In some embodiments, ring C 1 This is a 4-7 member saturated or partially unsaturated condensed tricyclic heterocyclenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, the ring C 1 This is a condensed 5-6 member heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0155] In some embodiments, ring A is [ka] That is the case.

[0156] In some embodiments, ring A is a 9-10 membered bicyclic partially unsaturated heterocyclyl or heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 12 membered tricyclic partially unsaturated heterocyclyl or heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0157] In some embodiments, ring A is as shown in the compounds in Table 1 below.

[0158] As defined herein and as described above, ring B is a condensed ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0159] In some embodiments, ring B is a benzo. In some embodiments, ring B is a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring B is a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0160] In some embodiments, ring B is as shown in the compounds in Table 1 below.

[0161] In some embodiments, [ka] teeth, [ka] [ka] That is the case.

[0162] In some embodiments, [ka] teeth, [ka] [ka] [ka] [ka] [ka] [ka] [ka] That is the case.

[0163] As defined herein and as described above, ring C is an 8-15 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, spirocyclic or tricyclic carbocyclinyl or heterocyclinyl having 1-3 heteroatoms independently selected from phenylenyl, pyridylenyl, nitrogen, oxygen and sulfur, or a 5-10 member monocyclic or bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0164] In some embodiments, ring C is an 8-15 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, spirocyclic, or tricyclic carbocyclilenyl. In some embodiments, ring C is an 8-15 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, spirocyclic, or tricyclic heterocyclilenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring C is an 8 member saturated or partially unsaturated bicyclic heterocyclilenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring C is a 5-10 member monocyclic or bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring C is an 8 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring C is a five-membered heteroarylenyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0165] As defined herein and as described above, ring C is a 9-10 member saturated or partially unsaturated bicyclic heterocyclinyl having 1-3 heteroatoms independently selected from phenylenyl, pyridylenyl, nitrogen, oxygen, and sulfur; an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 12-15 member saturated or partially unsaturated tricyclic spirocyclic heterocyclinyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0166] In some embodiments, ring C is a 9-10 member saturated or partially unsaturated bicyclic heterocyclinyl having 1-3 heteroatoms independently selected from phenylenyl, nitrogen, oxygen, and sulfur; an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 12-15 member saturated or partially unsaturated tricyclic spirocyclic heterocyclinyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0167] In some embodiments, ring C is phenylenyl. In some embodiments, ring C is pyridyl. In some embodiments, ring C is a 9-10 member saturated or partially unsaturated bicyclic heterocyclinyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring C is an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring C is a 12-15 member saturated or partially unsaturated tricyclic spirocyclic heterocyclinyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0168] In some embodiments, ring C is a 9-membered saturated or partially unsaturated bicyclic heterocyclenyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring C is a 9-membered partially unsaturated bicyclic heterocyclenyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring C is a 9-membered partially unsaturated bicyclic heterocyclenyl having 1 to 2 nitrogen heteroatoms. In some embodiments, ring C is a 9-membered partially unsaturated bicyclic heterocyclenyl having 1 nitrogen heteroatom.

[0169] In some embodiments, ring C is a 14-membered partially unsaturated tricyclic spirocyclic heterocyclenyl having 1 to 3 heteroatoms independently selected from nitrogen and oxygen. In some embodiments, ring C is a 14-membered partially unsaturated tricyclic spirocyclic heterocyclenyl having 1 to 2 nitrogen heteroatoms.

[0170] In some embodiments, ring C is an N-bonded ring. In some embodiments, ring C is a C-bonded ring. In some embodiments, ring C is an N-bonded 9-membered partially unsaturated bicyclic heterocyclelynyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring C is a C-bonded 9-membered partially unsaturated bicyclic heterocyclelynyl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0171] In some embodiments, ring C is [ka] Here, both connection points to ring C are on ring S, and ring S is a 5-6 member heterocyclinyl, a 5-6 member heteroarylenyl, or a 10-12 member spiro-ring heterocyclinyl; each R 5 is a halogen, and n is either 0 or 1.

[0172] In some embodiments, each 5-6 membered heterocyclinyl, 5-6 membered heteroarylenyl, or 10-12 membered spirocyclic heterocyclinyl contains one or two ring nitrogens. In some embodiments, each linkage to ring C is located on the ring nitrogen of ring S. In some embodiments, each linkage to ring C is located on the ring carbon of ring S. In some embodiments, one of the linkages to ring C is located on the ring nitrogen of ring S and the other is located on the ring carbon of ring S.

[0173] In some embodiments, ring S is a 10-12 membered spirocyclic heterocyclinyl containing one or two ring nitrogen atoms.

[0174] In some embodiments, ring C is [ka] Here, both linkages to ring C are on ring S, where ring S is a 5-6 member heterocyclenyl, a 5 or 6 member heteroaryrenyl, or a 10-12 member spirocyclic heterocyclenyl. In some embodiments, each 5-6 member heterocyclenyl, 5-6 member heteroaryrenyl, or 10-12 member spirocyclic heterocyclenyl contains one or two ring nitrogens. In some embodiments, each linkage to ring C is on the ring nitrogen of ring S. In some embodiments, each linkage to ring C is on the ring carbon of ring S. In some embodiments, one of the linkages to ring C is on the ring nitrogen of ring S and the other is on the ring carbon of ring S.

[0175] In some embodiments, S is a 10-12 membered spirocyclic heterocyclinyl containing one or two ring nitrogen atoms.

[0176] In some embodiments, ring C is [ka] Here, ring S is a 5-6 member heterocyclinyl, a 5-6 member heteroarylenyl, or a 10-12 member spiro-ring heterocyclinyl; each R 5is a halogen, and n is 0 or 1. In some embodiments, each 5 or 6-membered heterocyclelenyl, 5-6 membered heteroarylenyl, or 10-12 membered spirocyclic heterocyclelenyl contains one or two ring nitrogens. In some embodiments, the linkage point from ring S to ring C is on the ring nitrogen. In some embodiments, the linkage point from ring S to ring C is on the ring carbon.

[0177] In some embodiments, the ring S is a 5-6 membered heterocyclenyl containing one or two ring heteroatoms selected from nitrogen and oxygen.

[0178] In some embodiments, ring C is [ka] Here, ring S is a 5-6 member heterocyclenyl, a 5-6 member heteroaryrenyl, or a 10-12 member spirocyclic heterocyclenyl. In some embodiments, each 5-6 member heterocyclenyl, 5-6 member heteroaryrenyl, or 10-12 member spirocyclic heterocyclenyl contains one or two ring nitrogens. In some embodiments, the linkage point on ring S to ring C is on the ring nitrogen. In some embodiments, the linkage point on ring S to ring C is on the ring carbon.

[0179] In some embodiments, the ring S is a 5-6 membered heterocyclenyl containing one or two ring heteroatoms selected from nitrogen and oxygen.

[0180] In some embodiments, ring C is [ka] And here, Z is -C(R 103 )2-, -O- or NR 102 And; R 101 This is H, halogen, or C optionally substituted with one or more halogens. 1-3 Alkoxy or C 1-3 Alkyl; R 102 is H or C1-3 It is alkyl, and each R 103 These are independently H, halogens, and C, which is optionally substituted with one or more halogens. 1-3 Alkoxy or C 1-3 It is alkyl.

[0181] In some embodiments, ring C is [ka] That is the case.

[0182] In some embodiments, ring C is [ka] And here, each R 5 is a halogen, and n is either 0 or 1.

[0183] In some embodiments, ring C is [ka] That is the case.

[0184] In some embodiments, ring C is as shown in the compounds in Table 1 below.

[0185] In some embodiments, the ring C and its R 5 The substituents are [ka] That is the case.

[0186] In some embodiments, X 2 And ring C is, [ka] That is the case.

[0187] In some embodiments, X 2 and ring C, and its R 5 The substituents are [ka] That is the case.

[0188] As defined herein and as described above, ring D is a divalent ring selected from a 4-7 member saturated or partially unsaturated carbocyclenyl or heterocyclenyl having 1-2 heteroatoms independently selected from phenylenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroarylenyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0189] In some embodiments, ring D is phenylenyl. In some embodiments, ring D is a 4- to 7-membered saturated or partially unsaturated carbocyclelenyl. In some embodiments, ring D is a 4- to 7-membered saturated or partially unsaturated heterocyclelenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring D is a 5- to 6-membered heteroarylenyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0190] In some embodiments, ring D is as shown in the compounds in Table 1 below.

[0191] As defined herein and as described above, ring E is a divalent ring selected from a 4-7 member saturated or partially unsaturated carbocycllenyl or heterocyclenyl having 1-2 heteroatoms independently selected from phenylenyl, naphthylenyl, nitrogen, oxygen, and sulfur; a 5-6 member heteroarylenyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 9-10 member saturated or partially unsaturated bicyclic heterocyclenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0192] In some embodiments, ring E is phenylenyl. In some embodiments, ring E is naphthylenyl. In some embodiments, ring E is a 4-7 member saturated or partially unsaturated carbocyclylenel. In some embodiments, ring E is a 4-7 member saturated or partially unsaturated heterocyclylenel having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring E is a 5-6 member heteroarylenyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring E is a 9-10 member saturated or partially unsaturated bicyclic heterocyclylenel having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring E is an 8-10 member bicyclic heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0193] In some embodiments, ring E is a 10-membered bicyclic heteroarylenyl having 1 to 4 nitrogen atoms.

[0194] In some embodiments, ring E is as shown in the compounds in Table 1 below.

[0195] As defined herein and as described above, ring F is a 4-7 member saturated or partially unsaturated carbocyclyl or heterocyclyl having 1-2 heteroatoms independently selected from phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0196] In some embodiments, ring F is phenyl. In some embodiments, ring F is a 4- to 7-membered saturated or partially unsaturated carbocyclyl. In some embodiments, ring F is a 4- to 7-membered saturated or partially unsaturated heterocyclyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring F is a 5- to 6-membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0197] In some embodiments, ring F is a six-membered heteroaryl ring having one or two nitrogen heteroatoms.

[0198] In some embodiments, ring F is [ka] In some embodiments, the ring F is [ka] In some embodiments, the ring F is [ka] That is the case.

[0199] In some embodiments, ring F and its R 5 The substituents are [ka] That is the case.

[0200] In some embodiments, ring F is as shown in the compounds in Table 1 below.

[0201] As defined herein and as described above, R b R 1 It binds to the nitrogen that is bonded, R 1 It forms an optionally substituted 5-6 member partially unsaturated or aromatic heterocycle having 0-2 heteroatoms selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom to which it is bonded.

[0202] In some embodiments, R b is hydrogen. In some embodiments, R b R 1 Connected to R 1In addition to the nitrogen atom to which it is bonded, it forms an optionally substituted 5-6 member partially unsaturated or aromatic heterocycle having 0-2 heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R b R 1 Connected to R 1 In addition to the nitrogen atom to which it is bonded, it forms an optionally substituted five-membered partial unsaturated heterocycle having 0 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R b R 1 Connected to R 1 In addition to the nitrogen atom to which it is bonded, it forms an optionally substituted 6-membered partial unsaturated heterocycle having 0 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R b R 1 Connected to R 1 In addition to the nitrogen atom to which it is bonded, it forms an optionally substituted five-membered aromatic heterocycle having 0 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R b R 1 Connected to R 1 In addition to the nitrogen atom to which it is bonded, it forms an optionally substituted 6-membered aromatic heterocycle having 0 to 2 heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, R b R 1 It links with other molecules to form condensed pyrrolidinyl, imidazolyl, piperdinyl, or morpholinyl.

[0203] In some embodiments, R b These are as shown in the compounds in Table 1 below.

[0204] As defined herein and as described above, R 1a R 1 NHR 1 , OR 1 , or SR 1 That is the case.

[0205] In some embodiments, R1a R 1 In some embodiments, R 1a NHR 1 In some embodiments, R 1a is OR 1 In some embodiments, R 1a , SR 1 That is the case.

[0206] As defined herein and as described above, R 1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl, or C 1-6 Alkyl-OC 1-6 It is alkyl.

[0207] In some embodiments, R 1 C 3-6 It is heterocycloalkyl. In some embodiments, R 1 C 1-6 Alkyl-OC 1-6 It is alkyl.

[0208] In some embodiments, R 1a R 1 And R 1 C 1-6 Alkyl, C 1-6 Haloalkyl or C 3-6 It is cycloalkyl. In some embodiments, R 1a It is methyl, cyclopropyl, or -CHF2.

[0209] In some embodiments, R 1a , SR 1 And R 1 C 1-6 It is alkyl. In some embodiments, R 1a It is -SMe.

[0210] In some embodiments, R 1aNHR 1 And R 1 C 1-6 Alkyl-OC 1-6 It is alkyl. In some embodiments, R 1a This is -NHCH2CH2OMe.

[0211] In some embodiments, R 1a These are as shown in the compounds in Table 1 below.

[0212] As defined herein and as described above, R 1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 It is a cycloalkyl group.

[0213] In some embodiments, R 1 is hydrogen. In some embodiments, R 1 C 1-6 It is alkyl. In some embodiments, R 1 C 1-6 In some embodiments, R 1 C 3-6 It is a cycloalkyl group.

[0214] In some embodiments, R 1 It is methyl.

[0215] In some embodiments, R 1 These are as shown in the compounds in Table 1 below.

[0216] As defined herein and as described above, each R 2 , R 5 , R 6 , and R 7These are independently hydrogen, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)2, -O P(O)(OR)NR2, -OP(O)(NR2)2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N (R)P(O)R2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -N(R)P(O)(NR2)2, -N(R)S(O)2R, or R A or two R atoms on adjacent atoms 6 These link together to form an optionally substituted condensed 5-6 member partially saturated or aromatic heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur, or the two R of ring A 2 The groups, together with their interfacing atoms, form optionally substituted rings selected from 3-10 member saturated or partially unsaturated carbocyclyl or heterocyclyl; benzo; or 5-10 member heteroaryls having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0217] In some embodiments, R 2 is hydrogen. In some embodiments, R 2 is hydrogen. In some embodiments, R 2 is -CN. In some embodiments, R 2 is -NO2. In some embodiments, R 2 is -OR. In some embodiments, R 2 is an oxo. In some embodiments, R 2 is -SR. In some embodiments, R 2 is -NR2. In some embodiments, R 2 is -SiR3. In some embodiments, R 2is -S(O)2R. In some embodiments, R 2 is -S(O)2NR2. In some embodiments, R 2 is -S(O)R. In some embodiments, R 2 is -C(O)R. In some embodiments, R 2 is -C(O)OR. In some embodiments, R 2 is -C(O)NR2. In some embodiments, R 2 is -C(O)N(R)OR. In some embodiments, R 2 is -OC(O)R. In some embodiments, R 2 is -OC(O)NR2. In some embodiments, R 2 is -OP(O)R2. In some embodiments, R 2 is -OP(O)(OR)2. In some embodiments, R 2 is -OP(O)(OR)NR2. In some embodiments, R 2 is -OP(O)(NR2)2-. In some embodiments, R 2 is -N(R)C(O)OR. In some embodiments, R 2 is -N(R)C(O)R. In some embodiments, R 2 is -N(R)C(O)NR2. In some embodiments, R 2 is -N(R)S(O)2R. In some embodiments, R 2 is -N(R)P(O)R2. In some embodiments, R 2 is -N(R)P(O)(OR)2. In some embodiments, R 2 is -N(R)P(O)(OR)NR2. In some embodiments, R 2 is -N(R)P(O)(NR2)2. In some embodiments, R 2 is -N(R)S(O)2R. In some embodiments, R 2 R A That is the case.

[0218] In some embodiments, the two R's of ring A 2 The groups, together with their interfacing atoms, form optionally substituted rings selected from 3-10 member saturated or partially unsaturated carbocyclyl or heterocyclyl; benzo; or 5-10 member heteroaryls having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0219] In some embodiments, the two R's of ring A 2 The groups, together with their interfacing atoms, form an optionally substituted ring selected from 3- to 10-membered saturated or partially unsaturated carbocyclyls. In some embodiments, two R groups on the same or adjacent atoms 2 The groups, together with their interfacing atoms, form an optionally substituted ring selected from 5-6 member saturated or partially unsaturated carbocyclyl groups.

[0220] In some embodiments, the two R's of ring A 2 The groups, together with their intervening atoms, form an optionally substituted ring selected from a 3-10 member saturated or partially unsaturated heterocycline having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, the two R groups of ring A 2 The groups, together with their intervening atoms, form an optionally substituted ring selected from a 4-7 member saturated or partially unsaturated heterocycline having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, two R groups of ring A 2 The groups, together with their intervening atoms, form an optionally substituted ring selected from a 5-6 member saturated or partially unsaturated heterocycline having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0221] In some embodiments, the two R's of ring A 2 The groups, together with those intervening atoms, form optionally substituted benzos.

[0222] In some embodiments, the two R's of ring A 2 The groups, together with their intervening atoms, form an optionally substituted ring selected from a 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, two R groups of ring A 2 The groups, together with their intervening atoms, form an optionally substituted ring selected from a 5-6 membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0223] In some embodiments, R 2 is hydrogen, fluoro, chloro, methyl, ethyl, cyclopropyl, -CHF2, -CF3, oxo, -OMe, or -OEt. In some embodiments, R 2 is hydrogen, fluoro, chloro, methyl, ethyl, -CHF2, or -CF3. In some embodiments, R 2 is hydrogen, chloro, or methyl. In some embodiments, R 2 These are chloro and methyl.

[0224] In some embodiments, R 5 is hydrogen. In some embodiments, R 5 is hydrogen. In some embodiments, R 5 is -CN. In some embodiments, R 5 is -NO2. In some embodiments, R 5 is -OR. In some embodiments, R 5 is an oxo. In some embodiments, R 5 is -SR. In some embodiments, R 5 is -NR2. In some embodiments, R 5 is -SiR3. In some embodiments, R 5 is -S(O)2R. In some embodiments, R 5is -S(O)2NR2. In some embodiments, R 5 is -S(O)R. In some embodiments, R 5 is -C(O)R. In some embodiments, R 5 is -C(O)OR. In some embodiments, R 5 is -C(O)NR2. In some embodiments, R 5 is -C(O)N(R)OR. In some embodiments, R 5 is -OC(O)R. In some embodiments, R 5 is -OC(O)NR2. In some embodiments, R 5 is -OP(O)R2. In some embodiments, R 5 is -OP(O)(OR)2. In some embodiments, R 5 is -OP(O)(OR)NR2. In some embodiments, R 5 is -OP(O)(NR2)2-. In some embodiments, R 5 is -N(R)C(O)OR. In some embodiments, R 5 is -N(R)C(O)R. In some embodiments, R 5 is -N(R)C(O)NR2. In some embodiments, R 5 is -N(R)S(O)2R. In some embodiments, R 5 is -N(R)P(O)R2. In some embodiments, R 5 is -N(R)P(O)(OR)2. In some embodiments, R 5 is -N(R)P(O)(OR)NR2. In some embodiments, R 5 is -N(R)P(O)(NR2)2. In some embodiments, R 5 is -N(R)S(O)2R. In some embodiments, R 5 R A That is the case.

[0225] In some embodiments, R 5This is an optionally substituted 3-7 member saturated or partially unsaturated heterocycle having 1-2 heteroatoms independently selected from hydrogen, fluoro, chloro, methyl, ethyl, cyclopropyl, -CHF2, -CF3, oxo, -OMe, -OEt, or nitrogen, oxygen, and sulfur.

[0226] In some embodiments, R 5 teeth, [ka] That is the case.

[0227] In some embodiments, R 5 is methyl, [ka] That is the case.

[0228] In some embodiments, R 6 is hydrogen. In some embodiments, R 6 is hydrogen. In some embodiments, R 6 is -CN. In some embodiments, R 6 is -NO2. In some embodiments, R 6 is -OR. In some embodiments, R 6 is an oxo. In some embodiments, R 6 is -SR. In some embodiments, R 6 is -NR2. In some embodiments, R 6 is -SiR3. In some embodiments, R 6 is -S(O)2R. In some embodiments, R 6 is -S(O)2NR2. In some embodiments, R 6 is -S(O)R. In some embodiments, R 6 is -C(O)R. In some embodiments, R 6 is -C(O)OR. In some embodiments, R 6is -C(O)NR2. In some embodiments, R 6 is -C(O)N(R)OR. In some embodiments, R 6 is -OC(O)R. In some embodiments, R 6 is -OC(O)NR2. In some embodiments, R 6 is -OP(O)R2. In some embodiments, R 6 is -OP(O)(OR)2. In some embodiments, R 6 is -OP(O)(OR)NR2. In some embodiments, R 6 is -OP(O)(NR2)2-. In some embodiments, R 6 is -N(R)C(O)OR. In some embodiments, R 6 is -N(R)C(O)R. In some embodiments, R 6 is -N(R)C(O)NR2. In some embodiments, R 6 is -N(R)S(O)2R. In some embodiments, R 6 is -N(R)P(O)R2. In some embodiments, R 6 is -N(R)P(O)(OR)2. In some embodiments, R 6 is -N(R)P(O)(OR)NR2. In some embodiments, R 6 is -N(R)P(O)(NR2)2. In some embodiments, R 6 is -N(R)S(O)2R. In some embodiments, R 6 R A In some embodiments, two R atoms on adjacent atoms 6 These link together to form an optionally substituted condensed 5-6 member partially saturated or aromatic heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur. In some embodiments, two R atoms on adjacent atoms 6 teeth, [ka] It forms.

[0229] In some embodiments, R 6 These are hydrogen, fluoro, chloro, methyl, ethyl, cyclopropyl, -CHF2, -CF3, oxo, -OMe, -OEt, -NHCOMe, or -NHCOEt.

[0230] In some embodiments, R 7 is hydrogen. In some embodiments, R 7 is hydrogen. In some embodiments, R 7 is -CN. In some embodiments, R 7 is -NO2. In some embodiments, R 7 is -OR. In some embodiments, R 7 is an oxo. In some embodiments, R 7 is -SR. In some embodiments, R 7 is -NR2. In some embodiments, R 7 is -SiR3. In some embodiments, R 7 is -S(O)2R. In some embodiments, R 7 is -S(O)2NR2. In some embodiments, R 7 is -S(O)R. In some embodiments, R 7 is -C(O)R. In some embodiments, R 7 is -C(O)OR. In some embodiments, R 7 is -C(O)NR2. In some embodiments, R 7 is -C(O)N(R)OR. In some embodiments, R 7 is -OC(O)R. In some embodiments, R 7 is -OC(O)NR2. In some embodiments, R 7 is -OP(O)R2. In some embodiments, R 7 is -OP(O)(OR)2. In some embodiments, R 7 is -OP(O)(OR)NR2. In some embodiments, R 7is -OP(O)(NR2)2-. In some embodiments, R 7 is -N(R)C(O)OR. In some embodiments, R 7 is -N(R)C(O)R. In some embodiments, R 7 is -N(R)C(O)NR2. In some embodiments, R 7 is -N(R)S(O)2R. In some embodiments, R 7 is -N(R)P(O)R2. In some embodiments, R 7 is -N(R)P(O)(OR)2. In some embodiments, R 7 is -N(R)P(O)(OR)NR2. In some embodiments, R 7 is -N(R)P(O)(NR2)2. In some embodiments, R 7 is -N(R)S(O)2R. In some embodiments, R 7 R A That is the case.

[0231] In some embodiments, R 7 These are hydrogen, fluoro, chloro, methyl, ethyl, cyclopropyl, -CHF2, -CF3, oxo, -OMe, or -OEt.

[0232] In some embodiments, R 2 , R 5 , R 6 and R 7 These are as shown in the compounds in Table 1 below.

[0233] As defined herein and as described above, each of m, n, o, and p is independently 0, 1, 2, 3, or 4.

[0234] In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, m is 3. In some embodiments, m is 4.

[0235] In some embodiments, m is 0, 1, 2, or 3. In some embodiments, m is 0, 1, or 2. In some embodiments, m is 0 or 1. In some embodiments, m is 1 or 2. In some embodiments, m is 2 or 3.

[0236] In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, n is 3. In some embodiments, n is 4.

[0237] In some embodiments, n is 0, 1, 2, or 3. In some embodiments, n is 0, 1, or 2. In some embodiments, n is 0 or 1. In some embodiments, n is 1 or 2. In some embodiments, n is 2 or 3.

[0238] In some embodiments, o is 0. In some embodiments, o is 1. In some embodiments, o is 2. In some embodiments, o is 3. In some embodiments, o is 4.

[0239] In some embodiments, o is 0, 1, 2, or 3. In some embodiments, o is 0, 1, or 2. In some embodiments, o is 0 or 1. In some embodiments, o is 1 or 2. In some embodiments, o is 2 or 3.

[0240] In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4.

[0241] In some embodiments, p is 0, 1, 2, or 3. In some embodiments, p is 0, 1, or 2. In some embodiments, p is 0 or 1. In some embodiments, p is 1 or 2. In some embodiments, p is 2 or 3.

[0242] In some embodiments, m, n, o, and p are as shown in the compounds in Table 1 below.

[0243] As defined herein and as described above, R 3 is either hydrogen or C 1-6 The group is optionally substituted from 3-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclinyl or heterocyclinyl groups having 1-3 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and from 5-10 member monocyclic or bicyclic heteroaryl groups having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0244] In some embodiments, R 3 C is optionally substituted. 1-6 It is aliphatic. In some embodiments, R 3 is a phenyl compound that is optionally substituted. In some embodiments, R 3 R is an optionally substituted 3-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclirenyl. In some embodiments, R 3 R is an optionally substituted 3-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclinyl or heterocyclinyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 3 This is an optionally substituted 5-10 member monocyclic or bicyclic heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0245] As defined herein and as described above, R 3 is hydrogen, or halogen, -CN, C 1-6 C is optionally substituted with 1-2 substituents selected from alkyl and -OR groups. 1-6 Alkyl or C 3-6 It is either cycloalkyl or R 3 and R 5 This refers to divalent saturated or partially unsaturated linear or branched C 3-6 It is linked by a hydrocarbon chain, where the 0-2 methylene units of the chain are independently -CR2-, -CRF-, -CF2-, -O-, -NR-, and -C(O)-.

[0246] In some embodiments, R 3 is hydrogen. In some embodiments, R 3 C 1-6 It is alkyl. In some embodiments, R 3 C is substituted with one or two substituents selected from halogen, -CN, and -OR. 1-6 It is alkyl. In some embodiments, R 3 C 3-6 It is cycloalkyl. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6 C substituted with 1-2 substituents selected from haloalkyl and -OR 3-6 It is cycloalkyl. In some embodiments, R 3 C 4-6 It is cycloalkyl. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6 C substituted with 1-2 substituents selected from haloalkyl and -OR 4-6 It is cycloalkyl. In some embodiments, R 3 C 4-5 It is cycloalkyl. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6C substituted with 1-2 substituents selected from haloalkyl and -OR 4-5 It is cycloalkyl. In some embodiments, R 3 is a C4 cycloalkyl group. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6 It is a C4 cycloalkyl substituted with one or two substituents selected from haloalkyl and -OR. In some embodiments, R 3 C is replaced with -OR 4-6 It is cycloalkyl. In some embodiments, R 3 C is replaced with -OR 4-5 It is cycloalkyl. In some embodiments, R 3 is a C4 cycloalkyl substituted with -OR. In some embodiments, R 3 is, -OC 1-6 C substituted with alkyl 4-6 It is cycloalkyl. In some embodiments, R 3 is, -OC 1-6 C substituted with alkyl 4-5 It is cycloalkyl. In some embodiments, R 3 is, -OC 1-6 It is a C4 cycloalkyl group substituted with alkyl. In some embodiments, R 3 C is replaced with -OMe 4-6 It is cycloalkyl. In some embodiments, R 3 C is replaced with -OMe 4-5 It is cycloalkyl. In some embodiments, R 3 is a C4 cycloalkyl substituted with -OMe. In some embodiments, R 3 and R 5 This refers to divalent saturated or partially unsaturated linear or branched carbon atoms. 3-6 It is linked by a hydrocarbon chain, where the 0-2 methylene units of the chain are independently -CR2-, -CRF-, -CF2-, -O-, -NR-, and -C(O)-.

[0247] As defined herein and as described above, R 3 is hydrogen, or halogen, -CN, C 1-6 Alkyl, C 1-6 C 1-6 A 3- to 9-membered saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring having alkyl or 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0248] In some embodiments, R 3 C 1-6 It is alkyl. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6 C is a 5-membered heteroaryl group having 1 to 3 heteroatoms independently selected from haloalkyl, -OR, -CH2OR, or nitrogen, oxygen, and sulfur, substituted with 1 to 2 substituents. 1-6 It is alkyl.

[0249] In some embodiments, R 3 is a 3- to 9-membered saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclyl ring. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6 A 3-9 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclyl ring, optionally substituted with 1-2 substituents selected from haloalkyl, -OR, -CH2OR, or 5-membered heteroaryls having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0250] In some embodiments, R 3R is a 4-9 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclyl ring. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6 A 4-9 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclyl ring, optionally substituted with 1-2 substituents selected from haloalkyl, -OR, -CH2OR, or 5-membered heteroaryls having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0251] In some embodiments, R 3 R is a 3-9 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic heterocycle having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6 A 3-9 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic heterocycle having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted with 1-2 substituents selected from haloalkyl, -OR, -CH2OR, or 5-membered heteroaryls having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0252] In some embodiments, R 3 R is a 3-5 member or 7-9 member saturated monocyclic, 3-9 member partially unsaturated monocyclic, or 3-9 member saturated or partially unsaturated bicyclic, bridging bicyclic, or spirocyclic heterocycle having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6A 3-5 member or 7-9 member saturated monocyclic, 3-9 member partially unsaturated monocyclic, or 3-9 member saturated or partially unsaturated bicyclic, bridging bicyclic, or spirocyclic heterocyclic having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted with 1 to 2 substituents selected from a haloalkyl, -OR, -CH2OR, or 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0253] In some embodiments, R 3 C is substituted with a 5-membered heteroaryl having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 1-6 It is alkyl. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6 A 3-6 member saturated monocyclic or bridged bicyclic carbon ring, optionally substituted with 1-2 substituents selected from haloalkyl, -OR, or -CH2OR. In some embodiments, R 3 Halogen, -CN, C 1-6 Alkyl, C 1-6 It is a 7-8 member saturated or partially unsaturated bicyclic heterocycle having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, substituted with 1-2 substituents selected from haloalkyl, -OR, or -CH2OR.

[0254] In some embodiments, R 3 teeth, [ka] And here, Each R 3aThese are independently hydrogen, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)2, -OP(O)(OR)NR2, -OP(O)(NR2)2, -N (R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)P(O)R2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -N(R)P(O)(NR2)2, -N(R)S(O)2R, -P(O)R2, -P(O)(OR)2, -P(O)(OR)NR2, -P(O)(NR2)2, or RA; or: Two R atoms on the same carbon atom or adjacent carbon atoms 3a The groups, optionally together with their intervening atoms, form 3-9 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic rings having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; b is 0, 1, 2, 3, 4, or 5.

[0255] In some embodiments, R 3a is hydrogen. In some embodiments, R 3a is a halogen. In some embodiments, R 3a is -CN. In some embodiments, R 3a is -NO2. In some embodiments, R 3a is -OR. In some embodiments, R 3a is an oxo. In some embodiments, R 3a is -SR. In some embodiments, R 3a is -NR2. In some embodiments, R 3a is -SiR3. In some embodiments, R 3a These are -S(O)2R and -S(O)2NR2. In some embodiments, R 3ais -S(O)R. In some embodiments, R 3a is -C(O)R. In some embodiments, R 3a is -C(O)OR. In some embodiments, R 3a is -C(O)NR2. In some embodiments, R 3a is -C(O)N(R)OR. In some embodiments, R 3a is -OC(O)R. In some embodiments, R 3a is -OC(O)NR2, -OP(O)R2. In some embodiments, R 3a is -OP(O)(OR)2. In some embodiments, R 3a is -OP(O)(OR)NR2. In some embodiments, R 3a is -OP(O)(NR2)2-. In some embodiments, R 3a is -N(R)C(O)OR. In some embodiments, R 3a is -N(R)C(O)R, -N(R)C(O)NR2. In some embodiments, R 3a is -N(R)S(O)2R. In some embodiments, R 3a is -N(R)P(O)R2. In some embodiments, R 3a is -N(R)P(O)(OR)2. In some embodiments, R 3a is -N(R)P(O)(OR)NR2. In some embodiments, R 3a is -N(R)P(O)(NR2)2. In some embodiments, R 3a is -N(R)S(O)2R. In some embodiments, R 3a is -P(O)R2. In some embodiments, R 3a is -P(O)(OR)2. In some embodiments, R 3a is -P(O)(OR)NR2. In some embodiments, R 3a is -P(O)(NR2)2. In some embodiments, R 3a is R AIn some embodiments, two R atoms are located on the same carbon atom or adjacent carbon atoms. 3a The groups, optionally together with their intervening atoms, form 3-9 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic rings having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0256] In some embodiments, R 3a Halogen, -CN, C 1-6 Alkyl, C 1-6 Haloalkyl, -OR, -CH2OR, or two R atoms on the same carbon atom or adjacent carbon atoms 3a The groups, together with their intervening atoms, form a 3-5 member saturated or partially unsaturated monocyclic or heterocyclic carbocyclic ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0257] In some embodiments, R 3a is either fluoro, chloro, -CN, methyl, ethyl, -OMe, -OEt, -CH2OMe, -CH2OEt, or two R on adjacent carbon atoms 3a The groups, together with their intercalating atoms, form a five-membered saturated or partially unsaturated monocyclic heterocycle having one heteroatom independently selected from nitrogen, oxygen, and sulfur.

[0258] In some embodiments, b is 0. In some embodiments, b is 1. In some embodiments, b is 2. In some embodiments, b is 3. In some embodiments, b is 4. In some embodiments, b is 5. In some embodiments, b is 1 or 2. In some embodiments, b is 1, 2 or 3. In some embodiments, b is 2 or 3.

[0259] In some embodiments, R 3 hydrogen, methyl, ethyl, isopropyl, [ka] [ka] That is the case.

[0260] In some embodiments, R 3 These are as shown in the compounds in Table 1 below.

[0261] As defined herein and as described above, R 4 Hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl, or -OC 1-6 It is a haloalkyl group.

[0262] In some embodiments, R 4 is hydrogen. In some embodiments, R 4 is hydrogen. In some embodiments, R 4 C 1-6 It is alkyl. In some embodiments, R 4 C 1-6 In some embodiments, R 4 C 3-6 It is cycloalkyl. In some embodiments, R 4 is, -OC 1-6 It is alkyl. In some embodiments, R 4 is, -OC 1-6 It is a haloalkyl group.

[0263] In some embodiments, R 4 These are fluoro, chloro, methyl, oxo, or -OMe.

[0264] In some embodiments, R 4 These are as shown in the compounds in Table 1 below.

[0265] As defined herein and described above, L is a covalent, -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C 1-10 It is a hydrocarbon chain, where the 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, and -C(O)-.

[0266] In some embodiments, L is a covalent bond. In some embodiments, L is -CR2-. In some embodiments, L is -CRF-. In some embodiments, L is -CF2-. In some embodiments, L is -O-. In some embodiments, L is -NR-. In some embodiments, L is -C(O)-. In some embodiments, L is a divalent saturated or partially unsaturated linear or branched carbon atom. 1-10 It is a hydrocarbon chain, where the 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, and -C(O)-.

[0267] In some embodiments, L is a divalent saturated or partially unsaturated linear or branched C 1-10 It is a hydrocarbon chain, where 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, -C(O)-, or S(O)2.

[0268] In some embodiments, L is a divalent saturated or partially unsaturated linear or branched C 1-5 It is a hydrocarbon chain, where 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, -C(O)-, or S(O)2.

[0269] In some embodiments, L is a divalent saturated or partially unsaturated linear or branched C1-5 It is a hydrocarbon chain, where the 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, and -C(O)-.

[0270] In some embodiments, L is a divalent saturated or partially unsaturated straight or branched C5 hydrocarbon chain, where 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, and -C(O)-.

[0271] In some embodiments, L includes one -Cy- group.

[0272] In some embodiments, L includes two -Cy- groups.

[0273] In some embodiments, L includes 4-7 member saturated or partially unsaturated heterocyclenyl molecules having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted with 1-3 methylene, -C(O)-, and 1-2 halogens, and 6-11 member saturated or partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl molecules having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted with 1-2 halogens.

[0274] In some embodiments, L is -O-(C 1-5 It is aliphatic. In some embodiments, L is -Cy-(C 1-5 It is aliphatic. In some embodiments, L is (CH2) 1-5 -Cy-(C 1-5 It is aliphatic. In some embodiments, L is -(CH2) 1-5 -Cy-O-(C 1-5 It is aliphatic. In some embodiments, L is (CH2) 1-5 -Cy-Cy-(C 1-5 It is aliphatic. In some embodiments, L is (CH2) 1-5-Cy-Cy-O-(C 1-5 is aliphatic).

[0275] In some embodiments, L is -(CH2) 1-5 -Cy-. In some embodiments, L is -(CH2) 1-5 -Cy-CH(OR)-. In some embodiments, L is -(CH2) 1-5 -Cy-(CH2) 1-5 -. In some embodiments, L is -O-(CH2) 1-5 -Cy-. In some embodiments, L is -O-(CH2) 1-5 -Cy-(CH2) 1-5 -. In some embodiments, L is -(CH2) 1-5 -O-Cy-. In some embodiments, L is -(CH2) 1-5 -O-Cy-(CH2) 1-5 -. In some embodiments, L is -(CH2) 1-5 -CO-Cy-(CH2) 1-5 -. In some embodiments, L is -(CH2) 1-5 -NR-Cy-. In some embodiments, L is -(CH2) 1-5 -NR-Cy-CO-. In some embodiments, L is -(CH2) 1-5 -Cy-NR-. In some embodiments, L is -O-Cy-NR-. In some embodiments, L is -(CH2) 1-5 -NR-Cy-(CH2) 1-5 -. In some embodiments, L is -(CH2) 1-5 -CO-. In some embodiments, L is -(CH2) 1-5 -Cy-CO-. In some embodiments, L is -Cy-CO-. In some embodiments, L is -O-Cy-CO-. In some embodiments, L is -O-Cy-(CH2) 1-5 -. In some embodiments, L is -(CH2) 1-5 -Cy-CHF-. In some embodiments, L is -(CH2) 1-5-Cy-CF2-. In some embodiments, L is -(CH2) 1-5 -Cy-(CH2) 1-5 -CF2-

[0276] In some embodiments, L is -Cy-Cy-. In some embodiments, L is -(CH2) 1-5 -Cy-Cy-. In some embodiments, L is -(CH2) 1-5 -Cy-Cy-CO-. In some embodiments, L is -Cy-(CH2) 1-5 -Cy-. In some embodiments, L is -Cy-(CH2) 1-5 It is -Cy-CO-. In some embodiments, L is -(CH2) 1-5 -Cy-(CH2) 1-5 It is -Cy-CO-. In some embodiments, L is -Cy-(CH2) 1-5 -Cy-(CH2) 1-5 -. In some embodiments, L is -(CH2) 1-5 -Cy-Cy-(CH2) 1-5 -. In some embodiments, L is -O-(CH2) 1-5 -Cy-Cy-. In some embodiments, L is -O-(CH2) 1-5 -Cy-Cy-(CH2) 1-5 -. In some embodiments, L is -(CH2) 1-5 -O-Cy-Cy-. In some embodiments, L is -(CH2) 1-5 -O-Cy-Cy-(CH2) 1-5 -. In some embodiments, L is -(CH2) 1-5 -NR-Cy-Cy-. In some embodiments, L is -(CH2) 1-5 -Cy-NR-Cy-. In some embodiments, L is -(CH2) 1-5 -NR-Cy-Cy-(CH2) 1-5 -. In some embodiments, L is -(CH2) 1-5It is -Cy-Cy-CO-. In some embodiments, L is -O-Cy-Cy-CO-. In some embodiments, L is -O-Cy-Cy-(CH2) 1-5 - is

[0277] In some embodiments, L is -Cy-Cy-Cy-. In some embodiments, L is -Cy-Cy-Cy-CO-. In some embodiments, L is -(CH2) 1-5 -Cy-Cy-Cy-. In some embodiments, L is -(CH2) 1-5 -Cy-Cy-Cy-CO-. In some embodiments, L is -Cy-(CH2) 1-5 -Cy-Cy-. In some embodiments, L is -Cy-(CH2) 1-5 -Cy-Cy-CO-. In some embodiments, L is -Cy-(CH2) 1-5 -Cy-(CH2) 1-5 -Cy-. In some embodiments, L is -Cy-(CH2) 1-5 -Cy-(CH2) 1-5 -Cy-CO

[0278] As defined herein and as described above, each -Cy- is independently a phenylenyl, an 8-10 membered bicyclic aryrenyl, a 4-7 membered saturated or partially unsaturated carbocyclilenyl, a 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, an 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, a 4-7 membered saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur The optionally substituted divalent ring is selected from a 6-11 member saturated or partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0279] In some embodiments, -Cy- is an optionally substituted phenylenyl. In some embodiments, -Cy- is an optionally substituted 8-10 member bicyclic aryrenyl. In some embodiments, -Cy- is an optionally substituted 4-7 member saturated or partially unsaturated carbocyclilenyl. In some embodiments, -Cy- is an optionally substituted 6-11 member saturated or partially unsaturated spirocyclic bicyclic carbocyclilen. In some embodiments, -Cy- is an optionally substituted 6-11 member saturated or partially unsaturated bridged bicyclic carbocyclilen. In some embodiments, -Cy- is an optionally substituted 8-10 member saturated or partially unsaturated bicyclic carbocyclilen. In some embodiments, -Cy- is an optionally substituted 4-7 member saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- is an optionally substituted 6-11 member saturated or partially unsaturated spirocyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- is an optionally substituted 6-11 member saturated or partially unsaturated bridged bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- is an optionally substituted 8-10 member saturated or partially unsaturated bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- is an optionally substituted 5-6 member heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, -Cy- is an optionally substituted bicyclic 8-10 membered heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0280] In some embodiments, -Cy- is not substituted. In some embodiments, -Cy- is substituted. In some embodiments, -Cy- is a halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, -OH, -OC 1-6 Alkyl, or -OC 1-6 It is substituted with a haloalkyl group. In some embodiments, -Cy- is substituted with fluoro, geminal difluoro, methyl, geminal dimethyl, -OH, -CHF2, or -CF3. In some embodiments, one -Cy- group of L is substituted. In some embodiments, two -Cy- groups of L are substituted. In some embodiments, one -Cy- group of L is substituted with one or two halogens. In some embodiments, two -Cy- groups of L are substituted with one or two halogens. In some embodiments, -Cy- is substituted with geminal difluoro. In some embodiments, one -Cy- group of L is substituted with geminal difluoro. In some embodiments, two -Cy- groups of L are substituted with geminal difluoro.

[0281] In some embodiments, L is -(CR2) a -Cy-C(O)-, where -Cy- is [ka] And here, A is -N- or -CH-; Each R aa It is a halogen; Each R2 independently controls H and C 1-3 It is alkyl, -O-, or -N(CH3)-; a is an integer between 0 and 3; d is an integer between 1 and 3; e is an integer between 0 and 2; k is an integer between 1 and 3.

[0282] In some embodiments, A is N. In some embodiments, A is -CH-. In some embodiments, R2 is H. In some embodiments, a is 0. In some embodiments, a is 1. In some embodiments, a is 2. In some embodiments, a is 3. In some embodiments, d is 1. In some embodiments, d is 2. In some embodiments, d is 3. In some embodiments, R aa is fluoro. In some embodiments, e is 0. In some embodiments, e is 1. In some embodiments, each e is 2. In some embodiments, k is 1. In some embodiments, k is 2. In some embodiments, k is 3. In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] In some embodiments, -Cy- is [ka] In some embodiments, L is [ka] That is the case.

[0283] In some embodiments, L is -(CR2) a -Cy-Cy-(CR2) b -Cy-C(O)-, where each -Cy- is independent of, [ka] And here, D is either -N- or -CH-; Each R bb It is a halogen; Each R2 independently controls H and C 1-3 It is alkyl, -O-, or -N(CH3)-; a is either 0 or 1; b is either 0 or 1; g is an integer between 1 and 3; h is an integer between 0 and 2.

[0284] In some embodiments, D is N. In some embodiments, D is -CH-. In some embodiments, each R bb is fluoro. In some embodiments, each R2 is H. In some embodiments, g is 1. In some embodiments, g is 2. In some embodiments, g is 3. In some embodiments, h is 0. In some embodiments, h is 1. In some embodiments, h is 2.

[0285] In some embodiments, L is -(CR2) a -Cy-(CR2) b -Cy-C(O)-, where each -Cy- is independent of, [ka] And here, A is -N- or -CH-; D is either -N- or -CH-; T is -N- or -CH-; Each R aa It is a halogen; Each R bb It is a halogen; Each R2 independently controls H and C 1-3 It is alkyl, -O-, or -N(CH3)-; a is either 0 or 1; b is either 0 or 1; d is an integer between 1 and 3; e is an integer between 0 and 2; g is an integer between 1 and 3; j is an integer between 0 and 2; k is an integer between 1 and 3.

[0286] In some embodiments, A is -N-. In some embodiments, A is -CH-. In some embodiments, T is -N-. In some embodiments, T is -CH-. In some embodiments, R aa is fluoro. In some embodiments, each R bb is fluoro. In some embodiments, each R2 is H. In some embodiments, a is 0. In some embodiments, a is 1. In some embodiments, b is 0. In some embodiments, b is 1. In some embodiments, d is 1. In some embodiments, d is 2. In some embodiments, d is 3. In some embodiments, h is 0. In some embodiments, e is 0. In some embodiments, e is 1. In some embodiments, e is 2. In some embodiments, g is 1. In some embodiments, g is 2. In some embodiments, g is 3. In some embodiments, j is 0. In some embodiments, j is 1. In some embodiments, j is 2. In some embodiments, k is 1. In some embodiments, k is 2. In some embodiments, k is 3.

[0287] In some embodiments, each -Cy- is independently, [ka] In some embodiments, each -Cy- is independently, [ka] In some embodiments, each -Cy- is independently, [ka] In some embodiments, each -Cy- is independently, [ka] In some embodiments, L is [ka] In some embodiments, L is [ka] That is the case.

[0288] In some embodiments, -Cy- is, [ka] [ka] That is the case.

[0289] In some embodiments, -Cy- is as shown in the compounds in Table 1 below.

[0290] In some embodiments, L is a covalent bond, -CH2-, -CH2CH2-, -C(O)-, [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] That is the case.

[0291] In some embodiments, L is as shown in the compounds in Table 1 below.

[0292] As defined herein and as described above, each R is independently hydrogen or C 1-6 The R group is optionally substituted by a 3-7 member saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, or by an optionally substituted group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or by two R groups on the same carbon or nitrogen optionally together with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which these two R groups are linked.

[0293] In some embodiments, R is hydrogen. In some embodiments, R is optionally substituted with C. 1-6It is aliphatic. In some embodiments, R is optionally substituted phenyl. In some embodiments, R is optionally substituted 3- to 7-membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R is optionally substituted 3- to 7-membered saturated or partially unsaturated heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is optionally substituted 5- to 6-membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, two R groups on the same carbon or nitrogen optionally combine with their intervening atoms to form a 4- to 11-membered saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked.

[0294] In some embodiments, R is as shown in the compounds in Table 1 below.

[0295] As defined herein and as described above, each R A Independently, C 1-6 The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0296] In some embodiments, R A C is a C that is optionally substituted. 1-6 It is aliphatic. In some embodiments, R A is a phenyl compound that is optionally substituted. In some embodiments, R A R is a 3- to 7-membered saturated or partially unsaturated carbon ring that is optionally substituted. In some embodiments, R AR is an optionally substituted 3-7 member saturated or partially unsaturated heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R A This is an optionally substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0297] In some embodiments, R A C 1-6 It is alkyl. In some embodiments, R A C 1-6 It is a haloalkyl group.

[0298] In some embodiments, R A These are methyl, ethyl, isopropyl, cyclopropyl, -CHF2, or CF3.

[0299] In some embodiments, R A These are as shown in the compounds in Table 1 below.

[0300] The divalent group of this disclosure (e.g., Y 1 , rings A, L, X 1 , X 2 , X 3 The connection points of rings A, C, D, E and F) are non-directional, for example, L is [ka] If that is the case, then it is, [ka] Rings A and X 1 Includes binding to.

[0301] In some embodiments, the present invention relates to compounds of formula Ia or I-a' as compounds of formula Ia-1: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0302] In some embodiments, the present invention relates to compounds of formula Ia or I-a' as compounds of formula Ia-2: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0303] In some embodiments, the present invention relates to compounds of formula Ia or I-a' as compounds of formula Ia-3: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0304] In some embodiments, the present invention relates to compounds of formula Ia or I-a' as compounds of formula Ia-4: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0305] In some embodiments, the present invention relates to compounds of formula Ia or I-a' as compounds of formula Ia-5: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0306] In some embodiments, the present invention relates to compounds of formula Ia or I-a' as compounds of formula Ia-6: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0307] In some embodiments, the present invention relates to compounds of formula Ia-7 as compounds of formula Ia: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0308] In some embodiments, the present invention relates to compounds of formula Ia or I-a' as compounds of formula Ia-8: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0309] In some embodiments, the present invention relates to compounds of formula Ia or I-a' as compounds of formula Ia-9: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0310] In some embodiments, the present invention relates to any one compound of the following formulas: [ka] [ka] [ka] Alternatively, we provide compounds of formula Ia or I-a' as pharmaceutically acceptable salts thereof, where each of the variable elements is defined by the above formula Ia or I-a', as described in the embodiments herein, both individually and in combination.

[0311] In some embodiments, the present invention relates to compounds of formula Ia-23: [ka] Or provide a pharmaceutically acceptable salt thereof, here, X 1 Covalent bond, [ka] , or optionally substituted rings selected from 4-6 member saturated carbocycllenyl or heterocycllenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, phenylenyl, 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-8 member saturated bridged bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Y 1 is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Ring A is phenylenyl, pyridinyl, [ka] It is a ring selected from; Ring B is a fused ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring C is a 9-10 member saturated or partially unsaturated bicyclic heterocyclenyl having 1-3 heteroatoms independently selected from phenylenyl, nitrogen, oxygen, and sulfur; an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 12-15 member saturated or partially unsaturated tricyclic spirocyclic heterocyclenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R a These are hydrogen, halogen, -CN, -OR, oxo, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms a These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; R b is hydrogen, or: R b R 1 It binds to the nitrogen that is bonded, R 1 It forms an optionally substituted 5-6 membered partially unsaturated or aromatic heterocycle having 0-2 heteroatoms selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom to which it is bonded; R 1 is hydrogen, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-6 It is a cycloalkyl; Each R2 and R 5 These are independently hydrogen, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -SiR3, -S(O)2R, -S(O)2NR2, -S(O)R, -C(O)R, -C(O)OR, -C(O)NR2, -C(O)N(R)OR, -OC(O)R, -OC(O)NR2, -OP(O)R2, -OP(O)(OR)2, - OP(O)(OR)NR2, -OP(O)(NR2)2, -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR2, -N(R)S(O)2R, -N(R)P(O)R2, -N(R)P(O)(OR)2, -N(R)P(O)(OR)NR2, -N(R)P(O)(NR2)2, -N(R)S(O)2R, or R A and; m and n are independently 0, 1, 2, 3, or 4; R 3 is hydrogen, or halogen, -CN, C 1-6 Alkyl, C 1-6 C is optionally substituted with 1-2 substituents selected from haloalkyl and -OR. 1-6 Alkyl or C 4-6 It is cycloalkyl, or R 3 and R 5 This refers to divalent saturated or partially unsaturated linear or branched carbon atoms. 3-6 Linked by hydrocarbon chains, where 0-2 methylene units in the chain are independently -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-; R 4 Hydrogen, halogen, C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl, or -OC 1-6 It is a haloalkyl; L is a covalent bond, -CR2-, -CRF-, -CF2-, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C 1-10It is a hydrocarbon chain, where 0 to 6 methylene units of L are independently replaced by -Cy-, -CR2-, -CRF-, -CF2-, -CR(OR)-, -O-, -NR-, and -C(O)-; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroaryrenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroaryrenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C 1-6 A optionally substituted group selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings, heterocycles, and 5-6 member heteroaryl rings having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or: Two R groups on the same carbon or nitrogen atom may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring, having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R A Independently, C 1-6The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0312] In some embodiments, the present invention relates to a compound of formula Ia-23 as a compound of formula Ia-24: [ka] [ka] [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by formula Ia-23 above, as described in the embodiments herein, both individually and in combination.

[0313] In some embodiments, the present invention relates to a compound of formula Ib as a compound of formula Ib-1: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by formula Ib above, as described in the embodiments herein, both alone and in combination.

[0314] In some embodiments, the present invention relates to a compound of formula Ib as a compound of formula Ib-2: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by formula Ib above, as described in the embodiments herein, both alone and in combination.

[0315] In some embodiments, the present invention relates to a compound of formula Ib as a compound of formula Ib-3: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by formula Ib above, as described in the embodiments herein, both alone and in combination.

[0316] In some embodiments, the present invention relates to a compound of formula Ib as a compound of formula Ib-4: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by formula Ib above, as described in the embodiments herein, both alone and in combination.

[0317] In some embodiments, the present invention relates to a compound of formula Ib as a compound of formula Ib-5: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by formula Ib above, as described in the embodiments herein, both alone and in combination.

[0318] In some embodiments, the present invention relates to a compound of formula Ib as a compound of formula Ib-6: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by formula Ib above, as described in the embodiments herein, both alone and in combination.

[0319] In some embodiments, the present invention relates to a compound of formula Ib as a compound of formula Ib-7: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by formula Ib above, as described in the embodiments herein, both alone and in combination.

[0320] In some embodiments, the present invention relates to a compound of formula Ib as a compound of formula Ib-8: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by formula Ib above, as described in the embodiments herein, both alone and in combination.

[0321] In some embodiments, the present invention relates to a compound of formula Ic as a compound of formula Ic-1: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ic, as described in the embodiments herein, both individually and in combination.

[0322] In some embodiments, the present invention relates to a compound of formula Ic as a compound of formula Ic-2: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ic, as described in the embodiments herein, both individually and in combination.

[0323] In some embodiments, the present invention relates to a compound of formula Ic as a compound of formula Ic-3: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ic, as described in the embodiments herein, both individually and in combination.

[0324] In some embodiments, the present invention relates to a compound of formula Ic as a compound of formula Ic-4: [ka] Alternatively, a pharmaceutically acceptable salt thereof is provided, where each of the variable elements is defined by the above formula Ic, as described in the embodiments herein, both individually and in combination.

[0325] As defined herein and as described below, formulas are enclosed in square brackets, for example, [ka] When indicated using, L is linked to a modifiable carbon, oxygen, or nitrogen atom within the TYK2 binder genus mentioned, including substitution or replacement of a defined variable element within the TYK2 binder genus mentioned.

[0326] In some embodiments, the present invention relates to a compound of formula II-a: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element within is defined by the above formula (e.g., formula Ia) and is as described in the embodiments herein, both individually and in combination. Ar is a five-membered heteroaryl ring, and a five-membered heteroaryl ring can be a halogen, substituted or unsubstituted C 1-6 Alkyl, substituted, or unsubstituted C 1-6 Hydroxyalkyl, substituted, or unsubstituted C 1-4 Alkylene-OC 1-6 Alkyl, substituted, or unsubstituted C1-4 Alkilen-SC 1-6 It is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of alkyl groups; Y is either CH or N; X is either CH or N; R3 is H, halogen, substituted or unsubstituted C 1-6 Alkyl, hydroxyl, substituted, or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 Selected from the group consisting of alkylthio; R4 is either absent, or is a halogen, substituted, or unsubstituted C. 1-3 Represents one or two substituents selected from the group consisting of alkyl groups; W 1a and W 1b Each of these is independently selected from the group consisting of covalent bonds, -O-, -S-, -SO2-, -CO-, and -NR5-; W 2a and W 2b Each of these is independently selected from the group consisting of covalent bonds, -O-, -S-, -SO2-, -CO-, and -NR5-; R5 is independently H, substituted or unsubstituted C. 1-4 Selected from alkyl groups; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2023 / 030335, which is incorporated herein by reference in its entirety.

[0327] In some embodiments, the present invention relates to compounds of formula II-b: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element within is defined by the above formula (e.g., formula Ia) and is as described in the embodiments herein, both individually and in combination. R1 to R5 are each independently H, hydroxyl, and C.1-6 Alkoxy, -CO2C 1-6 Selected from alkyl groups; R6 is H or C 1-6 It is alkyl; R7 and R8 are independently H, halogen, cyano, nitro, hydroxy, amino, carboxyl, and C, respectively. 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-4 Alkoxy, C 1-4 Alkyl, C 1-6 Alkyl sulfonyl, C 1-6 Alkylamino, di(C 1-6 Alkyl)amino, C 1-6 Alkylcarbonyl, C 1-4 Selected from alkoxycarbonyls; L is C 1-6 It is alkylene; Het is selected from optionally substituted heterocycloalkyl groups that contain at least one nitrogen atom and are bonded to the carbonyl group via the nitrogen atom; Alternatively, one or more of the variable elements are as defined in CN115677676, which is incorporated herein by reference in its entirety.

[0328] In some embodiments, the present invention relates to compounds of formula II-c: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element within is defined by the above formula (e.g., formula Ia) and is as described in the embodiments herein, both individually and in combination. L is selected from -NH-, -NHC(O)-, -NHC(O)O-, and -NHC(O)NH-; T, T, and T are independently selected from N and CH, and CH is optionally substituted with one halogen; R1 is C 1-3 Selected from alkoxy, C 1-3 Alkoxy has 1, 2, or 3 R a It is optionally replaced by; R2 is H and C 1-3 Selected from alkyl, the C 1-3 Alkyl groups consist of 1, 2, or 3 R groups. b It is optionally replaced by; Ring C is selected from phenyl and 6-membered heteroaryl; R3 is -P(O)(C 1-3 Alkyl)2,-P(O)(C 3-5 Cycloalkyl)2,-S(O) n C 1-4 Alkyl, -S(O) n C 1-3 Alkylamino, -S(O) n -4- to 5-membered ring heterocycloalkyl, -S(O) n NH2, -S(O)(NR)C 1-4 Alkyl, -S(O)(NR)C 1-3 Alkylamino, -S(O)(NR)C 3-5 Cycloalkyl, [ka] Selected from, where -P(O)(C 1-3 Alkyl)2,-P(O)(C 3-5 Cycloalkyl)2,-S(O) n C 1-4 Alkyl, -S(O) n C 1-3 Alkylamino, -S(O) n -4- to 5-membered ring heterocycloalkyl, -S(O) n NH2, -S(O)(NR)C 1-4 Alkyl, -S(O)(NR)C 1-3 Alkylamino, -S(O)(NR)C 3-5 Cycloalkyl, [ka] Each of these is independently and optionally substituted with 1, 2, or 3. In some embodiments, the present invention provides compounds of formula II-d:halogens; R5 is C 1-3 Alkyl, C 3-5 Selected from cycloalkyl and 5-6 membered heteroaryls, C 1-3 Alkyl, C 3-5 Cycloalkyls and 5-6 membered heteroaryls independently have 1, 2, or 3 R c It is optionally replaced by; R4 and R6 are independently selected from H, F, Cl, Br, and I; Alternatively, R3 and R4, together with the carbon atoms to which they are bonded, [ka] form; R a and R b It is independently selected from H, D, F, Cl, Br, and I; R c These are F, Cl, Br, I and C 1-3 Selected from alkyl groups; R is H and C 1-3 Selected from alkyl groups; n is either 1 or 2; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2023 / 284869, which is incorporated herein by reference in its entirety.

[0329] [ka] or a pharmaceutically acceptable salt thereof, where, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, n is 0, 1, 2, or 3; X1 is either N or CH; Each of X2, X3, and X4 is independently N or CR. 8 and; Ring A is C 6-10 It is an aryl or a 5- to 10-membered heteroaryl; R 1 C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Cycloalkyl, -NH(deuterated C 1-6 Alkyl), or -NH(C 1-6 It is alkyl, and here, C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 2-6 Alkenil, C 2-6 Alkinyl and C 3-6 The cycloalkyl group is either unsubstituted or R aa It is replaced by one or more elements independently selected from; Preferably, R 1 Independently, C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 2-6 Alkenil, C 2-6 Alkinyl, or C 3-6 It is a cycloalkyl, where C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 2-6 Alkenil, C 2-6 Alkinyl, or C 3-6 The cycloalkyl group is either unsubstituted or R aa It is replaced by one or more elements independently selected from; R aa is hydrogen, deuterium, halide, amino, -NO2, -CN, -OH, or C 1-3 It is alkyl; R 2 Alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -NR bR c , -C(O)R a -C(O)NR b R c ,-S(O)R a -S(O)2R a , -C(O)OR a , -NR d C(O)R a , -NR d C(O)NR b R c , -NR d S(O)R a , -NR d S(O)2R a , -NR d S(O)NR b R c , -NR d S(O)2NR b R c , or -NR d C(O)OR a Here, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are either unsubstituted or hydrogen, deuterium, halide, amino, -NO2, -CN, -OH, C 1-3 alkyl, deuterated C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, deuterated C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 2-6 Alkenil, C 2-6 It is substituted with one or more groups independently selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, and substituted or unsubstituted aryl; R 3 These are hydrogen, halides, -OH, amino, -SH, -NO2, -CN, and C. 1-6 Alkyl, -C(O)NH2, C 1-6 Alkyl deuterated, -O(C 1-6 Alkyl), -O(C 1-6 (Alkyl deuterated), C 2-6 Alkenil, C 2-6 Alkinyl, C3-6 Cycloalkyl, C 3-6 Heterocycloalkyl, C 6-10 It is an aryl or a 5-10 membered ring heteroaryl, where C 1-6 Alkyl, C 1-6 Alkyl deuterated, -O(C 1-6 Alkyl), -O(C 1-6 (Alkyl deuterated), C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl, C 6-10 Aryls and 5-10 member heteroaryls are either unsubstituted or R aa It is replaced by one or more elements independently selected from; If present, each R 4 These are independently hydrogen, deuterium, halide, -OH, amino, -CN, -CF3, and C. 1-6 Alkyl, C 3-6 Cycloalkyl, -O(C 1-6 Alkyl), -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 2-6 Alkenyl or C 2-6 It is an alkinyl, and here, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-6 Alkenyls and C2-6 alkynyls are either unsubstituted or R bb It is replaced by one or more elements independently selected from; R bb These are hydrogen, deuterium, halides, aminos, -NO2, -CN, and -OH; R 5 and R 6 Each of these is independent of C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 2-6 Alkenil, C 2-6 Alkinyl, or C 3-6 It is a cycloalkyl, where C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 2-6 Alkenil, C2-6 Alkinyl and C 3-6 The cycloalkyl group is either unsubstituted or R aa It is replaced by one or more elements independently selected from; Preferably, R 5 and R 6 Each of these is independent of C 1-3 It is alkyl, and here, C 1-3 Alkyl is either unsubstituted or R bb Substituted with one or more groups selected from; or R 5 and R 6 It, together with the P bonded to it, forms a 5-6 member heterocycloalkyl group, where the 5-6 member heterocycloalkyl group is either unsubstituted or R bb It is replaced by one or more elements selected from; R 7 These are hydrogen, deuterium, halides, -OH, amino, -CN, -CF3, and C 1-6 Alkyl, C 3-6 Cycloalkyl, -O(C 1-6 Alkyl), -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 2-6 Alkenyl or C 2-6 It is an alkinyl, and here, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-6 Alkenyls and C2-6 alkynyls are either unsubstituted or R bb It is replaced by one or more elements independently selected from; If present, each R 8 These are independently hydrogen, deuterium, halide, -OH, amino, -CN, -CF3, and C. 1-6 Alkyl, C 3-6 Cycloalkyl, -O(C 1-6 Alkyl), -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)2, C 2-6 Alkenyl or C 2-6 It is an alkinyl, and here, C 1-6 Alkyl, C 3-6Cycloalkyl, C 2-6 Alkenyls and C2-6 alkynyls are either unsubstituted or R bb It is replaced by one or more elements independently selected from; R a , R b , R c and R d Each of these is independently hydrogen, deuterium, halide, amino, -NO2, -CN, -OH, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are either unsubstituted or hydrogen, deuterium, halide, amino, -NO2, -CN, -OH, C 1-6 alkyl, deuterated C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkenil, C 2-6 Substituted with one or more groups independently selected from alkynyl, substituted or unsubstituted cycloalkyl, substituted and unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; or Adjacent or non-adjacent R a , R b , R c and R d Any two of these form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, where the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups are either unsubstituted or composed of hydrogen, deuterium, a halide, amino, -NO2, -CN, -OH, or C 1-6 alkyl, deuterated C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Haloalkoxy, C 2-6 Alkenil, C 2-6Alkinyl, substituted, or unsubstituted C 3-6 Substituted with one or more groups selected from cycloalkyl, substituted and unsubstituted 3- to 6-membered heterocycloalkyl, substituted or unsubstituted 6- to 10-membered aryl, and substituted or unsubstituted 5- to 10-membered heteroaryl; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 261524, which is incorporated herein by reference in its entirety.

[0330] In some embodiments, the present invention relates to compounds of formula II-e: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, n is selected from 0, 1, 2, and 3; X1 is selected from N and CH; Ring A is C 6-10 Selected from aryls and 5-10 membered heteroaryls; R 1 is amino, C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Cycloalkyl and -NHC 1-6 Selected from alkyl, the C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Cycloalkyl and -NHC 1-6 Each alkyl group is independently substituted with one or more substituents from hydrogen, deuterium, halogen, amino, nitro, cyano, hydroxy, and alkyl groups. 1-3 Selected from alkyl groups; R 2 Alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -NR c R b , -C(O)R a -C(O)NR c R b ,-S(O)R a -S(O)2R a , -C(O)OR a , -NR d C(O)R a , -NR d C(O)NR c R b , -NR d S(O)R a , -NR d S(O)2R a , -NR d S(O)NR b R c , -NR d S(O)2NR b R c , and -NR d C(O)OR a Selected from the group consisting of, where alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are each independently substituted with one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, cyano, hydroxyl, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; R 3 These are hydrogen, deuterium, halogen, hydroxyl, amino, cyano, trifluoromethyl, and C. 1-6 Alkyl, C 3-6 Cycloalkyl, -OC 1-6 Alkyl, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C2-6 Alkenyl and C 2-6 Selected from alkynyl, the C 1-6 Alkyl, C 3-6 Cycloalkyl, C 2-6 Alkenyl and C 2-6 Alkynyl, where each group is independently substituted with one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, cyano, and hydroxy; If present, each R 4 These are, independently, hydrogen, deuterium, halogen, hydroxyl, amino, mercapto, nitro, cyano, and C. 1-6 Alkyl, C 1-6 Alkyl deuterated, -OC 1-6 Alkyl, -OC 1-6 Alkyl deuterated, -NHC 1-6 Alkyl, -N(C 1-6 Alkyl)2, C 2-6 Alkenyl and C 2-6 Alkinyl, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl, P(O)R5R6, C 6-10 Aryl, and C 5-10 Selected from heteroaryls, the C 1-6 Alkyl, C 1-6 Alkyl deuterated, -OC 1-6 Alkyl, -OC 1-6 Alkyl deuterated, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-6 Cycloalkyl, C 3-6 Heterocycloalkyl, C 6-10 Aryl and C 5-10 Each heteroaryl is independently substituted with one or more substituents from hydrogen, deuterium, halogen, amino, nitro, cyano, hydroxy, and alkyl groups. 1-3 Selected from alkyl groups; If present, R 5 and R 6 Each of them is independent of C 1-3 Selected from alkyl, the C 1-3Alkyl is substituted with one or more substituents selected from hydrogen, deuterium, halogen, amino, nitro, cyano, and hydroxy; or R 5 and R 6 These, together with the phosphorus atom to which they are bonded, form a 5-6 membered heterocycloalkyl group, and the 5-6 membered heterocycloalkyl group is substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, cyano, and hydroxyl; R 8 is hydrogen and C 1-6 Selected from alkyl groups; or R 8 and R 4 Together with ring a, it forms a 5- to 10-membered complex ring; R a , R b , R c , and R d Each is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, cyano, hydroxy, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, where each of the alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, heteroaryl, cyano, hydroxy, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; or Adjacent or non-adjacent R a , R b , R c , and R dAny two of these combine to form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, wherein the cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group is substituted with one or more substituents selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, cyano, hydroxy, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; Alternatively, one or more of the variable elements are as defined in CN115466257, which is incorporated herein by reference in its entirety.

[0331] In some embodiments, the present invention relates to compounds of formula II-f: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, T, Y, Y1, Y2, and Y3 are selected from N and CH, where CH is one halogen, C 1-3 Alkyl and C 1-3 It is optionally substituted with an alkoxy; R 11 C 2-4 Alkenil, C 2-4 Selected from alkynyl and CH2CN, C 2-4 Alkenil, C 2-4 The alkynyl and CH2CN groups are optionally substituted with one, two, or three halogen substituents; R 12 This is selected from -N(R2)2 and -C(R2)3; R 13 C 3-6Cycloalkyl, 3-6 member heterocycloalkyl, phenyl, 5-6 member heteroaryl, -NHC(O)C 3-6 Selected from cycloalkyl, -NHC(O)-3~6 member heterocycloalkyl, -NHC(O)phenyl, and -NHC(O)-5~6 member heteroaryl, C 3-6 Cycloalkyl, 3-6 member heterocyclic alkyl, phenyl, 5-6 member heteroaryl, -NHC(O)C 3-6 Cycloalkyl, -NHC(O)-3~6 member heterocycloalkyl, -NHC(O)-phenyl, and -NHC(O)-5~6 member heteroaryl are composed of 1, 2, or 3 halogens, C 1-3 Alkyl and C 1-3 It is optionally substituted with an alkoxy; R1 is C 1-3 Alkyl and C 1-3 Selected from alkoxy, the C 1-3 Alkyl and C 1-3 Alkoxy has 1, 2, or 3 R a It is optionally replaced by; R2 is H, C 1-3 Alkyl and C 1-3 Selected from alkoxy, the C 1-3 Alkyl and C 1-3 Alkoxy has 1, 2, or 3 R b It is optionally replaced by; Ring B does not exist; Alternatively, ring B is C 5-10 Cycloalkyl, 5-10 member heterocycloalkyl, C 6-10 Selected from aryls and 5-10 member heteroaryls, C 5-10 Cycloalkyl, 5-10 member heterocycloalkyl, C 6-10 Aryls and 5- to 10-membered heteroaryls are optionally substituted with 1, 2, or 3 Rc members; E is -(CH2) s NR3-, [ka] and -C(O)NR3-C 3-6 Selected from cycloalkyl-NR3-; s is 0, 1, or 2; n and m are independently selected from 0, 1, 2, and 3; R3 is H and C 1-3 Selected independently of alkyl; Each R a It is independently selected from F, Cl, Br, I, and OH; Each R b It is independently selected from H, D, F, Cl, Br, and I; Each R c These are H, F, Cl, Br, I, and C 1-3 Selected independently of alkyl, C 1-3 The alkyl group is optionally substituted with one, two, or three halogens; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 253333, which is incorporated herein by reference in its entirety.

[0332] In some embodiments, the present invention relates to compounds of formula II-g: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, T is selected from CH and N, which are optionally substituted with one halogen; R1 is C 1-3 Alkyl and C 1-3 Selected from alkoxy, the C 1-3 Alkyl and C 1-3 Alkoxy has 1, 2, or 3 R a It is optionally replaced by; R2 is H, C 1-3 Alkyl and C 1-3 Selected from alkoxy, the C 1-3 Alkyl and C1-3 Alkoxy has 1, 2, or 3 R b It is optionally replaced by; R3 consists of F, Cl, Br, I, and C 1-3 Selected from alkyl groups; Ring B has 1, 2, or 3 R c Selected from a 5-member heteroaryl group that has been optionally substituted; R a and R b It is independently selected from H, D, F, Cl, Br, and I; Each R c These are H, F, Cl, Br, I, and C 1-3 Selected independently of alkyl, C 1-3 The alkyl group is optionally substituted with 1, 2, or 3 R atoms; Each R is selected from F, Cl, Br, and I; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 253335, which is incorporated herein by reference in its entirety.

[0333] In some embodiments, the present invention relates to compounds of formula II-h: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, Ring A is selected from aryl, heteroaryl, or partially unsaturated heterocycles; X and Y are selected from C or N; R1 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogenated C1-C6 alkyl, deuterated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, halogen, cyano, nitro, -C(O)NR a Rb , -C(O)R a , -C(O)OR a , -OR a , -R a Ure b -OC(O)R a , -OC(O)OR a -OC(O)NR a R b , -NR a R b , -SR a ,-S(O)R a -S(O)2R a Alternatively, selected from 3-10 member saturated or unsaturated rings containing 0-3 heteroatoms, wherein the 3-10 member saturated ring contains 0-3 heteroatoms, or the unsaturated ring contains 1-3 R a It is optionally replaced by; R2 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogenated C1-C6 alkyl, deuterated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, halogen, cyano, nitro, -C(O)NR a R b , -C(O)R a , -C(O)OR a , -OR a , -R a Ure b -OC(O)R a , -OC(O)OR a -OC(O)NR a R b , -NR a R b , -SR a ,-S(O)R a -S(O)2R a Alternatively, selected from 3-10 member saturated or unsaturated rings containing 0-3 heteroatoms, wherein the 3-10 member saturated ring contains 0-3 heteroatoms, or the unsaturated ring contains 1-3 R a It is optionally replaced by; R3 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogenated C1-C6 alkyl, deuterated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, halogen, cyano, nitro, carbonyl, -C(O)NR a R b , -C(O)R a , -C(O)OR a , -OR a , -R a Ure b , -OR a Ure b -OC(O)R a , -OR a , -C(O)R b , -OC(O)OR a -OC(O)NR a R b , -NR a R b -NC(O)R a , -R c NR a R b , -SR a ,-S(O)R a -S(O)2R a , -R a A saturated or unsaturated ring with 3 to 10 members containing CN or 0 to 3 heteroatoms, and a saturated or unsaturated ring with 3 to 10 members containing 0 to 3 heteroatoms contains 1 to 3 R a It is optionally replaced by; R4 is hydrogen, [ka] or 1 to 3 R a Selected from a 3-10 member saturated or unsaturated ring containing 0-3 heteroatoms optionally substituted by, where Z is -NH-, -N(CH2)-, or a direct bond; R5 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogenated C1-C6 alkyl, deuterated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, halogen, cyano, nitro, -C(O)NR a Rb , -C(O)R a , -C(O)OR a , -OR a , -R a Ure b -OC(O)R a , -OC(O)OR a -OC(O)NR a R b , -NR a R b , -SR a ,-S(O)R a -S(O)2R a Alternatively, selected from 3-10 member saturated or unsaturated rings containing 0-3 heteroatoms, wherein the 3-10 member saturated ring contains 0-3 heteroatoms, or the unsaturated ring contains 1-3 R a It is optionally replaced by; R6 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogenated C1-C6 alkyl, deuterated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, halogen, cyano, nitro, -C(O)NR a R b , -C(O)R a , -C(O)OR a , -OR a , -R a Ure b -OC(O)R a , -OC(O)OR a -OC(O)NR a R b , -NR a R b , -SR a ,-S(O)R a -S(O)2R a Alternatively, selected from 3-10 member saturated or unsaturated rings containing 0-3 heteroatoms, wherein the 3-10 member saturated ring contains 0-3 heteroatoms, or the unsaturated ring contains 1-3 R a It is optionally replaced by; Each R a , R b , R cThis includes hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogenated C1-C6 alkyl, deuterated C1-C6 alkyl, halogenated C2-C6 alkenyl, halogenated C2-C6 alkynyl, halogen, cyano, nitro, amino, carboxyl, carbonyl, hydroxy, hydroxyalkyl, alkoxy, haloalkoxy, deuterated alkoxy, C3-C6 cycloalkyl, haloC3-C6 cycloalkyl, alkoxy-substituted C3-C6 cycloalkyl, C3-C6 heterocyclyl, halogenated C3-C6 heterocyclyl, alkyl-substituted C3-C6 heteroaryl, -S(O)2R d , -OR d Ure e , -R d Ure e , -C(O)R d or -OC(O)R d Selected independently from each R d , R e These are independently selected from C1-C6 alkyl groups; n is 0, 1, 2, or 3; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 242697, which is incorporated herein by reference in its entirety.

[0334] In some embodiments, the present invention relates to compounds of formula II-i: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X is either -N- or -CH-; R 1 is -C(0)R 1a It is either a 5-8 membered heterocycle containing 1-2 heteroatoms selected from N, O, and S, and each heterocycle contains 0-2 R1b It has been replaced with; R 1a COOC 1-3 Alkyl, or C 3-6 It is a cycloalkyl group, and the cycloalkyl group has 0 to 2 R 1b It is replaced with;R 1b Each instance is independently either F or C 1-3 It is alkyl; R 2 It is either OMe or OCHF2; R 3 CD3, C 1-3 Alkyl, C 3-6 It is cycloalkyl or CH2F; R 4 is hydrogen, halo, C 1-4 Alkyl, C 1.4 Alkoxy or C 3-6 It is a cycloalkyl; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 241171, which is incorporated herein by reference in its entirety.

[0335] In some embodiments, the present invention relates to compounds of formula II-j: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X is either -N- or -CH-; R 1 C 1-3 It is alkyl; R 2 is F or C 1-3 It is alkyl; R 3These are oxadiazole, oxazole, pyridine, pyrimidine, thiadiazole, pyrazine, thiazole, pyrazole, or isothiazole, all of which contain 0 to 3 R 3a It is substituted with the base; R 3a These are H, F, Cl, CN, NO2, C 1-3 Alkyl, OC M Alkyl, C 3-6 Cycloalkyl, (CH2) n F, CHF 2; Hydroxy C 1-3 Alkyl or cyano C 1-3 It is alkyl; n is either 1 or 2; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 241172, which is incorporated herein by reference in its entirety.

[0336] In some embodiments, the present invention relates to compounds of formula II-k: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X is either -N- or -CH-; R 1 C 1-3 It is alkyl or -NHCD3; R 2 -N(CH3)2, -OR 2a , or 0 to 2 R 2b C replaced by 3-6 It is a cycloalkyl; R 2a C 1-3 Alkyl; R 2b is F or C 1-3 Alkyl; R 3 C1-3 Fluoroalkyl or C 3-6 It is a cycloalkyl; R 4 is hydrogen, halogen or C 1-3 It is alkyl, Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 241173, which is incorporated herein by reference in its entirety.

[0337] In some embodiments, the present invention relates to compounds of formula II-1: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X is either -N- or -CH-; R 1 is -C(O)R 1a and; R 1a C 3-6 It is a cycloalkyl; R 2 C 1-6 It is an alkoxy; R 3 C 1-6 Alkyl or C 3-6 It is a cycloalkyl; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 241174, which is incorporated herein by reference in its entirety.

[0338] In some embodiments, the present invention relates to compounds of formula II-m: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X, X 1 and X 2 is -N- or -CH-, provided that X is -CH-, then X 1 and X 2 One of them must be -N-, and if X is -N-, then X 1 and X 2 One of them must be -N-; Y is either -CH- or -N-; R 1 is -OR la , -NR la R lb or R 2 and; R la and R lb Independently, hydrogen or C1-3 It is alkyl; R 2 This is 0 to 2 R 2a C replaced by 3-6 It is a cycloalkyl; R 2a is F or C 1-3 It is alkyl; R 3 C 1-3 Alkyl or C 3-6 It is cycloalkyl; R 4 is hydrogen, halogen or C 1-3 It is alkyl; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 241175, which is incorporated herein by reference in its entirety.

[0339] In some embodiments, the present invention relates to compounds of formula II-n: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, L is alkyl, deuterated alkyl, haloalkyl, amino, alkylamino, deuterated alkylamino, cycloalkyl, cycloalkylamino, deuterated cycloalkylamino; Ring B is an aryl, heteroaryl, or heterocyclyl group, and ring B consists of the following groups: [ka] Selected from, where T, G, Y, Z, and M are independently oxygen atoms, CR A1 , CR A2 , nitrogen atom or NR B Selected from; E is either a nitrogen atom or a carbon atom; R A1 , R A2 is hydrogen, deuterium, C 1-6 Alkyl, halogen, and the following structures: [ka] Selected from; R B is hydrogen, C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 1-6 Alkyl-C(O)-, C 1-6 Haloalkyl-C(O)-, cycloalkane-base-C(O)-, aryl-C(O)-, substituted amino-C(O)-, C 1-6 Alkyl-S(O)2-, alkenyl, deuterated alkenyl, alkynyl, deuterated alkynyl, and the following structures: [ka] [ka] Selected from; Q is a chemical bond or -C(O)-, -C(S)-, -S(O)-, -S(O)2-, -C(NR 8 )-, in other words, [ka] and; P is either an oxygen atom or a sulfur atom; X is a chemical bond, an oxygen atom, or NH or NR. A and; R A These are alkyl, deuterated alkyl, and haloalkyl; U is either a nitrogen atom or a carbon atom; Ring A is an aryl, heteroaryl, or heterocyclyl group, and ring A consists of the following groups: [ka] Selected from; C is alkyl, cycloalkyl, amino, substituted amino, aryl, heteroaryl, or heterocyclyl, and C is one of the following groups: [ka] Selected from; Here, R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 8 The bases are selected from hydrogen, deuterium, halogen, amino, alkynyl, deuterated alkynyl, alkenyl, deuterated alkenyl, alkenylcarbonyl, deuterated alkenylcarbonyl, alkyl, deuterated alkyl, alkylcarbonyl, and deuterated alkylcarbonyl; where the alkynyl, alkenyl, deuterated alkynyl, deuterated alkenyl, alkyl, and deuterated alkane bases are optionally substituted with halogen, alkyl, hydroxyl, amino, cycloalkyl, aryl, and heteroaryl; n is 1, 2, 3, 4, 5, 6; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 233286, which is incorporated herein by reference in its entirety.

[0340] In some embodiments, the present invention relates to compounds of formula II-o: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, R 1 , R 2 Each of these is independently and optionally substituted with a halogen C 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkynyl, deuterium-optionally substituted C 1-6 C is optionally substituted with alkyl or deuterium. 2-6 C is optionally substituted with alkenyl or deuterium. 2-6 Selected from alkynyl, hydrogen, and deuterium; R 3 and R 4 These are C, which is independently and selectively substituted with hydrogen and halogen, respectively. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkinyl, -C 0-4 Alkilen-OR 3a , -C 0-4 Alkylene-OC(O)R 3a , -C 0-4 Alkilen-SR 3a , -C 0-4 Alkilen-S(O)2R 3a , -C 0-4 Alkylene-S(O)R 3a, -C 0-4 Alkylene-S(O)2NR 3a R 3b , -C 0-4 Alkylene-S(O)NR 3a R 3b , -C 0-4 Alkylene-C(O)R 3a , -C 0-4 Alkylene-C(O)OR 3a , -C 0-4 Alkylene-C(O)NR 3a R 3b , -C 0-4 Alkilen-NR 3a R 3b , -C 0-4 Alkilen-NR 3a C(O)R 3b , -C 0-4 Alkylene-(saturated or unsaturated 3-10 membered carboncyclic group), -C 0-4 Alkylene-(saturated or unsaturated 4-10 member heterocycloalkyl), -C 0-4 Alkylene-(6-10 membered aromatic ring group), -C 0-4 Selected from alkylene-(5-10 member aromatic heterocyclic group); where alkylene, carbocykyl, heterocycloalkyl, aromatic ring, aromatic heterocycle, 1, 2, or 3 independent R groups. 3c It may also be further substituted with substituents; R 3a and R 3b These are C, which is independently and selectively substituted with hydrogen and halogen, respectively. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkinyl, -C 0-4 Alkylene-(saturated or unsaturated 3-10 membered carboncyclic group), -C 0-4 Alkylene-(saturated or unsaturated 4-10 member heterocycloalkyl), -C 0-4 Alkylene-(6-10 membered aromatic ring group), -C 0-4 Selected from alkylene-(5-10 member aromatic heterocyclic group); where alkylene, carbocykyl, heterocycloalkyl, aromatic ring, aromatic heterocycle, 1, 2, or 3 independent R groups.3c It may also be further substituted with substituents; R 3c These are C, which is optionally substituted with halogen, cyano, and halogen, respectively, independently. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkinyl, -C 0-4 Alkilen-OR 3d , -C 0-4 Alkylene-OC(O)R 3d , -C 0-4 Alkilen-SR 3d , -C 0-4 Alkilen-S(O)2R 3d , -C 0-4 Alkylene-S(O)R 3d , -C 0-4 Alkylene-S(O)2NR 3d R 3e , -C 0-4 Alkylene-S(O)NR 3d R 3e , -C 0-4 Alkylene-C(O)R 3d , -C 0-4 Alkylene-C(O)OR 3d , -C 0-4 Alkylene-C(O)NR 3d R 3e , -C 0-4 Alkilen-NR 3d R 3e , -C 0-4 Alkilen-NR 3d C(O)R 3e , -C 0-4 Alkylene-(saturated or unsaturated 3-10 membered carboncyclic group), -C 0-4 Alkylene-(saturated or unsaturated 4-10 member heterocycloalkyl), -C 0-4 Alkylene-(6-10 membered aromatic ring group), -C 0-4 Selected from alkylene-(5-10 member aromatic heterocyclic group); where alkylene, carbocyryl, heterocycloalkyl, aromatic ring, aromatic heterocycle, one, two, or three independent R groups. 3f They may be further substituted with substituents; or two independent R3c It, together with the linked atoms, [ka] form; R 3d and R 3e These are C, which is independently and selectively substituted with hydrogen and halogen, respectively. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkinyl, -C 0-4 Alkylene-(saturated or unsaturated 3-10 membered carboncyclic group), -C 0-4 Alkylene-(saturated or unsaturated 4-10 member heterocycloalkyl), -C 0-4 Alkylene-(6-10 membered aromatic ring group), -C 0-4 Selected from alkylene-(5-10 membered aromatic heterocyclic group); or R 3d and R 3e These atoms, together with linked atoms, form saturated or unsaturated 4- to 10-membered heterocycloalkyl groups; R 3f This is C, independently and optionally substituted with halogen, cyano, and halogen. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Selected from Alkinir; x is N or CR x Selected from; R 5 C is optionally substituted with hydrogen, halogen, cyano, or halogen. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkynyl, deuterium-optionally substituted C 1-6 C is optionally substituted with alkyl or deuterium. 2-6 C is optionally substituted with alkenyl or deuterium. 2-6 Alkinyl, -C 0-4 Alkilen-OR 5a , -C0-4 Alkilen-SR 5a , -C 0-4 Alkilen-NR 5a R 5b Selected from; R 5a and R 5b Each of these is independently and optionally substituted with a halogen C 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkynyl, deuterium-optionally substituted C 1-6 C is optionally substituted with alkyl or deuterium. 2-6 C is optionally substituted with alkenyl or deuterium. 2-6 Selected from alkynyl, hydrogen, and deuterium; R x , R 6 , R 7 , R 8 Each of these is independently and selectively substituted with hydrogen, halogen, cyano, and halogen C. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkynyl, -OH, -O (-C optionally substituted with halogen) 1-6 Alkyl), -SH, -S (optionally halogenated -C) 1-6 Alkyl), -NH2, -NH(optionally substituted with halogen -C 1-6 Alkyl), -N (-C optionally substituted with halogen) 1-6 Selected from alkyl)2; R 8 and R 2 These atoms, together with linked atoms, form saturated or unsaturated 4- to 10-membered heterocycloalkyl groups; Ring A is selected from saturated or unsaturated 3-10 membered carbocyclyl, saturated or unsaturated 4-10 membered heterocycloalkyl, 6-10 membered aromatic cyclyl, and 5-10 membered aromatic heterocyclyl; where carbocyclyl, heterocycloalkyl, aromatic ring, and aryl heterocyclyl are 1, 2, 3, 4, or 5 independent RA1 It may also be further substituted with substituents; R A1 This is C, independently and optionally substituted with halogen, cyano, and halogen. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkinyl, -C 0-4 Alkilen-OR A2 , -C 0-4 Alkylene-OC(O)R A2 , -C 0-4 Alkilen-SR A2 , -C 0-4 Alkilen-S(O)2R A2 , -C 0-4 Alkylene-S(O)R A2 , -C 0-4 Alkylene-S(O)2NR A2 R A3 , -C 0-4 Alkylene-S(O)NR A2 R A3 , -C 0-4 Alkylene-C(O)R A2 , -C 0-4 Alkylene-C(O)OR A2 , -C 0-4 Alkylene-C(O)NR A2 R A3 , -C 0-4 Alkilen-NR A2 R A3 , -C 0-4 Alkilen-NR A2 C(O)R A3 , -C 0-4 Alkilen-NR A2 S(O)2R A3 , -C 0-4 Alkilen-NR A2 S(O)R A3 , -C 0-4 Alkylene-(saturated or unsaturated 3-10 membered carboncyclic group), -C 0-4 Alkylene-(saturated or unsaturated 4-10 member heterocycloalkyl), -C 0-4 Alkylene-(6-10 membered aromatic ring group), -C 0-4Selected from alkylene-(5-10 member aromatic heterocyclic group); where alkylene, carbocyryl, heterocycloalkyl, aromatic ring, aromatic heterocyclic group, 1, 2, or 3 independent R A4 They may be further substituted with substituents; or Two independent R A1 It, together with the linked atoms, [ka] Forming, Forms saturated or unsaturated 5-8 membered carbocyclyls, saturated or unsaturated 5-8 membered heterocycloalkyls, 5-8 membered aromatic cyclyls, and 5-8 membered aromatic heterocyclyls; R A2 and R A3 These are C, which is independently and selectively substituted with hydrogen and halogen, respectively. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkinyl, -C 0-4 Alkylene-(saturated or unsaturated 3-10 membered carboncyclic group), -C 0-4 Alkylene-(saturated or unsaturated 4-10 member heterocycloalkyl), -C 0-4 Alkylene-(6-10 membered aromatic ring group), -C 0-4 Alkylene-(5-10 member aromatic heterocyclic group) selected; where alkyl, alkenyl, alkynyl, alkylene, carbocykyl, heterocycloalkyl, arylcyclyl, arylheterocyclyl is selected from 1, 2, 3, 4, or 5 independent R groups. A4 It may also be further substituted with substituents; R A4 This is C, independently and optionally substituted with halogen, cyano, and halogen. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Alkinyl, -C 0-4 Alkilen-OR A5 , -C 0-4 Alkylene-OC(O)R A5, -C 0-4 Alkilen-SR A5 , -C 0-4 Alkilen-S(O)2R A5 , -C 0-4 Alkylene-S(O)R A5 , -C 0-4 Alkylene-S(O)2NR A5 R A6 , -C 0-4 Alkylene-S(O)NR A5 R A6 , -C 0-4 Alkylene-C(O)R A5 , -C 0-4 Alkylene-C(O)OR A5 , -C 0-4 Alkylene-C(O)NR A5 R A6 , -C 0-4 Alkilen-NR A5 R A6 , -C 0-4 Alkilen-NR A5 C(O)R A6 , -C 0-4 Alkilen-NR A5 S(O)2R A6 , -C 0-4 Alkilen-NR A5 S(O)R A6 Selected from; Two independent R A4 It, together with the linked atoms, [ka] Forming, R A5 and R A6 These are C, which is independently and selectively substituted with hydrogen and halogen, respectively. 1-6 C is optionally substituted with alkyl or halogen. 2-6 C is optionally substituted with alkenyls or halogens. 2-6 Selected from Alkinir; The heteroatoms in saturated or unsaturated heterocyclic alkyl and aromatic heterocyclic groups are independently selected from one or more of O, S, B, or N; unsaturated carbocyclic groups do not contain aryl groups, and unsaturated heterocycloalkyl groups do not contain aromatic heterocyclic groups; Alternatively, one or more of the variable elements are as defined in the specification CN115197196, which is incorporated herein by reference in its entirety.

[0341] In some embodiments, the present invention relates to compounds of formula II-p: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X is selected from CH and N; R 1 is hydrogen, C 1-6 alkyl, deuterated C 1-6 Selected from alkyl and cycloalkyl groups; R 8 is hydrogen, C 1-6 Alkyl, C 1-6 Selected from alkoxy; or R 1 R 8 It is linked to, and together with the nitrogen atom to which it is linked, it forms a heterocycle; X 1 and X 2 It is independently selected from CH2, NH, and O; Ring C is selected from aryl, heteroaryl, cycloalkyl, and heterocyclyl; R is independent, R 2 or R 3 Selected from; n is selected from 0, 1, 2, and 3; R 2 is hydrogen, -OH, C1-6 alkyl, deuterated C 1-6 Alkyl, C 1-6 Alkoxy, deuterated C 1-6 Alkoxy, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-S-, C 1-6 Alkyl-S(O)-, C 1-6 Selected from alkyl-S(O)2, R 3 is hydrogen, C 1-6 Alkoxy-C(O)-, (R 5 )(R 6 )NC(O)-, or one or more R a The following groups are optionally substituted: selected from phenyl, heteroaryl, heterocyclyl, and cycloalkyl groups; R a is hydrogen, halogen, -CN, carboxyl, (R 5 )(R 6 )NC(O)-, C 1-6 Alkyl, C 1-6 Alkyl-C(O)-, C 1-6 Alkyl-C(O)-NH-, halogenated C 1-6 Alkyl, halogenated C 1-6 Alkoxy, Hydroxy C 1-6 Alkyl, C 1-6 Alkoxy, cycloalkyl, cycloalkyl-(CH2) p Selected from O-,NC-cycloalkyl or any two adjacent R a These atoms, together with the atoms they are linked to, form a heterocycle; p is selected from 0, 1, 2, and 3; L 1 is one or more R b C is optionally replaced by 1-8 Selected from alkylene, the C 1-8 In alkylenes, one or more CH2 groups are -C(O)-, -NR 7 Substituted with -, -S-, -S(O)-, -S(O)2-, and / or -O-; R b C 1-6Selected from alkyl groups, or two R groups located on the same carbon atom. b And the carbon atoms to which it is bonded, together form cycloalkyl and heterocyclyl groups; Or, L 1 teeth, [ka] Selected from, where the A-terminus of the ring is X 2 It is connected to the ring C, and the L-terminus is connected to the ring C; Ring A is selected from aryl and heteroaryl rings; L 2 is one or more R c C is optionally replaced by 1-6 Selected from alkylene, the C 1-6 In alkylenes, one or more CH2 groups are -C(O)-, -NR 7 Substituted with -, -S-, -S(O)-, -S(O)2- and / or -O-; R c C 1-6 Selected from alkyl groups, or both located on the same carbon atom, R c And the bonded carbon atoms together form cycloalkyl and heterocyclyl groups; R 4 Hydrogen, halogen, C 1-6 Alkyl, halogenated C 1-6 Selected from alkyl, phenyl, and cycloalkyl, phenyl is optionally a halogen, C 1-6 Alkyl, C 1-6 alkoxy or substituted halogenated C 1-6 Composed of one or more alkyl groups selected from the alkyl groups; m is selected from 0, 1, 2, or 3; R 5 and R 6 These are independently hydrogen, -OH, and C. 1-6 Selected from alkyl, cycloalkyl, or R 5 and R 6 They are linked together, and together with the nitrogen atom to which they are linked, they form a heterocycle; R 7is hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Selected from alkyl-C(O)- and -C(O)OCH2Ph; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 213980, which is incorporated herein by reference in its entirety.

[0342] In some embodiments, the present invention relates to compounds of formula II-q: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X and Y are independently CR5 or N; Z is either CR6 or N; W1 and W2 are, independently, O, S, SO2, CO, NR7CO, and CONR7, respectively; W3 is a divalent group selected from the group consisting of CO, NR7, NR7CO, and CONR7; R3 is either substituted or unsubstituted C 3-6 It is a cycloalkyl; R4 is either substituted or unsubstituted C 1-6 Alkyl, substituted, or unsubstituted C 3-6 Selected from the group consisting of cycloalkyl groups; R4 is also optionally substituted with R1 and R2; R1 and R2 are, independently, H, substituted, or unsubstituted C. 1-6 Selected from the group consisting of alkyl groups; or R1 and R2 and the carbon atoms to which they are bonded together are substituted or unsubstituted C 3-6 Forms a cycloalkyl group; R5, R6, and R7 are each independently H, substituted, or unsubstituted C. 1-4Selected from the group consisting of alkyl groups; n is either 1 or 2; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 206705, which is incorporated herein by reference in its entirety.

[0343] In some embodiments, the present invention relates to compounds of formula II-r-1 or II-r-2: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X is either CH or N; R 1 This is a carbon atom substituted with 0 to 7 deuterium atoms. 1-3 It is alkyl; R 2 C is replaced by arbitrary selection. 1-6 Alkyl, optionally substituted C 1-4 Heteroalkyl, optionally substituted cycloalkyl (e.g., C 3-6 A cycloalkyl, optionally substituted heterocyclyl (e.g., a 4- to 8-membered heterocyclyl), or optionally substituted heteroaryl; R 3 Each instance is independently substituted with a halogen or optionally substituted C. 1-4 Alkyl or optionally substituted C 1-4 It is heteroalkyl; j is 0, 1, 2, or 3; R 4 This is 1 to 3 R A , S(O) p R B , OR C C is optionally replaced by 1-6 It is alkyl; p is 0, 1, or 2. R A Each instance is independently of a halogen, OH, and 1-3 R atoms. A1 C is optionally replaced by 1-6 It is alkyl, R B This is 1 to 3 R A1 C is optionally replaced by 1-6 It is alkyl, R C is hydrogen or 1-3 R A2 C is optionally replaced by 1-6 It is alkyl, R A1 Each instance is independently a halogen, OH, or CN; R A2 Each instance is independently either F or OH; R 5 This refers to an optionally substituted heterocyclyl or optionally substituted heteroaryl, for example, [ka] is or R 5 is, -L 1 -L 2 -QG is; R 10 Each instance is independently and selectively substituted with a cycloalkyl (e.g., C 3-6 A cycloalkyl group, or an optionally substituted heterocycline (e.g., a 4- to 8-membered heterocycline); R 10B Each instance is independently of halogen, CN, and optionally substituted C. 1-6 Alkyl, optionally substituted cycloalkyl (e.g., C 3-6 A cycloalkyl group, or an optionally substituted heterocycline (e.g., a 4- to 8-membered heterocycline); L 1 is O, C(O), NH, or null; L 2 C 1-4 It is alkylene or null; Q is an arbitrarily substituted heterocycle or an arbitrarily substituted heteroaryl, G is CN, [ka] or Michael receptor; R 11 C is a hydrogen atom that is optionally substituted with other carbon atoms. 1-6 Alkyl or optionally substituted C 3-6 It is a cycloalkyl; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 193499, which is incorporated herein by reference in its entirety.

[0344] In some embodiments, the present invention relates to compounds of formula II-s: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X and Y are independently CR5 or N; Z is either CR6 or N; W1 and W2 are, independently, O, S, SO2, CO, NR7CO, and CONR7, respectively; W3 is a divalent group selected from the group consisting of CO, NR7, NR7CO, and CONR7; R3 is either substituted or unsubstituted C 3-6 It is a cycloalkyl; R4 is either substituted or unsubstituted C 1-6 Alkyl, substituted, or unsubstituted C 3-6 Selected from the group consisting of cycloalkyl groups; R4 is also optionally substituted with R1 and R2; R1 and R2 are, independently, H, substituted, or unsubstituted C.1-6 Selected from the group consisting of alkyl groups; or R1 and R2 and the carbon atoms to which they are bonded together are substituted or unsubstituted C 3-6 Forms a cycloalkyl group; R5, R6, and R7 are each independently H, substituted, or unsubstituted C. 1-4 Selected from the group consisting of alkyl groups; n is either 1 or 2; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 206705, which is incorporated herein by reference in its entirety.

[0345] In some embodiments, the present invention relates to compounds of formula II-t: [ka] The invention provides a pharmaceutically acceptable salt thereof, where each of the variable elements is defined by the above formula (e.g., formula Ia), as described in the embodiments herein, both individually and in combination.

[0346] In some embodiments, the present invention relates to compounds of formula II-u: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, Ring A is an unsubstituted or substituted five-membered hetero ring, where A 1 and A 2 Independently, are N or C, and if ring A is substituted, then ring A has p R 8 It has been replaced with; Each R 8These are independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocyclic, unsubstituted or substituted heterocyclic, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17 , or -SO2N(R 16 )2; R 8 If R is bonded to a nitrogen atom, 8 This includes hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted polycarbonate, unsubstituted or substituted heterocycle, and -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -S(=O)R 17 , -SO2R 17 Or -SO2N(R 16 )2 or Two R atoms bonded to the same carbon atom 8 These combine to form =O, =S, or =NH; Z is -NR 10 -, -O-, -S-, -S(=O)-, or -SO2-; R 10 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle; X 1 , X 2 , and X 3 Each of them operates independently, CR 11 or N; Each R 11 These are independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocyclic, unsubstituted or substituted heterocyclic, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17 , or -SO2N(R 16 )2; B 1 is N or CR 12a and; B 2 is N or CR 12b and; R 12a and R 12b These are, independently, hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocyclic, unsubstituted or substituted heterocyclic, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17 , or -SO2N(R 16 )2; R 1 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl; R 2R is a ring B which is an unsubstituted or substituted heterocycle or an unsubstituted or substituted carbon ring, and if ring B is substituted, ring B has q R 13 It has been replaced with; Each R 13 These are, independently, halogens, unsubstituted or substituted C1-C6 alkyls, unsubstituted or substituted C2-C6 alkenyls, unsubstituted or substituted C2-C6 alkynyls, unsubstituted or substituted C1-C6 fluoroalkyls, unsubstituted or substituted C1-C6 heteroalkyls, unsubstituted or substituted carbocyclics, unsubstituted or substituted heterocyclics, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17 , or -SO2N(R 16 )2 or Two R atoms on adjacent atoms of ring B 13 The groups, together with the intervening atoms to which they are bonded, form an unsubstituted or substituted five- or six-membered monocyclic carbocyclic ring or an unsubstituted or substituted five- or six-membered monocyclic heterocyclic ring; or R 2 is -C(=O)R 14 -C(=O)NR 14 R 15 , or -C(=O)OR 14 and; R 14 This includes hydrogen, unsubstituted or substituted C1-C6 alkyl, C1-C6 deuteroalkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, or unsubstituted or substituted bicyclic heterocycle; R 15 is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl; or R14 and R 15 They, together with the intervening atoms to which they are bonded, form unsubstituted or substituted 4- to 6-membered monocyclic heterocycles; or R 1 and R 15 These, together with the intervening atoms to which they are bonded, form unsubstituted or substituted five- or six-membered monocyclic heterocycles; W is -NR 3 -or -O-; R 3 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle; R 4 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle; or R 3 and R 4 They, together with the N atoms to which they are bonded, form substituted or unsubstituted N-containing heterocycles; or R 3 and R 12a These, together with the intervening atoms to which they are bonded, form substituted or unsubstituted 5- or 6-membered heterocycles; R 5 These are hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle; Each R 6 and R 7 These are independently hydrogen, deuterium, halogen, C1-C6 alkyl, C1-C6 deuterated alkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17, or -SO2N(R 16 ) Selected from the group consisting of 2; or One R bonded to the same carbon atom 6 and one R 7 These, together with the carbon atoms to which they are bonded, form C=O or C3-C4 cycloalkyl groups; Each R 16 Independently, these are hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3-8 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or Two R atoms on the same N atom 16 These, together with the N atoms to which they are bonded, form substituted or unsubstituted N-containing heterocycles; Each R 17 These are independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3-8 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; where substituted alkyl, substituted fluoroalkyl, substituted deuteroalkyl, substituted alkoxy, substituted fluoroalkoxy, substituted heteroalkyl, substituted carbocyclic, and substituted heterocyclic are deuterium, halogen, C1-C6 alkyl, monocyclic carbocyclic, monocyclic heterocyclic, -CN, -CH2CN, -OR 18 -CH2OR 18 , -CO2R 18 , -CH2CO2R 18 -C(=O)N(R 18 )2, -CH2C(=O)N(R 18 )2, -N(R 18 )2, -CH2N(R 18 )2, -NR 18 C(=O)R 18 -CH2NR 18 C(=O)R 18 , -NR18 SO2R 19 -CH2NR 18 SO2R 19 , -SR 18 -CH2SR 18 -S(=O)R 19 -CH2S(=O)R 19 , -SO2R 19 -CH2SO2R 19 , -SO2N(R 18 )2, or -CH2SO2N(R 18 )One or more R independently selected from the group consisting of 2 S Substituted with each R 18 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl; or Two R's 18 The groups, together with the N atoms to which they are bonded, form an N-containing heterocycle; Each R 19 This is selected from the group consisting of C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl, and 6-membered heteroaryl; n is 1, 2, or 3; p is 0, 1, 2, or 3; q is 0, 1, 2, 3, or 4; Alternatively, one or more of the variable elements are as defined in International Publication No. 2022 / 175745, International Publication No. 2022 / 175746, International Publication No. 2022 / 175747, and International Publication No. 2022 / 175752, which are incorporated herein by reference in their entirety.

[0347] In some embodiments, the present invention relates to compounds of formula II-v: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, Cy 1 and Cy 2 Each of them is independent of C 6-10 Selected from aryl or 5-10 membered heteroaryls; Each R 1 or R 2 These are independently halogen, hydroxyl, amino, cyano, and C 1-8 Alkyl, C 3-10 Selected from cycloalkyl or 5-10 member heterocycloalkyl, the C 1-8 Alkyl, C 3-10 Cycloalkyl or 5-10 membered heterocycloalkyl groups are optionally substituted with one or more halogens, deuterium, hydroxyl, or cyano compounds; m is selected from 0, 1, 2, 3, 4, or 5; n is selected from 0, 1, 2, 3, 4, or 5; L is selected from -C(O)- or other bonds; R 3 These are 5-10 member heteroaryl compounds, C 3-10 Cycloalkyl, C 6-10 Selected from aryl or 3-10 membered heterocycloalkyl, where the 5-10 membered heteroaryl, C 3-10 Cycloalkyl, C 6-10 An aryl or 3-10 membered heterocycloalkyl group contains one or more R a The substituents are optionally substituted; Each R 4 Each is independently selected from halogens; p is selected from 0, 1, 2, or 3; R a These are halogen, cyano, and C 1-8 Alkyl, C 1-8 Alkoxy, C 3-10 Cycloalkyloxy, C3-10 Cycloalkyl, 5-10 member heteroaryl, 3-10 member heterocycloalkyl, amino, C 1-8 Alkyl NH-, (C 1-8 Alkyl)2N-,C 3-10 C substituted with cycloalkyl NH- or one or more halogens 1-8 Selected from alkyl groups; Alternatively, one or more of the variable elements are as defined in CN114907326, which is incorporated herein by reference in its entirety.

[0348] In some embodiments, the present invention relates to compounds of formula II-w: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X is selected from N or CH; Each R 1 It is selected independently of halogens; q is selected from 0, 1, or 2; Each R is independently selected from halogen, hydroxyl, amino, cyano, or nitro; n is selected from 0, 1, or 2; T 1 , T 2 , T 3 , T 4 , or T 5 Each is independently selected from CH or N, with at least one of them being selected from CH; Ring A is C 3-10 Cycloalkyl, 3-10 membered heterocyclyl, C 6-10 Selected from aryl or 5-10 membered heteroaryls; Each R 3is =O, halogen, hydroxy, amino, cyano, nitro, C 1-8 Alkyl or C 1-8 Selected independently of alkoxy, the C 1-8 Alkyl or C 1-8 Alkoxy is one or more R a It is optionally replaced by; m is selected from 0, 1, 2, 3, or 4; Each R a These are independently selected from halogen, hydroxyl, amino, or cyano; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 166917, which is incorporated herein by reference in its entirety.

[0349] In some embodiments, the present invention relates to compounds of formula II-x: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, -LR 1 is -CONH-R 1 , -NHCO-R 1 ,-CO-R 1 -CONHNH-R 1 , -NHNHCO-R 1 or -R 1 Selected from; R 1 These are 5-10 member heteroaryl compounds, C 2-6 Alkinyl, Cyano, C 1-6 Alkyl, hydrogen, C 3-10 Cycloalkyl, C 6-10 Selected from aryl or 3-10 membered heterocycloalkyl, where the 5-10 membered heteroaryl, C 6-10 Ariel, C 3-10Cycloalkyl or 3-10 member heterocycloalkyl groups include one or more R a The substituents are optionally substituted; R a These are halogen, carboxyl, cyano, aldehyde groups, and C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, -CONH2 or -CO2C 1-4 It is alkyl, where the C 1-6 Alkyl or C 1-6 The alkoxy is optionally substituted with one or more groups selected from hydroxyl and halogens, where the C 3-10 Cycloalkyl, 5-10 membered heteroaryl, or 3-10 membered heterocycloalkyl are C 1-6 It is optionally substituted with one or more groups selected from alkyl, hydroxyl, and halogen, where C 1-6 The alkyl group is optionally substituted with one or more hydroxyl or halogen groups; R 2 C 1-6 Selected from alkoxy, where C 1-6 The alkoxy is optionally substituted with one or more groups selected from halogens or hydroxyls; n is 0, 1, 2, or 3; R 3 and R 4 Each of them is independent of C 1-6 Selected from alkyl groups; Each R 5 These are, independently, halogen, C 1-6 Alkyl, C 1-6 Alkyl-O-,C 1-6 Alkyl-S-, C 1-6 Alkyl-NH-, C 3-10 Cycloalkyl-NH-, C 6-10 Aryl-NH-, 5-10 member heteroaryl-NH-, C 3-10 Cycloalkyl-CONH-, C 6-10 Selected from aryl or 5-10 member heteroaryl, where C 1-6alkyl radical, C 3-10 Cycloalkyl-CONH-, C 6-10 Aryl-NH- or 5-10 member heteroaryl-NH-, C 6-10 The aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more groups selected from halogens, hydroxyls, or cyanos; t is selected from CH or N; Alternatively, one or more of the variable elements are as defined in the specification CN114805438, which is incorporated herein by reference in its entirety.

[0350] In some embodiments, the present invention relates to any one compound of the following formulas: [ka] [ka] [ka] The invention provides a pharmaceutically acceptable salt thereof, where each of the variable elements is defined by the above formula (e.g., formula Ia), as described in the embodiments herein, both individually and in combination.

[0351] In some embodiments, the present invention relates to compounds of formula II-z-1 or II-z-2: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, L 1 is a combination, NR 10 O, C which is optionally substituted. 1-4 alkylene or optionally substituted C1-4 It is a heteroalkylene; R 1 is an arbitrarily substituted carbon ring, an arbitrarily substituted heterocycle, an arbitrarily substituted aryl ring, or an arbitrarily substituted heteroaryl ring; X is N or CR 2 And here, R 2 C is a hydrogen, hydroxyl, halogen, or optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Heteroalkyl, optionally substituted C 1-6 Alkoxy, optionally substituted C 3-6 A cycloalkyl or optionally substituted 4- to 8-membered heterocycline; R 3 C is a hydrogen atom that is optionally substituted with other carbon atoms. 1-6 Alkyl, optionally substituted C 1-6 Heteroalkyl, optionally substituted C 3-6 It is a cycloalkyl or optionally substituted 4- to 8-membered heterocycline; or R 2 and R 3 Together with intervening atoms, these form a 5- to 8-membered heterocyclic ring or a 5 or 6-membered heteroaryl ring, each of which is optionally substituted and has one ring nitrogen atom and one or two additional ring heteroatoms optionally independently selected from nitrogen, oxygen, and sulfur; Q is a 6-14 member heterocyclyl or a 5-10 member heteroaryl, which is either optionally substituted or Q is [ka] And, Here, R 4 and R 5 Each is independently of hydrogen or optionally substituted C 1-6 Alkyl or R 4 and R 5 These atoms bond to form 3- to 8-membered carbon rings or heterocycles, each of which is optionally substituted; L2 is a combination, NR 11A O, C which is optionally substituted. 1-4 alkylene or optionally substituted C 1-4 It is a heteroalkylene; R 6 is a hydrogen atom, a 3- to 8-membered heterocyclic ring, or a 5 or 6-membered heteroaryl ring, each of which is optionally substituted; where, R 10 and R 11A These are, independently, hydrogen and optionally substituted C. 1-6 Alkyl, optionally substituted C 3-6 The cycloalkyl, optionally substituted aryl (e.g., phenyl), optionally substituted heteroaryl (e.g., 5- or 6-membered heteroaryl), or optionally substituted 4- to 8-membered heterocyclyl; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 156657, which is incorporated herein by reference in its entirety.

[0352] In some embodiments, the present invention relates to compounds of formula II-aa: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, [ka] The bonds are single or double bonds, provided that the rings containing X1, X2, X3, X4, X5, X6, and X7 are bicyclic heteroaryl rings; X1 is N, NH, or CR 1 and; X2 is N or CR 2 and; X3 is N or CR 3 and; X4 is N or CR 4 and; The X5 is NR 5 or CR 5 and; Both X6 and X7 are C, or one of X6 and X7 is N and the other is C; Y is either C(O) or S(O)2; R 1 , R 2 , R 3 and R 4 If present, these are H, Halogen, -CN, and -NR, respectively, independently. 1a R 1b , -OR 1c , C 1-4 Alkyl and C 1-4 Selected from haloalkyl; R 5 H, Halo, CN, -NR 1a R 1b , -OR 1c , C 1-6 Alkyl, C 3-8 Cycloalkyl, C 6-10 Selected from aryls, 4-10 membered heterocycloalkyls, 5-7 membered partially saturated heterocyclyls, and 5-10 membered heteroaryls, where R 5 C represented by 1-6 Alkyl, C 3-8 Cycloalkyl, C 6-10 Aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl each contain one or more R 7 It is optionally replaced by; R 6 H, C 1-6 Alkyl, C 3-8 Cycloalkyl, C 6-10 The aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl, where R 6 C represented by 1-6 Alkyl, C 3-8 Cycloalkyl, C 6-10Aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl each contain one or more R 8 It is optionally replaced by; R 7 For each occurrence, the following are represented: halo, -CN, oxo (=O), -NR 1a R 1b , -OR 1c , -C(O)OR 1c , C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 6-10 R is independently selected from aryl, 4-7 membered monocyclic heterocycloalkyl, and 5-6 membered heteroaryl rings; where R 7 C represented by 1-6 Alkyl, C 1-6 Haloalkyl, C 3-6 Cycloalkyl, C 6-10 Aryls, 4-7 membered monocyclic heterocycloalkyls, and 5-6 membered heteroaryls are, respectively, halos and C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -NR 1a R 1b , -OR 1c and are optionally substituted with one or more substituents independently selected from 4- to 6-membered monocyclic heterocycloalkyl groups; R 8 For each occurrence, Halo, -NR 1a R 1b , -OR 1c ,-CN,C 1-6 Alkyl, C 1-3 Hydroxyalkyl, -C(=O)OR 1c , and C 1-6 Selected independently from haloalkyls, R 1a and R 1b These are, independently, H or C 1-4 Alkyl; R 1c H, C 1-4 Alkyl or C 1-4 It is a haloalkyl; m is an integer from 0 to 6; Alternatively, one or more of the variable elements are as set forth in International Publication No. 2022 / 150446, which is incorporated herein by reference in its entirety.

[0353] In some embodiments, the present invention relates to compounds of formula II-bb: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, R is a methyl, a phenyl substituted with at least one F atom, an optionally substituted heteroaryl containing 1, 2, or 3 N atoms, -CH2-R 2 , or -CH2CH2-R 3 and; R 2 This is cyclopropyl substituted with 1 to 3 substituents selected from cyclopropyl, F, and methyl; cyclobutyl substituted with 1 to 3 substituents selected from cyclobutyl, F, and methyl; oxetane; oxetane substituted with 1 to 3 substituents selected from F and methyl; tetrahydrofuran; or tetrahydrofuran substituted with 1 to 3 substituents selected from F and methyl; R 3 These are -OH, -OMe, -OEt, -OPr, -OiPr, NH2, -NHMe, and -NMe2; Alternatively, as set forth in International Publication No. 2023 / 064223, which is incorporated herein by reference in its entirety.

[0354] In some embodiments, the present invention relates to compounds of formula II-cc: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X 1 and X 2 Each of these is independently selected from CH and N; X 4 and X 5 Each of these is independently selected from CH, CF, and N; X 3 These are NR, O, CH2, or CF2; R 11 is H, F, C1-C3 alkyl, or CD3; R 12 C(=O)R 12’ or R 12’ And here, R 12’ These are C1-C6 alkyl, C3-C6 cycloalkyl, aryl, or heteroaryl compounds optionally substituted with halogens, CF3, CN, OR, amino, alkyl, cycloalkyl, heterocyclic, aryl, or heteroaryl compounds; R 13 These are C1-C3 alkyl, CD3, or CF3; R 14 is either H, or a 5 or 6-membered heteroaryl group containing 1, 2 or 3 heteroatoms selected from N, O and S, or R 14 is OR 14’ And here, R 14’ These are C1-C6 alkyl or heteroalkyl, or C3-C6 cycloalkyl or heterocycloalkyl; R 15 Each instance is independently selected from F, Cl, CN, OR, and C1-C3 alkyl groups; R is independently either H or C1-C6 alkyl in each instance; k is 0, 1, 2, or 3; Alternatively, as set forth in International Publication No. 2023 / 064223, which is incorporated herein by reference in its entirety.

[0355] In some embodiments, the present invention relates to compounds of formula II-dd: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, X is N or CR x and; R 1 is -NH2, C 1-6 Alkyl, C 1-6 Alkyl deuterated, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylamino, C 3-8 cyclic alkyl groups, heterocyclic groups consisting of 3 to 8 atoms, C 6-10 An aryl group, or a heteroaryl group consisting of 5 to 12 atoms, where C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylamino, C 3-8 Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, C 6-10 Aryls and heteroaryls consisting of 5 to 12 atoms are independently D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 It is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the hydroxyalkoxy group; R 2 H, D, C 1-6 Alkyl, C2-6 Alkenil, C 2-6 Alkinyl, C 3-8 Cycloalkyl, heterocyclic group consisting of 3 to 8 atoms, C 6-10 An aryl or heteroaryl composed of 5 to 12 atoms, where the C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 3-8 Cycloalkyl is a 3-heterocyclic group consisting of 8 atoms, C 6-10 Aryl groups and heteroaryl groups composed of 5 to 12 atoms are independently D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, and C. 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 It is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the hydroxyalkoxy group; R 3 H, D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, or C 1-6 It is an alkylamino, where the C 1-6 Alkyl and C 1-6 Alkoxy are independently D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, oxo, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylamino or C 3-8 It is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from cycloalkyl groups; R 4 is -OR c or -NHR c And here, each R c C 3-8 Cycloalkyl, heterocyclyl consisting of 3 to 8 atoms, heterocyclyl consisting of 9 to 12 atoms, C 6-10Aryl, heteroaryl, consisting of 5 to 12 atoms, -C 1-6 Alkylene (C 3-8 Cycloalkyl), -C 1-6 Alkylene (heteroaryl cyclic group consisting of 3 to 8 atoms), -C 1-6 Alkilen-NR d -(heterocyclic group consisting of 3 to 8 atoms), -C 1-6 Alkylene (C 6-10 (aryl) or -C 1-6 An alkylene group (a heteroaryl group consisting of 5 to 12 atoms), where C 3-8 Cycloalkyl groups, heterocyclic groups consisting of 3 to 8 atoms, and heterocyclic groups consisting of 9 to 12 atoms, C 6-10 Aryl, heteroaryl, consisting of 5 to 12 atoms, -C 1-6 Alkylene (C 3-8 Cycloalkyl), -C 1-6 Alkylene (3-8 atoms), -C 1-6 Alkilen-NR d -(heterocyclic group consisting of 3 to 8 atoms), -C 1-6 Alkylene (C 6-10 Aryl) and -C 1-6 Alkylenes (heteroaryls consisting of 5 to 12 atoms) independently have 1, 2, 3, 4, or 5 R atoms. 4a It is optionally substituted in the base; R d H, D, C 1-6 Alkyl, C 3-8 A cycloalkyl group or a heterocyclic group consisting of 3 to 8 atoms; V 1 , V 2 , V 3 , and V 4 Each of these is independent of -(CR 5 R 6 ) n -,-(CR 5 R 6 ) n -O-, -(CR 5 R 6 ) n -S-, -(CR 5 R 6 ) n -NR7 -,-(CR 5 R 6 ) n -C(=O)-, -(CR 5 R 6 ) n -OC(=O)-, -(CR 5 R 6 ) n -C(=O)-O-, -(CR 5 R 6 ) n -S(=O)- or -(CR 5 R 6 ) n -S(=O)²-; Each R 5 and R 6 These are independently H, D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, C 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy or C 3-8 It is a cycloalkyl, where the C 1-6 Alkyl and C 3-8 Cycloalkyls are independently D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 C substituted with alkoxy or haloalkoxy 1-3 and C 1-3 It is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from hydroxyalkoxy groups; R 5 , R 6 And the carbon atoms to which they are bonded together are C 3-8 It forms a cycloalkyl group or a heterocyclic group consisting of 3 to 8 atoms, where C 3-8 Cycloalkyl groups and 3-8 heterocyclic groups consisting of 3-8 atoms are independently D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, oxo, and C. 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3It is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from hydroxyalkoxy; R 7 H, D, C 1-6 Alkyl, C 1-6 Haloalkyl, or C 3-8 It is a cycloalkyl, where the C 1-6 Alkyl and C 3-8 Cycloalkyls are independently D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, oxo, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy, C 1-3 Hydroxyalkoxy and C 3-6 It is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from cycloalkyl groups; R x H, D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, C 1-6 Alkyl, C 1-6 Haloalkyl and C 1-6 It is an alkoxy, where the C 1-6 Alkyl and C 1-6 Alkoxy are independently D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Haloalkoxy and C 1-3 It is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from hydroxyalkoxy groups; R 4a D, F, Cl, Br, I, -NO2, -CN, oxo, C 1-6 Alkyl, C 2-6 Alkenil, C 2-6 Alkinyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Alkylamino, C 3-8 Cycloalkyl, heterocyclic group consisting of 3 to 8 atoms, -OR 8 -C(=O)R8 , -C(=O)OR 8 , -NR 8 R 9 -C(=O)NR 8 R 9 -C(=O)NR 8 S(=O)2R 9 , -NR 8 S(=O)2R 9 -S(=O)2R 8 Or -S(=O)2NR 8 R 9 And here, C 1-6 Alkyl alkyl group, C 2-6 Alkenyl group, C 2-6 Alkynyl group, C 1-6 Alkoxyl group, C 1-6 Alkylamino group, C 3-8 Cycloalkyl groups and heterocyclic groups consisting of 3 to 8 atoms are independently D, F, Cl, Br, I, -NO2, -CN, -OH, -NH2, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, C 1-3 Alkylamino, C 1-3 Haloalkoxy and C 1-3 It is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the hydroxyalkoxy group; Each R 8 and R 9 These are H, D, and C, independently. 1-6 Alkyl, C 3-8 Cycloalkyl, heterocyclic group consisting of 3 to 8 atoms, C 6-10 An aryl group, or a heteroaryl group consisting of 5 to 12 atoms, where C 1-6 Alkyl alkyl group, C 3-8 Cycloalkyl groups, heterocyclic groups consisting of 3 to 8 atoms, C 6-10 The aryl group, or the heteroaryl group consisting of 5 to 12 atoms, is independently and optionally substituted with 1, 2, 3, 4, or 5 substituents selected from D, F, Cl, Br, I, oxo, -NO2, -CN, -OH, -NH2, -COOMe, and -COOH; Each n is independently 0, 1, or 2; Alternatively, as set forth in International Publication No. 2023 / 116748, which is incorporated herein by reference in its entirety.

[0356] In some embodiments, the present invention relates to compounds of formula II-ee: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, z is selected from either a carbon atom or a nitrogen atom; w is selected from a carbon atom or a nitrogen atom; L is -O(CH)2) m -,-(CH2) m -, -NH-(CH2) m -,-(CH2) n O(CH2) m -,-(CH2) n -NH-(CH2) m - Selected from; Y is CR 2 or selected from N; Ring A is a heteroaryl or heterocyclyl, preferably a 5-10 membered heteroaryl or a 3-10 membered heterocyclyl, more preferably a 5-6 membered heteroaryl; this is R 1 Further selected from the above, and substituted with one or more elements; R 1 (Hydrogen, deuterium, halogen, amino, nitro, hydroxy, mercapto, cyano, oxo, thio, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -(CH)2) q C(O)R c ,-(CH2) q C(O)NR a R b ,-(CH2)q NR a R b ,-(CH2) q NR b C(O)R c Selected from, where alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl are further optionally substituted with one or more groups selected from deuterium, halogen, amino, nitro, hydroxy, mercapto, cyano, oxo, thio, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl; R 2 This is selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, deuterated alkoxy, and halogen; R 3 These are selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, deuterated alkoxy, halogen, amino, mercapto, nitro, hydroxy, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl; Each R 4 is independently selected from hydrogen, deuterium, alkyl, deuterated alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, amino, hydroxy, mercapto, nitro, cyano, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; R 5 These are alkyl, cycloalkyl, heterocyclyl, and -NR 6 R 7 , -OR 6Selected from aryl or heteroaryl groups; alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl groups are optionally further substituted with one or more groups selected from deuterium, halogen, amino, nitro, cyano, hydroxy, mercapto, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl groups; R 6 and R 7 is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, cyano, hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, where alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are further optionally substituted with one or more groups selected from deuterium, halogen, amino, nitro, cyano, hydroxy, mercapto, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; Alternatively, R 6 and R 7 These, together with the atoms to which they are bonded, form a heterocyclic group, which is optionally further substituted with one or more groups selected from deuterium, halogens, amino, nitro, cyano, hydroxy, mercapto, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; R a and R bThe group is independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, cyano, hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, where alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups are defined as deuterium, halogen, amino, nitro, cyano, hydroxy, mercapto, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, -S(O) p R d -, -C(O) p R d -, -NR e R f -C(O)NR e R f , further optionally substituted with members selected from substituted or unsubstituted alkenyls, substituted or unsubstituted alkynyls, substituted or unsubstituted cycloalkyls, substituted or unsubstituted heterocyclyls, substituted or unsubstituted aryls, and substituted or unsubstituted heteroaryls; Alternatively, R a and R b These, together with the atoms to which they are bonded, form a heterocyclic group, which can be deuterium, halogen, amino, nitro, cyano, hydroxy, mercapto, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, -S(O) p R d , -C(O) p R d , -NR e R f -C(O)NR e R f , further optionally substituted with a portion selected from substituted or unsubstituted alkenyls, substituted or unsubstituted alkynyls, substituted or unsubstituted cycloalkyls, substituted or unsubstituted heterocyclyls, substituted or unsubstituted aryls, and substituted or unsubstituted heteroaryls; R cThe group is selected from hydrogen, deuterium, halogen, amino, nitro, cyano, hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, where alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are deuterium, halogen, amino, nitro, cyano, hydroxy, mercapto, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, -S(O) p R d -, -C(O) p R d -, -NR e R f -C(O)NR e R f The group is further optionally substituted with a portion selected from the group consisting of substituted or unsubstituted alkenyl groups, substituted or unsubstituted alkynyl groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted heterocyclic groups, substituted or unsubstituted aryl groups, and substituted or unsubstituted heteroaryl group substitutions; R d The alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups are further optionally substituted with one or more groups selected from the group consisting of deuterium, halogen, amino, nitro, cyano, hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups, where the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups are further optionally substituted with one or more groups selected from deuterium, halogen, amino, nitro, cyano, hydroxy, mercapto, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl groups; R e and R fis independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, cyano, hydroxy, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, where alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl are further optionally substituted with one or more groups selected from deuterium, halogen, amino, nitro, cyano, hydroxy, mercapto, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; Alternatively, R e and R f These, together with the atoms to which they are bonded, form a heterocyclic group, which is optionally further substituted with one or more groups selected from deuterium, halogens, amino, nitro, cyano, hydroxy, mercapto, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; If substituted, the substituent is selected from the group consisting of deuterium, alkyl, deuterium alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, alkylsulfonyl, alkylamino, halogen, amino, nitro, cyano, hydroxy, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl; m is an integer between 0 and 6; n is an integer between 1 and 6; p is 0, 1, or 2; q is an integer between 0 and 6; x is 0, 1, or 2; Alternatively, as specified in the entirety of Specification No. CN116284040, which is incorporated herein by reference.

[0357] In some embodiments, the present invention relates to compounds of formula II-ff: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, The dotted line represents a single bond or a double bond; X and Y are independently selected from N or C; X and Y are not the same; R1 is selected from hydrogen, C1-C8 alkoxy, halogen, or substituted or unsubstituted C1-C8 alkyl; L1 is selected from -O-, -S-, -NR3-, -CR3R4-, -S(=O)-, -S(=O)2-, -C(=O)-, -OC(=O)-, -C(=O)O-, -C(=O)NR3-, -OC(=O)NR3-, -NR3C(=O)NR4-, -NR3C(=O)-, or -NR3C(=O)O-; L2 is selected from -O-, -S-, -NR3-, -CR3R4-, -S(=O)-, -S(=O)2-, -C(=O)-, -OC(=O)-, -C(=O)O-, -C(=O)NR3-, -OC(=O)NR3-, -NR3C(=O)NR4-, -NR3C(=O)-, or -NR3C(=O)O-; R 3 and R 4 This is independently selected from hydrogen, substituted or unsubstituted C1-C8 alkyl groups, substituted or unsubstituted C2-C8 alkenyl groups, substituted or unsubstituted C2-C8 alkynyl groups, substituted or unsubstituted 3-12 member cycloalkyl groups, substituted or unsubstituted 3-12 member heterocycloalkyl groups, substituted or unsubstituted 5-12 member aryl groups, or substituted or unsubstituted 5-12 member heteroaryl bases; R2 is selected from substituted or unsubstituted 3- to 12-membered cycloalkyl groups, substituted or unsubstituted 3- to 12-membered heterocycloalkyl groups, substituted or unsubstituted 5- to 12-membered aryl groups, or substituted or unsubstituted 5- to 12-membered aryl groups or 12-membered heteroaryl groups; Ring A is selected from substituted or unsubstituted 5- to 12-membered aryl groups or substituted or unsubstituted 5- to 12-membered heteroaryl groups; Ring B is selected from substituted or unsubstituted 5- to 12-membered aryl groups or substituted or unsubstituted 5- to 12-membered heteroaryl groups; The substituents of the alkyl, alkenyl, or alkynyl group are independently selected from deuterium, halogen, hydroxyl, amino, carboxyl, nitro, cyano, or C1-C8 alkoxy; The substituents of a cycloalkyl or heterocycloalkyl group are deuterium, ester groups, halogens, hydroxyl, amino, carboxyl, nitro, cyano, C1-C8 alkoxy, or substituted or unsubstituted C1-C8 alkyl groups; the heteroatoms of a heterocycloalkyl group are selected from N, O, or S, and the number of heteroatoms is 1, 2, or 3; The substituents of the aryl or heteroaryl group are deuterium, ester groups, halogens, hydroxyl, amino, carboxyl, nitro, cyano, C1-C8 alkoxy, or substituted or unsubstituted C1-C8 alkyl groups; or the aryl or heteroaryl consists of two substituents = O on the same carbon atom; the heteroatoms of the heteroaryl are selected from N, O, or S, and the number of heteroatoms is 1, 2, or 3. Alternatively, as set forth in International Publication No. 2023 / 169336, which is incorporated herein by reference in its entirety.

[0358] In some embodiments, the present invention relates to compounds of formula II-gg: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, Ring A is a 6,5 ​​or 6,6 condensed bicyclic heteroaryl containing 2, 3 or 4 ring nitrogen atoms; R A For each occurrence, hydrogen, halogen, and -NR a R b A C1-C6 alkyl group and a C1-C6 alkoxy group are independently selected from the group consisting of these elements; where the C1-C6 alkyl and C1-C6 alkoxy groups may optionally be substituted with one or more halogens or deuterium atoms; Ring B is a 6,5-6,6 condensed bicyclic heteroaryl containing 1, 2, or 3 ring nitrogen atoms; R B For each occurrence, hydrogen, halogen, and -NR a R b A C1-C6 alkyl group and a C1-C6 alkoxy group are independently selected from the group consisting of these elements; where the C1-C6 alkyl and C1-C6 alkoxy groups may optionally be substituted with one or more halogens or deuterium atoms; Y is O, N(R a ), S(O) w Selected from the group consisting of CH2 and bonds; Z is N(R a Selected from the group consisting of ) and O; R 2 and R 3 These are, independently, hydrogen, deuterium, and independently, R P Selected from the group consisting of C1-C6 alkyl groups optionally substituted with one or more substituents selected from; or: R 2 and R 3 These, together with the carbon atoms to which they are bonded, each independently become R P A C3-C6 cycloalkyl group may be formed by optionally substituting one or more substituents selected from the following; R 4 and R 5For each occurrence, independently, hydrogen, deuterium, and independently R P Selected from the group consisting of C1-C6 alkyl groups optionally substituted with one or more substituents selected from; or: R 4 and R 5 These, together with the carbon atoms to which they are bonded, each independently become R P A C3-C6 cycloalkyl group may be formed by optionally substituting one or more substituents selected from the following; R 6 and R 7 Hydrogen, deuterium, halogen, hydroxyl, -NR a R b Independently selected from the group consisting of cyano, oxo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, and C1-C6 alkoxy; Here, R 4 is a hydroxyl or R on an available carbon. P They may be substituted with one or more substituents independently selected from each; or: R 6 and R 7 These, together with the carbon atoms to which they are bonded, each independently become R P A C3-C6 cycloalkyl group may be formed by optionally substituting one or more substituents selected from the following; R P For each occurrence, deuterium, halogen, hydroxyl, -NR a R b Independently selected from the group consisting of cyano, oxo, C1-C6 alkyl, and C1-C6 alkoxy; R a and R b For each occurrence, is independently selected from the group consisting of hydrogen and C1-C6 alkyl, where the C1-C6 alkyl may be optionally substituted with one or more halogens or deuterium; m is either 1 or 2; n is either 0 or 1; p is 0, 1, or 2; q is 0, 1, or 2; w is 0, 1, or 2. Alternatively, as set forth in International Publication No. 2023 / 178235, which is incorporated herein by reference in its entirety.

[0359] In some embodiments, the present invention relates to compounds of formula II-hh: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, Ring A is a 6,5 ​​or 6,6 condensed bicyclic heteroaryl containing 2, 3 or 4 ring nitrogen atoms; R A For each occurrence, hydrogen, halogen, and -NR a R b A C1-C6 alkyl group and a C1-C6 alkoxy group are independently selected from the group consisting of these elements; where the C1-C6 alkyl and C1-C6 alkoxy groups may optionally be substituted with one or more halogens or deuterium atoms; Ring B is a 6,5-6,6 condensed bicyclic heteroaryl containing 1, 2, or 3 ring nitrogen atoms; R B For each occurrence, hydrogen, halogen, and -NR a R b , C 1-6 Alkyl and C 1-6 Independently selected from the group consisting of alkoxys; where C 1-6 Alkyl and C 1-6 The alkoxy may optionally be substituted with one or more halogens or deuterium; Y is O, N(R a ), S(O) w Selected from the group consisting of CH2 and bonds; Z is N(Ra Selected from the group consisting of ) and O; R 1 For each occurrence, hydrogen, deuterium, halogen, hydroxyl, -NR a R b , independently selected from the group consisting of cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, and C1-C6 alkoxy; where R 4 The available carbon atoms may be substituted with hydroxyl or one or more halogens; R 2 and R 3 Each is independently selected from the group consisting of hydrogen, deuterium, and C1-C6 alkyl groups optionally substituted with one or more halogens; or: R 2 and R 3 These may also form a C1-C6 cycloalkyl group together with the carbon atoms to which they are bonded; R a and R b For each occurrence, is independently selected from the group consisting of hydrogen and C1-C6 alkyl, where the C1-C6 alkyl may be optionally substituted with one or more halogens or deuterium; m is either 1 or 2; n is either 0 or 1; p is 0, 1, 2, 3, or 4; w is 0, 1, or 2. Alternatively, as set forth in International Publication No. 2023 / 178234, which is incorporated herein by reference in its entirety.

[0360] In some embodiments, the present invention relates to the compound of formula II-ii: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, L1 is selected from single bonds and NH; L2 is selected from -NH-C(=O)-; L3 consists of -O-, -NH-, and -C 1-3 Alkyl-O-, -C 1-3 Alkyl-NH- and -C 1-3 Alkyl-OC 1-3 Selected from alkyl-, where -C 1-3 Alkyl-O-, -C 1-3 Alkyl-NH- and -C 1-3 Alkyl-OC 1-3 Alkyl- is a group of 1, 2, or 3 R c It is optionally substituted in the base; R1 is -NH-C 1-3 R2 is selected from alkyl, and R2 is selected from H; Alternatively, R1 and R2, along with the atoms to which they are linked, together constitute a 5-6 membered heterocyclic alkenyl group; R3 consists of H, F, Cl, Br, I, OH, CN, NH2, and C. 1-4 Alkyl, C 1-3 Selected from alkoxy and 6-membered heteroaryls, C 1-4 Alkyl, C 1-3 Alkoxy groups and 6-membered heteroaryl groups have 1, 2, or 3 R a It is optionally substituted in the base; Ring A does not exist; Alternatively, ring A is C 3-5 Selected from cycloalkyl, 5-6 member heterocycloalkyl, and 5-6 member heteroaryl, where C 3-5 Cycloalkyl, 5-6 membered heterocycloalkyl, and 5-6 membered heteroaryl groups have 1, 2, or 3 R b It is optionally substituted in the base; Ring B is selected from phenyl, 5-6 member heteroaryl, 5-6 member heterocycloalkyl, pyridopyrrolyl, benzoxazolyl, benzopyrrolyl, benzimidazolyl, and benzopyrazolyl; Ring C is C 5-6 Cycloalkyl, C 5-6 Selected from cycloalkenyls, 5-6 member heterocycloalkyls, and 5-6 member heterocycloalkenyls; Each R a It is independently selected from F, Cl, Br, I, CH3 and OCH3; Each R b F, Cl, Br, I, OH, C 1-3 Alkyl and C 1-3 Selected independently of alkoxy, where C 1-3 Alkyl and C 1-3 The alkoxy is optionally substituted with one, two, or three halogens; Alternatively, two R's b And the carbon atoms to which they are linked together are C 3-5 Constitutes a cycloalkyl group; Each R c C 1-3 Selected independently from alkyl and phenyl, Alternatively, as set forth in International Publication No. 2023 / 208244, which is incorporated herein by reference in its entirety.

[0361] In some embodiments, the present invention relates to compounds of formula II-jj: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, Ring A is an aromatic or heteroaromatic ring fused with ring B, which is a five-membered heteroaromatic ring; X 1 is N or CH; X 2 is N or CR 2 and; X3 is N or CR 3 and; X 4 is N or CR 4 and; Ring C is a phenyl ring, a 5- or 6-membered monocyclic heterocycle, or a 5- to 6-membered heteroaryl ring, each of which has one or more R groups. C It is optionally replaced by; Each Rc can independently be Halo, -CN, or -NR. N1 R N2 , -NR N3 C(O)R 7 , -NR N4 SO2R 7 , -C(O)R 7 , -SO2R 7 , -OR O1 , C 1-6 Alkyl, alkenyl, 3-7 member monocyclic carbocyclyl, phenyl, 5-12 member monocyclic or bicyclic heteroaryl, or 4-9 member monocyclic or bicyclic heterocyclyl, where each of the C1-6 alkyl, 3-7 member monocyclic carbocyclyl, phenyl, 5-12 member monocyclic or bicyclic heteroaryl, and 4-9 member monocyclic or bicyclic heterocyclyl represented by Rc is optionally one or more R Cl It is replaced by or two R C It, together with intervening atoms, forms a 3- to 7-membered monocyclic carbocycline that is optionally substituted with one or more halos; Each R Cl These are independently: halo, oxo, -CN, -OR O1 , -NR N1 R N2 , -NR N3 C(O)R 7 , -C(O)OR O3 , -SO2R 7 , C1-6 alkyl, C3-6 cycloalkyl, phenyl, 5-12 member monocyclic or bicyclic heteroaryl, or 4-7 member monocyclic heterocyclil, where R C1 The C1-6 alkyl, phenyl, 5-6 membered heteroaryl, and 4-7 membered monocyclic heterocyclils represented by these terms are halo, oxo, -CN, and -OR, respectively. O1, -NR N1 R N2 They are optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-4 haloalkyl, phenyl, 5-6 member heteroaryl, 3-7 member monocyclic carbocyrill and 4-8 member monocyclic heterocyclil; R 1 H, C1-6 alkyl, -OR 1A , -NR N1 R N2 The C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyrill, or 4-7 membered monocyclic heterocycline, where each of the C1-6 alkyl, phenyl, C3-6 cycloalkyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyrill, and 4-7 membered monocyclic heterocycline represented by le is one or more R 8 It is optionally replaced by; R 1A is H or C1-3 alkyl; or R 1 and R 1A These, together with the atoms to which they are bonded, form a monocyclic heterocycle of 5 or 6 members; R 2 is H or halo; R3 is H, -NR N1 R N2 -CN, Haro, -C(O)R 7 , -C(O)OR O3 , -SO2R 7 , -OR O4 , C1-6 alkyl, alkenyl, phenyl, 5-6 member heteroaryl, 3-7 member monocyclic carbocyrill, or 4-9 member monocyclic or bicyclic heterocycline, where R 3 C1.6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyclyl and 4-9 membered monocyclic or bicyclic heterocyclyl are each represented by one or more R 9 It is optionally replaced by; R 4 is H or halo; Each R 7These are independently C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyclyl, or 4-7 membered monocyclic heterocyclyl; where R7 represents the C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyclyl, and 4-7 membered monocyclic heterocyclyl, respectively, halo, oxo, -CN, and -OR. O1 , -NR N1 R N2 , optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-4 haloalkyl, 3-7 membered monocyclic carbocyrills, and 4-7 membered monocyclic heterocyclines; Each R 8 These are independently: halo, oxo, -CN, -OR O1 These are C1.6 alkyl, C1-4 haloalkyl, phenyl, 5-6 member heteroaryl, 3-7 member monocyclic carbocyrill, or 4-7 member monocyclic heterocycline; Each R 9 These are independently: halo, oxo, -OR O1 , -NR N1 R N2 -CN, -C(O)OR O3 , -SO2R 10 , C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyrill, or 4-10 membered monocyclic or bicyclic heterocycline, where R 9 The C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyclyl and 4-10 membered monocyclic or bicyclic heterocyclyl represented by these terms are halo, oxo, -CN, and -OR, respectively. O1 , -NR N1 R N2 , optionally substituted with one or more substituents independently selected from C1-6 alkyl, C1-4 haloalkyl, phenyl, 5-6 member heteroaryl, 3-7 member monocyclic carbocyrill and 4-7 member monocyclic heterocyclyl; Each R O1 R is independently H, C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic or bicyclic carbocyrill, or 4-7 membered monocyclic or bicyclic heterocycline, where R O1C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic or bicyclic carbocyclyl, and 4-7 membered monocyclic or bicyclic heterocyclyl each have one or more R O2 It is optionally replaced by; Each R O2 These are independently halo, OH, -CN, C1-4 alkoxy, C1-4 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyrill, or 4-7 membered monocyclic or bicyclic heterocycline, where each of the C1-4 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyrill, and 4-7 membered monocyclic or bicyclic heterocycline is optionally substituted with one or more halo, C1-6 alkyl, or -OC1-6 alkyl; Each R O3 R is independently H, C1-6 alkyl, C1-4 haloalkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyrill, or 4-7 membered monocyclic heterocycline, where R O3 The C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyclyl, and 4-7 membered monocyclic heterocyclyl represented by each have one or more R O2 It is optionally replaced by; R O4 R is H, C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyrill or 4-7 membered monocyclic heterocycline, where R O4 The C1-6 alkyl, phenyl, 5-6 membered heteroaryl, 3-7 membered monocyclic carbocyclyl, and 4-7 membered monocyclic heterocyclyl represented by these terms are halo, oxo, -CN, and -OR, respectively. O1 , -NR N1 R N2 , optionally substituted with one or more substituents independently selected from alkyl, C1-4 haloalkyl, phenyl, 5-6 member heteroaryl, 3-7 member monocyclic carbocyrill and 4-7 member monocyclic heterocyclyl; R N1 and R N2Each of these is independently H, a C1-6 alkyl group, a 4-7 membered monocyclic heterocycline, a 5 or 6 membered heteroaryl ring, or a C3-6 cycloalkyl group, where R N1 and R N2 The C1-6 alkyl groups represented are each optionally substituted with C1-4 alkoxy or phenyl, where R N1 and R N2 The C3-6 cycloalkyl, 4-7 membered monocyclic heterocyclyl, and 5- or 6 membered heteroaryl compounds represented by these are each optionally substituted with C1-4 alkyl groups; Each R N3 These are independently H or C1-6 alkyl; Each R N4 These are independently H or C1-6 alkyl; Alternatively, as set forth in International Publication No. 2023 / 220046, which is incorporated herein by reference in its entirety.

[0362] In some embodiments, the present invention relates to compounds of formula II-kk: [ka] Or provide a pharmaceutically acceptable salt thereof, here, [ka] Each variable element in the above formula (e.g., formula Ia) is defined as described in the embodiments herein, both individually and in combination, where, Ring A is an unsubstituted or substituted carbon ring, where A 1 and A 2 Both are C, or non-substituted or substituted 5 or 6-membered complex rings, where A 1 and A 2 These are independently N or C, where if ring A is substituted, then ring A has p R 8 It has been replaced with; Each R 8These are independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 deuteroalkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocyclic, unsubstituted or substituted heterocyclic, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17 , or -SO2N(R 16 )2; R 8 If R is bonded to a nitrogen atom, 8 This includes hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 deuteroalkyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted polycarbonate, unsubstituted or substituted heterocycle, and -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -S(=O)R 17 , -SO2R 17 Or -SO2N(R 16 )2 or two R bonded to the same carbon atom 8 They combine to form =O, =S, or =NH; Z is -NR 10 -, -0-, -S-, -S(=O)-, or -SO2-; R 10 is hydrogen, C1-C6 alkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle; X 1 , X 2 , and X3 Each of them operates independently, CR 11 or N; Each R 11 These are independently hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocyclic, unsubstituted or substituted heterocyclic, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17 , or -SO2N(R 16 )2; B 1 is N or CR 12a and; B 2 is N or CR 12b and; R 12a and R 12b These are, independently, hydrogen, halogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted carbocyclic, unsubstituted or substituted heterocyclic, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17 , or -SO2N(R 16 )2; R 1is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl; R 2 R is a ring B which is an unsubstituted or substituted heterocycle or an unsubstituted or substituted carbon ring, and if ring B is substituted, ring B has q R 13 It has been replaced with; Each R 13 These are, independently, halogens, unsubstituted or substituted C1-C6 alkyls, unsubstituted or substituted C2-C6 alkenyls, unsubstituted or substituted C2-C6 alkynyls, unsubstituted or substituted C1-C6 fluoroalkyls, unsubstituted or substituted C1-C6 heteroalkyls, unsubstituted or substituted carbocyclics, unsubstituted or substituted heterocyclics, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17 , or -SO2N(R 16 )2 or two R on adjacent atoms of ring B 13 The groups, together with the intervening atoms to which they are bonded, form an unsubstituted or substituted five- or six-membered monocyclic carbocyclic ring or an unsubstituted or substituted five- or six-membered monocyclic heterocyclic ring; or R 2 is -C(=O)R 14 -C(=O)NR 14 R 15 , or -C(=O)OR 14 and; R 14 This includes hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or substituted C2-C6 alkenyl, unsubstituted or substituted C2-C6 alkynyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, or unsubstituted or substituted bicyclic heterocycle; R 15is hydrogen, C1-C6 alkyl, or C1-C6 fluoroalkyl; or R 14 and R 15 They, together with the intervening atoms to which they are bonded, form unsubstituted or substituted 4-6 member monocyclic heterocycles; or R 1 and R 15 These, together with the intervening atoms to which they are bonded, form unsubstituted or substituted five- or six-membered monocyclic heterocycles; R 4 is hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, C1-C6 deuteroalkyl, C1-C6 fluoroalkyl, or C3-C6 cycloalkyl; or R 4 and R 12a These, together with the intervening atoms to which they are bonded, form substituted or unsubstituted C5-C6 cycloalkyl groups; R 5 These are hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C3-C6 cycloalkyl, or monocyclic heterocycle; Each R 6 and R 7 These are independently hydrogen, deuterium, halogen, C1-C6 alkyl, C1-C6 deuterated alkyl, C1-C6 fluoroalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, monocyclic heterocyclic, -CN, -OH, -OR 17 -C(=O)R 16 , -CO2R 16 -C(=O)N(R 16 )2, -N(R 16 )2, -NR 16 C(=O)R 17 , -SR 16 -S(=O)R 17 , -SO2R 17 , or -SO2N(R 16 ) Selected from the group consisting of 2; or one R bonded to the same carbon atom 6 and one R 7 These, together with the carbon atoms to which they are bonded, form C=O or C3-C6 cycloalkanes; Each R 16Independently, these are hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3-8 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; or two R on the same N atom 16 These, together with the N atoms to which they are bonded, form substituted or unsubstituted N-containing heterocycles; Each R 17 These are independently substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted monocyclic 3-8 membered heterocycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted monocyclic heteroaryl; where substituted alkyl, substituted fluoroalkyl, substituted deuteroalkyl, substituted alkoxy, substituted fluoroalkoxy, substituted heteroalkyl, substituted carbocyclic, and substituted heterocyclic are deuterium, halogen, C1-C6 alkyl, monocyclic carbocyclic, monocyclic heterocyclic, -CN, -CH2CN, -OR 18 -CH2OR 18 , -CO2R 18 , -CH2CO2R 18 -C(=O)N(R 18 )2, -CH2C(=O)N(R 18 )2, -N(R 18 )2, -CH2N(R 18 )2, -NR 18 C(=O)R 18 -CH2NR 18 C(=O)R 18 , -NR 18 SO2R 19 -CH2NR 18 SO2R 19 , -SR 18 -CH2SR 18 -S(=O)R 19 -CH2S(=O)R 19 , -SO2R 19 -CH2SO2R 19 , -SO2N(R18 )2, or -CH2SO2N(R 18 )One or more R independently selected from the group consisting of 2 S It is substituted with the base; Each R 18 is independently selected from hydrogen, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R 18 The groups, together with the N atoms to which they are bonded, form an N-containing heterocycle; Each R 19 n is selected from the group consisting of C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C2-C6 heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl, and 6-membered heteroaryl; n is 1, 2, or 3; p is 1, 2, 3, or 4; q is 0, 1, 2, 3, or 4. Alternatively, as set forth in International Publication No. 2023 / 227946, which is incorporated herein by reference in its entirety.

[0363] In certain embodiments, the present invention relates to a compound of formula III: [ka] Or provide a pharmaceutically acceptable salt thereof, here, TBM is a TYK2 binding site that can bind to the TYK2 protein; L is the divalent part that connects TBM to KBM; KBM is the KLHDC2 E3 ubiquitin ligase binding site that can bind to the KLHDC2 protein.

[0364] In some embodiments, the present invention provides compounds of formula III, where TBM-L- is: [ka] It is one of the following: Here, each of the variable elements is defined above in formulas Ia, I-a', I-a'', Ib, II-cc, and Ic or their subgenres, as described in the embodiments herein, and can be either alone or in combination.

[0365] As described above, in certain embodiments, the present invention relates to a compound of formula III-a: [ka] Or, the compound of formula III is provided as a pharmaceutically acceptable salt thereof, where TBM and L are as described and defined herein, R 1 , R 1a and R 1b Each of these is independently of hydrogen or optionally substituted C 1-6 It is aliphatic; Each R a , R b , and R c These are, independently, hydrogen and R A , halogen, -CN, -NO2, oxo, -OR, thioxo, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -S(O)(NR)R, -P(O)(OR)2, -P(O)(NR2)2, -CFR2, CRF2, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, or -C(O)NR2; Each R A Independently, C 1-10 An optionally substituted group selected from a 3-7 member saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or carbon. 1-6An optionally substituted group selected from a 4-7 member saturated or partially unsaturated heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or Two R groups on the same or adjacent atoms may optionally combine with their intervening atoms to form an optionally substituted 4-11 member saturated or partially unsaturated carbocyclic or heterocyclic monocyclic, bicyclic, bridging bicyclic, spirocyclic, or heteroaryl ring, having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the atom to which they are bonded; Ring A is selected from a 4-10 member saturated or partially unsaturated monocyclic or bicyclic carbocyclyl or heterocyclyl having 1-3 heteroatoms independently selected from phenyl, naphthyl, nitrogen, oxygen, and sulfur, or a 5-10 member monocyclic or bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring B is a divalent ring selected from a 3-10 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclyl or heterocyclyl having 1-3 heteroatoms independently selected from phenyl, nitrogen, oxygen, and sulfur, or a 5-10 member monocyclic or bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring C is a divalent ring selected from a 4-13 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclyl or heterocyclyl having 1-4 heteroatoms independently selected from phenyl, nitrogen, oxygen, and sulfur, or a 5-10 member monocyclic or bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; L a and L b Each of these is independently covalently bonded, or linear or branched saturated or unsaturated divalent carbon atoms. 1-3It is a hydrocarbon chain, where 1 to 3 methylene units in the chain are independently -O-, -C(O)-, -C(S)-, -C(R)2-, -CF(R)-, -C(F)2-, -N(R)-, -S-, -S(O) 2 - or -CR=CR- is optionally substituted; a, b, and c are each independently 0, 1, 2, 3, or 4; e is either 0 or 1; X is -O-, -N(R)-, or -S-; Y is O, N(R), or S.

[0366] As set forth above and as described herein, R 1 , R 1a and R 1b Each of these is independently of hydrogen or optionally substituted C 1-6 It is an aliphatic.

[0367] In some embodiments, R 1 is hydrogen. In some embodiments, R 1 C is optionally substituted. 1-6 It is aliphatic. In some embodiments, R 1a is hydrogen. In some embodiments, R 1a C is optionally substituted. 1-6 It is aliphatic. In some embodiments, R 1b is hydrogen. In some embodiments, R 1b C is optionally substituted. 1-6 It is an aliphatic.

[0368] In some embodiments, R 1 , R 1a and R 1b The following selection is made from the options shown in Table 1.

[0369] As set forth above and as described herein, each R a , R b , and R c These are, independently, hydrogen and R AThese are halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, S(O)(NR)R, -P(O)(OR)2, -P(O)(NR2)2, -CFR2, -CRF2, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, or -C(O)NR2.

[0370] In some embodiments, R a is hydrogen. In some embodiments, R a R A In some embodiments, R a is a halogen. In some embodiments, R a is -CN. In some embodiments, R a is -NO2. In some embodiments, R a is -OR. In some embodiments, R a is an oxo. In some embodiments, R a is -SR. In some embodiments, R a is -NR2. In some embodiments, R a is -S(O)2R. In some embodiments, R a is -S(O)2NR2. In some embodiments, R a is -S(O)R. In some embodiments, R a is -S(O)(NR)R. In some embodiments, R a is -P(O)(OR)2. In some embodiments, R a is -P(O)(NR2)2. In some embodiments, R a is -CFR2. In some embodiments, R a is -CRF2. In some embodiments, R a is -CF3. In some embodiments, R a is -CR2(OR). In some embodiments, R a This is -CR2(NR2). In some embodiments, R ais -C(O)R. In some embodiments, R a is -C(O)OR. In some embodiments, R a This is -C(O)NR2.

[0371] In some embodiments, R a C 1-3 Aliphatic, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -S(O)(NR)R, -P(O)(OR)2, -P(O)(NR2)2, -CFR2, CRF2, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, or -C(O)NR2.

[0372] In some embodiments, R a C 1-3 Aliphatic, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -CFR2, -CRF2, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, or -C(O)NR2.

[0373] In some embodiments, R a is halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Fluoroalkyl, C 3-6 Fluorocycloalkyl, -OH, oxo, -OC 1-6 Alkyl, -OC 3-6 Cycloalkyl, -OC 1-6 Fluoroalkyl, -OC 3-6 It is a fluorocycloalkyl.

[0374] In some embodiments, R a These are fluoro, chloro, methyl, cyclopropyl, -CF3, or -OMe.

[0375] In some embodiments, R b is hydrogen. In some embodiments, R b R AIn some embodiments, R b is a halogen. In some embodiments, R b is -CN. In some embodiments, R b is -NO2. In some embodiments, R b is -OR. In some embodiments, R b is an oxo. In some embodiments, R b is -SR. In some embodiments, R a is -NR2. In some embodiments, R b is -S(O)2R. In some embodiments, R b is -S(O)2NR2. In some embodiments, R b is -S(O)R. In some embodiments, R b is -S(O)(NR)R. In some embodiments, R b is -P(O)(OR)2. In some embodiments, R b is -P(O)(NR2)2. In some embodiments, R b is -CFR2. In some embodiments, R b is -CRF2. In some embodiments, R b is -CF3. In some embodiments, R b is -CR2(OR). In some embodiments, R b This is -CR2(NR2). In some embodiments, R b is -C(O)R. In some embodiments, R b is -C(O)OR. In some embodiments, R b This is -C(O)NR2.

[0376] In some embodiments, R b C 1-3 Aliphatic, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -S(O)2R, -S(O)2NR 2、These are -S(O)R, -S(O)(NR)R, -P(O)(OR)2, -P(O)(NR2)2, -CFR2, -CRF2, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, or -C(O)NR2.

[0377] In some embodiments, R b C 1-3 Aliphatic, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -CFR2, -CRF2, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, or -C(O)NR2.

[0378] In some embodiments, R b is halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Fluoroalkyl, C 3-6 Fluorocycloalkyl, -OC 1-6 Alkyl, -OC 3-6 Cycloalkyl, -OC 1-6 Fluoroalkyl, -OC 3-6 It is a fluorocycloalkyl.

[0379] In some embodiments, R b These are fluoro, chloro, methyl, cyclopropyl, -CF3, or -OMe.

[0380] In some embodiments, R c is hydrogen. In some embodiments, R c R A In some embodiments, R c is a halogen. In some embodiments, R c is -CN. In some embodiments, R c is -NO2. In some embodiments, R c is -OR. In some embodiments, R c is an oxo. In some embodiments, R c is -SR. In some embodiments, Rc is -NR2. In some embodiments, R c is -S(O)2R. In some embodiments, R c is -S(O)2NR2. In some embodiments, R c is -S(O)R. In some embodiments, R c is -S(O)(NR)R. In some embodiments, R c is -P(O)(OR)2. In some embodiments, R c is -P(O)(NR2)2. In some embodiments, R c is -CFR2. In some embodiments, R c is -CRF2. In some embodiments, R c is -CF3. In some embodiments, R c is -CR2(OR). In some embodiments, R c This is -CR2(NR2). In some embodiments, R c is -C(O)R. In some embodiments, R c is -C(O)OR. In some embodiments, R c This is -C(O)NR2.

[0381] In some embodiments, R c C 1-3 Aliphatic, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -S(O)2R, -S(O)2NR2, -S(O)R, -S(O)(NR)R, -P(O)(OR)2, -P(O)(NR2)2, -CFR2, CRF2, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, or -C(O)NR2.

[0382] In some embodiments, R c C 1-3 Aliphatic, halogen, -CN, -NO2, -OR, oxo, -SR, -NR2, -CFR2, -CRF2, -CF3, -CR2(OR), -CR2(NR2), -C(O)R, -C(O)OR, or -C(O)NR2.

[0383] In some embodiments, R c is halogen, C 1-6 Alkyl, C 3-6 Cycloalkyl, C 1-6 Fluoroalkyl, C 3-6 Fluorocycloalkyl, -OC 1-6 Alkyl, -OC 3-6 Cycloalkyl, -OC 1-6 Fluoroalkyl, -OC 3-6 It is a fluorocycloalkyl.

[0384] In some embodiments, R c These are fluoro, chloro, methyl, cyclopropyl, -CF3, or -OMe.

[0385] In some embodiments, R a , R b and R c The following selection is made from the options shown in Table 1.

[0386] As set forth above and as described herein, each R A Independently, C 1-10 The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0387] Several embodiments, each R A Independently, C 1-10 These are optionally substituted groups selected from aliphatic groups. In some embodiments, each R A R is independently and optionally substituted phenyl. In some embodiments, each R AR is an optionally substituted 3-7 member saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, each R A It is an arbitrarily substituted 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0388] In some embodiments, R A is -(CH2)3NH2. In some embodiments, R A is -(CH2)3NHCO2tBu. In some embodiments, R A is -(CH2)6NH2. In some embodiments, R A is -(CH2)6NHCO2tBu. In some embodiments, R A is -(CH2)9NH2. In some embodiments, R A is -(CH2)9NHCO2tBu. In some embodiments, R A is -(CH2)2CO2H. In some embodiments, R A is -(CH2)5CO2H. In some embodiments, R A is -(CH2)6CO2H. In some embodiments, R A It is -(CH2)8CO2H.

[0389] Several embodiments, each R A The following selection is made from the options shown in Table 1.

[0390] As defined above and as described herein, each R is independently either hydrogen or C 1-6The R groups are optionally substituted, selected from a 4-7 member saturated or partially unsaturated heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or two R groups on the same atom optionally combine with their intervening atom to form an optionally substituted 4-11 member saturated or partially unsaturated carbocyclic or heterocyclic monocyclic, bicyclic, bridging bicyclic, spirocyclic, or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur in addition to the atom to which they are bonded.

[0391] In some embodiments, R is hydrogen. In some embodiments, R is optionally substituted with C. 1-6 It is aliphatic. In some embodiments, R is optionally substituted phenyl. In some embodiments, R is optionally substituted 4-7 member saturated or partially unsaturated heterocycle having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, R is optionally substituted 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, two R groups on the same or adjacent atoms optionally combine with their intervening atoms to form optionally substituted 4-11 member saturated or partially unsaturated carbocyclic or heterocyclic monocyclic, bicyclic, bridging bicyclic, spirocyclic, or heteroaryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the atom to which they are bonded.

[0392] In some embodiments, R is selected from those shown in Table 1 below.

[0393] As set forth above and as described herein, ring A is a ring selected from a 4-10 member saturated or partially unsaturated monocyclic or bicyclic carbocyclyl or heterocyclyl having 1-3 heteroatoms independently selected from phenyl, naphthyl, nitrogen, oxygen, and sulfur, or a 5-10 member monocyclic or bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0394] In some embodiments, ring A is phenyl. In some embodiments, ring A is naphthyl. In some embodiments, ring A is a 4-10 member saturated or partially unsaturated monocyclic or bicyclic carbocyclyl or heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 5-10 member monocyclic or bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0395] In some embodiments, ring A is selected from phenyl, naphthyl, or a 5-10 membered monocyclic or bicyclic heteroaryl having 1-4 nitrogen atoms. In some embodiments, ring A is a ring selected from phenyl and naphthyl. In some embodiments, ring A is [ka] That is the case.

[0396] In some embodiments, ring A is selected from a 5-10 member monocyclic or bicyclic heteroaryl having 1-4 nitrogen atoms. In some embodiments, ring A is a 5-6 member monocyclic heteroaryl having 1-4 nitrogen atoms. In some embodiments, ring A is pyridyl. In some embodiments, ring A is [ka] That is the case.

[0397] In some embodiments, ring A is a 7-10 membered bicyclic heteroaryl having 1-4 nitrogen atoms. In some embodiments, ring A is indolyl, quinolinyl, or isoquinolinyl. In some embodiments, ring A is indolyl. In some embodiments, ring A is [ka] In some embodiments, ring A is quinolinyl or isoquinolinyl. In some embodiments, ring A is [ka] That is the case.

[0398] In some embodiments, ring A is a 4-10 member saturated or partially unsaturated monocyclic or bicyclic carbocyclyl or heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is a 5-6 member saturated or partially unsaturated monocyclic carbocyclyl, or a 5-6 member heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0399] In some embodiments, ring A is cyclohexyl or piperidinyl.

[0400] In some embodiments, ring A is [ka] That is the case.

[0401] In some embodiments, ring A is an 8-10 member saturated or partially uns...

Claims

1. Compound of formula I-a': 【Chemical 631】 or a pharmaceutically acceptable salt thereof (in the formula, X is -CH ２ It is a divalent part selected from - or -C(O)-; X １ Covalent bonds, 【Chemical 632】 , or optionally substituted rings selected from 4-6 member saturated carbocycllenyl or heterocycllenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, phenylenyl, 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-8 member saturated bridged bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; X ２ The bond is covalent, -O-, or -NR-; Y is either N or CH; Y １ is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Z １ and Z ２ is, independently, N or C, where １ and Z ２ one of which is N and １ and Z ２ the other is C; each 【Chemical Formula 633】 These are, independently, single or double bonds; Ring A is phenylenyl, pyridinyl, 【Transformation 634】 It is a ring selected from; Ring B is a fused ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring C is a 9-10 member saturated or partially unsaturated bicyclic heterocyclinyl having 1-3 heteroatoms independently selected from phenylenyl, pyridylenyl, nitrogen, oxygen, and sulfur; an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 12-15 member saturated or partially unsaturated tricyclic spirocyclic heterocyclinyl having 1-3 heteroatoms independently selected from nitrogen and oxygen; R ａ These are hydrogen, halogen, -CN, -OR, oxo, and C. １－６ Alkyl, C １－６ Haloalkyl, C ３－６ It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms ａ These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; R ｂ is hydrogen, or: R ｂ R １ It binds to the nitrogen that is bonded, R １ It forms an optionally substituted 5-6 member partially unsaturated or aromatic heterocycle having 0-2 heteroatoms selected from nitrogen, oxygen, and sulfur in addition to the nitrogen atom to which it is bonded; R １ is hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, or C ３－６ It is a cycloalkyl; Each R ２ and R ５ These are independently hydrogen, halogen, -CN, and -NO ２ -OR, oxo, -SR, -NR ２ , -SiR ３ , -S(O) ２ R, -S(O) ２ NR ２ , -S(O)R, -C(O)R, -C(O)OR, -C(O)NR ２ , -C(O)N(R)OR, -OC(O)R, -OC(O)NR ２ , -OP(O)R ２ , -OP(O)(OR) ２ , -OP(O)(OR)NR ２ , -OP(O)(NR ２ ) ２ , -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR ２ , -N(R)S(O) ２ R, -N(R)P(O)R ２ , -N(R)P(O)(OR) ２ , -N(R)P(O)(OR)NR ２ , -N(R)P(O)(NR ２ ) ２ , -N(R)S(O) ２ R, or R Ａ And; m and n are independently 0, 1, 2, 3, or 4; R ３ is hydrogen, or halogen, -CN, C １－６ Alkyl, C １－６ Haloalkyl, -OR, -CH ２ C is optionally substituted with one or two substituents selected from OR or five-membered heteroaryl compounds having one to three heteroatoms independently selected from nitrogen, oxygen, and sulfur. １－６ A 3-9 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring having 0-3 heteroatoms independently selected from alkyl, nitrogen, oxygen, and sulfur; or R ３ and R ５ This refers to divalent saturated or partially unsaturated linear or branched carbon atoms. ３－６ Linked by hydrocarbon chains, where 0 to 2 methylene units in the chain are independently -CR ２ -, -CRF-, -CF ２ -, -O-, -NR-, -C(O)-; R ４ is hydrogen, halogen, C １－６ Alkyl, C １－６ Haloalkyl, C ３－６ Cycloalkyl, -OC １－６ Alkyl, or -OC １－６ It is a haloalkyl; L is a covalent bond, -CR ２ -, -CRF-, -CF ２ -, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C １－１０ It is a hydrocarbon chain, where the 0 to 6 methylene units of L are independently -Cy-, -CR ２ -, -CRF-, -CF ２ It is replaced by -, -CR(OR)-, -O-, -NR-, -C(O)-; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C １－６ A optionally substituted group selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings having 1-2 heteroatoms, or heterocycles and 5-6 member heteroaryl rings having 1-4 heteroatoms, or: Two R groups on the same carbon or nitrogen may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R Ａ Independently, C １－６ The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

2. Compound of formula I-a: 【Chemical 635】 or a pharmaceutically acceptable salt thereof (in the formula, X is -CH ２ It is a divalent part selected from - or -C(O)-; X １ Covalent bonds, 【Chemical Formula 636】 , or optionally substituted rings selected from 4-6 member saturated carbocycllenyl or heterocycllenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, phenylenyl, 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-8 member saturated bridged bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; X ２ The bond is covalent, -O-, or -NR-; Y is either N or CH; Y １ is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Z １ and Z ２ Independently, is N or C, where Z １ and Z ２ One of them is N, and Z １ and Z ２ The other side is C; Ring A is phenylenyl, pyridinyl, 【Chemical 637】 It is a ring selected from; Ring B is a fused ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring C is a 9-10 member saturated or partially unsaturated bicyclic heterocyclinyl having 1-3 heteroatoms independently selected from phenylenyl, pyridylenyl, nitrogen, oxygen, and sulfur; an 8-10 member bicyclic heteroarylenyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or a 12-15 member saturated or partially unsaturated tricyclic spirocyclic heterocyclinyl having 1-3 heteroatoms independently selected from nitrogen and oxygen; R ａ These are hydrogen, halogen, -CN, -OR, oxo, and C. １－６ Alkyl, C １－６ Haloalkyl, C ３－６ It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms ａ These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; R ｂ is hydrogen, or: R ｂ is linked to the nitrogen to which R １ is attached, and forms an optionally substituted 5- to 6-membered partially unsaturated or aromatic heterocyclic ring having 0 to 2 heteroatoms selected from nitrogen, oxygen and sulfur in addition to the nitrogen atom to which R １ is attached; R １ is hydrogen, C １－６ Alkyl, C １－６ Haloalkyl, or C ３－６ It is a cycloalkyl; Each R ２ and R ５ is, independently, hydrogen, halogen, -CN, -NO ２ , -OR, oxo, -SR, -NR ２ , -SiR ３ , -S(O) ２ R, -S(O) ２ NR ２ , -S(O)R, -C(O)R, -C(O)OR, -C(O)NR ２ , -C(O)N(R)OR, -OC(O)R, -OC(O)NR ２ , -OP(O)R ２ , -OP(O)(OR) ２ , -OP(O)(OR)NR ２ , -OP(O)(NR ２ ) ２ , -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR ２ , -N(R)S(O) ２ R, -N(R)P(O)R ２ , -N(R)P(O)(OR) ２ , -N(R)P(O)(OR)NR ２ , -N(R)P(O)(NR ２ ) ２ , -N(R)S(O) ２ R, or R Ａ ; m and n are independently 0, 1, 2, 3, or 4; R ３ is hydrogen, or halogen, -CN, C １－６ Alkyl, C １－６ C is optionally substituted with one or two substituents selected from haloalkyl and -OR. １－６ Alkyl or C ３－６ It is cycloalkyl, or R ３ and R ５ This refers to divalent saturated or partially unsaturated linear or branched carbon atoms. ３－６ Linked by hydrocarbon chains, where 0 to 2 methylene units in the chain are independently -CR ２ -, -CRF-, -CF ２ It is replaced by -, -O-, -NR-, and -C(O)-; R ４ is hydrogen, halogen, C １－６ Alkyl, C １－６ Haloalkyl, C ３－６ Cycloalkyl, -OC １－６ Alkyl, or -OC １－６ It is a haloalkyl; L is a covalent bond, -CR ２ -, -CRF-, -CF ２ -, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C １－１０ It is a hydrocarbon chain, where the 0 to 6 methylene units of L are independently -Cy-, -CR ２ -, -CRF-, -CF ２ It is replaced by -, -CR(OR)-, -O-, -NR-, -C(O)-; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C １－６ A optionally substituted group selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings having 1-2 heteroatoms, or heterocycles and 5-6 member heteroaryl rings having 1-4 heteroatoms, or: Two R groups on the same carbon or nitrogen may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R Ａ Independently, C １－６ The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

3. X ２ The compound according to claim 1 or 2, wherein the bond is covalent.

4. The compound according to any one of claims 1 to 3, wherein ring C is a nine-membered partially unsaturated bicyclic heterocyclinyl having one to three heteroatoms independently selected from phenylenyl, pyridylenyl, nitrogen, oxygen, and sulfur, a nine-membered bicyclic heteroarylenyl having one to three heteroatoms independently selected from nitrogen, oxygen, and sulfur, or a 14-membered partially unsaturated tricyclic spirocyclic heterocyclinyl having one to three heteroatoms independently selected from nitrogen and oxygen.

5. Ring C is 【Chemical 638】 The compound according to any one of claims 1 to 4.

6. X １ が, shared combination, 【Chemistry 639】 The compound according to any one of claims 1 to 5, wherein the ring is optionally substituted, selected from a 4-6 member saturated carbocyclilenyl or heterocyclilenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a phenylenyl, a 6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8 member saturated bridged bicyclic heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

7. X １ が, shared combination, 【Chemical 640】 The compound according to any one of claims 1 to 6.

8. A compound according to any one of claims 1 to 7, wherein the compound is one of the following formulas: 【Chemistry 641】 【Chemistry 642】 【Chemistry 643】 【Chemical Formula 644】 【Chemistry 645】 A compound, or a pharmaceutically acceptable salt thereof.

9. R １ However, hydrogen or C １－６ A compound according to any one of claims 1 to 8, wherein it is alkyl.

10. R ３ However, hydrogen, methyl, ethyl, isopropyl, 【Chemical 646】 【Chemical 647】 The compound according to any one of claims 1 to 9.

11. Compounds of formula I-b: 【Chemical 648】 or a pharmaceutically acceptable salt thereof (in the formula, X is -CH ２ It is a divalent part selected from - or -C(O)-; X ２ and X ３ These are independently covalent, -O-, or -NR-; Y is either N or CH; Y １ is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Ring A is phenylenyl, pyridinyl, 【Chemical Formula 649】 It is a ring selected from; Ring B is a fused ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring D is a divalent ring selected from a 4-7 member saturated or partially unsaturated carbocyclenyl or heterocyclenyl having 1-2 heteroatoms independently selected from phenylenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroarylenyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring E is a divalent ring selected from a 4-7 member saturated or partially unsaturated carbocycllenyl or heterocyclenyl having 1-2 heteroatoms independently selected from phenylenyl, naphthylenyl, nitrogen, oxygen, and sulfur; a 5-6 member heteroaryrenyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 9-10 member saturated or partially unsaturated bicyclic heterocyclenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and an 8-10 member bicyclic heteroaryrenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring F is a 4-7 member saturated or partially unsaturated carbocyclyl or heterocyclyl having 1-2 heteroatoms independently selected from phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R ａ These are hydrogen, halogen, -CN, -OR, oxo, and C. １－６ Alkyl, C １－６ Haloalkyl, C ３－６ It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms ａ These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; Each R ２ , R ５ , R ６ , and R ７ These are independently hydrogen, halogen, -CN, and -NO ２ -OR, oxo, -SR, -NR ２ , -SiR ３ , -S(O) ２ R, -S(O) ２ NR ２ , -S(O)R, -C(O)R, -C(O)OR, -C(O)NR ２ , -C(O)N(R)OR, -OC(O)R, -OC(O)NR ２ , -OP(O)R ２ , -OP(O)(OR) ２ , -OP(O)(OR)NR ２ , -OP(O)(NR ２ ) ２ , -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR ２ , -N(R)S(O) ２ R, -N(R)P(O)R ２ , -N(R)P(O)(OR) ２ , -N(R)P(O)(OR)NR ２ , -N(R)P(O)(NR ２ ) ２ , -N(R)S(O) ２ R, or R Ａ And; Each of m, n, o, and p is independently 0, 1, 2, 3, or 4; R ４ is hydrogen, halogen, C １－６ Alkyl, C １－６ Haloalkyl, C ３－６ Cycloalkyl, -OC １－６ Alkyl, or -OC １－６ It is a haloalkyl; L is a covalent bond, -CR ２ -, -CRF-, -CF ２ -, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C １－１０ It is a hydrocarbon chain, where the 0 to 6 methylene units of L are independently -Cy-, -CR ２ -, -CRF-, -CF ２ It is replaced by -, -CR(OR)-, -O-, -NR-, -C(O)-; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C １－６ A optionally substituted group selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings having 1-2 heteroatoms, or heterocycles and 5-6 member heteroaryl rings having 1-4 heteroatoms, or: Two R groups on the same carbon or nitrogen may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R Ａ Independently, C １－６ The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

12. A compound according to claim 11, wherein the compound is any one of the following formulas: 【Chemical 650】 【Chemical 651】 A compound, or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 11 or claim 12, wherein ring F is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from phenyl, nitrogen, oxygen, and sulfur.

14. Compounds of formula I-c: 【Chemical 652】 or a pharmaceutically acceptable salt thereof (in the formula, X is -CH ２ It is a divalent part selected from - or -C(O)-; X １ Covalent bonds, 【Chemical 653】 , or optionally substituted rings selected from 4-6 member saturated carbocycllenyl or heterocycllenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, phenylenyl, 5-6 member heteroarylenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5-8 member saturated bridged bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Y is either N or CH; Y １ is a covalent bond, -O-, -S-, -NR-, or -C(O)NR-; Z １ and Z ２ Independently, is N or C, where Z １ and Z ２ One of them is N, and Z １ and Z ２ The other side is C; each 【Chemical 654】 These are, independently, single or double bonds; Ring A is phenylenyl, pyridinyl, 【Chemical 655】 It is a ring selected from; Ring B is a fused ring selected from a 5-6 member saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from benzo, nitrogen, oxygen, and sulfur, or a 5-6 member heteroaryl containing 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Ring F is a 4-7 member saturated or partially unsaturated carbocyclyl or heterocyclyl having 1-2 heteroatoms independently selected from phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R ａ These are hydrogen, halogen, -CN, -OR, oxo, and C. １－６ Alkyl, C １－６ Haloalkyl, C ３－６ It is either cycloalkyl or: Two R atoms on the same carbon atom or adjacent carbon atoms ａ These are linked together to form a 3-6 member saturated carbon ring or heterocycle having 1-2 heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0, 1, or 2; Each R ２ , R ５ , and R ６ These are independently hydrogen, halogen, -CN, and -NO ２ -OR, oxo, -SR, -NR ２ , -SiR ３ , -S(O) ２ R, -S(O) ２ NR ２ , -S(O)R, -C(O)R, -C(O)OR, -C(O)NR ２ , -C(O)N(R)OR, -OC(O)R, -OC(O)NR ２ , -OP(O)R ２ , -OP(O)(OR) ２ , -OP(O)(OR)NR ２ , -OP(O)(NR ２ ) ２ , -N(R)C(O)OR, -N(R)C(O)R, -N(R)C(O)NR ２ , -N(R)S(O) ２ R, -N(R)P(O)R ２ , -N(R)P(O)(OR) ２ , -N(R)P(O)(OR)NR ２ , -N(R)P(O)(NR ２ ) ２ , -N(R)S(O) ２ R, or R Ａ is or: Two Rs on adjacent atoms ６ These link together to form optionally substituted condensed 5-6 member partially saturated or aromatic heterocycles having one or two heteroatoms selected from nitrogen, oxygen, and sulfur; Each of m, n, and o is independently 0, 1, 2, 3, or 4; R ４ is hydrogen, halogen, C １－６ Alkyl, C １－６ Haloalkyl, C ３－６ Cycloalkyl, -OC １－６ Alkyl, or -OC １－６ It is a haloalkyl; L is a covalent bond, -CR ２ -, -CRF-, -CF ２ -, -O-, -NR-, -C(O)-, or divalent saturated or partially unsaturated linear or branched C １－１０ It is a hydrocarbon chain, where the 0 to 6 methylene units of L are independently -Cy-, -CR ２ -, -CRF-, -CF ２ It is replaced by -, -CR(OR)-, -O-, -NR-, -C(O)-; Each -Cy- is independently phenylenyl, 8-10 membered bicyclic aryrenyl, 4-7 membered saturated or partially unsaturated carbocyclilenyl, 6-11 membered saturated or partially unsaturated spirocyclic or bridged bicyclic carbocyclilen, 8-10 membered bicyclic saturated or partially unsaturated carbocyclilen, 4-7 membered saturated or partially unsaturated heterocyclilen having 1-2 heteroatoms independently selected from nitrogen, oxygen and sulfur, 6-11 membered saturated or This is an optionally substituted divalent ring selected from a partially unsaturated spirocyclic or bridging bicyclic heterocyclenyl, an 8-10 member bicyclic saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 member heteroarylenyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 member bicyclic heteroarylenyl having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R is independently either hydrogen or C １－６ A optionally substituted group selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur-independently-selected 3-7 member saturated or partially unsaturated carbon rings having 1-2 heteroatoms, or heterocycles and 5-6 member heteroaryl rings having 1-4 heteroatoms, or: Two R groups on the same carbon or nitrogen may optionally combine with their intervening atoms to form a 4-11 member saturated or partially unsaturated monocyclic, bicyclic, bridging bicyclic, or spirocyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, in addition to the carbon or nitrogen to which the two R groups are linked; Each R Ａ Independently, C １－６ The group is optionally substituted, selected from a 3-7 member saturated or partially unsaturated carbon ring or heterocycle having 1-2 heteroatoms independently selected from aliphatic, phenyl, nitrogen, oxygen, and sulfur, and a 5-6 member heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

15. A compound according to claim 14, wherein the compound is one of the following formulas: 【Chemical Formula 656】 A compound, or a pharmaceutically acceptable salt thereof. 【Request Item 16】 【Chemistry 657】 but, 【Chemical Formula 658】 The compound according to any one of claims 1 to 15. 【Request Item 17】 【Chemistry 659】 but, 【Chemical 660】 The compound according to any one of claims 1 to 16.

18. R ２ However, hydrogen, fluoro, chloro, methyl, ethyl, cyclopropyl, -CHF ２ , -CF ３ A compound according to any one of claims 1 to 17, wherein the compound is oxo, -OMe, or -OEt.

19. L is a divalent saturated or partially unsaturated linear or branched C １－５ It is a hydrocarbon chain, and the 0 to 6 methylene units of L are independently -Cy-, -CR ２ -, -CRF-, -CF ２ The compound according to any one of claims 1 to 18, which is replaced by -, -CR(OR)-, -O-, -NR-, and -C(O)-.

20. L is a divalent saturated or partially unsaturated linear or branched C ５ It is a hydrocarbon chain, and the 0 to 6 methylene units of L are independently -Cy-, -CR ２ -, -CRF-, -CF ２ The compound according to any one of claims 1 to 19, which is replaced by -, -CR(OR)-, -O-, -NR-, and -C(O)-.

21. The compound according to any one of claims 1 to 20, wherein L contains one -Cy- group.

22. The compound according to any one of claims 1 to 21, wherein L comprises two -Cy- groups.

23. The compound according to any one of claims 1 to 22, wherein L comprises a 4- to 7-membered saturated or partially unsaturated heterocyclenyl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted with 1 to 3 methylene, -C(O)-, and 1 to 2 halogens, and a 6- to 11-membered saturated or partially unsaturated spirocyclic or bridged bicyclic heterocyclenyl having 1 to 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted with 1 to 2 halogens.

24. X １ The compound according to any one of claims 1 to 23, wherein the bond is covalent.

25. X １ and X ２ The compound according to any one of claims 1 to 24, wherein the bond is covalent.

26. X １ , X ２ and Y １ The compound according to any one of claims 1 to 25, wherein the bond is covalent.

27. X １ , X ２ and Y １ The compound according to any one of claims 1 to 26, wherein the bond is covalent and L contains one -Cy- group.

28. X １ , X ２ and Y １ The compound according to any one of claims 1 to 27, wherein the bond is covalent and L contains two -Cy- groups.

29. X １ , X ２ and Y １ The compound according to any one of claims 1 to 28, wherein L is covalently bonded and comprises a 4-7 member saturated or partially unsaturated heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted with 1-3 methylene groups, -C(O)-, and 1-2 halogens, and a 6-11 member saturated or partially unsaturated spirocyclic or bridged bicyclic heterocyclenyl having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, optionally substituted with 1-2 halogens.

30. L is, -O-(C １－５ aliphatic)-, -Cy-(C １－５ aliphatic)-, -(CH ２ ) １－５ -Cy-(C １－５ aliphatic)-, -(CH ２ ) １－５ -Cy-O-(C １－５ aliphatic)-, -(CH ２ ) １－５ -Cy-Cy-(C １－５ aliphatic)-, -(CH ２ ) １－５ -Cy-Cy-O-(C １－５ aliphatic)-, -(CH ２ ) １－５ -Cy-, -(CH ２ ) １－５ -Cy-CH(OR)-, -(CH ２ ) １－５ -Cy-(CH ２ ) １－５ -, -O-(CH ２ ) １－５ -Cy-, -O-(CH ２ ) １－５ -Cy-(CH ２ ) １－５ -, -(CH ２ ) １－５ -O-Cy-, -(CH ２ ) １－５ -O-Cy-(CH ２ ) １－５ -, -(CH ２ ) １－５ -CO-Cy-(CH ２ ) １－５ -, -(CH ２ ) １－５ -NR-Cy-, -(CH ２ ) １－５ -NR-Cy-CO-, -(CH ２ ) １－５ -Cy-NR-, -O-Cy-NR-, -(CH ２ ) １－５ -NR-Cy-(CH ２ ) １－５ -, -(CH ２ ) １－５ -CO-, -(CH ２ ) １－５ -Cy-CO-、-Cy-CO-、-O-Cy-CO-、-O-Cy-(CH ２ ) １－５ -、-(CH ２ ) １－５ -Cy-CHF-、-(CH ２ ) １－５ -Cy-CF ２ -、-(CH ２ ) １－５ -Cy-(CH ２ ) １－５ -CF ２ -、-Cy-Cy-、-(CH ２ ) １－５ -Cy-Cy-、-(CH ２ ) １－５ -Cy-Cy-CO-、-Cy-(CH ２ ) １－５ -Cy-、-Cy-(CH ２ ) １－５ -Cy-CO-、-(CH ２ ) １－５ -Cy-(CH ２ ) １－５ -Cy-CO-、-Cy-(CH ２ ) １－５ -Cy-(CH ２ ) １－５ -、-(CH ２ ) １－５ -Cy-Cy-(CH ２ ) １－５ -、-O-(CH ２ ) １－５ -Cy-Cy-、-O-(CH ２ ) １－５ -Cy-Cy-(CH ２ ) １－５ -、-(CH ２ ) １－５ -O-Cy-Cy-、-(CH ２ ) １－５ -O-Cy-Cy-(CH ２ ) １－５ -、-(CH ２ ) １－５ -NR-Cy-Cy-、-(CH ２ ) １－５ -Cy-NR-Cy-、-(CH ２ ) １－５ -NR-Cy-Cy-(CH ２ ) １－５ -, -(CH ２ ) １－５ -Cy-Cy-CO-, -O-Cy-Cy-CO-, -O-Cy-Cy-(CH ２ ) １－５ -, -Cy-Cy-Cy-, -Cy-Cy-Cy-CO-, -(CH ２ ) １－５ -Cy-Cy-Cy-, -(CH ２ ) １－５ -Cy-Cy-Cy-CO-, -Cy-(CH ２ ) １－５ -Cy-Cy-, -Cy-(CH ２ ) １－５ -Cy-Cy-CO-, -Cy-(CH ２ ) １－５ -Cy-(CH ２ ) １－５ -Cy-, or -Cy-(CH ２ ) １－５ -Cy-(CH ２ ) １－５ The compound according to any one of claims 1 to 29, which is -Cy-CO.

31. -Cy- is, 【Chemical 661】 【Chemical Formula 662】 【Chemical 663】 The compound according to any one of claims 1 to 30.

32. The compound according to any one of claims 1 to 31, wherein the compound is selected from any one of the compounds shown in Table 1 or from pharmaceutically acceptable salts thereof.

33. A pharmaceutical composition comprising a compound according to any one of claims 1 to 32 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

34. A method for inhibiting or degrading TYK2 in a patient or biological sample, comprising administering a compound or pharmaceutical composition thereof according to any one of claims 1 to 32 to the patient, or bringing the biological sample into contact with it.

35. A method for treating a TYK2-mediated disorder, disease, or condition in a subject requiring such treatment, comprising administering a compound or pharmaceutical composition thereof according to any one of claims 1 to 32 to the subject.

36. The method according to claim 35, wherein the TYK2-mediated disorder is an autoimmune disease, an inflammatory disease, a proliferative disorder, a cardiovascular disease, an endocrine disorder, a neurological disorder, a dysplasia-related disorder, a genetic disorder, and a transplant-related disorder.

37. The aforementioned TYK2-mediated disorder, (a) Autoimmune disorders selected from type 1 diabetes, ankylosing spondylitis, cutaneous lupus erythematosus, systemic lupus erythematosus, lupus nephritis, multiple sclerosis, systemic sclerosis, psoriasis, Crohn's disease, ulcerative colitis, proteasome-associated autoinflammatory syndrome (PRAAS), ISG15 deficiency, and inflammatory bowel disease; (b) Inflammatory disorders selected from rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, psoriasis, Crohn's disease, ulcerative colitis, infant-onset STING-associated vasculitis (SAVI), and inflammatory bowel disease; (c) Proliferative disorders selected from hematological malignancies, polycythemia vera, myelofibrosis, essential thrombocythemia, and thrombocytosis; (d) Endocrine disorders selected from polycystic ovary syndrome, Crouzon syndrome, and type 1 diabetes; (e) Neurological disorders selected from Alzheimer's disease, Ecardi-Goutier syndrome (AGS), Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, cerebral ischemia, and neurodegenerative diseases caused by traumatic injury, glutamate neurotoxicity and hypoxia; or (f) Transplant-related disorders selected from transplant rejection and graft-versus-host disease. The method according to claim 35.

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