PI3Kalpha inhibitors

Abstract

The present disclosure provides compounds, compositions, and methods useful for inhibiting PI3K [alpha] and / or treating diseases, disorders, or disorders associated with PI3K [alpha] and / or treating cancer.

Description

Technical Field

[0001] The present disclosure provides compounds that modulate PI3Kα activity and are useful for treating various diseases associated with PI3Kα, including cancer, and pharmaceutical compositions thereof. Background Art

[0002] Over the past few decades, signal transduction events have been studied to demonstrate their key role in almost all aspects of regulating biological responses. Abnormal activation of signaling pathways that regulate cell survival and proliferation is often observed in many human cancers. Records show that the phosphoinositide 3-kinase (PI3K) signaling pathway is one of the highly mutated pathways in human cancer (Vogelstein et al., Science, 2013, 339 (6127), 1546-1558). The PI3K signaling pathway regulates cell survival and proliferation. Increased activity of this pathway is associated with tumor progression and resistance to cancer therapy (Fusco et al., Front Oncol., 2021, 11, 644737).

[0003] PI3K belongs to the lipid kinase family, which catalyzes the phosphorylation of lipids contained in or associated with cell membranes. The PI3K family has 15 kinases with different substrates, expression patterns, and regulatory patterns. Class I PI3K (p110α, p110β, p110δ, and p110γ) are typically activated by tyrosine receptor kinases or G protein-coupled receptors to generate PIP3, which activates downstream effectors such as Akt, mTOR, or RhoGTPases (Fruman et al., Nat. Rev. Drug Discov., 2014, 13(2), 140-156).

[0004] Genetic mutations in the gene encoding PI3Kα are hotspot point mutations within the helical and kinase domains, such as E542K, E545K, and H1047R. These mutations have been observed in many cancer types, such as lung cancer, gastric cancer, endometrial cancer, ovarian cancer, bladder cancer, breast cancer, colon cancer, brain cancer, prostate cancer, and skin cancer. Because these gain-of-function mutations in PI3Kα are associated with tumor progression, targeting this pathway may provide valuable therapeutic opportunities (Courtney et al., J. Clin. Oncol., 2010, 28(6), 1075-1083). Although a variety of PI3K inhibitors have been developed (e.g., taselisib, alpelisib, buparlisib, and others), these molecules inhibit multiple PI3K isoforms. These "pan-PI3K" inhibitors have encountered significant obstacles in clinical development because they are unable to achieve the desired level of tumor-targeted inhibition while avoiding toxicity to cancer patients (Fruman et al., Nat. Rev. Drug Discov., 2014, 13 (2), 140-156). The toxicity of PI3K inhibitors depends on their isoform selectivity profile. Inhibition of PI3Kα is associated with hyperglycemia and rash, while inhibition of PI3Kδ or PI3Kγ is associated with diarrhea, bone marrow suppression, and elevated transaminases (Hanker et al., Cancer Discov., 2019, 9 (4), 482-491). Therefore, selective inhibitors of PI3Kα can extend the therapeutic window, enabling sufficient targeted inhibition to be achieved in tumors while avoiding dose-limiting toxicities in cancer patients. However, given the important role of PI3Kα in regulating glucose homeostasis and other key physiological processes, current PI3Kα selective inhibitors that are equally potent against wild-type and mutant PI3Kα often cause hyperglycemia and / or hyperinsulinemia (Busaidy et al., J. Clin. Oncol., 2012, 30, 2919-2928). In summary, the development of inhibitors that are more selective for mutant PI3Kα than for wild-type PI3Kα will be able to overcome the problems of compensatory insulin production and hyperglycemia. Summary of the Invention

[0005] The present disclosure provides compounds and / or compositions that can be used to inhibit PI3K α. In some embodiments, the compounds and / or compositions provided can be used to selectively inhibit PI3K α relative to other PI3K isoforms. In some embodiments, the compounds and / or compositions provided can be used to selectively inhibit mutant PI3K α relative to wild-type PI3K α. In some embodiments, the compounds and / or compositions provided are particularly useful for treating and / or preventing diseases, disorders or conditions associated with PI3K α. In some embodiments, the compounds and / or compositions provided are particularly useful for treating and / or preventing diseases, disorders or conditions associated with mutant PI3K α.

[0006] In some embodiments, the present disclosure provides certain compounds and / or compositions that are useful in medicine, and in particular, for the treatment of cancer.

[0007] In some embodiments, the present disclosure provides a compound of Formula I:

[0008]

[0009] or a pharmaceutically acceptable salt thereof, wherein X, Y, Z, U, Ring A, L A 、R A 、R 1 、R 3 、R 5 Each of and n is as defined herein.

[0010] In some embodiments, provided compounds have the structure of any one of Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, Formula Via, Formula VII, Formula Vila, and Formula VIIb as described herein.

[0011] In some embodiments, provided compounds have the structure of any one of Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, and Formula Via as described herein.

[0012] In some embodiments, the present disclosure provides compositions that contain and / or deliver provided compounds. In some embodiments, such compositions are pharmaceutical compositions that include a pharmaceutically acceptable carrier.

[0013] The present disclosure further provides methods of inhibiting PI3Kα activity, comprising contacting the PI3Kα with a compound described herein or a pharmaceutically acceptable salt thereof.

[0014] The present disclosure further provides methods of treating a disease or condition associated with PI3Kα in a patient by administering to the patient a therapeutically effective amount of a compound of the present disclosure or a pharmaceutically acceptable salt thereof.

[0015] The present disclosure further provides a compound described herein, or a pharmaceutically acceptable salt thereof, for use in any of the methods described herein.

[0016] The present disclosure further provides the use of a compound described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for use in any of the methods described herein. DETAILED DESCRIPTION

[0017] Compounds and Definitions

[0018] The compounds of the present invention include those compounds summarized above and are further illustrated by the classes, subclasses and species disclosed herein. As used herein, unless otherwise indicated, the following definitions shall apply. For the purposes of the present invention, chemical elements are identified according to the periodic table of the elements (CAS version, Handbook of Chemistry and Physics, 75th edition). In addition, the general principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999 and "March's Advanced Organic Chemistry", 5th edition, editors: Smith, MB and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.

[0019] Unless otherwise indicated, the structures depicted herein are intended to include all stereoisomeric (e.g., enantiomeric or diastereomeric) forms of the structure, as well as all geometric or conformational isomeric forms of the structure. For example, the R and S configurations of each stereocenter are considered as part of this disclosure. Therefore, single stereochemical isomers of the provided compounds, as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures are within the scope of this disclosure. For example, in some cases, Table 1 shows one or more stereoisomers of the compound, and unless otherwise indicated, represents each individual stereoisomer and / or as a mixture. Unless otherwise indicated, all tautomeric forms of the provided compounds are within the scope of this disclosure.

[0020] Unless otherwise indicated, structures depicted herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. One or more atoms of an isotopically labeled compound may be replaced by an atom having an atomic mass or mass number normally found in nature. Examples of isotopes present in the compounds of the present disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as, but not limited to, 2H. 3 H. 13 C. 14 C. 15 N. 17 O. 18 O. 35 S and 18 F. In addition to being useful as therapeutic agents, certain isotopically labeled compounds of the present disclosure may also be useful as analytical tools in drug and / or substrate tissue distribution assays or as probes in other biological assays. In one aspect of the present disclosure, tritiated (e.g., 3 H) and carbon-14 (e.g. 14 C) isotopes are useful because they are easy to detect. In another aspect of the invention, deuterium (e.g. 2 The replacement of one or more hydrogen atoms by heavier isotopes of H) may offer certain therapeutic advantages.

[0021] As used herein, and unless otherwise specified, the suffix "-ene" is used to describe a divalent group. Thus, any of the above terms can be modified with the suffix "-ene" to describe the divalent form of the moiety. For example, a divalent carbocyclic ring is a "carbocyclylene," a divalent aryl ring is an "arylene," a divalent benzene ring is a "phenylene," a divalent heterocyclic ring is a "heterocyclylene," a divalent heteroaryl ring is a "heteroarylene," a divalent alkyl chain is an "alkylene," a divalent alkenyl chain is an "alkenylene," a divalent alkynyl chain is an "alkynylene," and so on.

[0022] Aliphatic: As used herein, the term "aliphatic" refers to an optionally substituted straight (i.e., unbranched) or branched hydrocarbon chain that is fully saturated or contains one or more unsaturated units, or a monocyclic or bicyclic hydrocarbon (also referred to herein as "carbocycle" or "alicyclic") that is fully saturated or contains one or more unsaturated units but is not aromatic, and unless otherwise specified, has a single point of attachment to the rest of the molecule. Unless otherwise specified, an aliphatic group contains 1-12 aliphatic carbon atoms. In some embodiments, an aliphatic group contains 1-6 aliphatic carbon atoms (e.g., C 1-6 In some embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms (e.g., C 1-5 In other embodiments, aliphatic groups contain 1-4 aliphatic carbon atoms (e.g., C 1-4 In other embodiments, aliphatic groups contain 1-3 aliphatic carbon atoms (e.g., C 1-3 ), and in other embodiments, aliphatic groups contain 1-2 aliphatic carbon atoms (e.g., C 1-2Suitable aliphatic groups include, but are not limited to, substituted or unsubstituted straight or branched chain alkyls, alkenyls, alkynyls, and hybrids thereof. In some embodiments, "aliphatic" refers to an optionally substituted straight (i.e., unbranched) or branched hydrocarbon chain that is fully saturated or contains one or more unsaturated units, and has a single point of attachment to the rest of the molecule.

[0023] Alkyl: The term "alkyl" when used alone or as part of a larger moiety refers to a group having (unless otherwise specified) 1-12, 1-10, 1-8, 1-6, 1-4, 1-3, or 1-2 carbon atoms (e.g., C 1-12 、C 1-10 、C 1-8 、C 1-6 、C 1-4 、C 1-3 or C 1-2 ) is an optionally substituted straight or branched chain saturated hydrocarbon group. Exemplary alkyl groups include methyl, ethyl, propyl, butyl, pentyl, hexyl and heptyl.

[0024] Alkenyl: The term "alkenyl" when used alone or as part of a larger moiety refers to a group having at least one double bond and having (unless otherwise specified) 2-12, 2-10, 2-8, 2-6, 2-4, or 2-3 carbon atoms (e.g., C 2-12 、C 2-10 、C 2-8 、C 2-6 、C 2-4 or C 2-3 ) is an optionally substituted straight or branched hydrocarbon chain. Exemplary alkenyl groups include ethenyl, propenyl, butenyl, pentenyl, hexenyl, and heptenyl.

[0025] Alkynyl: The term "alkynyl" when used alone or as part of a larger moiety refers to a group having at least one triple bond and having (unless otherwise specified) 2-12, 2-10, 2-8, 2-6, 2-4, or 2-3 carbon atoms (e.g., C 2-12 、C 2-10 、C 2-8 、C 2-6 、C 2-4 or C 2-3 ) is an optionally substituted straight or branched chain hydrocarbon group. Exemplary alkynyl groups include ethynyl, propynyl, butynyl, pentynyl, hexynyl, and heptynyl.

[0026] Aryl: As used herein, the term "aryl" refers to a group having a total of 6 to 14 ring members (e.g., C 6-14) monocyclic, bicyclic and polycyclic ring systems, wherein at least one ring in the system is aromatic and wherein each ring in the system contains 3 to 7 ring members. The term "aryl" can be used interchangeably with the term "aryl ring". In some embodiments, "aryl" refers to an aromatic ring system, which includes (but is not limited to) phenyl, naphthyl, anthracenyl, etc., which may bear one or more substituents. Unless otherwise specified, "aryl" is a hydrocarbon.

[0027] Divalent: As used herein, the term "divalent" refers to a chemical moiety that has two points of attachment to the rest of the molecule. For example, "divalent C 1-6 "Aliphatic" refers to a divalent aliphatic group as defined herein containing 1 to 6 aliphatic carbon atoms.

[0028] Carbocyclyl: As used herein, the terms "carbocyclyl" and "carbocycle" refer to a saturated or partially unsaturated cyclic aliphatic monocyclic, bicyclic, or polycyclic ring system having 3 to 14 members as described herein, wherein the aliphatic ring system is optionally substituted as described herein. Carbocyclic groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, norbornyl, adamantyl, and cyclooctadienyl. In some embodiments, "carbocyclyl" (or "alicyclic") refers to an optionally substituted monocyclic C3-C8 hydrocarbon or optionally substituted C5-C8 hydrocarbon that is fully saturated or contains one or more unsaturated units, but is not aromatic. 10 Bicyclic hydrocarbons have a single point of attachment to the rest of the molecule. The term "cycloalkyl" refers to an optionally substituted saturated ring system having from about 3 to about 10 ring carbon atoms. In some embodiments, the cycloalkyl has 3-6 carbon atoms. Exemplary monocyclic cycloalkyl rings include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. The term "cycloalkenyl" refers to an optionally substituted non-aromatic monocyclic or polycyclic ring system containing at least one carbon-carbon double bond and having from about 3 to about 10 carbon atoms. Exemplary monocyclic cycloalkenyl rings include cyclopentenyl, cyclohexenyl, and cycloheptenyl.

[0029] Carrier: As used herein, the term "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which a composition is administered. In some embodiments, carriers can include sterile liquids such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil, and the like. In some embodiments, a carrier is or includes one or more solid components.

[0030] Excipients: As used herein, the term "excipient" refers to non-therapeutic agents that may be included in a pharmaceutical composition, for example, to provide or contribute to a desired consistency or stabilizing effect. Suitable pharmaceutical excipients include, for example, starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, skim milk powder, glycerol, propylene, glycol, water, ethanol, and the like.

[0031] Heteroaryl: As used herein, the terms "heteroaryl" and "heteroar-" when used alone or as part of a larger moiety (e.g., "heteroaralkyl" or "heteroaralkoxy") refer to monocyclic or bicyclic groups having 5 to 10 ring atoms (e.g., a 5- to 6-membered monocyclic heteroaryl or a 9- to 10-membered bicyclic heteroaryl); having 6, 10, or 14 pi electrons shared in the cyclic array; and having 1 to 5 heteroatoms in addition to carbon atoms. Exemplary heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyridonyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, pteridinyl, imidazo[1,2-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, thienopyrimidinyl, triazolopyridinyl, and benzisoxazolyl. As used herein, the terms "heteroaryl" and "heteroar-" also include groups in which a heteroaromatic ring is fused to one or more aryl, alicyclic, or heterocyclyl rings, wherein the radical or point of attachment is on the heteroaromatic ring (i.e., a bicyclic heteroaryl ring having from 1 to 3 heteroatoms). Non-limiting examples include indolyl, isoindolyl, benzothiophenyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzothiazolyl, benzothiadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, pyrido[2,3-b]-1,4-oxazin-3(4H)-one and benzisoxazolyl. The term "heteroaryl" may be used interchangeably with the terms "heteroaryl ring," "heteroaryl group," or "heteroaromatic," any of which includes rings that are optionally substituted.

[0032] Heteroatom: As used herein, the term "heteroatom" as used herein refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur and any quaternized form of a basic nitrogen.

[0033] Heterocycle: As used herein, the terms "heterocycle," "heterocyclyl," and "heterocyclic ring" are used interchangeably and refer to a stable 3- to 8-membered monocyclic or 5- to 10-membered bicyclic heterocyclic moiety that is saturated or partially unsaturated and has one or more (e.g., one to four) heteroatoms as defined above in addition to carbon atoms. The term "nitrogen," when used with respect to the ring atoms of a heterocycle, includes 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 (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or NR + (as in N-substituted pyrrolidinyl). The heterocycle may be attached to its side group at any heteroatom or carbon atom to provide a stable structure, and any ring atom may be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic groups include, but are not limited to, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolane, diazepine, oxazepine, thiazepine, morpholinyl, and thiomorpholinyl. The heterocyclic group may be monocyclic, bicyclic, tricyclic, or polycyclic, preferably monocyclic, bicyclic, or tricyclic, more preferably monocyclic or bicyclic. Bicyclic heterocycles also include groups in which the heterocycle is fused to one or more aryl, heteroaryl, or alicyclic rings. Exemplary bicyclic heterocyclic groups include indolinyl, isoindolinyl, benzodioxolyl, 1,3-dihydroisobenzofuranyl, 2,3-dihydrobenzofuranyl, and tetrahydroquinolinyl. The bicyclic heterocycle can also be a spirocyclic system (e.g., a 7- to 11-membered spirofused heterocycle having, in addition to carbon atoms, one or more heteroatoms as defined above (e.g., one, two, three, or four heteroatoms)).

[0034] Partially Unsaturated: As used herein, the term "partially unsaturated" when referring to a ring moiety means a ring moiety that includes at least one double or triple bond between ring atoms. The term "partially unsaturated" is intended to encompass rings with multiple sites of unsaturation, but is not intended to include aromatic (e.g., aryl or heteroaryl) moieties as defined herein.

[0035] Patient or subject: As used herein, the term "patient" or "subject" refers to any organism to which a provided composition is or can be administered, for example, for experimental, diagnostic, preventive, cosmetic, and / or therapeutic purposes. Typical patients or subjects include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and / or humans). In some embodiments, the patient is human. In some embodiments, the patient or subject suffers from or is susceptible to one or more conditions or disorders. In some embodiments, the patient or subject exhibits one or more symptoms of a condition or disorder. In some embodiments, the patient or subject has been diagnosed with one or more conditions or disorders. In some embodiments, the patient or subject is receiving or has received a therapy to diagnose and / or treat a disease, condition, or disorder.

[0036] Pharmaceutical composition: As used herein, the term "pharmaceutical composition" refers to an active agent formulated with one or more pharmaceutically acceptable carriers. In some embodiments, the active agent is present in a unit dosage amount suitable for administration in a treatment regimen that shows a statistically significant likelihood of achieving a predetermined therapeutic effect when administered to a relevant population. In some embodiments, the pharmaceutical composition can be specifically formulated for administration in solid or liquid form, including those suitable for the following administration: oral administration, such as a solution (aqueous or non-aqueous solution or suspension), a tablet (e.g., intended for buccal, sublingual, and systemic absorption), a bolus, a powder, a granule, a paste for application to the tongue; parenteral administration, such as by subcutaneous, intramuscular, intravenous, or epidural injection, such as, for example, a sterile solution or suspension, or a sustained-release formulation; topical application, such as a cream, ointment, or controlled-release patch or spray applied to the skin, lungs, or mouth; intravaginal or rectal, such as a pessary, cream, or foam; sublingual; ophthalmic; transdermal; or nasal, pulmonary, and other mucosal surfaces.

[0037] Pharmaceutically acceptable: As used herein, the phrase "pharmaceutically acceptable" refers to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, and are commensurate with a reasonable benefit / risk ratio.

[0038] Pharmaceutically acceptable carrier: As used herein, the term "pharmaceutically acceptable carrier" means a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, or solvent encapsulating material, which participates in carrying or transporting the subject compound from one organ or part of the body to another organ or part of the body. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials that can be used as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose, and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; glycols, such as propylene glycol; polyols, such as glycerol, sorbitol, mannitol, and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffers, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol; pH buffered solutions; polyesters, polycarbonates, and / or polyanhydrides; and other nontoxic, compatible substances employed in pharmaceutical formulations.

[0039] Pharmaceutically acceptable salts: As used herein, the term "pharmaceutically acceptable salts" refers to salts of compounds suitable for use in a pharmaceutical setting, i.e., salts that are suitable for use in contact with the tissues of humans and lower animals without excessive toxicity, irritation, allergic response, etc., within the scope of sound medical judgment and commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S.M. Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66:1-19 (1977).

[0040] Prevent (prevent or prevention): As used herein, the term "prevent" or "prevention" when used in connection with the occurrence of a disease, condition, and / or disorder refers to reducing the risk of developing the disease, condition, and / or disorder and / or delaying the onset of one or more characteristics or symptoms of the disease, condition, or disorder. Prevention can be considered complete when the onset of the disease, condition, or disorder has been delayed for a predefined period of time.

[0041] Substituted or Optionally Substituted: As described herein, compounds of the present disclosure may contain "optionally substituted" moieties. In general, the term "substituted," whether preceded by the term "optionally" or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent (i.e., as described below for optionally substituted groups). "Substituted" applies to one or more hydrogens that are explicit or implicit according to the structure (e.g., means at least and means at least ). Unless otherwise indicated, a group that is "optionally substituted" may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure can be substituted by more than one substituent selected from a specified group, the substituent at each position may be the same or different. The substituent combinations contemplated by the present invention are preferably those that can form stable or chemically feasible compounds. As used herein, the term "stable" refers to a compound that does not undergo substantial changes when subjected to various conditions to allow its production, detection, and in certain embodiments, its recovery, purification, and use for one or more purposes provided herein. The group described as "substituted" preferably has 1 to 4 substituents, more preferably 1 or 2 substituents. The group described as "optionally substituted" may be unsubstituted or "substituted" as described above.

[0042] Suitable monovalent substituents on the substitutable carbon atoms of an "optionally substituted" group are independently halogen; -(CH2) 0-4 R o ; -(CH2) 0-4 OR o ;-O(CH2) 0-4 R o 、-O-(CH2) 0-4 C(O)OR o ; -(CH2) 0-4 CH(OR o )2;-(CH2) 0- 4SR o ; -(CH2) 0-4 Ph, which can be R o Substitution; -(CH2) 0-4 O(CH2) 0-1 Ph, which can be R o Substituted; -CH=CHPh, which can be R o Substitution; -(CH2) 0-4 O(CH2) 0-1 -pyridyl, which may be R o Substitution; -NO2; -CN; -N3; ​​-(CH2) 0-4 N(Ro )2;-(CH2) 0-4 N(R o )C(O)R o ;-N(R o )C(S)R o ;-(CH2) 0-4 N(R o )C(O)NR o 2;-N(R o )C(S)NR o 2;-(CH2) 0-4 N(R o )C(O)OR o ;-N(R o )N(R o )C(O)R o ;-N(R o )N(R o )C(O)NR o 2;-N(R o )N(R o )C(O)OR o ;-(CH2) 0-4 C(O)R o ;-C(S)R o ;-(CH2) 0-4 C(O)OR o ;-(CH2) 0-4 C(O)SR o ;-(CH2) 0-4 C(O)OSiR o 3;-(CH2) 0-4 OC(O)R o ;-OC(O)(CH2) 0-4 SR o ;-(CH2) 0-4 SC(O)R o ;-(CH2) 0-4 C(O)NR o 2;-C(S)NR o 2;-C(S)SR o ;-SC(S)SR o 、-(CH2) 0- 4OC(O)NR o 2;-C(O)N(OR o )R o ;-C(O)C(O)R o ;-C(O)CH2C(O)R o ;-C(NOR o )R o ;-(CH2)0-4 SSR o ; -(CH2) 0-4 S(O)2R o ; -(CH2) 0-4 S(O)(=NR o )R o ; -(CH2) 0-4 S(O)2OR o ; -(CH2) 0-4 OS(O)2R o ; -(CH2) 0-4 -S(O)2NR o 2; -(CH2) 0-4 S(O)(=NR o )NR o 2; -(CH2) 0-4 S(O)R o ;-N(R o )S(O)2NR o 2;-N(R o )S(O)2R o ;-N(R o )S(O)(=NR o )R o ;-N(OR o )R o ;-C(NH)NR o 2;-P(O)2R o ;-P(O)R o 2;-OP(O)R o 2;-OP(O)(OR o )2;-SiR o 3;-(C 1-4 linear or branched alkylene)ON(R o )2; or -(C 1-4 linear or branched alkylene) C(O)ON(R o )2, where each R o may be substituted as defined below and are independently hydrogen, C 1-6 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph, -CH2-(5- to 6-membered heteroaryl ring) or a 3- to 6-membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, or, notwithstanding the above definitions, two independent occurrences of R o Together with its intervening atoms, it forms a 3- to 12-membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, which may be substituted as defined below.

[0043] Ro (or two independent occurrences of R o Suitable monovalent substituents on the ring formed by the ring and its intervening atoms are independently halogen, -(CH2) 0-2 R · 、-(halogen R · ), -(CH2) 0-2 OH, -(CH2) 0-2 OR · 、-(CH2) 0-2 CH(OR · )2、-O(halogen R · ), -(CH2) 0-2 CN, -N3, -(CH2) 0-2 C(O)R · 、-(CH2) 0-2 C(O)OH, -(CH2) 0-2 C(O)OR · 、-(CH2) 0-2 C(O)NH2, -(CH2) 0-2 C(O)NHR · 、-(CH2) 0-2 C(O)NR · 2. -(CH2) 0-2 SR · 、-(CH2) 0-2 SH, -(CH2) 0-2 NH2, -(CH2) 0- 2NHR · 、-(CH2) 0-2 NR · 2. -(CH2) 0-2 NHC(O)R · 、-(CH2) 0-2 NR · C(O)R · 、-NO2、-SiR · 3. -OSiR · 3. -C(O)SR · 、-(C 1-4 linear or branched alkylene)C(O)OR · or -SSR · , where each R · is unsubstituted or, in the case of "halo" in front, is substituted only with one or more halogens, and is independently selected from C 1-4 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph or a 3- to 6-membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur. oSuitable divalent substituents on a saturated carbon atom of include =0 and =S.

[0044] Suitable divalent substituents on a saturated carbon atom of an "optionally substituted" group include the following: =0 ("oxo"), =S, =NNR * 2. =NNHC(O)R * 、=NNHC(O)OR * 、=NNHS(O)2R * 、=NR * 、=NOR * 、-O(C(R * 2)) 2- 3O-or-S(C(R * 2)) 2-3 S-, where each independent occurrence of R * is selected from hydrogen, C 1-6 an aliphatic group or an unsubstituted 3- to 6-membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur. Suitable divalent substituents attached to the ortho-substitutable carbon of an "optionally substituted" group include: -O(CR * 2) 2-3 O-, where each independent occurrence of R * is selected from hydrogen, C which may be substituted as defined below 1-6 an aliphatic or an unsubstituted 5- to 6-membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0045] R * Suitable substituents on the aliphatic group include halogen, -R · 、-(halogen R · ), -OH, -OR · 、-O(halogen R · )、-CN、-C(O)OH、-C(O)OR · 、-NH2、-NHR · 、-NR · 2 or -NO2, where each R · is unsubstituted or, in the case of "halo" in the preceding case, is substituted only with one or more halogens, and is independently C 1-4 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph or a 3- to 6-membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0046] Suitable substituents on a substitutable nitrogen of an "optionally substituted" group include or Each of these are independently hydrogen, C 1-6 an aliphatic group or an unsubstituted 3- to 6-membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur, or, notwithstanding the above definitions, two independent occurrences of Together with its intervening atoms, it forms an unsubstituted 3- to 12-membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0047] Suitable substituents on the aliphatic group are independently halogen, -R · 、-(halogen R · ), -OH, -OR · 、-O(halogen R · )、-CN、-C(O)OH、-C(O)OR · 、-NH2、-NHR · 、-NR · 2 or -NO2, where each R · is unsubstituted or, in the case of "halo" in the preceding case, is substituted only with one or more halogens, and is independently C 1-4 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph or a 3- to 6-membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0048] Treatment: As used herein, the term "treat" (and "treatment" or "treating") refers to any administration of a therapy that partially or completely alleviates, ameliorates, alleviates, suppresses, delays the onset of, reduces the severity of, and / or reduces the incidence of one or more symptoms, features, and / or causes of a particular disease, disorder, and / or condition. In some embodiments, this treatment may be for subjects who do not exhibit signs of the relevant disease, disorder, and / or condition and / or subjects who exhibit only early signs of the disease, disorder, and / or condition. Alternatively or additionally, this treatment may be for subjects who exhibit one or more established signs of the relevant disease, disorder, and / or condition. In some embodiments, treatment may be for subjects who have been diagnosed with the relevant disease, disorder, and / or condition.

[0049] The provided compounds

[0050] In some embodiments, the present disclosure provides a compound of Formula I:

[0051]

[0052] or a pharmaceutically acceptable salt thereof, wherein:

[0053] is a single bond or a double bond;

[0054] X is N or C;

[0055] Y is N or C;

[0056] Ring A is phenyl, a 5- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0057] Each L A are independently covalent bonds or optionally substituted divalent C 1-6 aliphatic groups;

[0058] Each R A are independently oxo, halogen, -CN, -OR A1 、-SR A1 、-N(R A1 )2、-C(O)R A1 、-C(O)OR A1 、-C(O)N(R A1 )2、-C(O)NR A1 (OR A1 ),-OC(O)R A1 -OC(O)N(R A1 )2. -OC(O)OR A1 、-OSO2R A1 、-OSO2N(R A1 )2、-N(R A1 )C(O)R A1 、-NR A1 C(O)OR A1 、-NR A1 C(O)N(R A1 )2、-N(R A1 )SO2R A1 、-NR A1 S(O)2N(R A1 )2、-NR A1 OR A1 、-NR A1 S(O)R A1 、-NR A1 S(O)N(R A1 )2、-S(O)R A1 、-SO2R A1 、-S(O)N(RA1 )2、-SO2N(R A1 )2, -SO3R A1 、-C(=NR m )R A1 、-C(=NR m )N(R A1 )2、-NR A1 C(=NR m )R A1 、-NR A1 C(=NR m )N(R A1 )2、-NR A1 S(O)(=NR m )R A1 、-NR A1 S(O)(=NR m )N(R A1 )2, -OS(O)(=NR m )R A1 、-S(O)(=NR m )R A1 、-S(O)(=NR m )N(R A1 )2、-P(O)(R A1 )2、C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0059] where R A The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0060] or two L A -R AThe phenyl group, together with the atoms to which it is attached, forms a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated The 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the phenyl, the 8- to 10-membered bicyclic aryl, the 3- to 7-membered monocyclic heterocyclyl, the 5- to 10-membered bicyclic heterocyclyl, the 5- to 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are independently optionally substituted by 1, 2, 3, 4, 5, or 6 R AG Substituent substitution;

[0061] R 1 is hydrogen or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0062] or R 1 and an L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5- to 14-membered saturated or partially unsaturated bicyclic heterocyclic group, together with the atoms to which they are attached, have 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 7-membered monocyclic heterocyclic group and the 5- to 14-membered bicyclic heterocyclic group is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0063] Z is N or CR 2 ;

[0064] U is N or CR 4 ;

[0065] R 2 and R 4Each independently hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, - NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0066] R 3 is -F, -Cl, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OS O2N(R)2, -N(R)C(O)R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NRO R, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m)R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0067] R 5 -L 5 -R 5A ;

[0068] L 5 is a covalent bond or an optionally substituted divalent C 1-6 aliphatic groups;

[0069] or L 5 and an L A -R A The 3- to 16-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 16-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 16-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 16-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 16-membered monocyclic carbocyclyl, the 5- to 16-membered bicyclic carbocyclyl, the 3- to 16-membered monocyclic heterocyclyl and the 5- to 16-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0070] R 5A For-OR 5A11 、-SR 5A1 、-NHR 5A12 、-N(R 5A12 )2、-C(O)R 5A1 、-C(O)N(R 5A1 )2、-C(O)NR 5A1 (OR 5A1 ),-OC(O)R 5A1 、-OC(O)N(R 5A1 )2. -OC(O)OR 5A1 、-OSO2R 5A1 、-OSO2N(R5A1 ) 2, -N(R 5A1 ) C(O)R 5A1 , -NR 5A1 C(O)OR 5A1 , -NR 5A1 C(O)N(R 5A1 ) 2, -N(R 5A1 ) SO2R 5A1 , -NR 5A1 S(O)2N(R 5A1 ) 2, -NR 5A1 OR 5A1 , -NR 5A1 S(O)R 5A1 , -NR 5A1 S(O)N(R 5A1 ) 2, -S(O)R 5A1 , -SO2R 5A1 , -S(O)N(R 5A1 ) 2, -SO2N(R 5A1 ) 2, -SO3R 5A1 , -C(=NR m ) R 5A1 , -C(=NR m ) N(R 5A1 ) 2, -NR 5A1 C(=NR m ) R 5A1 , -NR 5A1 C(=NR m ) N(R 5A1 ) 2, -NR 5A1 S(O)(=NR m ) R 5A1 , -NR 5A1 S(O)(=NR m ) N(R 5A1 ) 2, -OS(O)(=NR m ) R 5A1 , -S(O)(=NR m ) R 5A1 , -S(O)(=NR m ) N(R 5A1 ) 2, -P(O)(R 5A1 ) 2, Methyl, C 2-6an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0071] where R 5A The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R 5AG Substitution by a substituent; or

[0072] R 5A The methyl group is replaced by 1, 2 or 3 R 5AG Substituent substitution;

[0073] R A1 and R 5A1 are independently hydrogen, C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0074] where R A1 or R 5A1 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution;

[0075] or two R A1 when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0076] or two R 5A1 when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0077] R 5A11 Methyl, C 2-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0078] where R 5A11 The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substitution by a substituent; or

[0079] R 5A11 The methyl group is replaced by 1, 2 or 3 R G1 Substituent substitution;

[0080] Each R 5A12 Independently C 1-6an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0081] where R 5A12 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution;

[0082] or two R 5A12 when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0083] R AG 、R 5AG and R G1 Each independently is halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O) R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m)R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

[0084] Each R is independently hydrogen or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or

[0085] two R's when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0086] Each R m are independently -OH, -CN or R; and

[0087] n is 0, 1, 2, 3 or 4.

[0088] In some embodiments of the preceding embodiments, L 5 and an L A -R AThe 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the 3- to 7-membered monocyclic heterocyclyl and the 5- to 10-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0089] In some embodiments:

[0090] is a single bond or a double bond;

[0091] X is N or C;

[0092] Y is N or C;

[0093] Ring A is phenyl, a 5- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0094] Each L A are independently covalent bonds or divalent C 1-6 aliphatic group, wherein the divalent C 1-6 The aliphatic group is optionally replaced by 1, 2, 3 or 4 independently selected R LA1 Substituent substitution;

[0095] Each R A are independently oxo, halogen, -CN, -OR A1 、-SR A1 、-N(R A1 )2、-C(O)R A1 、-C(O)OR A1 、-C(O)N(R A1 )2、-C(O)NR A1 (OR A1 ),-OC(O)R A 1 -OC(O)N(R A1 )2、-OC(O)OR A1 、-OSO2R A1 、-OSO2N(R A1 )2、-N(R A1 )C(O)R A1、-NR A1 C(O)OR A1 、-NR A1 C(O)N(R A1 )2、-N(R A1 )SO2R A1 、-NR A1 S(O)2N(R A1 )2、-NR A1 OR A1 、-NR A1 S(O)R A1 、-NR A1 S(O)N(R A1 )2、-S(O)R A1 、-SO2R A1 、-S(O)N(R A1 )2、-SO2N(R A1 )2、-SO3R A1 、-C(=NR m )R A1 、-C(=NR m )N(R A1 )2、-NR A1 C(=NR m )R A1 、-NR A1 C(=NR m )N(R A1 )2、-NR A1 S(O)(=NR m )R A1 、-NR A1 S(O)(=NR m )N(R A1 )2、-OS(O)(=NR m )R A1 、-S(O)(=NR m )R A1 、-S(O)(=NR m )N(R A1 )2、-P(O)(R A1 )2、C 1-6an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0096] where R A The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0097] or two L A -R A The phenyl group, together with the atoms to which it is attached, forms a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated The 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the phenyl, the 8- to 10-membered bicyclic aryl, the 3- to 7-membered monocyclic heterocyclyl, the 5- to 10-membered bicyclic heterocyclyl, the 5- to 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are independently optionally substituted by 1, 2, 3, 4, 5, or 6 R AG Substituent substitution;

[0098] R 1 is hydrogen or a group selected from the following: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R 1A Substituent substitution;

[0099] or R 1 and an L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5- to 14-membered saturated or partially unsaturated bicyclic heterocyclic group, together with the atoms to which they are attached, have 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 7-membered monocyclic heterocyclic group and the 5- to 14-membered bicyclic heterocyclic group is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0100] Z is N or CR 2 ;

[0101] U is N or CR 4 ;

[0102] R 2 and R 4 Each independently hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, - NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C 1-6aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R 2A Substituent substitution;

[0103] R 3 is -F, -Cl, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OS O2N(R)2, -N(R)C(O)R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NRO R, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R 3A Substituent substitution;

[0104] R5 -L 5 -R 5A ;

[0105] L 5 Covalent bond or divalent C 1-6 aliphatic group, wherein the divalent C 1-6 The aliphatic group is optionally replaced by 1, 2, 3 or 4 independently selected R L5A Substituent substitution;

[0106] or L 5 and an L A -R A The 3- to 16-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 16-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 16-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 16-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 16-membered monocyclic carbocyclyl, the 5- to 16-membered bicyclic carbocyclyl, the 3- to 16-membered monocyclic heterocyclyl and the 5- to 16-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0107] R 5A For-OR 5A11 、-SR 5A1 、-NHR 5A12 、-N(R 5A12 )2、-C(O)R 5A1 、-C(O)N(R 5A1 )2、-C(O)NR 5A1 (OR 5A1 ),-OC(O)R 5A1 、-OC(O)N(R 5A1 )2、-OC(O)OR 5A1 、-OSO2R 5A1 、-OSO2N(R 5A1 )2、-N(R 5A1 )C(O)R 5A1 、-NR 5A1 C(O)OR 5A1 、-NR 5A1 C(O)N(R 5A1 )2、-N(R 5A1 )SO2R 5A1 、-NR 5A1 S(O)2N(R 5A1 )2、-NR 5A1 OR 5A1、-NR 5A1 S(O)R 5A1 、-NR 5A1 S(O)N(R 5A1 )2、-S(O)R 5A1 、-SO2R 5A1 、-S(O)N(R 5A1 )2、-SO2N(R 5A1 )2, -SO3R 5A1 、-C(=NR m )R 5A1 、-C(=NR m )N(R 5A1 )2、-NR 5A1 C(=NR m )R 5A1 、-NR 5A1 C(=NR m )N(R 5A1 )2、-NR 5A1 S(O)(=NR m )R 5A1 、-NR 5A1 S(O)(=NR m )N(R 5A1 )2, -OS(O)(=NR m )R 5A1 、-S(O)(=NR m )R 5A1 、-S(O)(=NR m )N(R 5A1 )2、-P(O)(R 5A1 )2, methyl, C 2-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0108] where R 5A The C 2-6Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R 5AG Substitution by a substituent; or

[0109] R 5A The methyl group is replaced by 1, 2 or 3 R 5AG Substituent substitution;

[0110] R A1 and R 5A1 are independently hydrogen, C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0111] where R A1 or R 5A1 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution;

[0112] or two R A1 When attached to the same nitrogen atom, they together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally replaced by 1, 2, 3 or 4 independently selected R A11 Substituent substitution;

[0113] or two R 5A1When attached to the same nitrogen atom, they together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally replaced by 1, 2, 3 or 4 independently selected R A11 Substituent substitution;

[0114] R 5A11 Methyl, C 2-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0115] where R 5A11 The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substitution by a substituent; or

[0116] R 5A11 The methyl group is replaced by 1, 2 or 3 R G1 Substituent substitution;

[0117] Each R 5A12 Independently C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0118] where R 5A12 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution;

[0119] or two R 5A12 When attached to the same nitrogen atom, they together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally replaced by 1, 2, 3 or 4 independently selected R 5B12 Substituent substitution;

[0120] R AG 、R 5AG and R G1 each independently represents oxo, halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R), -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8-membered to 10-membered bicyclic aryl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, the 5-membered to 6-membered monocyclic heteroaryl group and the 8-membered to 10-membered bicyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R AG1 Substituent substitution;

[0121] Each R is independently selected from oxo, hydrogen, C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8-membered to 10-membered bicyclic aryl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, the 5-membered to 6-membered monocyclic heteroaryl group and the 8-membered to 10-membered bicyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R N Substitution by a substituent; or

[0122] Two R when attached to the same nitrogen atom together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally replaced by 1, 2, 3 or 4 independently selected R N Substituent substitution;

[0123] Each R LA1 、R 1A 、R 2A 、R 3A 、R L5A 、R A11 、R 5B12 、R AG1 and R N independently selected from oxo, halogen, -(CH2) 0- 4R o 、-(CH2) 0-4 OR o 、-O(CH2) 0-4 R o 、-O-(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 CH(OR o )2、-(CH2) 0-4 SR o 、-(CH2) 0-4 Ph, -(CH2) 0-4 O(CH2) 0-1 Ph, -CH=CHPh, -(CH2) 0-4 O(CH2) 0-1 -pyridyl, -NO2, -CN, -N3, -(CH2) 0-4 N(R o )2、-(CH2) 0-4 N(R o )C(O)R o 、-N(R o )C(S)R o 、-(CH2) 0-4 N(R o )C(O)NR o 2. -N(R o )C(S)NR o 2. -(CH2) 0-4 N(R o )C(O)OR o 、-N(Ro )N(R o )C(O)R o 、-N(R o )N(R o )C(O)NR o 2、-N(R o )N(R o )C(O)OR o 、-(CH2) 0-4 C(O)R o 、-C(S)R o 、-(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 C(O)SR o 、-(CH2) 0-4 C(O)OSiR o 3、-(CH2) 0-4 OC(O)R o 、-OC(O)(CH2) 0-4 SR o 、-(CH2) 0-4 SC(O)R o 、-(CH2) 0-4 C(O)NR o 2、-C(S)NR o 2、-C(S)SR o 、-SC(S)SR o 、-(CH2) 0-4 OC(O)NR o 2、-C(O)N(OR o )R o 、-C(O)C(O)R o 、-C(O)CH2C(O)R o 、-C(NOR o )R o 、-(CH2) 0-4 SSR o 、-(CH2) 0-4 S(O)2R o 、-(CH2) 0-4 S(O)(=NR o )R o 、-(CH2) 0-4 S(O)2OR o 、-(CH2) 0-4 OS(O)2R o 、-(CH2) 0-4 -S(O)2NR o 2、-(CH2) 0-4S(O)(=NR o )NR o 2. -(CH2) 0-4 S(O)R o 、-N(R o )S(O)2NR o 2. -N(R o )S(O)2R o 、-N(R o )S(O)(=NR o )R o 、-N(OR o )R o 、-C(NH)NR o 2. -P(O)2R o 、-P(O)R o 2. -OP(O)R o 2. -OP(O)(OR o )2、-SiR o 3. -(C 1-4 linear or branched alkylene)ON(R o )2 and -(C 1-4 linear or branched alkylene) C(O)ON(R o )2;

[0124] Each R o are independently oxo, hydrogen, C 1-6 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph, -CH2-(5- to 6-membered heteroaryl ring) or a 3- to 6-membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur;

[0125] or two independent occurrences of R o Together with its intervening atoms, it forms a 3- to 12-membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur;

[0126] Each R m are independently oxo, -OH, -CN or R; and

[0127] n is 0, 1, 2, 3 or 4.

[0128] In some embodiments of the preceding embodiments:

[0129] R AG 、R 5AG and R G1Each independently is halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O) R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8-membered to 10-membered bicyclic aryl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, the 5-membered to 6-membered monocyclic heteroaryl group and the 8-membered to 10-membered bicyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R AG1 Substituent substitution;

[0130] Each R is independently selected from hydrogen, C 1-6an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8-membered to 10-membered bicyclic aryl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, the 5-membered to 6-membered monocyclic heteroaryl group and the 8-membered to 10-membered bicyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R N Substitution by a substituent; or

[0131] Two R when attached to the same nitrogen atom together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally replaced by 1, 2, 3 or 4 independently selected R N Substituent substitution;

[0132] Each R LA1 、R 1A 、R 2A 、R 3A 、R L5A 、R A11 、R 5B12 、R AG1 and R N independently selected from halogen, -(CH2) 0-4 R o 、-(CH2) 0-4 OR o 、-O(CH2) 0-4 R o 、-O-(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 CH(OR o )2、-(CH2) 0-4 SR o, -(CH2) 0- 4Ph, -(CH2) 0-4 O(CH2) 0-1 Ph, -CH=CHPh, -(CH2) 0-4 O(CH2) 0-1 -pyridyl, -NO2, -CN, -N3, -(CH2) 0-4 N(R o )2, -(CH2) 0-4 N(R o )C(O)R o , -N(R o )C(S)R o , -(CH2) 0-4 N(R o )C(O)NR o 2, -N(R o )C(S)NR o , -(CH2) 0-4 N(R o )C(O)OR<000086​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​OC(O)NR o 2. -C(O)N(OR o )R o 、-C(O)C(O)R o 、-C(O)CH2C(O)R o 、-C(NOR o )R o 、-(CH2) 0-4 SSR o 、-(CH2) 0-4 S(O)2R o 、-(CH2) 0-4 S(O)(=NR o )R o 、-(CH2) 0-4 S(O)2OR o 、-(CH2) 0-4 OS(O)2R o 、-(CH2) 0-4 -S(O)2NR o 2. -(CH2) 0-4 S(O)(=NR o )NR o 2. -(CH2) 0-4 S(O)R o 、-N(R o )S(O)2NR o 2. -N(R o )S(O)2R o 、-N(R o )S(O)(=NR o )R o 、-N(OR o )R o 、-C(NH)NR o 2. -P(O)2R o 、-P(O)R o 2. -OP(O)R o 2. -OP(O)(OR o )2、-SiR o 3. -(C 1-4 linear or branched alkylene)ON(R o )2 and -(C 1-4 linear or branched alkylene) C(O)ON(R o )2;

[0133] Each R o are independently hydrogen, C 1-6 Aliphatic groups, -CH2Ph, -O(CH2) 0-1Ph, -CH2-(5- to 6-membered heteroaryl ring) or a 3- to 6-membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur;

[0134] or two independent occurrences of R o Together with its intervening atoms, it forms a 3- to 12-membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; and

[0135] Each R m is independently -OH, -CN or R.

[0136] In some embodiments of the preceding embodiments, L 5 and an L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the 3- to 7-membered monocyclic heterocyclyl and the 5- to 10-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0137] In some embodiments:

[0138] is a single bond or a double bond;

[0139] X is N or C;

[0140] Y is N or C;

[0141] Ring A is phenyl or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0142] Each L A are independently covalent bonds or optionally substituted divalent C 1-6 aliphatic groups;

[0143] Each R A are independently oxo, halogen, -CN, -OR A1 、-SR A1 、-N(R A1 )2、-C(O)R A1 、-C(O)OR A1 、-C(O)N(R A1)2、-C(O)NR A1 (OR A1 )、-OC(O)R A 1 -OC(O)N(R A1 )2、-OC(O)OR A1 、-OSO2R A1 、-OSO2N(R A1 )2、-N(R A1 )C(O)R A1 、-NR A1 C(O)OR A1 、-NR A1 C(O)N(R A1 )2、-N(R A1 )SO2R A1 、-NR A1 S(O)2N(R A1 )2、-NR A1 OR A1 、-NR A1 S(O)R A1 、-NR A1 S(O)N(R A1 )2、-S(O)R A1 、-SO2R A1 、-S(O)N(R A1 )2、-SO2N(R A1 )2、-SO3R A1 、-C(=NR m )R A1 、-C(=NR m )N(R A1 )2、-NR A1 C(=NR m )R A1 、-NR A1 C(=NR m )N(R A1 )2、-NR A1 S(O)(=NR m )R A1 、-NR A1 S(O)(=NR m )N(R A1 )2、-OS(O)(=NR m )R A1 、-S(O)(=NR m )R A1 、-S(O)(=NR m )N(R A1 )2、-P(O)(R A1 )2、C1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0144] where R A The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0145] R 1 is hydrogen or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0146] Z is N or CR 2 ;

[0147] U is N or CR 4 ;

[0148] R 2 and R 4 Each independently hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, - NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NRm )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0149] R 3 is -F, -Cl, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OS O2N(R)2, -N(R)C(O)R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NRO R, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0150] R 5 -L 5 -R 5A ;

[0151] L 5 is a covalent bond or an optionally substituted divalent C 1-6 aliphatic groups;

[0152] R 5A For-OR 5A11 、-SR 5A1 、-NHR 5A12 、-N(R 5A12 )2、-C(O)R 5A1 、-C(O)N(R 5A1 )2、-C(O)NR 5A1 (OR 5A1 ),-OC(O)R 5A1 、-OC(O)N(R 5A1 )2、-OC(O)OR 5A1 、-OSO2R 5A1 、-OSO2N(R 5A1 )2、-N(R 5A1 )C(O)R 5A1 、-NR 5A1 C(O)OR 5A1 、-NR 5A1 C(O)N(R 5A1 )2、-N(R 5A1 )SO2R 5A1 、-NR 5A1 S(O)2N(R 5A1 )2、-NR 5A1 OR 5A1 、-NR 5A1 S(O)R 5A1 、-NR 5A1 S(O)N(R 5A1 )2、-S(O)R 5A1 、-SO2R 5A1 、-S(O)N(R 5A1 )2、-SO2N(R 5A1 )2, -SO3R 5A1 、-C(=NR m )R 5A1 、-C(=NR m )N(R 5A1 )2、-NR 5A1 C(=NR m )R 5A1 、-NR 5A1 C(=NRm )N(R 5A1 )2、-NR 5A1 S(O)(=NR m )R 5A1 、-NR 5A1 S(O)(=NR m )N(R 5A1 )2, -OS(O)(=NR m )R 5A1 、-S(O)(=NR m )R 5A1 、-S(O)(=NR m )N(R 5A1 )2、-P(O)(R 5A1 )2, methyl, C 2-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0153] where R 5A The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R 5AG Substitution by a substituent; or

[0154] R 5A The methyl group is replaced by 1, 2 or 3 R 5AG Substituent substitution;

[0155] R A1 and R 5A1 are independently hydrogen, C 1-6an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0156] where R A1 or R 5A1 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution;

[0157] or two R A1 when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0158] or two R 5A1 when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0159] R 5A11 Methyl, C 2-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0160] where R 5A11 The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substitution by a substituent; or

[0161] R 5A11 The methyl group is replaced by 1, 2 or 3 R G1 Substituent substitution;

[0162] Each R 5A12 Independently C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0163] where R 5A12 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution;

[0164] or two R 5A12 when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0165] R AG 、R 5AG and R G1Each independently is halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O) R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

[0166] Each R is independently hydrogen or an optionally substituted group selected from the group consisting of: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or

[0167] two R's when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0168] Each R m are independently -OH, -CN or R; and

[0169] n is 0, 1, 2, 3 or 4.

[0170] In some embodiments:

[0171] is a single bond or a double bond;

[0172] X is N or C;

[0173] Y is N or C;

[0174] Ring A is phenyl or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0175] Each L A are independently covalent bonds or divalent C 1-6 aliphatic group, wherein the divalent C 1-6 The aliphatic group is optionally replaced by 1, 2, 3 or 4 independently selected R LA1 Substituent substitution;

[0176] Each R A are independently oxo, halogen, -CN, -OR A1 、-SR A1 、-N(R A1 )2、-C(O)R A1 、-C(O)OR A1 、-C(O)N(R A1 )2、-C(O)NR A1 (OR A1 ),-OC(O)R A 1 -OC(O)N(R A1 )2、-OC(O)OR A1 、-OSO2R A1 、-OSO2N(R A1 )2、-N(R A1 )C(O)R A1 、-NR A1 C(O)OR A1 、-NR A1 C(O)N(RA1 )2、-N(R A1 )SO2R A1 、-NR A1 S(O)2N(R A1 )2、-NR A1 OR A1 、-NR A1 S(O)R A1 、-NR A1 S(O)N(R A1 )2、-S(O)R A1 、-SO2R A1 、-S(O)N(R A1 )2、-SO2N(R A1 )2, -SO3R A1 、-C(=NR m )R A1 、-C(=NR m )N(R A1 )2、-NR A1 C(=NR m )R A1 、-NR A1 C(=NR m )N(R A1 )2、-NR A1 S(O)(=NR m )R A1 、-NR A1 S(O)(=NR m )N(R A1 )2, -OS(O)(=NR m )R A1 、-S(O)(=NR m )R A1 、-S(O)(=NR m )N(R A1 )2、-P(O)(R A1 )2、C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0177] where R A The C1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0178] R 1 is hydrogen or a group selected from the following: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R 1A Substituent substitution;

[0179] Z is N or CR 2 ;

[0180] U is N or CR 4 ;

[0181] R 2 and R 4 Each independently hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, - NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m)R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R 2A Substituent substitution;

[0182] R 3 is -F, -Cl, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OS O2N(R)2, -N(R)C(O)R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NRO R, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R 3A Substituent substitution;

[0183] R 5 -L 5 -R 5A ;

[0184] L 5 Covalent bond or divalent C 1-6 aliphatic group, wherein the divalent C 1-6 The aliphatic group is optionally replaced by 1, 2, 3 or 4 independently selected R L5A Substituent substitution;

[0185] R 5A For-OR 5A11 、-SR 5A1 、-NHR 5A12 、-N(R 5A12 )2、-C(O)R 5A1 、-C(O)N(R 5A1 )2、-C(O)NR 5A1 (OR 5A1 ),-OC(O)R 5A1 、-OC(O)N(R 5A1 )2、-OC(O)OR 5A1 、-OSO2R 5A1 、-OSO2N(R 5A1 )2、-N(R 5A1 )C(O)R 5A1 、-NR 5A1 C(O)OR 5A1 、-NR 5A1 C(O)N(R 5A1 )2、-N(R 5A1 )SO2R 5A1 、-NR 5A1 S(O)2N(R 5A1 )2、-NR 5A1 OR 5A1 、-NR 5A1 S(O)R 5A1 、-NR 5A1 S(O)N(R 5A1 )2、-S(O)R 5A1 、-SO2R 5A1 、-S(O)N(R 5A1 )2、-SO2N(R 5A1 )2, -SO3R5A1 、-C(=NR m )R 5A1 、-C(=NR m )N(R 5A1 )2、-NR 5A1 C(=NR m )R 5A1 、-NR 5A1 C(=NR m )N(R 5A1 )2、-NR 5A1 S(O)(=NR m )R 5A1 、-NR 5A1 S(O)(=NR m )N(R 5A1 )2, -OS(O)(=NR m )R 5A1 、-S(O)(=NR m )R 5A1 、-S(O)(=NR m )N(R 5A1 )2、-P(O)(R 5A1 )2, methyl, C 2-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0186] where R 5A The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R 5AG Substitution by a substituent; or

[0187] R 5A The methyl group is replaced by 1, 2 or 3 R 5AG Substituent substitution;

[0188] R A1 and R 5A1are independently hydrogen, C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0189] where R A1 or R 5A1 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution;

[0190] or two R A1 When attached to the same nitrogen atom, they together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally replaced by 1, 2, 3 or 4 independently selected R A11 Substituent substitution;

[0191] or two R 5A1 When attached to the same nitrogen atom, they together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally replaced by 1, 2, 3 or 4 independently selected R A11 Substituent substitution;

[0192] R 5A11 Methyl, C 2-6an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0193] where R 5A11 The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substitution by a substituent; or

[0194] R 5A11 The methyl group is replaced by 1, 2 or 3 R G1 Substituent substitution;

[0195] Each R 5A12 Independently C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur,

[0196] where R 5A12 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution;

[0197] or two R 5A12When attached to the same nitrogen atom, they together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally replaced by 1, 2, 3 or 4 independently selected R 5B12 Substituent substitution;

[0198] R AG 、R 5AG and R G1 Each independently is halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O) R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8-membered to 10-membered bicyclic aryl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, the 5-membered to 6-membered monocyclic heteroaryl group and the 8-membered to 10-membered bicyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R AG1 Substituent substitution;

[0199] Each R is independently selected from hydrogen, C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8-membered to 10-membered bicyclic aryl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, the 5-membered to 6-membered monocyclic heteroaryl group and the 8-membered to 10-membered bicyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R N Substitution by a substituent; or

[0200] Two R when attached to the same nitrogen atom together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally replaced by 1, 2, 3 or 4 independently selected R N Substituent substitution;

[0201] Each R LA1 、R 1A 、R 2A 、R 3A 、R L5A 、R A11 、R 5B12 、R AG1 and R NIndependently selected from halogen, -(CH2) 0-4 R o 、-(CH2) 0-4 OR o 、-O(CH2) 0-4 R o 、-O-(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 CH(OR o )2、-(CH2) 0-4 SR o 、-(CH2) 0- 4Ph、-(CH2) 0-4 O(CH2) 0-1 Ph、-CH=CHPh、-(CH2) 0-4 O(CH2) 0-1 -pyridyl, -NO2, -CN, -N3, -(CH2) 0-4 N(R o )2、-(CH2) 0-4 N(R o )C(O)R o 、-N(R o )C(S)R o 、-(CH2) 0-4 N(R o )C(O)NR o 2、-N(R o )C(S)NR o 2、-(CH2) 0-4 N(R o )C(O)OR o 、-N(R o )N(R o )C(O)R o 、-N(R o )N(R o )C(O)NR o 2、-N(R o )N(R o )C(O)OR o 、-(CH2) 0-4 C(O)R o 、-C(S)R o 、-(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 C(O)SR o 、-(CH2) 0-4 C(O)OSiR o 3、-(CH2) 0-4OC(O)R o 、-OC(O)(CH2) 0-4 SR o 、-(CH2) 0-4 SC(O)R o 、-(CH2) 0-4 C(O)NR o 2、-C(S)NR o 2、-C(S)SR o 、-SC(S)SR o 、-(CH2) 0-4 OC(O)NR o 2、-C(O)N(OR o )R o 、-C(O)C(O)R o 、-C(O)CH2C(O)R o 、-C(NOR o )R o 、-(CH2) 0-4 SSR o 、-(CH2) 0-4 S(O)2R o 、-(CH2) 0-4 S(O)(=NR o )R o 、-(CH2) 0-4 S(O)2OR o 、-(CH2) 0-4 OS(O)2R o 、-(CH2) 0-4 -S(O)2NR o 2、-(CH2) 0-4 S(O)(=NR o )NR o 2、-(CH2) 0-4 S(O)R o 、-N(R o )S(O)2NR o 2、-N(R o )S(O)2R o 、-N(R o )S(O)(=NR o )R o 、-N(OR o )R o 、-C(NH)NR o 2、-P(O)2R o 、-P(O)R o 2、-OP(O)R o 2、-OP(O)(OR o)2、-SiR o 3. -(C 1-4 linear or branched alkylene)ON(R o )2 and -(C 1-4 linear or branched alkylene) C(O)ON(R o )2;

[0202] Each R o are independently hydrogen, C 1-6 Aliphatic groups, -CH2Ph, -O(CH2) 0-1 Ph, -CH2-(5- to 6-membered heteroaryl ring) or a 3- to 6-membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur;

[0203] or two independent occurrences of R o Together with its intervening atoms, it forms a 3- to 12-membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur;

[0204] Each R m are independently -OH, -CN or R; and

[0205] n is 0, 1, 2, 3 or 4.

[0206] In some embodiments, the present disclosure provides compounds of Formula II:

[0207]

[0208] or a pharmaceutically acceptable salt thereof, wherein X, Y, Z, U, Ring A, L A 、R A 、R 1 、R 3 、L 5 、R 5A12 Each of and n is as defined above for Formula I and described in classes and subclasses herein, both individually and in combination.

[0209] In some embodiments, the present disclosure provides compounds of Formula III:

[0210]

[0211] or a pharmaceutically acceptable salt thereof, wherein Z, U, Ring A, L A 、R A 、R 1 、R 3 、L 5 、R 5A12 Each of and n is as defined above for Formula I and described in classes and subclasses herein, both individually and in combination.

[0212] As described above, in some embodiments of any of Formula I and Formula II, is a single bond or a double bond. In some embodiments, Is a single bond. In some embodiments, For double bonds.

[0213] As described above, in some embodiments of any of Formula I and Formula II, X is N or C. In some embodiments, X is N. In some embodiments, X is C.

[0214] As described above, in some embodiments of any of Formula I and Formula II, Y is N or C. In some embodiments, Y is N. In some embodiments, Y is C.

[0215] In some embodiments, X is C and Y is N. In some embodiments, X is N and Y is C. In some embodiments, X is C and Y is C.

[0216] As described above, in some embodiments of any one of Formula I, Formula II, and Formula III, Ring A is phenyl or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, and Formula Va, Ring A is phenyl or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0217] In some embodiments, Ring A is a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is a 5-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is a 5-membered monocyclic heteroaryl group having 1-3 nitrogen atoms. In some embodiments, Ring A is a 5-membered monocyclic heteroaryl group having 1-2 nitrogen atoms. In some embodiments, Ring A is a 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Ring A is a 6-membered monocyclic heteroaryl group having 1-3 nitrogen atoms. In some embodiments, Ring A is a 6-membered monocyclic heteroaryl group having 1-2 nitrogen atoms. In some embodiments, Ring A is selected from pyrazolyl, imidazolyl, triazolyl, and pyridyl. 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 pyridinyl.

[0218] As described above, in some embodiments of any one of Formula I, Formula II, and Formula III, each L Aare independently covalent bonds or optionally substituted divalent C 1-6 In some embodiments of any one of Formula I, Formula II, Formula III, and Formula IV, each L A are independently covalent bonds or optionally substituted divalent C 1-6 In some embodiments, L A Covalent bond or divalent C 1-2 In some embodiments, L A is a covalent bond. In some embodiments, L A For divalent C 1-6 In some embodiments, L A For divalent C 1-3 In some embodiments, L A For divalent C 1-2 In some embodiments, L A is a divalent C1 aliphatic group (e.g., -CH2-). A It is a divalent C2 aliphatic group (e.g., -CH2CH2-).

[0219] In some embodiments of any one of Formula I, Formula II, Formula III, and Formula IV, each R A are independently oxo, halogen, -CN, -OR A1 、-SR A1 、-N(R A1 )2、-C(O)R A1 、-C(O)OR A1 、-C(O)N(R A1 )2、-C(O)NR A1 (OR A1 ),-OC(O)R A1 -OC(O)N(R A1 )2、-OC(O)OR A1 、-OSO2R A1 、-OSO2N(R A1 )2、-N(R A1 )C(O)R A1 、-NR A1 C(O)OR A1 、-NR A1 C(O)N(R A1 )2、-N(R A1 )SO2R A1 、-NR A1 S(O)2N(R A1 )2、-NRA1 OR A1 、-NR A1 S(O)R A1 、-NR A1 S(O)N(R A1 )2、-S(O)R A1 、-SO2R A1 、-S(O)N(R A1 )2、-SO2N(R A1 )2, -SO3R A1 、-C(=NR m )R A1 、-C(=NR m )N(R A1 )2、-NR A1 C(=NR m )R A1 、-NR A1 C(=NR m )N(R A1 )2、-NR A1 S(O)(=NR m )R A1 、-NR A1 S(O)(=NR m )N(R A1 )2, -OS(O)(=NR m )R A1 、-S(O)(=NR m )R A1 、-S(O)(=NR m )N(R A1 )2、-P(O)(R A1 )2、C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R A The C 1-6Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0220] As described above, in some embodiments of any one of Formula I, Formula II, and Formula III, each R A are independently oxo, halogen, -CN, -OR A1 、-SR A1 、-N(R A1 )2、-C(O)R A1 、-C(O)OR A1 、-C(O)N(R A1 )2、-C(O)NR A1 (OR A1 ),-OC(O)R A1 -OC(O)N(R A1 )2、-OC(O)OR A1 、-OSO2R A1 、-OSO2N(R A1 )2、-N(R A1 )C(O)R A1 、-NR A1 C(O)OR A1 、-NR A1 C(O)N(R A1 )2、-N(R A1 )SO2R A1 、-NR A1 S(O)2N(R A1 )2、-NR A1 OR A1 、-NR A1 S(O)R A1 、-NR A1 S(O)N(R A1 )2、-S(O)R A1 、-SO2R A1 、-S(O)N(R A1 )2、-SO2N(R A1 )2, -SO3R A1 、-C(=NR m )R A1 、-C(=NR m )N(R A1 )2、-NR A1 C(=NRm )R A1 、-NR A1 C(=NR m )N(R A1 )2、-NR A 1 S(O)(=NR m )R A1 、-NR A1 S(O)(=NR m )N(R A1 )2, -OS(O)(=NR m )R A1 、-S(O)(=NR m )R A1 、-S(O)(=NR m )N(R A1 )2、-P(O)(R A1 )2、C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R A The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0221] In some embodiments, each R A Independently C 1-6 Aliphatic group, -OR A1 、-N(R A1) 2- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl group, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein R A The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0222] In some embodiments, each R A Independently C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2、-C(O)R A1 、-C(O)N(R A1 )2, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A The C 1-6 Alkyl, the C 2-6 The alkenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl are each independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0223] In some embodiments, each R A Independently C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2、-C(O)R A1 、-C(O)N(R A1)2, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A The C 1-6 Alkyl, the C 2-6 The alkenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl are each independently optionally substituted by 1, 2, 3 or 4 R AG Substituent substitution.

[0224] In some embodiments, each R A Independently C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2、-C(O)R A1 、-C(O)N(R A1 )2, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A The C 1-6 Alkyl, the C 2-6 The alkenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl are each independently optionally substituted by 1 or 2 R AG Substituent substitution.

[0225] In some embodiments, each R A Independently C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R AThe C 1-6 Alkyl, the C 2-6 Each of the alkenyl, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0226] In some embodiments, each R A Independently C 1-6 Aliphatic group, -OR A1 、-N(R A1 )2, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R A The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl, and the 8-membered to 10-membered bicyclic heteroaryl is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R AG Substituent substitution.

[0227] In some embodiments, each R A Independently C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein RA The C 1-6 Alkyl, the C 2-6 each of the alkenyl, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl, and the 8-membered to 10-membered bicyclic heteroaryl, is optionally substituted by 1, 2, 3, or 4 independently selected R AG Substituent substitution.

[0228] In some embodiments, each R A Independently C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R A The C 1-6 Alkyl, the C 2-6 each of the alkenyl, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl, and the 8-membered to 10-membered bicyclic heteroaryl is optionally substituted by 1 or 2 independently selected R AG Substituent substitution.

[0229] In some embodiments, each R A Independently C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A The C 1-6 Alkyl, the C 2-6The alkenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl are each independently optionally substituted by 1 or 2 R AG Substituent substitution.

[0230] In some embodiments, each R A Independently C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A The C 1-6 Alkyl, the C 2-6 The alkenyl, the phenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl are each independently optionally substituted by 1 or 2 R AG Substituent substitution.

[0231] In some embodiments, each R A Independently C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A The C 1-6 Alkyl, the C 2-6 The alkenyl, the phenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl are each independently optionally substituted by 1 or 2 R AG Substituent substitution.

[0232] In some embodiments, each R A independently selected from phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic radicals having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and 5- to 6-membered monocyclic heteroaryl radicals having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, each of which is optionally substituted by 1, 2, 3, 4, 5, or 6 independently selected R AG Substituent substitution.

[0233] In some embodiments, each R Aindependently selected from phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic radicals having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl radicals having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, each of which is optionally substituted by 1 or 2 independently selected R AG Substituent substitution.

[0234] In some embodiments, each R A independently selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic groups having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, each of which is optionally substituted by 1 or 2 independently selected R AG Substituent substitution.

[0235] In some embodiments, each R A independently selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic groups having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, each of which is optionally replaced by 1 or 2 independently selected R AG Substituent substitution.

[0236] In some embodiments, each R A independently selected from 5- to 6-membered monocyclic heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, each of which is optionally substituted by 1 or 2 independently selected R AG Substituent substitution.

[0237] In some embodiments, R A is optionally replaced by 1, 2, 3, 4, 5 or 6 R AG In some embodiments, R A It is phenyl.

[0238] In some embodiments, R A is optionally replaced by 1, 2, 3, 4, 5 or 6 R AG Substituent-substituted C 1-6 In some embodiments, R A is optionally replaced by 1, 2, 3, 4, 5 or 6 R AG Substituent-substituted C 1-3 In some embodiments, R A is optionally replaced by 1, 2, 3, 4 or 5 R AG Substituent-substituted C 1-2 In some embodiments, R A is optionally replaced by 1, 2, 3, 4 or 5 R AG Substituent-substituted C 1-2 In some embodiments, RA is optionally replaced by 1, 2 or 3 R AG In some embodiments, R A It is -CH=CH2.

[0239] In some embodiments, two L A -R A The phenyl group, together with the atoms to which it is attached, forms a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated The 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the phenyl, the 8- to 10-membered bicyclic aryl, the 3- to 7-membered monocyclic heterocyclyl, the 5- to 10-membered bicyclic heterocyclyl, the 5- to 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are independently optionally substituted by 1, 2, 3, 4, 5, or 6 R AG Substituent substitution.

[0240] In some embodiments, each R A1 are independently hydrogen, C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R A1 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substituted; or two R A1When attached to the same nitrogen atom, they together form an optionally substituted ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0241] In some embodiments, each R A1 Independently C 1-6 an aliphatic group or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A1 Each C 1-6 The aliphatic group and the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group are optionally substituted by 1, 2, 3, 4, 5 or 6 independently selected R G1 Substituent substitution.

[0242] In some embodiments, each R A1 Independently C 1-6 an aliphatic group or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A1 Each C 1-6 The aliphatic group and the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group are optionally substituted by 1 or 2 independently selected R G1 Substituent substitution.

[0243] In some embodiments, each R A1 Independently C 1-6 alkyl or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A1 Each C 1-6 The aliphatic group and the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group are optionally substituted by 1, 2, 3, 4, 5 or 6 independently selected R G1 Substituent substitution.

[0244] In some embodiments, each R A1 Independently C 1-6 alkyl or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A1 Each C 1-6 The aliphatic group and the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group are optionally substituted by 1 or 2 independently selected R G1 Substituent substitution.

[0245] In some embodiments, each R A1 Independently C 1-6aliphatic group, where R A1 Each C 1-6 The aliphatic group is optionally replaced by 1, 2, 3, 4, 5 or 6 independently selected R G1 Substituent substitution.

[0246] In some embodiments, each R A1 Independently C 1-6 Alkyl, where R A1 Each C 1-6 The alkyl group is optionally replaced by 1, 2, 3, 4, 5 or 6 independently selected R G1 In some embodiments, each R A1 Independently C 1-6 Alkyl, where R A1 Each C 1-6 The alkyl group is optionally replaced by 1, 2, 3 or 4 independently selected R G1 In some embodiments, each R A1 Independently C 1-6 Alkyl, where R A1 Each C 1-6 The alkyl group is optionally replaced by 1 or 2 independently selected R G1 Substituent substitution.

[0247] In some embodiments, each R G1 are independently selected from OR, wherein each R is hydrogen or C 1-6 In some embodiments, each R G1 are independently selected from OR, wherein each R is hydrogen or C 1-6 In some embodiments, each R G1 are independently selected from OR, wherein each R is C 1-6 In some embodiments, each R G1 are independently selected from OR, wherein each R is C 1-3 In some embodiments, each R G1 In some embodiments, each R G1 In some embodiments, each R G1 It is a hydroxyl group.

[0248] In some embodiments, each R A1 Independently C 1-6 an aliphatic group or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A1 Each C 1-6 The alkyl group and the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group are optionally substituted by a hydroxy group or a methoxy group.

[0249] In some embodiments, each R A1 Independently C 1-6 alkyl or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A1 Each C 1-6 The alkyl group and the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group are optionally substituted by a hydroxy group or a methoxy group.

[0250] In some embodiments, each R A1 Independently C 1-6 Alkyl, where R A1 Each C 1-6 The alkyl group is optionally substituted with a methoxy group.

[0251] In some embodiments, each R AG Independently halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R , -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0252] In some embodiments, each R AG independently selected from halogen and C 1-6 In some embodiments, each R AG is an independently selected halogen. In some embodiments, each R AG C for independent selection 1-6 In some embodiments, each R AG C for independent selection 1-6 In some embodiments, each R AG C for independent selection 1-3 In some embodiments, each R AG In some embodiments, each R AG In some embodiments, each R AG It is a methyl group.

[0253] In some embodiments, each R A independently selected from methyl, ethyl, n-propyl, isopropyl, vinyl, methoxy, methoxyethoxy, dimethylamino, dimethylaminocarbonyl, azetidinylcarbonyl, (hydroxyazetidinyl)carbonyl, cyclopropyl, cyclopentyl, phenyl, pyridyl, pyrimidinyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydro-2H-pyranyl, morpholinyl, tetrahydrofuranyl, piperazinyl, 5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl, wherein the methyl The alkyl, ethyl, n-propyl, isopropyl, vinyl, cyclopropyl, cyclopentyl, phenyl, pyridyl, pyrimidinyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydro-2H-pyranyl, morpholinyl, tetrahydrofuranyl, piperazinyl and 5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl are each optionally replaced by 1, 2, 3 or 4 independently selected R AG Substituent substitution.

[0254] In some embodiments, each R A are independently selected from methyl, ethyl, n-propyl, isopropyl, vinyl, methoxy, methoxyethoxy, dimethylamino, dimethylaminocarbonyl, azetidinylcarbonyl, (hydroxyazetidinyl)carbonyl, cyclopropyl, cyclopentyl, phenyl, pyridyl, pyrimidinyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydro-2H-pyranyl, morpholinyl, tetrahydrofuranyl, piperazinyl, 5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl, wherein The methyl, ethyl, n-propyl, isopropyl, vinyl, cyclopropyl, cyclopentyl, phenyl, pyridinyl, pyrimidinyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydro-2H-pyranyl, morpholinyl, tetrahydrofuranyl, piperazinyl and 5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl are each optionally replaced by 1 or 2 independently selected R AG Substituent substitution.

[0255] In some embodiments, each R A Independently selected from methyl, ethyl, n-propyl, isopropyl, vinyl, methoxy, methoxyethoxy, dimethylamino, cyclopropyl, cyclopentyl, phenyl, methylphenyl, pyridyl, fluoropyridyl, methylpyridyl, pyrimidinyl, tetrahydrofuranyl and tetrahydropyranyl.

[0256] In some embodiments, each R A Independently selected from methyl, ethyl, propyl, vinyl, methoxy, methoxyethoxy, dimethylamino, phenyl, methylphenyl, pyridyl, fluoropyridyl, methylpyridyl, pyrimidinyl and tetrahydropyranyl.

[0257] In some embodiments, each L A Covalent bond or C 1-3 In some embodiments, each L A Covalent bond or C 1-2 In some embodiments, each L A is a covalent bond. In some embodiments, each L A C 1-3 In some embodiments, each L A C 1-2 Aliphatic group.

[0258] In some embodiments, each L A Covalent bond or C 1-2 aliphatic group, and each R Aare independently selected from methyl, ethyl, n-propyl, isopropyl, vinyl, methoxy, methoxyethoxy, dimethylamino, dimethylaminocarbonyl, azetidinylcarbonyl, (hydroxyazetidinyl)carbonyl, cyclopropyl, cyclopentyl, phenyl, pyridyl, pyrimidinyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydro-2H-pyranyl, morpholinyl, tetrahydrofuranyl, piperazinyl, 5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl, wherein The methyl, ethyl, n-propyl, isopropyl, vinyl, cyclopropyl, cyclopentyl, phenyl, pyridinyl, pyrimidinyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydro-2H-pyranyl, morpholinyl, tetrahydrofuranyl, piperazinyl and 5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl are each optionally replaced by 1 or 2 independently selected R AG Substituent substitution.

[0259] In some embodiments, each L A is a covalent bond or a C2 aliphatic group, and each R A Independently selected from methyl, ethyl, propyl, vinyl, methoxy, methoxyethoxy, dimethylamino, phenyl, methylphenyl, pyridyl, fluoropyridyl, methylpyridyl, pyrimidinyl and tetrahydropyranyl.

[0260] In some embodiments, each L A is a covalent bond, and each R A Independently selected from methyl, ethyl, propyl, vinyl, methoxy, methoxyethoxy, dimethylamino, phenyl, methylphenyl, pyridyl, fluoropyridyl, methylpyridyl, pyrimidinyl and tetrahydropyranyl.

[0261] In some embodiments, each L A is a C2 aliphatic group, and each R A L is independently selected from methyl, ethyl, propyl, vinyl, methoxy, methoxyethoxy, dimethylamino, phenyl, methylphenyl, pyridinyl, fluoropyridinyl, methylpyridinyl, pyrimidinyl, and tetrahydropyranyl. A is a C2 aliphatic group, and each R A It is phenyl.

[0262] In some embodiments, for

[0263]

[0264]

[0265]

[0266] In some embodiments, for

[0267] In some embodiments, for

[0268] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula VI, and Formula Via, R 1 is hydrogen or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0269] As described above, in some embodiments of any one of Formula I, Formula II, and Formula III, R 1 is hydrogen or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0270] In some embodiments, R 1 is optionally substituted C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0271] In some embodiments, R 1 is optionally substituted C 1-6 Alkyl, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0272] In some embodiments, R 1 is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group. 1 It is cyclopropyl.

[0273] In some embodiments, R 1 is a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. 1 It is tetrahydrofuranyl.

[0274] In some embodiments, R 1 is optionally substituted C 1-6 In some embodiments, R 1 is optionally substituted C 1-3 In some embodiments, R 1 is optionally substituted C 1-2 Aliphatic group.

[0275] In some embodiments, R 1 C 1-6 In some embodiments, R 1 C 1-3 In some embodiments, R 1 C 1-2 In some embodiments, R 1 is optionally substituted C 1-2 In some embodiments, R 1 C 1-2 Alkyl, which is optionally substituted with 1, 2, 3 or 4 halogen groups. In some embodiments, R 1 is optionally substituted C 1-2 In some embodiments, R 1 C 1-2 Alkyl, which is optionally substituted with 1 or 2 halogen groups. In some embodiments, R 1 is an optionally substituted C1 aliphatic group. 1 is methyl, ethyl or difluoroethyl. In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 In some embodiments, R 1 It is difluoroethyl.

[0276] In some embodiments, R 1 is methyl, trideuterated methyl, ethyl, difluoroethyl, hydroxyethyl, cyclopropyl or tetrahydrofuranyl.

[0277] In some embodiments, R 1 and an L A -R AThe 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5- to 14-membered saturated or partially unsaturated bicyclic heterocyclic group, together with the atoms to which they are attached, have 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 7-membered monocyclic heterocyclic group and the 5- to 14-membered bicyclic heterocyclic group is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0278] In some embodiments, R 1 and an L A -R A Together with the atoms to which they are attached, they form a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0279] In some embodiments, R 1 and an L A -R A Together with the atoms to which they are attached, they form a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1, 2, 3 or 4 R AG Substituent substitution.

[0280] In some embodiments, R 1 and an L A -R A Together with the atoms to which it is attached, it forms a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1 or 2 R AG Substituent substitution.

[0281] In some embodiments, R 1 and an L A -R A Together with the atoms to which they are attached, they form a 6-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0282] In some embodiments, R 1 and an L A -R A Together with the atoms to which they are attached, they form a 6-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1, 2, 3 or 4 R AG Substituent substitution.

[0283] In some embodiments, R 1 and an L A -R A Together with the atoms to which it is attached, it forms a 6-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1 or 2 R AG Substituent substitution.

[0284] In some embodiments, R 1 and an L A -R A Together with the atoms to which it is attached, it forms a 6-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1 or 2 R AG Substituent substitution.

[0285] In some embodiments, the compound of formula I is a compound of formula IV:

[0286]

[0287] or a pharmaceutically acceptable salt thereof.

[0288] In some embodiments of Formula IV:

[0289] L 5 For divalent C 1-3 an aliphatic group, which is optionally substituted by 1, 2, 3 or 4 independently selected R L5A Substituent substitution;

[0290] or L 5 and an L A -R A The 3- to 16-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 16-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 16-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 16-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 16-membered monocyclic carbocyclyl, the 5- to 16-membered bicyclic carbocyclyl, the 3- to 16-membered monocyclic heterocyclyl and the 5- to 16-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0291] Ring B is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclyl, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and

[0292] m is 0, 1, 2, 3, 4, 5 or 6.

[0293] In some embodiments of Formula IV:

[0294] L 5 For divalent C 1-3 an aliphatic group, which is optionally substituted by 1, 2, 3 or 4 independently selected R L5A Substituent substitution;

[0295] or L 5 and an L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the 3- to 7-membered monocyclic heterocyclyl and the 5- to 10-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution;

[0296] Ring B is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclyl, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and

[0297] m is 0, 1, 2, 3, 4, 5 or 6.

[0298] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, Formula Via, Formula VII, Formula Vila, and Formula VIIb, Z is N or CR 2 In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, and Formula Via, Z is N or CR 2 As described above, in some embodiments of any one of Formula I, Formula II, and Formula III, Z is N or CR 2 In some embodiments, Z is CR 2 In some embodiments, Z is CH.

[0299] In some embodiments, R 2 For hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, -NRC (O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0300] In some embodiments, R 2 For hydrogen.

[0301] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, Formula Via, Formula VII, Formula Vila, and Formula VIIb, R 3 is -F, -Cl, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, -NR C(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0302] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, and Formula Via, R 3is -F, -Cl, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, -NR C(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0303] As described above, in some embodiments of any one of Formula I, Formula II, and Formula III, R 3 is -F, -Cl, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OS O2N(R)2, -N(R)C(O)R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NRO R, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m)N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0304] In some embodiments, R 3 is -F, -Cl, -CN or optionally substituted C 1-6 In some embodiments, R 3 In some embodiments, R 3 In some embodiments, R 3 is optionally substituted C 1-6 In some embodiments, R 3 is optionally substituted C 1-6 In some embodiments, R 3 is optionally substituted C 1-3 In some embodiments, R 3 is optionally substituted C 1-3 In some embodiments, R 3 is optionally substituted C 1-2 In some embodiments, R 3 is optionally substituted C 1-2 In some embodiments, R 3 is an optionally substituted C1 aliphatic group. 3 is methyl, -CF3 or -CF2H. In some embodiments, R 3 In some embodiments, R 3 In some embodiments, R 3 In some embodiments, R 3 is methyl or -CF3. In some embodiments, R 3 It is -CF3 (i.e. trifluoromethyl).

[0305] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, Formula Via, Formula VII, Formula VIIb, and Formula VIIb, U is N or CR 4 In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, and Formula Via, U is N or CR 4 As described above, in some embodiments of any one of Formula I, Formula II, and Formula III, U is N or CR 4 In some embodiments, U is CR 4 In some embodiments, U is CH.

[0306] In some embodiments, R 4 For hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, -NRC (O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0307] In some embodiments, R 4 For hydrogen.

[0308] As described above, in some embodiments of Formula I, R5 -L 5 -R 5A .

[0309] As described above, in some embodiments of any one of Formula I, Formula II, and Formula III, L 5 is a covalent bond or an optionally substituted divalent C 1-6 In some embodiments, L 5 is an optionally substituted divalent C 1-6 In some embodiments, L 5 For divalent C 1-6 aliphatic, which is optionally substituted with hydroxyl. 5 is an optionally substituted divalent C 1-3 In some embodiments, L 5 For divalent C 1-3 aliphatic, which is optionally substituted with hydroxyl. 5 is an optionally substituted divalent C 1-2 In some embodiments, L 5 For divalent C 1-2 An aliphatic group, which is optionally substituted with a hydroxy group.

[0310] In some embodiments, L 5 For divalent C 1-2 an aliphatic group which is optionally substituted by a hydroxyl group or a 5- to 6-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and wherein the 5- to 6-membered saturated or partially unsaturated monocyclic heterocyclic group is optionally substituted by a C 1-6 Alkyl substitution.

[0311] In some embodiments, L 5 For divalent C 1-2 an aliphatic group which is optionally substituted by a hydroxyl group or a 5- to 6-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and wherein the 5- to 6-membered saturated or partially unsaturated monocyclic heterocyclic group is optionally substituted by a C 1-3 Alkyl substitution.

[0312] In some embodiments, L 5 For divalent C 1-2 an aliphatic group, which is optionally substituted with hydroxy or piperazinyl, wherein the piperazinyl group is optionally substituted with C 1-6 Alkyl substitution.

[0313] In some embodiments, L 5 For divalent C 1-2an aliphatic group, which is optionally substituted with hydroxy or piperazinyl, wherein the piperazinyl group is optionally substituted with C 1-3 Alkyl substitution.

[0314] In some embodiments, L 5 For divalent C 1-2 An aliphatic group, which is optionally substituted with a hydroxy group or a methylpiperazinyl group.

[0315] In some embodiments, L 5 is -CH(CH3)-. In some embodiments, L 5 is -CH(CH3)- or -CH(CH2OH)-. In some embodiments, L 5 is -CH(CH2OH)-. In some embodiments, L 5 -CH2-, -CH(CH3)-, -CH(CH2OH)- or In some embodiments, L 5 for

[0316] In some embodiments, L 5 and an L A -R A The 3- to 16-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 16-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 16-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 16-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 16-membered monocyclic carbocyclyl, the 5- to 16-membered bicyclic carbocyclyl, the 3- to 16-membered monocyclic heterocyclyl and the 5- to 16-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

[0317] In some embodiments, L 5 and an L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the 3- to 7-membered monocyclic heterocyclyl and the 5- to 10-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AGSubstituent substitution.

[0318] As described above, in some embodiments of Formula I, R 5A For-OR 5A11 、-SR 5A1 、-NHR 5A12 、-N(R 5A12 )2、-C(O)R 5A1 、-C(O)N(R 5A1 )2、-C(O)NR 5A1 (OR 5A1 ),-OC(O)R 5A1 、-OC(O)N(R 5A1 )2、-OC(O)OR 5A1 、-OSO2R 5A1 、-OSO2N(R 5A1 )2、-N(R 5A1 )C(O)R 5A1 、-NR 5A1 C(O)OR 5A1 、-NR 5A1 C(O)N(R 5A1 )2、-N(R 5A1 )SO2R 5A1 、-NR 5A1 S(O)2N(R 5A1 )2、-NR 5A1 OR 5A1 、-NR 5A1 S(O)R 5A1 、-NR 5A1 S(O)N(R 5A1 )2、-S(O)R 5A1 、-SO2R 5A1 、-S(O)N(R 5A1 )2、-SO2N(R 5A1 )2, -SO3R 5A1 、-C(=NR m )R 5A1 、-C(=NR m )N(R 5A1 )2、-NR 5A1 C(=NR m )R 5A1 、-NR 5A1 C(=NR m )N(R 5A1 )2、-NR 5A1 S(O)(=NR m )R 5A1 、-NR 5A1 S(O)(=NR m)N(R 5A1 )2, -OS(O)(=NR m )R 5A1 、-S(O)(=NR m )R 5A1 、-S(O)(=NR m )N(R 5A1 )2、-P(O)(R 5A1 )2, methyl, C 2-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 5A The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R 5AG Substituent substituted; or R 5A The methyl group is replaced by 1, 2 or 3 R 5AG Substituent substitution.

[0319] In some embodiments, R 5A NHR 5A12 OR 5A11 .

[0320] In some embodiments, R 5A For-OR 5A11 .

[0321] In some embodiments, R 5A NHR 5A12 .

[0322] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, Formula Via, Formula VII, and Formula Vila, each R 5A12 Independently C 1-6an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 5A12 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substituted; or two R 5A12 When attached to the same nitrogen atom, they together form an optionally substituted ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0323] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, and Formula Via, each R 5A12 Independently C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 5A12 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1Substituent substituted; or two R 5A12 When attached to the same nitrogen atom, they together form an optionally substituted ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0324] In some embodiments of any one of Formula I, Formula II, and Formula III, each R 5A12 Independently C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 5A12 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substituted; or two R 5A12 When attached to the same nitrogen atom, they together form an optionally substituted ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0325] In some embodiments, each R 5A12 is independently a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R5A12 Each of the 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the phenyl, the 8- to 10-membered bicyclic aryl, the 3- to 7-membered monocyclic heterocyclyl, the 5- to 10-membered bicyclic heterocyclyl, the 5- to 6-membered monocyclic heteroaryl and the 8- to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution.

[0326] In some embodiments, each R 5A12 is independently phenyl, 8- to 10-membered bicyclic aryl, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 5A12 Each of the phenyl, the 8- to 10-membered bicyclic aryl, the 5- to 6-membered monocyclic heteroaryl and the 8- to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution.

[0327] In some embodiments, each R 5A12 is independently phenyl or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R 5A12 Each of the phenyl group and the 5- to 6-membered monocyclic heteroaryl group is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution.

[0328] In some embodiments, each R 5A12 is independently phenyl or pyridinyl, each of which is optionally substituted by 1, 2, 3, 4, 5 or 6 independently selected R G1 In some embodiments, each R 5A12 is independently phenyl, optionally substituted by 1, 2, 3, 4 or 5 independently selected R G1 Substituent substitution.

[0329] In some embodiments, R 5A12 A single example of is phenyl or pyridinyl, each optionally substituted with 1, 2 or 3 independently selected R G1 In some embodiments, R 5A12 A single example is phenyl or pyridinyl, each optionally substituted with 1 or 2 independently selected R G1 In some embodiments, R 5A12 A single example is phenyl or pyridyl, each optionally substituted with 1 R G1 Substituent substitution.

[0330] In some embodiments, each R 5A12 is independently phenyl, optionally substituted with 1, 2, 3, 4, 5 or 6 independently selected R G1 In some embodiments, R 5A12 A single instance of R is selected by 1, 2, or 3 independent G1 In some embodiments, R 5A12 A single instance of R is selected by 1 or 2 independently G1 In some embodiments, R 5A12 A single instance of R G1 Substituents substituted phenyl.

[0331] In some embodiments, each R 5A12 is independently pyridinyl, optionally substituted with 1, 2, 3, 4, 5 or 6 independently selected R G1 In some embodiments, R 5A12 A single instance of R is selected by 1, 2, or 3 independent G1 In some embodiments, R 5A12 A single example is pyridinyl, which is optionally substituted with 1 or 2 independently selected R G1 In some embodiments, R 5A12 A single instance of R is selected by 1 or 2 independently G1 In some embodiments, R 5A12 A single instance of R G1 Substituents include substituted pyridinyl.

[0332] In some embodiments of Formula I, each R 5A1 are independently hydrogen, C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 5A1 The C 1-6Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substituted; or two R 5A1 When attached to the same nitrogen atom, they together form an optionally substituted ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0333] As described above, in some embodiments of Formula I, R 5A11 Methyl, C 2-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein R 5A11 The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substituted; or R 5A11 The methyl group is replaced by 1, 2 or 3 R G1 Substituent substitution.

[0334] In some embodiments, R 5A11 is a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution.

[0335] In some embodiments, R 5A11 is a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1 or 2 RG1 Substituent substitution.

[0336] In some embodiments, R 5A11 is pyridinyl, which is optionally substituted by 1 or 2 independently selected R G1 Substituent substitution.

[0337] In some embodiments of Formula I, each R 5AG Independently halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R , -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0338] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, Formula Via, Formula VII, Formula Vila, and Formula VIIb, each R G1Independently halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R , -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0339] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, and Formula Via, each R G1Independently halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R , -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0340] In some embodiments of any one of Formula I, Formula II, and Formula III, each R G1Independently halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R , -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2、-NRC(=NR m )R、-NRC(=NR m )N(R)2、-NRS(O)(=NR m )R、-NR S(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the group consisting of: C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0341] In some embodiments, each R G1 independently selected from halogen, C 1-6 alkyl, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein each C 1-6alkyl, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl, 5- to 6-membered monocyclic heteroaryl, and 8- to 10-membered bicyclic heteroaryl are optionally substituted by 1, 2, 3, or 4 independently selected R AG1 Substituent substitution.

[0342] In some embodiments, each R G1 independently selected from halogen, C 1-6 alkyl, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein each C 1-6 alkyl, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, 5- to 6-membered monocyclic heteroaryl and 8- to 10-membered bicyclic heteroaryl are optionally substituted by 1 or 2 independently selected R AG1 Substituent substitution.

[0343] In some embodiments, each R G1 independently selected from halogen, C 1-6 alkyl, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein each C 1-6 alkyl, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, 5- to 6-membered monocyclic heteroaryl, optionally substituted by 1, 2, 3 or 4 independently selected R AG1 Substituent substitution.

[0344] In some embodiments, each R AG1 independently selected from halogen, -(CH2) 0-4 R o 、-(CH2) 0-4 OR o 、-(CH2) 0-4 C(O)NR o 2. -(CH2) 0-4C(O)OR o 、-(CH2) 0-4 C(O)R o 、-O(CH2) 0-4 R o 、CN、-(CH2) 0-4 C(O)NR o 2 and -C(O)N(OR o )R o , where each R o are independently hydrogen, C 1-6 alkyl or a 3- to 6-membered saturated ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0345] In some embodiments, each R AG1 independently selected from halogen, -(CH2) 0-4 R o 、-(CH2) 0-4 OR o 、-(CH2) 0-4 C(O)NR o 2. -(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 C(O)R o and -C(O)N(OR o )R o .

[0346] In some embodiments, each R o are independently hydrogen or C 1-6 In some embodiments, each R o are independently hydrogen or C 1-3 In some embodiments, each R o are independently hydrogen or methyl.

[0347] In some embodiments, each R AG1 independently selected from halogen, -(CH2) 0-4 R o 、-(CH2) 0-4 OR o 、-(CH2) 0-4 C(O)NR o 2. -(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 C(O)R o and -C(O)N(OR o )R o , where each R o are independently hydrogen or C1-6 alkyl.

[0348] In some embodiments, each R AG1 Independently selected from fluoro, methyl, ethyl, hydroxyethyl, -COOH, methylaminocarbonyl, dimethylaminocarbonyl, methylcarbonyl, methoxyaminocarbonyl, cyano, cyclopropyl, hydroxy, methoxy, dimethylamino, dimethylaminomethyl and tetrahydropyranyl.

[0349] In some embodiments, each R AG1 Independently selected from fluoro, methyl, hydroxyethyl, -COOH, methylaminocarbonyl, dimethylaminocarbonyl, methylcarbonyl and methoxyaminocarbonyl.

[0350] In some embodiments, each R G1 independently selected from halogen, C 1-6 aliphatic and -C(O)OR. In some embodiments, each R G1 independently selected from halogen, C 1-6 In some embodiments, each R G1 independently selected from halogen, C 1-3 In some embodiments, each R G1 independently selected from halogen, C 1-6 In some embodiments, each R G1 independently selected from halogen, C 1-3 In some embodiments, each R G1 Independently selected from fluoro, chloro, methyl and -C(O)OH.

[0351] In some embodiments, each R G1independently selected from methyl, chloro, pyridinyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, triazolyl, oxadiazolyl, indazolyl, quinolinyl, piperidinyl, piperazinyl, morpholinyl, isoindolinonyl, hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein said The pyridyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, triazolyl, oxadiazolyl, indazolyl, quinolinyl, piperidinyl, piperazinyl, morpholinyl, isoindolinonyl, hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl are each optionally substituted with 1 or 2 R AG1 Substituent substitution.

[0352] In some embodiments, each R G1 independently selected from methyl, chloro, pyridinyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, triazolyl, oxadiazolyl, indazolyl, quinolinyl, piperidinyl, piperazinyl, morpholinyl, isoindolinonyl, hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein the pyridinyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, triazolyl, oxadiazolyl, indazolyl, quinolinyl, piperidinyl, piperazinyl, morpholinyl, isoindolinonyl, hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein the -tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, the 1,2,4-oxadiazol-5(4H)-onyl, the tetrazolyl, the triazolyl, the oxadiazolyl, the indazolyl, the quinolinyl, the piperidinyl, the piperazinyl, the morpholinyl, the isoindolinonyl, the hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, the 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, each optionally substituted by 1 or 2 R independently selected from fluoro, methyl, ethyl, hydroxyethyl, -COOH, methylaminocarbonyl, dimethylaminocarbonyl, methylcarbonyl, methoxyaminocarbonyl, cyano, cyclopropyl, hydroxy, methoxy, dimethylamino, dimethylaminomethyl and tetrahydropyranyl AG1Substituent substitution.

[0353] In some embodiments, each R G1 independently selected from methyl, chloro, pyridyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein the pyridyl, the pyridonyl, the phenyl, the pyrazolyl, the pyrimidinyl, the piperazinyl, the 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, the 1,2,4-oxadiazol-5(4H)-onyl and the tetrazolyl are each optionally substituted by 1 or 2 R independently selected from fluoro, methyl, hydroxyethyl, -COOH, methylaminocarbonyl, dimethylaminocarbonyl, methylcarbonyl and methoxyaminocarbonyl. AG1 Substituent substitution.

[0354] In some embodiments, R G1 In some embodiments, R G1 In some embodiments, one R G1 is -C(O)OR, and the second R G1 Selected from halogen and C 1-6 In some embodiments, one R G1 is -C(O)OR, and the second R G1 Selected from halogen and C 1-6 In some embodiments, one R G1 is -C(O)OR, and the second R G1 Selected from halogen and C 1-3 In some embodiments, one R G1 is -C(O)OH, and the second R G1 Selected from halogen and C 1-6 In some embodiments, one R G1 is -C(O)OH, and the second R G1 Selected from halogen and C 1-3 In some embodiments, one R G1 is -C(O)OH, and the second R G1 is selected from fluorine, chlorine and methyl.

[0355] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, Formula Via, Formula VII, Formula Vila, and Formula VIIb, each R is independently hydrogen or an optionally substituted group selected from: C1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated or two R when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl with 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl with 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0356] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, and Formula Via, each R is independently hydrogen or an optionally substituted group selected from: C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated or two R when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl with 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl with 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0357] As described above, in some embodiments of any one of Formula I, Formula II, and Formula III, each R is independently hydrogen or an optionally substituted group selected from: C 1-6aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated or two R when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl with 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl with 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0358] In some embodiments, each R is independently selected from hydrogen, C 1-6 alkyl, a 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5-membered to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group is optionally replaced by C 1-6 Alkyl substitution.

[0359] In some embodiments, each R is independently selected from hydrogen, methyl, methylpiperidinyl, and pyridinyl.

[0360] In some embodiments, each R is independently selected from hydrogen, methyl, methylpiperidinyl, and pyridinyl. In some embodiments, R is hydrogen.

[0361] In some embodiments:

[0362] Each R G1independently selected from methyl, chloro, pyridinyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, triazolyl, oxadiazolyl, indazolyl, quinolinyl, piperidinyl, piperazinyl, morpholinyl, isoindolinonyl, hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein the pyridinyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, triazolyl, oxadiazolyl, indazolyl, quinolinyl, piperidinyl, piperazinyl, morpholinyl, isoindolinonyl, hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein the -tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, the 1,2,4-oxadiazol-5(4H)-onyl, the tetrazolyl, the triazolyl, the oxadiazolyl, the indazolyl, the quinolinyl, the piperidinyl, the piperazinyl, the morpholinyl, the isoindolinonyl, the hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, the 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, each optionally substituted by 1 or 2 R independently selected from fluoro, methyl, ethyl, hydroxyethyl, -COOH, methylaminocarbonyl, dimethylaminocarbonyl, methylcarbonyl, methoxyaminocarbonyl, cyano, cyclopropyl, hydroxy, methoxy, dimethylamino, dimethylaminomethyl and tetrahydropyranyl AG1 Substituents are substituted; and

[0363] Each R is independently selected from hydrogen, methyl, methylpiperidinyl, and pyridinyl.

[0364] In some embodiments:

[0365] Each R G1 independently selected from methyl, chloro, pyridyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein the pyridyl, the pyridonyl, the phenyl, the pyrazolyl, the pyrimidinyl, the piperazinyl, the 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, the 1,2,4-oxadiazol-5(4H)-onyl and the tetrazolyl are each optionally substituted by 1 or 2 R independently selected from fluoro, methyl, hydroxyethyl, -COOH, methylaminocarbonyl, dimethylaminocarbonyl, methylcarbonyl and methoxyaminocarbonyl. AG1 Substituents are substituted; and

[0366] Each R is independently selected from hydrogen, C 1-6alkyl, a 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5-membered to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group is optionally replaced by C 1-6 Alkyl substitution.

[0367] In some embodiments:

[0368] Each R G1 independently selected from methyl, chloro, pyridyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein the pyridyl, the pyridonyl, the phenyl, the pyrazolyl, the pyrimidinyl, the piperazinyl, the 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, the 1,2,4-oxadiazol-5(4H)-onyl and the tetrazolyl are each optionally substituted by 1 or 2 R independently selected from fluoro, methyl, hydroxyethyl, -COOH, methylaminocarbonyl, dimethylaminocarbonyl, methylcarbonyl and methoxyaminocarbonyl. AG1 Substituents are substituted; and

[0369] Each R is independently selected from hydrogen, methyl, methylpiperidinyl, and pyridinyl.

[0370] In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, Formula Via, Formula VII, Formula Vila, and Formula VIIb, each R m is independently -OH, -CN, or R. In some embodiments of any one of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula Va, Formula VI, and Formula Via, each R m is independently -OH, -CN or R. As described above, in some embodiments of any one of Formula I, Formula II and Formula III, each R m is independently -OH, -CN or R.

[0371] In some embodiments of any of Formula I, II, III, IV, V, Va, VI, Via, VII, Vila, and VIIb, each n is 0, 1, 2, 3, or 4. In some embodiments of any of Formula I, II, III, IV, V, Va, VI, and Via, each n is 0, 1, 2, 3, or 4. As described above, in some embodiments of any of Formula I, II, and III, each n is 0, 1, 2, 3, or 4. In some embodiments, n is 0. In some embodiments, n is 1, 2, 3, or 4. In some embodiments, n is 0 or 1. In some embodiments, n is 1.

[0372] In some embodiments, the compound of formula I is a compound of formula V:

[0373]

[0374] or a pharmaceutically acceptable salt thereof, wherein z is 0, 1, 2 or 3, and U, Z, Ring A, R 3 、R 5 and R AG Each of is as defined above for Formula I and described both individually and in combination in classes and subclasses herein.

[0375] In some embodiments, the compound of formula I is a compound of formula Va:

[0376]

[0377] or a pharmaceutically acceptable salt thereof, wherein z is 0, 1, 2 or 3, and U, Z, Ring A, Ring B, R 3 、L 5 、R G1 、R AG Each of m and m is as defined above for Formula I and described in classes and subclasses herein, both individually and in combination.

[0378] In some embodiments, the compound of formula I is a compound of formula VI:

[0379]

[0380] or a pharmaceutically acceptable salt thereof, wherein U, Z, R 1 、R 3 、R 5A and R AG Each of is as defined above for Formula I and described both individually and in combination in classes and subclasses herein.

[0381] In some embodiments, the compound of Formula I is a compound of Formula VIa:

[0382]

[0383] or a pharmaceutically acceptable salt thereof, wherein U, Z, R 1 、R 3 、R 5A12 and R AG Each of is as defined above for Formula I and described both individually and in combination in classes and subclasses herein.

[0384] In some embodiments, the compound is a compound of Formula VII:

[0385]

[0386] or a pharmaceutically acceptable salt thereof, wherein z is 0, 1, 2 or 3, and U, Z, R 3 、R 5 and R AG Each of is as defined above for Formula I and described both individually and in combination in classes and subclasses herein.

[0387] In some embodiments, the compound is a compound of Formula VIIa:

[0388]

[0389]

[0390] or a pharmaceutically acceptable salt thereof, wherein z is 0, 1, 2 or 3, and U, Z, R 3 、L 5 、R 5A12 and R AG Each of is as defined above for Formula I and described both individually and in combination in classes and subclasses herein.

[0391] In some embodiments, the compound is a compound of Formula VIIb:

[0392]

[0393] or a pharmaceutically acceptable salt thereof, wherein z is 0, 1, 2 or 3, and U, Z, Ring B, R 3 、L 5 、R G1 、R AG Each of m and m is as defined above for Formula I and described in classes and subclasses herein, both individually and in combination.

[0394] In some embodiments, the present disclosure provides a compound selected from Table 1 or a pharmaceutically acceptable salt thereof.

[0395] Table 1.

[0396]

[0397] In some embodiments, the compounds provided herein are selected from:

[0398] 2-((1-(4,7-dimethyl-5-oxo-4,5-dihydropyrazolo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0399] 2-((1-(4,7-dimethyl-5-oxo-3-phenyl-4,5-dihydropyrazolo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0400] 2-((1-(4,7-dimethyl-5-oxo-3-vinyl-4,5-dihydropyrazolo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0401] 2-((1-(4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0402] 2-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0403] 2-((1-(4,7-dimethyl-5-oxo-3-(pyridin-2-yl)-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0404] 2-((1-(3,4,7-trimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0405] 6-Methyl-3-((1-(3,4,7-trimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)picolinic acid;

[0406] 2-((1-(7-chloro-3-ethyl-4-methyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0407] 2-((1-(7-chloro-4-methyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0408] 2-((1-(7-chloro-3,4-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0409] 2-((1-(7-chloro-4-ethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0410] 2-((1-(7-chloro-3,4-diethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0411] 2-((1-(4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,2-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0412] 2-((1-(4,7-dimethyl-5-oxo-4,5-dihydro-[1,2,4]triazolo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid;

[0413] 2-((1-(3,4,7-trimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0414] 6-chloro-3-((1-(3,4,7-trimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)picolinic acid;

[0415] 2-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0416] 6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)picolinic acid;

[0417] 3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-methylpicolinic acid;

[0418] 2-((1-(4-ethyl-3,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0419] 6-chloro-3-((1-(4-ethyl-3,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)picolinic acid;

[0420] 2-((1-(3,4-diethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0421] 2-((1-(3,4-diethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-5-fluorobenzoic acid;

[0422] 3-((1-(3,4-diethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-methylpicolinic acid;

[0423] 2-((1-(4,7-dimethyl-5-oxo-2-propyl-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0424] 2-((1-(4,7-dimethyl-5-oxo-2-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0425] 2-((1-(4,7-dimethyl-5-oxo-2-phenethyl-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0426] 2-((1-(2-(2-fluoropyridin-4-yl)-4,7-dimethyl-5-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0427] 2-((1-(4,7-dimethyl-5-oxo-2-(pyrimidin-5-yl)-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0428] 6-chloro-3-((1-(4,7-dimethyl-5-oxo-2-(o-tolyl)-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)picolinic acid;

[0429] 2-[1-(3-Methoxy-5,8-dimethyl-6-oxo-benzo[c][1,8]naphthyridin-10-yl)ethylamino]benzoic acid;

[0430] 2-[1-[3-(Dimethylamino)-5,8-dimethyl-6-oxo-benzo[c][1,8]naphthyridin-10-yl]ethylamino]benzoic acid;

[0431] 2-[1-[3-(2-methoxyethoxy)-5,8-dimethyl-6-oxo-benzo[c][1,8]naphthyridin-10-yl]ethylamino]benzoic acid;

[0432] 2-((1-(7-chloro-3,4-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid;

[0433] 2-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)benzoic acid;

[0434] 6-Methyl-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)picolinic acid;

[0435] 2-((1-(3,8-dimethyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)benzoic acid;

[0436] 6-Chloro-3-((1-(3,8-dimethyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)picolinic acid;

[0437] 2-Ethyl-3,6-dimethyl-8-((6-methyl-[2,4'-bipyridinyl]-3-yl)amino)-8,9-dihydrobenzo[de]pyrazolo[4,5,1-ij][1,7]naphthyridin-4(3H)-one;

[0438] 9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0439] 4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide;

[0440] 9-(1-((6-chloro-2-(pyrimidin-4-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0441] 9-(1-((6-chloro-2-(pyrimidin-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0442] 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0443] 4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-N,N-dimethylbenzamide;

[0444] 4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)benzoic acid;

[0445] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0446] 9-(1-((6-chloro-2-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0447] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0448] 9-(1-((6-chloro-2-(1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0449] 3-Ethyl-4,7-dimethyl-9-(1-((6-methyl-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0450] 3-Ethyl-4,7-dimethyl-9-(1-((6-methyl-2-(1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0451] 3-Ethyl-4,7-dimethyl-9-(1-((6-methyl-2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0452] 4-(3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-methylpyridin-2-yl)-2-fluoro-N-methylbenzamide;

[0453] 3-Ethyl-9-(1-((2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)phenyl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0454] 9-(1-((2-(4-acetylpiperazin-1-yl)phenyl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0455] 9-(1-((2-(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)phenyl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0456] 3-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0457] 3-(6-chloro-3-((1-(4-(2,2-difluoroethyl)-3-ethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0458] 3-(6-chloro-3-((1-(3-cyclopentyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0459] 3-(6-chloro-3-((1-(3-isopropyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0460] 3-(6-chloro-3-((1-(7-chloro-3-ethyl-4-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0461] 3-(6-chloro-3-((1-(7-chloro-3-(cyclopropylmethyl)-4-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0462] 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-3-propyl-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0463] 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-3-(tetrahydrofuran-3-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0464] 3-(6-chloro-3-((1-(3-(2-methoxyethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0465] 3-(6-chloro-3-((1-(3-(cyclopropylmethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0466] 3-(6-chloro-3-((1-(3-ethyl-4-methyl-5-oxo-7-(trifluoromethyl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0467] 3-(6-chloro-3-((1-(3,8-dimethyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0468] 3-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0469] 9-(1-((2-(1H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0470] 6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-(1-methylpiperidin-4-yl)picolinamide;

[0471] 6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-(pyridin-4-yl)picolinamide;

[0472] 6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-methoxypicolinamide;

[0473] 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)-2-hydroxyethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0474] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0475] 9-(1-((6-chloro-2-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0476] 9-(1-((6-chloro-2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0477] 9-(1-((2-(4-acetylpiperazin-1-yl)-6-chloropyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0478] 9-(1-((6-chloro-2-(1-methyl1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0479] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0480] 9-(1-((6-chloro-2-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0481] 9-(1-((6-chloro-2-(1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0482] 9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0483] 5-(5-chloro-2-((1-(4,7-dimethyl-3-(1-methylazetidin-3-yl)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)phenyl)-N-methylpicolinamide;

[0484] 9-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0485] 9-(1-((6-chloro-2-(1-methyl-1H-indazol-5-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0486] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyethyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0487] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-cyclopropylazetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0488] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-((S)-2-hydroxypropyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0489] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-((R)-2-hydroxypropyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0490] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxy-2-methylpropyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0491] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2,2-difluoroethyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0492] 2-(3-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)azetidin-1-yl)acetonitrile;

[0493] 3-(3-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)azetidin-1-yl)propionitrile;

[0494] 3-(1-acetylazetidin-3-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0495] 3-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)azetidine-1-carboxylic acid methyl ester;

[0496] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methylsulfonyl)azetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0497] 3-(1-acetylazetidin-3-yl)-9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0498] 3-((1-(3-(1-acetylazetidin-3-yl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-chloro-N-methyl-[2,3'-bipyridine]-6'-carboxamide;

[0499] 3-(1-acetylazetidin-3-yl)-9-(1-((6-chloro-2-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0500] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyacetyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0501] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(dimethylglycyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0502] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-3-((S)-1-methylpyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0503] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0504] 3-((1-acetylpiperidin-4-yl)methyl)-9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0505] 4-((9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)methyl)-N,N-dimethylpiperidine-1-carboxamide;

[0506] 4-((9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)methyl)-N-ethylpiperidine-1-carboxamide;

[0507] 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-3-((1-(2,2-difluoroethyl)pyrrolidin-3-yl)methyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0508] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-hydroxyethyl)-4,7-dimethylimidazo[1,5-a]quinazolin-5(4H)-one;

[0509] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(pyridin-3-yl)imidazo[1,5-a]quinazolin-5(4H)-one;

[0510] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-methylpyridin-3-yl)imidazo[1,5-a]quinazolin-5(4H)-one;

[0511] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(pyrimidin-5-yl)imidazo[1,5-a]quinazolin-5(4H)-one;

[0512] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-methylpyridin-4-yl)imidazo[1,5-a]quinazolin-5(4H)-one;

[0513] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-methylpyridin-3-yl)imidazo[1,5-a]quinazolin-5(4H)-one;

[0514] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(pyrimidin-5-yl)imidazo[1,5-a]quinazolin-5(4H)-one;

[0515] 4-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-3-yl)-N-methylpicolinamide;

[0516] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0517] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0518] 3-(azetidine-1-carbonyl)-9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethylimidazo[1,5-a]quinazolin-5(4H)-one;

[0519] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(3-hydroxyazetidine-1-carbonyl)-4,7-dimethylimidazo[1,5-a]quinazolin-5(4H)-one;

[0520] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-N,N,7-trimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0521] 9-(1-((6-chloro-2-(3-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0522] 9-(1-((6-chloro-2-(4-cyano-2-fluorophenyl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0523] 9-(1-((6-chloro-2-(4-cyanophenyl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0524] 9-(1-((6-chloro-2-morpholinylpyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0525] 9-(1-((4-fluoro-2-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0526] 9-(1-((6-chloro-2-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0527] 9-(1-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide;

[0528] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpiperidin-4-yl)imidazo[1,5-a]quinazolin-5(4H)-one;

[0529] 3-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethylimidazo[1,5-a]quinazolin-5(4H)-one;

[0530] 4-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-3-yl)piperidine-1-carboxylic acid ethyl ester;

[0531] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpiperidin-4-yl)imidazo[1,5-a]quinazolin-5(4H)-one;

[0532] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0533] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0534] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-ethylpyrrolidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0535] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyethyl)pyrrolidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0536] 9-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-3-(1-methylpyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0537] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyethyl)pyrrolidin-3-yl)-7-methyl-4-(methyl-d3)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0538] 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-3-(1-isopropylpyrrolidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0539] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2,2-difluoroethyl)pyrrolidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0540] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2,2-difluoroethyl)pyrrolidin-3-yl)-7-methyl-4-(methyl-d3)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0541] 2-(3-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidin-1-yl)acetonitrile;

[0542] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-3-(1-(2-hydroxyethyl)pyrrolidin-3-yl)-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0543] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-3-(1-(2-hydroxy-2-methylpropyl)pyrrolidin-3-yl)-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0544] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-3-(1-isopropylpyrrolidin-3-yl)-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0545] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-(1-(methylsulfonyl)pyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0546] 3-(1-acetylpyrrolidin-3-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0547] 3-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidine-1-carboxylic acid methyl ester;

[0548] 3-(9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)-N,N-dimethylpyrrolidine-1-carboxamide;

[0549] 3-(3-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidin-1-yl)propionitrile;

[0550] 3-(3-(9-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidin-1-yl)propionitrile;

[0551] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyacetyl)pyrrolidin-3-yl)-7-methyl-4-(methyl-d3)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0552] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(dimethylglycyl)pyrrolidin-3-yl)-7-methyl-4-(methyl-d3)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0553] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-3-(1-(1-methyl-1H-pyrazol-5-carbonyl)pyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0554] 1-(3-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidine-1-carbonyl)cyclopropane-1-carbonitrile;

[0555] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpiperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0556] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0557] 9-[1-[[6-chloro-2-(1-ethylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0558] 9-[1-[[6-chloro-2-(2-methyltetrazol-5-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0559] 9-[1-[[6-chloro-2-(1,3,4-oxadiazol-2-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0560] 5-[6-chloro-3-[1-[4,7-dimethyl-3-(1-methyl-4-piperidinyl)-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-N-methyl-pyridine-2-carboxamide;

[0561] 3-[6-chloro-3-[1-[4,7-dimethyl-3-(1-methyl-4-piperidinyl)-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-4H-1,2,4-oxadiazol-5-one;

[0562] 9-[1-[[6-chloro-2-(1,3-dimethylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0563] 9-[1-[[6-chloro-2-(1-methyl-6-oxo-3-pyridinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0564] 9-[1-[[6-chloro-2-(4-hydroxy-1-piperidinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0565] 9-[1-[[6-chloro-2-(3-fluoro-4-pyridinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0566] 9-[1-[[6-chloro-2-(3-pyridinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0567] 5-[3-[1-[4,7-dimethyl-3-(1-methyl-4-piperidinyl)-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-6-methyl-2-pyridinyl]-N-methyl-pyridine-2-carboxamide;

[0568] 9-[1-[[6-chloro-2-(1-methyl-2-oxo-4-pyridinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0569] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxy-2-methyl-propyl)-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0570] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-[(2R)-2-hydroxypropyl]-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0571] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-[(2S)-2-hydroxypropyl]-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0572] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxy-2-methylpropyl)piperidin-4-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0573] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0574] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxyethyl)-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0575] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-((1-methyl-1H-imidazol-2-yl)methyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0576] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(oxetan-3-yl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0577] 3-[4-[9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-3-yl]-1-piperidinyl]propionitrile;

[0578] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2,2-difluoroethyl)piperidin-4-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0579] 3-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0580] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methylsulfonyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0581] 4-[9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-3-yl]piperidine-1-carboxylic acid methyl ester;

[0582] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-(1-cyclopropylsulfonyl-4-piperidinyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0583] 4-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)-N,N-dimethylpiperidine-1-carboxamide;

[0584] 3-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0585] 3-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0586] 4,7-Dimethyl-9-(1-((6-methyl-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(methylsulfonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0587] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methylsulfonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0588] 9-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methylsulfonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0589] 9-(1-((6-chloro-2-(quinolin-6-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methylsulfonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0590] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxyacetyl)-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0591] 1-(4-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)piperidine-1-carbonyl)cyclopropane-1-carbonitrile;

[0592] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(1-methyl-1H-pyrazole-5-carbonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0593] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(dimethylglycyl)piperidin-4-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0594] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methyl-L-prolyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0595] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4-methyl-3-(1-methylpiperidin-4-yl)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinoline-7-carbonitrile;

[0596] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-2-(tetrahydro-2H-pyran-4-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0597] 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-2-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0598] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-2-(1-methylpiperidin-4-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0599] 2-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0600] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-2-(1-(2-hydroxyethyl)piperidin-4-yl)-7-methyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0601] 3-(4-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-5-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-2-yl)piperidin-1-yl)propionitrile;

[0602] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-2-(1-methylazetidin-3-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0603] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-2-(1-methylpiperidin-4-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0604] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-2-(1-isopropylpiperidin-4-yl)-4,7-dimethyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0605] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-2-(1-methylpiperidin-4-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0606] 2-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0607] 4-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-2-yl)piperidine-1-carboxylic acid ethyl ester;

[0608] 4-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-2-yl)-N,N-dimethylpiperidine-1-carboxamide;

[0609] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-2-(1-(2,2-difluoroethyl)piperidin-4-yl)-4,7-dimethyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0610] 3-[6-chloro-3-[1-[7-methyl-5-oxo-3-[(3S)-tetrahydrofuran-3-yl]-4-(trideuteriomethyl)pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-4H-1,2,4-oxadiazol-5-one;

[0611] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0612] 3-(6-chloro-3-((1-(4-ethyl-7-methyl-5-oxo-3-((S)-tetrahydrofuran-3-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0613] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0614] 9-(1-((6-chloro-2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0615] 9-(1-((6-chloro-2'-methyl-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0616] 9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0617] 6-chloro-3-((1-(4-ethyl-7-methyl-5-oxo-3-((S)-tetrahydrofuran-3-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-methyl-[2,3'-bipyridine]-6'-carboxamide;

[0618] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-cyclopropyl-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0619] 9-[1-[[6-chloro-2-(1-methyl-6-oxo-3-pyridinyl)-3-pyridinyl]amino]ethyl]-4-cyclopropyl-3-ethyl-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0620] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-3-ethyl-7-methyl-4-tetrahydrofuran-3-yl-pyrazolo[3,4-c]isoquinolin-5-one;

[0621] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-3-ethyl-4-(2-hydroxyethyl)-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0622] 4-(6-chloro-3-(((3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)methyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide;

[0623] 9-(1-((6-chloro-2-(3-methyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0624] 3-(6-chloro-3-((1-(3-ethyl-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0625] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0626] 9-(1-((6-chloro-2-(4-methyl-4H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0627] 9-(1-((6-chloro-2-(1H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0628] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,3-triazol-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0629] 4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)benzoic acid;

[0630] 4-(4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1H-pyrazol-1-yl)-N,N-dimethylpiperidine-1-carboxamide;

[0631] 3-(4-(4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1H-pyrazol-1-yl)piperidin-1-yl)propionitrile;

[0632] 3-Ethyl-4,7-dimethyl-9-(1-((6-methyl-2-(3-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0633] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0634] 9-(1-((6-chloro-2'-methyl-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0635] 9-(1-((6-chloro-2-(pyrimidin-5-yl)pyridin-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0636] 9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0637] 6-chloro-3-((1-(4-(2,2-difluoroethyl)-3-ethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-methyl-[2,3'-bipyridine]-6'-carboxamide;

[0638] 9-[1-[[2-(1-acetyl-4-piperidinyl)-6-chloro-3-pyridinyl]amino]ethyl]-3-ethyl-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0639] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0640] 4-(6-chloro-3-((1-(3-(2-hydroxyethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide;

[0641] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0642] 9-(1-((6-chloro-2-(4-hydroxypiperidin-1-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0643] 9-(1-((6-chloro-2-(quinolin-6-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0644] 9-(1-((6-chloro-2-(1-methyl-1H-indazol-5-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0645] 9-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0646] 3-(2-hydroxyethyl)-4,7-dimethyl-9-(1-((6-methyl-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0647] 9-(1-((6-chloro-2-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0648] 9-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0649] 9-(1-((6-chloro-2-(pyrimidin-5-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0650] 5-[6-chloro-3-[1-[3-(2-hydroxyethyl)-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-N-methyl-pyridine-2-carboxamide;

[0651] 9-[1-[[6-chloro-2-(1-methyl-6-oxo-3-pyridinyl)-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0652] 9-[1-[[6-chloro-2-(1-methyl-2-oxo-4-pyridinyl)-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0653] 9-[1-[[6-chloro-2-(2-methoxy-4-pyridinyl)-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0654] 9-[1-[[6-chloro-2-(1-methyl-4-piperidinyl)-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0655] 9-[1-[[2-(1-acetyl-4-piperidinyl)-6-chloro-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0656] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4-(2,2-difluoroethyl)-3-(2-hydroxyethyl)-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0657] 5-[6-chloro-3-[1-[4-(2,2-difluoroethyl)-3-(2-hydroxyethyl)-7-methyl-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-N-methyl-pyridine-2-carboxamide;

[0658] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4-ethyl-3-(2-hydroxyethyl)-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0659] 9-[1-[(6-chloro-2-morpholinyl-3-pyridinyl)amino]ethyl]-4-ethyl-3-(2-hydroxyethyl)-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0660] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(2-morpholinoethyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0661] 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-morpholinoethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0662] 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-(4-methylpiperazin-1-yl)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0663] 4-(6-chloro-3-((1-(4,7-dimethyl-3-(2-morpholinylethyl)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide;

[0664] 4-(6-chloro-3-((1-(4,7-dimethyl-3-(2-(4-methylpiperazin-1-yl)ethyl)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide;

[0665] 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-(2-(5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)ethyl)-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0666] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4-ethyl-7-methyl-3-(2-pyridinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0667] 9-(1-((6-chloro-2-morpholinylpyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-(pyridin-2-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0668] 6-chloro-3-((1-(4-ethyl-7-methyl-5-oxo-3-(pyridin-2-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-methyl-[2,3'-bipyridine]-6'-carboxamide;

[0669] 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-3-(pyridin-2-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0670] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(pyridin-2-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0671] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4-ethyl-7-methyl-3-(3-pyridinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0672] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(2-pyridinylmethyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0673] 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-3-(pyridin-2-ylmethyl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0674] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-3-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0675] 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxyethyl)-3-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0676] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-3-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one;

[0677] 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxyethyl)-3-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one;

[0678] 3-[9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-3-yl]piperidine-1-carboxylic acid methyl ester;

[0679] 5-[6-chloro-3-[1-[4,7-dimethyl-3-(1-methyl-4-piperidinyl)-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethoxy]-2-pyridinyl]-N-methyl-pyridine-2-carboxamide;

[0680] 5-[3-[1-[3-(1-acetyl-4-piperidinyl)-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethoxy]-6-chloro-2-pyridinyl]-N-methyl-pyridine-2-carboxamide;

[0681] 10-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0682] 10-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0683] 10-(1-((6-chloro-2-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0684] 10-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0685] 10-(1-((6-chloro-2-(3-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0686] 10-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0687] 10-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-((dimethylamino)methyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0688] 10-(1-((6-chloro-2-(4-hydroxypiperidin-1-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0689] 1-(6-chloro-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)-N-methylpiperidine-4-carboxamide;

[0690] 10-(1-((2-(4-acetylpiperazin-1-yl)-6-chloropyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0691] 10-(1-((6-chloro-2-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0692] 3-(6-chloro-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0693] 10-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0694] 10-(1-((6-chloro-2-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0695] 10-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0696] 10-(1-((6-chloro-2-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0697] 10-(1-((6-chloro-2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0698] 10-(1-((6-chloro-2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0699] 10-(1-((6-chloro-2-(1-(1-methylpiperidin-3-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0700] 10-(1-((6-chloro-2-(1-(1-methylpyrrolidin-3-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0701] 10-(1-((6-chloro-2-(1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0702] 4-(4-(6-chloro-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)-1H-pyrazol-1-yl)-N,N-dimethylpiperidine-1-carboxamide;

[0703] 10-(1-((6-chloro-2'-methyl-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0704] 10-(1-((6-chloro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0705] 10-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0706] 4-(6-chloro-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide;

[0707] 6-Chloro-N-methyl-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)-[2,3'-bipyridine]-6'-carboxamide;

[0708] 10-(1-((6-chloro-6'-methoxy-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0709] 10-(1-((6-chloro-2'-methoxy-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0710] 10-(1-((6-chloro-2'-(dimethylamino)-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0711] 10-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0712] 10-(1-((6-chloro-2-(quinolin-6-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0713] 10-(1-((6-chloro-2-(1-methyl-1H-indazol-5-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0714] 2-Fluoro-N-methyl-4-(6-methyl-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)benzamide;

[0715] 8-methyl-10-(1-((6-methyl-2-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0716] 10-(1-((2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-6-methylpyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0717] 10-(1-((2',6-dimethyl-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0718] 10-(1-((2-(1-cyclopropyl-1H-pyrazol-4-yl)-6-methylpyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0719] 7-(6-chloro-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)hexahydro-3H-oxazolo[3,4-a]pyrazin-3-one;

[0720] 10-(1-((6-chloro-2-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0721] 10-(1-((6-chloro-6'-((dimethylamino)methyl)-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0722] 3-(3-((1-(3,8-dimethyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)-6-methylpyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0723] 8-Methyl-10-(1-((6-methyl-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0724] 3-(3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-methylpyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one;

[0725] 10-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0726] 10-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0727] 10-(1-((6-chloro-2-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0728] 10-(1-((6-chloro-2-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0729] 10-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one;

[0730] 10-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinanthracen-6-one; and

[0731] 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-(4-methylpiperazin-1-yl)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one;

[0732] or a pharmaceutically acceptable salt thereof.

[0733] In some embodiments, the present disclosure encompasses the recognition that provided compounds, for example, exhibit certain desirable properties compared to other known compounds. For example, in some embodiments, provided compounds are more potent than other known compounds in one or more biochemical or cellular assays described herein and / or have one or more other properties that make them more suitable for drug development, such as selectivity for mutant PI3Kα over wild-type (WT) PI3Kα and / or better ADME (absorption, distribution, metabolism, and excretion) properties, including but not limited to better permeability, cytotoxicity, hepatocyte stability, solubility, and / or plasma protein binding profiles. In some embodiments, provided compounds exhibit certain desirable properties, for example, compared to other known compounds in one or more assays described herein.

[0734] In some embodiments, provided compounds are provided and / or utilized in salt form (e.g., pharmaceutically acceptable salt form). Unless otherwise indicated, reference to a compound provided herein should be understood to include reference to its salts.

[0735] It is understood that unless otherwise specified or prohibited by the foregoing definition of any of Formula I to Formula VIIb, the variables X, Y, Z, U, Ring A, L, and L as defined above and described in classes and subclasses herein, both individually and in combination, are A 、R A 、R A1 、R AG 、R 1 、R 2 、R 3 、R 4 、R 5 , L 5 、R 5A 、R 5A1 、R 5A11 、R 5A12 、R 5AG 、R G1 , R, R m The embodiments of and n apply to compounds of any one of Formula I to Formula VIIb.

[0736] It is understood that unless otherwise specified or prohibited by the foregoing definition of any of Formula I, Formula II and Formula III, the variables X, Y, Z, U, Ring A, L, and L as defined above and described in classes and subclasses herein, both individually and in combination, are A 、R A 、R A1 、R AG 、R 1 、R 2 、R 3 、R 4 、R 5 , L 5 、R 5A 、R 5A1 、R 5A11 、R 5A12 、R 5AG 、R G1 , R, R m The embodiments of and n apply to compounds of any one of Formula I, Formula II, and Formula III.

[0737] It should be understood that throughout this disclosure, unless otherwise indicated, references to compounds of Formula I are intended to also include any of Formula I, Formula II, and Formula III, as well as species of compounds of such formulae disclosed herein.

[0738] Preparation of provided compounds

[0739] Compounds of the present disclosure (including salts thereof) can be prepared using known organic synthesis techniques and can be synthesized according to numerous possible synthetic pathways, such as those in the schemes below. The schemes below provide general guidance for preparing compounds of the present disclosure. Those skilled in the art will appreciate that the preparations shown in the schemes can be modified or optimized using the general knowledge of organic chemistry to prepare various compounds of the present disclosure. The compounds provided can generally be prepared by the methods described in the subsequent schemes and examples.

[0740] In some embodiments, provided compounds are prepared according to the following scheme:

[0741]

[0742] Among them, Hal 1 Hal 2 and Hal 3 Each of X, Y, Z, U, R is independently a suitable halogen, and 1 、R 3 、R 5 , Ring A, L A 、R AEach of n is as defined above for Formula I and is described in the categories and subcategories herein in both individual and combined forms. Thus, in some embodiments, intermediate A-2 is prepared by a method comprising reacting a compound of formula A-1 with a suitable reagent (e.g., N-bromosuccinimide). In some embodiments, intermediate A-3 is prepared by a method comprising reacting intermediate A-2 under Sandmeyer reaction conditions. In some embodiments, intermediate A-4 is prepared by a method comprising reacting intermediate A-3 with a suitable reagent (e.g., oxalyl chloride or thionyl chloride). In some embodiments, intermediate A-6 is prepared by a method comprising contacting intermediate A-4 with a compound of formula A-5 under suitable conditions. In some embodiments, intermediate A-7 is prepared by a method comprising reacting intermediate A-6 under suitable cyclization conditions (e.g., S N Ar reaction or C—H activation). In some embodiments, intermediate A-9 is prepared by a method comprising reacting intermediate A-7 with a compound of formula A-8. In some embodiments, the compound of formula I is prepared by a method comprising reacting intermediate A-9 under suitable conditions (e.g., a transition metal-catalyzed cross-coupling reaction).

[0743] In some embodiments, provided compounds are prepared according to the following scheme:

[0744]

[0745] Among them, Hal and Hal 1 Each of X, Y, Z, U, R is a suitable halogen, M is a suitable reactive group (such as pinacol borate or tributyltin), and X, Y, Z, U, R 1 、R 3 、R 5A , Ring A, L A 、R A Each of n is as defined above for formula I and is set forth in categories and subclasses herein in both individual and combination modes. Therefore, in some embodiments, intermediate B-2 is prepared by including a method (such as metal-catalyzed cross-coupling reaction) for contacting formula A-7 compound with B-1 under suitable conditions. In some embodiments, intermediate B-3 is prepared by including a method for reacting intermediate B-2 under suitable reducing conditions. In some embodiments, intermediate B-4 is prepared by including a method for reacting intermediate B-3 with a suitable reagent (such as PBr ). In some embodiments, formula B-5 compound is prepared by including a method for reacting intermediate B-4 with a suitable nucleophile.

[0746] Composition

[0747] The present disclosure also provides compositions, which include compounds provided herein and one or more other components. In some embodiments, provided compositions include and / or deliver compounds described herein (e.g., compounds of any one of Formula I, Formula II, and Formula III).

[0748] In some embodiments, provided compositions are pharmaceutical compositions that contain and / or deliver a compound provided herein (e.g., a compound of any of Formula I, Formula II, and Formula III) and further contain a pharmaceutically acceptable carrier.

[0749] The pharmaceutical composition generally contains an active agent (e.g., compound as described herein) in an amount that effectively achieves the desired therapeutic effect while avoiding adverse side effects or minimizing them. In some embodiments, the pharmaceutical composition provided comprises a compound as described herein and one or more fillers, disintegrants, lubricants, glidants, antiadhesives, and / or antistatic agents. The pharmaceutical composition provided may be in various forms, including oral dosage forms, topical creams, topical patches, iontophoretic forms, suppositories, nasal sprays, and / or inhalants, eye drops, intraocular injection forms, storage forms, and injectable and infusible solutions. Methods for preparing pharmaceutical compositions are well known in the art.

[0750] In some embodiments, the compound provided is formulated in unit dosage form for ease of administration and uniform dosage. As used herein, the expression "unit dosage form" refers to a physical discrete unit of an active agent (e.g., compound described herein) for administration to a subject. Typically, each unit contains a predetermined amount of active agent. In some embodiments, the unit dosage form contains the entire single dose of the agent. In some embodiments, more than one unit dosage form is administered to achieve a total single dose. In some embodiments, it is necessary or expected that multiple unit dosage forms will need to be administered to achieve the desired effect. The unit dosage form can, for example, be a liquid pharmaceutical composition containing a predetermined amount of one or more active agents, a solid pharmaceutical composition (e.g., tablets, capsules, etc.) containing a predetermined amount of one or more active agents, a sustained release formulation containing a predetermined amount of one or more active agents, or a drug delivery device containing a predetermined amount of one or more active agents, etc.

[0751] Provided compositions can be administered using any amount and any route of administration effective for treating or lessening the severity of any disease or condition described herein.

[0752] use

[0753] The present disclosure provides the uses of the compounds and compositions described herein. In some embodiments, the compounds and compositions provided are used in medicine (e.g., as therapy). In some embodiments, the compounds and compositions provided can be used to treat diseases, disorders, or illnesses in which the underlying pathology is mediated in whole or in part by PI3Kα. In some embodiments, the compounds and compositions provided can be used as analytical tools and / or control compounds in, for example, bioassays in research.

[0754] In some embodiments, the present disclosure provides methods of administering provided compounds or compositions to a subject in need thereof. In some embodiments, the present disclosure provides methods of administering provided compounds or compositions to a subject suffering from or susceptible to a disease, disorder, or condition associated with PI3Kα. In some embodiments, the present disclosure provides methods of administering provided compounds or compositions to a subject suffering from or susceptible to a disease, disorder, or condition wherein the underlying pathology is mediated in whole or in part by PI3Kα.

[0755] In some embodiments, the compounds provided are useful as PI3Kα inhibitors. In some embodiments, the present disclosure provides methods of inhibiting PI3Kα in a subject, comprising administering a provided compound or composition. In some embodiments, the present disclosure provides methods of inhibiting PI3Kα in a biological sample, comprising contacting the sample with a provided compound or composition.

[0756] In some embodiments, the present disclosure provides a method for treating a disease, condition, or illness associated with PI3Kα in a subject in need thereof, comprising administering to the subject a provided compound or composition. In some embodiments, the disease, condition, or illness is associated with a mutation in PI3Kα. In some embodiments, the present disclosure provides a method for treating a disease, condition, or illness in a subject in need thereof, wherein the underlying pathology is mediated in whole or in part by PI3Kα, comprising administering to the subject a provided compound or composition.

[0757] In some embodiments, the present disclosure provides methods for treating a variety of PI3Kα-dependent diseases and conditions. In some embodiments, the disease or condition is cancer (e.g., breast cancer, brain cancer, prostate cancer, endometrial cancer, gastric cancer, leukemia, lymphoma, sarcoma, colorectal cancer, lung cancer, ovarian cancer, skin cancer, and head and neck cancer). In some embodiments, diseases or disorders associated with PI3Kα include, but are not limited to, CLOVES syndrome (congenital lipomatous overgrowth, vascular malformation, epidermal nevus, scoliosis / skeletal and spinal syndrome), PIK3CA-associated overgrowth syndrome (PROS), endometrial cancer, breast cancer, esophageal squamous cell carcinoma, cervical squamous cell carcinoma, cervical adenocarcinoma, colorectal adenocarcinoma, bladder urothelial carcinoma, glioblastoma, ovarian cancer, non-small cell lung cancer, esophagogastric cancer, schwannoma, head and neck squamous cell carcinoma, melanoma, esophagogastric adenocarcinoma, soft tissue sarcoma, prostate cancer, fibrolamellar carcinoma, hepatocellular carcinoma, diffuse glioma, colorectal cancer, pancreatic cancer, bile duct cancer, B-cell lymphoma, mesothelioma, adrenocortical carcinoma, renal non-clear cell carcinoma, renal clear cell carcinoma, germ cell carcinoma, thymic tumors, pheochromocytoma, mixed neuroepithelial tumor, thyroid cancer, leukemia, and encapsulated glioma.

[0758] Combination therapy

[0759] One or more additional therapeutic agents, such as chemotherapeutic agents or other anti-cancer agents, anti-inflammatory agents, steroids, immunosuppressants, anesthetics (e.g., for use in combination with surgical procedures), or other agents useful for treating diseases associated with PI3Kα can be used in combination with the compounds and salts provided herein. The agents can be combined with the compounds of the present invention in a single dosage form, or the agents can be administered simultaneously or sequentially as separate dosage forms.

[0760] The compounds described herein can be used in combination with one or more other kinase inhibitors for the treatment of diseases affected by various signaling pathways, such as cancer. For example, a combination can include one or more inhibitors of the following kinases for the treatment of cancer: Akt1, Akt2, Akt3, TGF-βR, Pim, PKA, PKG, PKC, CaM kinase, phosphorylase kinase, CDK4 / 6, MEKK, ERK, MAPK, mTOR, EGFR, HER2, HER3, HER4, INS-R, IGF-1R, IR-R, PDGFαR, PDGFβR, CSFIR, KIT, FLK-II, KDR / FLK-1, FLK-4, flt-1, FGFR1, FGFR2, FGFR3, FGFR4, c-Met, Ron, Sea, TRKA, TRKB, TRKC, FLT3, VEGFR / Flt2, Flt4, EphA1, EphA2, EphA3, EphB2, EphB4, Tie2, Src, Fyn, Lck, Fgr, Btk, Fak, SYK, FRK, JAK, ABL, ALK and B-Raf. In addition, the solid form of the inhibitor as described herein can be combined with inhibitors of kinases associated with the PIK3 / Akt / mTOR signaling pathway, such as PI3K, Akt (including Akt1, Akt2 and Akt3) and mTOR kinase.

[0761] For the treatment of cancer and other proliferative diseases, the compounds described herein can be used in combination with targeted therapies, including JAK kinase inhibitors (ruxolitinib, other JAK1 / 2 and JAK1 selective inhibitors, baricitinib or itacitinib), Pim kinase inhibitors (e.g., LGH447, INCB053914 and SGI-1776), PI3 kinase inhibitors (including PI3K-δ selective and broad-spectrum PI3K inhibitors (e.g., parsaclisib and INCB50797)), PI3K-γ inhibitors (e.g., PI3K-γ selective and broad-spectrum PI3K inhibitors), and PI3K-γ inhibitors (e.g., PI3K-γ selective and broad-spectrum PI3K inhibitors). inhibitors), MEK inhibitors, CSF1R inhibitors (e.g., PLX3397 and LY3022855), TAM receptor tyrosine kinase inhibitors (Tyro-3, Axl, and Mer; e.g., INCB81776), angiogenesis inhibitors, interleukin receptor inhibitors, cyclin-dependent kinase inhibitors (e.g., palbociclib, ribociclib, and abemaciclib), BRAF inhibitors, mTOR inhibitors, proteasome inhibitors (bortezomib, carfilzomib), HDAC-inhibitors (panobinostat, panobinostat), binostat, vorinostat), DNA methyltransferase inhibitors, dexamethasone, bromodomain and extra-terminal family member inhibitors (e.g., bromodomain inhibitors or BET inhibitors such as OTX015, CPI-0610, INCB54329, or INCB57643), LSD1 inhibitors (e.g., GSK2979552, INCB59872, and INCB60003), estrogen receptor modulators (e.g., fulvestrant), androgen receptor modulators (e.g., enzalutamide), BCL2 inhibitors (e.g., venetoclax), These include, but are not limited to, enetoclax, hypoxia-inducible factor-2α inhibitors (e.g., belzutifan), exportin-1 (XPO-1) inhibitors (e.g., selinexor), KRAS inhibitors (e.g., sotorasib), arginase inhibitors (e.g., INCB1158), indoleamine 2,3-dioxygenase inhibitors (e.g., epacadostat, NLG919, or BMS-986205), PARP inhibitors (e.g., olaparib or rucaparib), and BTK inhibitors (e.g., ibrutinib).

[0762] For the treatment of cancer and other proliferative diseases, the compounds described herein can be used in combination with chemotherapeutic agents, nuclear receptor agonists or antagonists or other antiproliferative agents. The compounds described herein can also be used in combination with medical therapies (such as surgery or radiotherapy, for example, gamma-irradiation, neutron beam radiotherapy, electron beam radiotherapy, proton therapy, brachytherapy and systemic radioisotopes).

[0763] Examples of suitable chemotherapeutic agents include any of the following: abarelix, abiraterone, afatinib, aflibercept, aldesleukin, alemtuzumab, alitretinoin, allopurinol, hexamethylmelamine, amidox, amsacrine, anastrozole, aphidilone, dapoxetine ... dicolon), arsenic trioxide, asparaginase, axitinib, azacitidine, bevacizumab, bexarotene, baricitinib, bendamustine, bicalutamide, bleomycin, bortezombi, bortezomib, brivanib, buparis, intravenous busulfan intravenous, oral busulfan, calusterone, camptosar, capecitabine, carboplatin, carmustine, cediranib, cetuximab, chlorambucil, cisplatin, cladribine, clofarabine, crizotinib, cyclophosphamide, cytarabine, dacarbazine, dacomitinib, dactinomycin, dalteparin sodium), dasatinib, actinomycin D, daunorubicin, decitabine, degarelix, denileukin, denileukin diftitox, deoxycoformycin, dexrazoxane, didox, docetaxel, doxorubicin, droloxafine, dromostanolone propionatepropionate, eculizumab, enzalutamide, epipodophyllotoxin, epirubicin, epothilone, erlotinib, estramustine, etoposide phosphate, etoposide, exemestane, fentanyl citrate, filgrastim, floxuridine, fludarabine, fluorouracil, flutamide, fulvestrant, gefitinib, gemcitabine, gemtuzumab ozogamicin, goserelin acetate, histrelin acetate acetate), ibritumomab tiuxetan, idarubicin, idelalisib, ifosfamide, imatinib mesylate, interferon alfa 2a, irinotecan, lapatinib ditosylate, lenalidomide, letrozole, leucovorin, leuprolide acetate acetate), levamisole, lonafarnib, lomustine, meclorethamine, megestrolacetate, melphalan, mercaptopurine, methotrexate, methoxsalen, mithramycin, mitomycin C, mitotane, mitoxantrone, nandrolone phenylpropionatephenpropionate, navelbene, necitumumab, nelarabine, neratinib, nilotinib, nilutamide, niraparib, nofetumomab, oserelin, oxaliplatin, paclitaxel, pamidronate, panitumumab, panobinostat, pazopanib, pegaspargase, pegfilgrastim, pemetrexeddisodium, pentostatin, pilaralisib, pipobroman, plicamycin, ponatinib, porfimer, prednisone, procarbazine, quinacrine, ranibizumab, rasburicase, regorafenib, reloxafine, revlimid, rituximab, rucaparib, ruxolitinib, sorafenib, streptozocin, sunitinib, sunitinib maleate, tamoxifen, tegafur, temozolomide, teniposide niposide, testolactone, tezacitabine, thalidomide, thioguanine, thiotepa, tipifarnib, topotecan, toremifene, tositumomab, trastuzumab, tretinoin, triapine, trimidox, triptorelin, uracil mustard, valrubicin, vandetanib, vinblastine, vincristine, vindesine, vinorelbine, vorinostat, veliparib, talazoparib, and zoledronic acid.

[0764] Methods for safely and effectively administering most of these chemotherapeutic agents are known to those skilled in the art. In addition, their administration is described in standard literature. For example, the administration of many chemotherapeutic agents is described in "Physicians' Desk Reference" (PDR, e.g., 1996 edition, Medical Economics Company, Montvale, NJ), the disclosure of which is incorporated herein by reference as if set forth in its entirety.

[0765] Example anti-inflammatory agents include, but are not limited to, aspirin, choline salicylate, celecoxib, diclofenac potassium, diclofenac sodium, diclofenac sodium combined with misoprostol, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, ketoprofen, meclofenamate sodium, mefenamic acid, nabumetone, naproxen, naproxen sodium, oxaprozin, piroxican, rofecoxib, bisalicylate, sodium salicylate, sulindac, tolmetin sodium, and valdecoxib.

[0766] Example steroids include, but are not limited to, corticosteroids such as cortisone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone, and prednisone.

[0767] Example immunosuppressants include, but are not limited to, azathioprine, chlorambucil, cyclophosphamide, cyclosporine, daclizumab, infliximab, methotrexate, and tacrolimus.

[0768] Example anesthetics include, but are not limited to, local anesthetics (e.g., lidocaine, procain, ropivacaine) and general anesthetics (e.g., desflurane, enflurane, halothane, isoflurane, methoxyflurane, nitrous oxide, sevoflurane, mmobarbital, methohexital, thiamylal, thiopental, diazepam, lorazepam, midazolam, midazolam, etomidate, ketamine, propofol, alfentanil, fentanyl, remifentanil, buprenorphine, butorphanol, hydromorphone, levorphanol, meperidine, methadone, morphine, nalbuphine, oxymorphone, pentazocine).

[0769] In some embodiments, the additional therapeutic agent is administered simultaneously with the compound or salt provided herein. In some embodiments, the additional therapeutic agent is administered after the compound or salt provided herein is administered. In some embodiments, the additional therapeutic agent is administered before the compound or salt provided herein is administered. In some embodiments, the compound or salt provided herein is administered during a surgical procedure. In some embodiments, the compound or salt provided herein is administered in combination with an additional therapeutic agent during a surgical procedure.

[0770] As provided herein, additional compounds, inhibitors, agents, etc. can be combined with the compounds provided herein in a single or sequential dosage form, or they can be administered simultaneously or sequentially as separate dosage forms.

[0771] Labeled compounds and assays

[0772] Another aspect of the present invention relates to compounds of the present invention that are labeled with fluorescent dyes, spin labels, heavy metals, or radioactive substances, which can be used not only for imaging but also...

Claims

1. A compound of formula I: or a pharmaceutically acceptable salt thereof, wherein: is a single bond or a double bond; X is N or C; Y is N or C; Ring A is phenyl, a 5- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Each L A is independently a covalent bond or an optionally substituted divalent C 1-6 aliphatic group; Each R A is independently an oxo group, a halogen, -CN, -OR A1 , -SR A1 , -N(R A1 )2, -C(O)R A1 , -C(O)OR A1 , -C(O)N(R A1 )2, -C(O)NR A1 (OR A1 ), -OC(O)R A1 -OC(O)N(R A1 )2, -OC(O)OR A1 , -OSO2R A1 , -OSO2N(R A1 )2, -N(R A1 )C(O)R A1 , -NR A1 C(O)OR A1 , -NR A1 C(O)N(R A1 )2, -N(R A1 )SO2R A1 , -NR A1 S(O)2N(R A1 )2, -NR A1 OR A1 , -NR A1 S(O)R A1 , -NR A1 S(O)N(R A1 )2, -S(O)R A1 , -SO2R A1 , -S(O)N(R A1 )2, -SO2N(R A1 )2, -SO3R A1 , -C(=NR m )R A1 , -C(=NR m )N(R A1 )2, -NR A1 C(=NR m )R A1 , -NR A1 C(=NR m )N(R A1 )2, -NR A1 S(O)(=NR m )R A1 , -NR A1 S(O)(=NR m )N(R A1 )2, -OS(O)(=NR m )R A1 、-S(O)(=NR m )R A1 、-S(O)(=NR m )N(R A1 )2、-P(O)(R A1 2. C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R A The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution; or two L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8- to 10-membered bicyclic aryl group, the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, The 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the phenyl, the 8- to 10-membered bicyclic aryl, the 3- to 7-membered monocyclic heterocyclyl, the 5- to 10-membered bicyclic heterocyclyl, the 5- to 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution; R 1 is hydrogen or an optionally substituted group selected from the following: C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or R 1 and an L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5- to 14-membered bicyclic heterocyclic group are independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution; Z is N or CR 2 ; U is N or CR 4 ; R 2 and R 4 Each independently hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, - NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2, -NRC(=NR m )R、-NRC(=NR m )N(R)2, -NRS(O)(=NR m )R, -NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the following: C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; R 3 is -F, -Cl, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, -NR C(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2, -NRC(=NR m )R、-NRC(=NR m )N(R)2, -NRS(O)(=NR m )R, -NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the following: C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; R 5 For -L 5 -R 5A ; L 5 is a covalent bond or an optionally substituted divalent C 1-6 aliphatic group; or L 5 and an L A -R A The 3- to 16-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 16-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 16-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 16-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 16-membered monocyclic carbocyclyl, the 5- to 16-membered bicyclic carbocyclyl, the 3- to 16-membered monocyclic heterocyclyl and the 5- to 16-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution; R 5A is -OR 5A11 、-SR 5A1 、-NHR 5A12 、-N(R 5A12 )2、-C(O)R 5A1 、-C(O)N(R 5A1 )2、-C(O)NR 5A1 (OR 5A1 )、-OC(O)R 5A1 、-OC(O)N(R 5A1 )2、-OC(O)OR 5A1 、-OSO2R 5A1 、-OSO2N(R 5A1 )2、-N(R 5A1 )C(O)R 5A1 、-NR 5A1 C(O)OR 5A1 、-NR 5A1 C(O)N(R 5A1 )2、-N(R 5A1 )SO2R 5A1 、-NR 5A1 S(O)2N(R 5A1 )2、-NR 5A1 OR 5A1 、-NR 5A1 S(O)R 5A1 、-NR 5A1 S(O)N(R 5A1 )2、-S(O)R 5A1 、-SO2R 5A1 、-S(O)N(R 5A1 )2、-SO2N(R 5A1 )2、-SO3R 5A1 、-C(=NR m )R 5A1 、-C(=NR m )N(R 5A1 )2、-NR 5A1 C(=NR m )R 5A1 、-NR 5A1 C(=NR m )N(R 5A1 )2、-NR 5A1 S(O)(=NR m )R 5A1 、-NR 5A1 S(O)(=NR m )N(R 5A1 )2、-OS(O)(=NR m )R 5A1 、-S(O)(=NR m )R 5A1 、-S(O)(=NR m )N(R 5A1 )2、-P(O)(R 5A1 )2, methyl, C 2-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R 5A The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R 5AG Substituent substitution; or R 5A The methyl group is replaced by 1, 2 or 3 R 5AG Substituent substitution; R A1 and R 5A1 are independently hydrogen, C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R A1 or R 5A1 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution; or two R A1 when attached to the same nitrogen atom together form an optionally substituted ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur; or two R 5A1 when attached to the same nitrogen atom together form an optionally substituted ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur; R 5A11 Methyl, C 2-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R 5A11 The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution; or R 5A11 The methyl group is replaced by 1, 2 or 3 R G1 Substituent substitution; Each R 5A12 Independently for C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R 5A12 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution; or two R 5A12 when attached to the same nitrogen atom together form an optionally substituted ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur; R AG , R 5AG and R G1 Each independently is halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O) R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2, -NRC(=NR m )R、-NRC(=NR m )N(R)2, -NRS(O)(=NR m )R, -NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2, -P(O)(R)2 or an optionally substituted group selected from the following: C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Each R is independently hydrogen or an optionally substituted group selected from the following: 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; or two R when attached to the same nitrogen atom together form an optionally substituted ring selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur; Each R m are independently -OH, -CN or R; and n is 0, 1, 2, 3 or 4.

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein: is a single bond or a double bond; X is N or C; Y is N or C; Ring A is phenyl, a 5- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Each L A Independently covalently bonded or divalent C 1-6 aliphatic group, wherein the divalent C 1-6 The aliphatic group is optionally substituted with 1, 2, 3 or 4 independently selected R LA1 Substituent substitution; Each R A is independently an oxo group, a halogen, -CN, -OR A1 , -SR A1 , -N(R A1 )2, -C(O)R A1 , -C(O)OR A1 , -C(O)N(R A1 )2, -C(O)NR A1 (OR A1 ), -OC(O)R A1 -OC(O)N(R A1 )2, -OC(O)OR A1 , -OSO2R A1 , -OSO2N(R A1 )2, -N(R A1 )C(O)R A1 , -NR A1 C(O)OR A1 , -NR A1 C(O)N(R A1 )2, -N(R A1 )SO2R A1 , -NR A1 S(O)2N(R A1 )2, -NR A1 OR A1 , -NR A1 S(O)R A1 , -NR A1 S(O)N(R A1 )2, -S(O)R A1 , -SO2R A1 , -S(O)N(R A1 )2, -SO2N(R A1 )2, -SO3R A1 , -C(=NR m )R A1 , -C(=NR m )N(R A1 )2, -NR A1 C(=NR m )R A1 , -NR A1 C(=NR m )N(R A1 )2, -NR A1 S(O)(=NR m )R A1 , -NR A1 S(O)(=NR m )N(R A1 )2, -OS(O)(=NR m )R A1 、-S(O)(=NR m )R A1 、-S(O)(=NR m )N(R A1 )2、-P(O)(R A1 2. C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R A The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution; or two L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8- to 10-membered bicyclic aryl group, the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, The 3- to 7-membered monocyclic carbocyclyl, the 5- to 10-membered bicyclic carbocyclyl, the phenyl, the 8- to 10-membered bicyclic aryl, the 3- to 7-membered monocyclic heterocyclyl, the 5- to 10-membered bicyclic heterocyclyl, the 5- to 6-membered monocyclic heteroaryl, and the 8- to 10-membered bicyclic heteroaryl are independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution; R 1 is hydrogen or a group selected from the following: C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R 1A Substituent substitution; or R 1 and an L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5- to 14-membered bicyclic heterocyclic group are independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution; Z is N or CR 2 ; U is N or CR 4 ; R 2 and R 4 Each independently hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, - NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2, -NRC(=NR m )R、-NRC(=NR m )N(R)2, -NRS(O)(=NR m )R, -NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R 2A Substituent substitution; R 3 is -F, -Cl, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O)R, -NR C(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2, -NRC(=NR m )R、-NRC(=NR m )N(R)2, -NRS(O)(=NR m )R, -NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 The aliphatic group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R 3A Substituent substitution; R 5 For -L 5 -R 5A ; L 5 Covalent bond or divalent C 1-6 aliphatic group, wherein the divalent C 1-6 The aliphatic group is optionally substituted with 1, 2, 3 or 4 independently selected R L5A Substituent substitution; or L 5 and an L A -R A The 3- to 16-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 16-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 16-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 16-membered monocyclic carbocyclyl, the 5- to 16-membered bicyclic carbocyclyl, the 3- to 16-membered monocyclic heterocyclyl and the 5- to 16-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution; R 5A is -OR 5A11 , -SR 5A1 , -NHR 5A12 , -N(R 5A12 )2, -C(O)R 5A1 , -C(O)N(R 5A1 )2, -C(O)NR 5A1 (OR 5A1 ), -OC(O)R 5A1 , -OC(O)N(R 5A1 )2, -OC(O)OR 5A1 , -OSO2R 5A1 , -OSO2N(R 5A1 )2, -N(R 5A1 )C(O)R 5A1 , -NR 5A1 C(O)OR 5A1 , -NR 5A1 C(O)N(R 5A1 )2, -N(R 5A1 )SO2R 5A1 , -NR 5A1 S(O)2N(R 5A1 )2, -NR 5A1 OR 5A1 , -NR 5A1 S(O)R 5A1 , -NR 5A1 S(O)N(R 5A1 )2, -S(O)R 5A1 , -SO2R 5A1 , -S(O)N(R 5A1 )2, -SO2N(R 5A1 )2, -SO3R 5A1 , -C(=NR m )R 5A1 , -C(=NR m )N(R 5A1 )2, -NR 5A1 C(=NR m )R 5A1 , -NR 5A1 C(=NR m )N(R 5A1 )2, -NR 5A1 S(O)(=NR m )R 5A1 , -NR 5A1 S(O)(=NR m )N(R 5A1 )2, -OS(O)(=NR m )R 5A1 、-S(O)(=NR m )R 5A1 、-S(O)(=NR m )N(R 5A1 )2、-P(O)(R 5A1 )2, methyl, C 2-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R 5A The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R 5AG Substituent substitution; or R 5A The methyl group is replaced by 1, 2 or 3 R 5AG Substituent substitution; R A1 and R 5A1 are independently hydrogen, C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R A1 or R 5A1 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution; or two R A1 When attached to the same nitrogen atom, they together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally substituted by 1, 2, 3 or 4 independently selected R A11 Substituent substitution; or two R 5A1 When attached to the same nitrogen atom, they together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally substituted by 1, 2, 3 or 4 independently selected R A11 Substituent substitution; R 5A11 Methyl, C 2-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R 5A11 The C 2-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution; or R 5A11 The methyl group is replaced by 1, 2 or 3 R G1 Substituent substitution; Each R 5A12 Independently for C 1-6 aliphatic, 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, Where R 5A12 The C 1-6 Each of the aliphatic, the 3-membered to 7-membered monocyclic carbocyclyl, the 5-membered to 10-membered bicyclic carbocyclyl, the phenyl, the 8-membered to 10-membered bicyclic aryl, the 3-membered to 7-membered monocyclic heterocyclyl, the 5-membered to 10-membered bicyclic heterocyclyl, the 5-membered to 6-membered monocyclic heteroaryl and the 8-membered to 10-membered bicyclic heteroaryl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R G1 Substituent substitution; or two R 5A12 When attached to the same nitrogen atom, they together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally substituted by 1, 2, 3 or 4 independently selected R 5B12 Substituent substitution; R AG , R 5AG and R G1 Each independently is halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -C(O)N(R)2, -C(O)NR(OR), -OC(O)R, -OC(O)N(R)2, -OC(O)OR, -OSO2R, -OSO2N(R)2, -N(R)C(O) R, -NRC(O)OR, -NRC(O)N(R)2, -N(R)SO2R, -NRS(O)2N(R)2, -NROR, -NRS(O)R, -NRS(O)N(R)2, -S(O)R, -SO2R, -S(O)N(R)2, -SO2N(R)2, -SO3R, -C(=NR m )R、-C(=NR m )N(R)2, -NRC(=NR m )R、-NRC(=NR m )N(R)2, -NRS(O)(=NR m )R, -NRS(O)(=NR m )N(R)2、-OS(O)(=NR m )R、-S(O)(=NR m )R、-S(O)(=NR m )N(R)2、-P(O)(R)2、C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 aliphatic, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8-membered to 10-membered bicyclic aryl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, the 5-membered to 6-membered monocyclic heteroaryl group and the 8-membered to 10-membered bicyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R AG1 Substituent substitution; Each R is independently selected from hydrogen, C 1-6 aliphatic, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, a phenyl group, an 8- to 10-membered bicyclic aryl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, and an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein said C 1-6 aliphatic, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, the phenyl group, the 8-membered to 10-membered bicyclic aryl group, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group, the 5-membered to 10-membered saturated or partially unsaturated bicyclic heterocyclic group, the 5-membered to 6-membered monocyclic heteroaryl group and the 8-membered to 10-membered bicyclic heteroaryl group are each optionally substituted by 1, 2, 3 or 4 independently selected R N Substituent substitution; or Two R when attached to the same nitrogen atom together form a ring selected from a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 0-2 additional heteroatoms independently selected from nitrogen, oxygen and sulfur and a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 0-3 additional heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl and the 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl are each optionally substituted by 1, 2, 3 or 4 independently selected R N Substituent substitution; Each R LA1 , R 1A , R 2A , R 3A , R L5A , R A11 , R 5B12 , R AG1 and R N independently selected from halogen, -(CH2) 0-4 R o 、-(CH2) 0- 4OR o 、-O(CH2) 0-4 R o 、-O-(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 CH(OR o )2, -(CH2) 0-4 SR o 、-(CH2) 0-4 Ph, -(CH2) 0-4 O(CH2) 0-1 Ph, -CH=CHPh, -(CH2) 0-4 O(CH2) 0-1 -pyridyl, -NO2, -CN, -N3, -(CH2) 0-4 N(R o )2, -(CH2) 0-4 N(R o )C(O)R o 、-N(R o )C(S)R o 、-(CH2) 0-4 N(R o )C(O)NR o 2. -N(R o )C(S)NR o 2. -(CH2) 0-4 N(R o )C(O)OR o 、-N(R o )N(R o )C(O)R o 、-N(R o )N(R o )C(O)NR o 2. -N(R o )N(R o )C(O)OR o 、-(CH2) 0-4 C(O)R o 、-C(S)R o 、-(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 C(O)SR o 、-(CH2) 0-4 C(O)OSiR o 3、-(CH2) 0- 4OC(O)R o 、-OC(O)(CH2) 0-4 SR o 、-(CH2) 0-4 SC(O)R o 、-(CH2) 0-4 C(O)NR o 2、-C(S)NR o 2、-C(S)SR o 、-SC(S)SR o 、-(CH2) 0-4 OC(O)NR o 2、-C(O)N(OR o )R o 、-C(O)C(O)R o 、-C(O)CH2C(O)R o 、-C(NOR o )R o 、-(CH2) 0-4 SSR o 、-(CH2) 0-4 S(O)2R o 、-(CH2) 0-4 S(O)(=NR o )R o 、-(CH2) 0-4 S(O)2OR o 、-(CH2) 0-4 OS(O)2R o 、-(CH2) 0-4 -S(O)2NR o 2、-(CH2) 0-4 S(O)(=NR o )NR o 2、-(CH2) 0-4 S(O)R o 、-N(R o )S(O)2NR o 2、-N(R o )S(O)2R o 、-N(R o )S(O)(=NR o )R o 、-N(OR o )R o 、-C(NH)NR o 2. -P(O)2R o 、-P(O)R o 2. -OP(O)R o 2. -OP(O)(OR o 2. -SiR o 3. -(C 1-4 Straight chain or branched alkylene)ON(R o )2 and -(C 1-4 Straight or branched alkylene)C(O)ON(R o )2; Each R o are independently hydrogen, C 1-6 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, -CH2-(5- to 6-membered heteroaryl ring) or a 3- to 6-membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; or two independent occurrences of R o Together with its intervening atoms, it forms a 3- to 12-membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur; Each R m are independently -OH, -CN or R; and n is 0, 1, 2, 3 or 4.

3. The compound or pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein the compound is a compound of formula II: or a pharmaceutically acceptable salt thereof.

4. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, wherein the compound is a compound of formula III: or a pharmaceutically acceptable salt thereof.

5. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein X is N and Y is C.

6. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein X is C and Y is C.

7. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, wherein Ring A is a 5- to 6-membered monocyclic heteroaryl group having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

8. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, wherein ring A is selected from pyrazolyl, imidazolyl, triazolyl and pyridinyl. 9 . The compound or pharmaceutically acceptable salt thereof according to claim 7 , wherein Ring A is a 5-membered monocyclic heteroaryl group having 1 to 2 nitrogen atoms. 10 . The compound or pharmaceutically acceptable salt thereof according to claim 9 , wherein Ring A is pyrazolyl.

11. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 10, wherein L A Covalent bond or divalent C 1-2 Aliphatic group.

12. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 10, wherein L A It is a covalent bond.

13. A compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, wherein each R A Independently for C 1-6 Alkyl, C 2-6 Alkenyl, -OR A1 、-N(R A1 )2. -C(O)R A1 、-C(O)N(R A1 )2, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, a phenyl group, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A The C 1-6 Alkyl, the C 2-6 The alkenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, the phenyl, the 3-membered to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5-membered to 6-membered monocyclic heteroaryl are each independently optionally substituted by 1 or 2 R AG Substituent substitution.

14. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 13, wherein each R A1 Independently for C 1-6 alkyl or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein R A1 Each C 1-6 The alkyl group and the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group are optionally substituted by hydroxy or methoxy.

15. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 12, wherein each R A independently selected from phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic radicals having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl radicals having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, each of which is optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

16. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 12, wherein each R A independently selected from 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic groups having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and 5- to 6-membered monocyclic heteroaryl groups having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, each of which is optionally substituted by 1 or 2 independently selected R AG Substituent substitution.

17. A compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, wherein R A It is phenyl.

18. A compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, wherein R A is optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent-substituted C 1-6 Aliphatic group.

19. A compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, wherein R A is optionally substituted by 1, 2, 3, 4 or 5 R AG Substituent-substituted C 1-2 Aliphatic group.

20. The compound according to claim 19 or a pharmaceutically acceptable salt thereof, wherein R A It is -CH=CH2.

21. A compound as claimed in any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, wherein each R A is independently selected from methyl, ethyl, n-propyl, isopropyl, vinyl, methoxy, methoxyethoxy, dimethylamino, dimethylaminocarbonyl, azetidinylcarbonyl, (hydroxyazetidinyl)carbonyl, cyclopropyl, cyclopentyl, phenyl, pyridyl, pyrimidinyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydro-2H-pyranyl, morpholinyl, tetrahydrofuranyl, piperazinyl, 5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl, wherein the methyl The yl, ethyl, n-propyl, isopropyl, vinyl, cyclopropyl, cyclopentyl, phenyl, pyridyl, pyrimidinyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydro-2H-pyranyl, morpholinyl, tetrahydrofuranyl, piperazinyl and 5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl are each optionally replaced by 1, 2, 3 or 4 independently selected R AG Substituent substitution.

22. A compound as described in any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein each R A Independently selected from methyl, ethyl, n-propyl, isopropyl, vinyl, methoxy, methoxyethoxy, dimethylamino, cyclopropyl, cyclopentyl, phenyl, methylphenyl, pyridyl, fluoropyridyl, methylpyridyl, pyrimidinyl, tetrahydrofuranyl and tetrahydropyranyl.

23. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, wherein: for 24. The compound or pharmaceutically acceptable salt thereof according to any one of claims 1 to 4, wherein: for 25. A compound as described in any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein R 1 is optionally substituted C 1-6 an aliphatic group, a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, or a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur.

26. A compound as described in any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein R 1 It is methyl, trideuterated methyl, ethyl, difluoroethyl, hydroxyethyl, cyclopropyl or tetrahydrofuranyl.

27. The compound of claim 25 or a pharmaceutically acceptable salt thereof, wherein R 1 It is methyl.

28. A compound as described in any one of claims 1 to 10, wherein R 1 and an L A -R A The 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5- to 10-membered bicyclic heterocyclic group are independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

29. A compound as described in any one of claims 1 to 10, wherein R 1 and an L A -R A Together with the atoms to which it is attached, it forms a 6-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally substituted by 1 or 2 R AG Substituent substitution.

30. The compound or pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 29, wherein Z is CR 2 .

31. The compound of claim 30, or a pharmaceutically acceptable salt thereof, wherein Z is CH.

32. A compound as described in any one of claims 1 to 31, or a pharmaceutically acceptable salt thereof, wherein R 3 is -F, -Cl, -CN or optionally substituted C 1-6 Aliphatic group.

33. The compound of claim 32 or a pharmaceutically acceptable salt thereof, wherein R 3 is optionally substituted C 1-6 Aliphatic group.

34. The compound of claim 33 or a pharmaceutically acceptable salt thereof, wherein R 3 is methyl or trifluoromethyl.

35. The compound or pharmaceutically acceptable salt thereof as claimed in any one of claims 1 to 34, wherein U is CR 4 .

36. The compound of claim 35, or a pharmaceutically acceptable salt thereof, wherein U is CH.

37. A compound as described in any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof, wherein L 5 is an optionally substituted divalent C 1-6 Aliphatic group.

38. The compound of claim 37 or a pharmaceutically acceptable salt thereof, wherein L 5 is an optionally substituted divalent C 1-3 Aliphatic group.

39. The compound of claim 38 or a pharmaceutically acceptable salt thereof, wherein L 5 is -CH2-, -CH(CH3)-, -CH(CH2OH)- or 40. A compound as described in any one of claims 1 to 39, or a pharmaceutically acceptable salt thereof, wherein R 5A NHR 5A12 OR 5A11 .

41. A compound as described in any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof, wherein each R 5A12 R is independently 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclic group, 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclic group, phenyl, 8- to 10-membered bicyclic aryl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, each of which is optionally substituted by 1, 2, 3, 4, 5 or 6 independently selected R G1 Substituent substitution.

42. A compound as described in any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof, wherein each R 5A12 is independently phenyl or a 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, each of which is optionally substituted by 1, 2, 3, 4, 5 or 6 independently selected R G1 Substituent substitution.

43. A compound as described in any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof, wherein each R 5A12 is independently phenyl or pyridinyl, each of which is optionally substituted by 1, 2, 3, 4, 5 or 6 independently selected R G1 Substituent substitution.

44. The compound of claim 41 or a pharmaceutically acceptable salt thereof, wherein each R 5A12 is independently optionally selected from 1, 2, 3, 4 or 5 R G1 Substituents: phenyl substituted.

45. A compound as described in any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof, wherein R 5A12 A single instance of R is selected by 1 or 2 independently G1 Substituents: phenyl substituted.

46. ​​A compound as described in any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof, wherein R 5A12 A single example is pyridinyl, which is optionally substituted with 1 or 2 independently selected R G1 Substituent substitution.

47. A compound as described in any one of claims 1 to 46, or a pharmaceutically acceptable salt thereof, wherein each R G1 independently selected from halogen, C 1-6 alkyl, phenyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclic group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, an 8- to 10-membered bicyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, -C(O)OR, -C(O)N(R)2 and -C(O)NR(OR), wherein each C 1-6 alkyl, phenyl, 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl, 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl, 5- to 6-membered monocyclic heteroaryl, and 8- to 10-membered bicyclic heteroaryl are optionally substituted by 1, 2, 3 or 4 independently selected R AG1 Substituent substitution.

48. A compound as described in any one of claims 1 to 47, or a pharmaceutically acceptable salt thereof, wherein each R is independently selected from hydrogen, C 1-6 alkyl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, and a 5- to 6-membered monocyclic heteroaryl group having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclic group and the 5- to 6-membered monocyclic heteroaryl group is optionally replaced by C 1-6 Alkyl substitution.

49. A compound as described in any one of claims 1 to 47, or a pharmaceutically acceptable salt thereof, wherein each R is independently selected from hydrogen, methyl, methylpiperidinyl and pyridinyl.

50. A compound as described in any one of claims 1 to 49, or a pharmaceutically acceptable salt thereof, wherein each R AG1 independently selected from halogen, -(CH2) 0-4 R o 、-(CH2) 0-4 OR o 、-(CH2) 0-4 C(O)NR o 2. -(CH2) 0-4 C(O)OR o 、-(CH2) 0-4 C(O)R o 、-O(CH2) 0-4 R o 、CN、-(CH2) 0-4 C(O)NR o 2 and -C(O)N(OR o )R o , where each R o are independently hydrogen, C 1-6 Alkyl or a 3- to 6-membered saturated ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

51. A compound as described in any one of claims 1 to 49, or a pharmaceutically acceptable salt thereof, wherein each R AG1 Independently selected from fluoro, methyl, ethyl, hydroxyethyl, -COOH, methylaminocarbonyl, dimethylaminocarbonyl, methylcarbonyl, methoxyaminocarbonyl, cyano, cyclopropyl, hydroxy, methoxy, dimethylamino, dimethylaminomethyl and tetrahydropyranyl.

52. A compound as described in any one of claims 1 to 46, or a pharmaceutically acceptable salt thereof, wherein each R G1 independently selected from methyl, chloro, pyridinyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, triazolyl, oxadiazolyl, indazolyl, quinolinyl, piperidinyl, piperazinyl, morpholinyl, isoindolinonyl, hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, -C(O)OR, -C(O)N(R)2, and -C(O)NR(OR), wherein the pyridinyl, pyridonyl, phenyl, pyrazolyl, pyrimidinyl, piperazinyl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, 1,2,4-oxadiazol-5(4H)-onyl, tetrazolyl, triazolyl, oxadiazolyl, indazolyl, quinolinyl, piperidinyl, piperazinyl, morpholinyl, isoindolinonyl, hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, -C(O)OR, -C(O)N(R)2, and -C(O)NR(OR). -tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl, the 1,2,4-oxadiazol-5(4H)-onyl, the tetrazolyl, the triazolyl, the oxadiazolyl, the indazolyl, the quinolyl, the piperidinyl, the piperazinyl, the morpholinyl, the isoindolinonyl, the hexahydro-3H-oxazolo[3,4-a]pyrazin-3-onyl, the 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl are each optionally substituted by 1 or 2 R independently selected from fluoro, methyl, ethyl, hydroxyethyl, -COOH, methylaminocarbonyl, dimethylaminocarbonyl, methylcarbonyl, methoxyaminocarbonyl, cyano, cyclopropyl, hydroxy, methoxy, dimethylamino, dimethylaminomethyl and tetrahydropyranyl. AG1 Substituents are substituted; and Each R is independently selected from hydrogen, methyl, methylpiperidinyl, and pyridinyl.

53. A compound as described in any one of claims 1 to 46, or a pharmaceutically acceptable salt thereof, wherein each R G1 independently selected from halogen, C 1-6 Alkyl and -C(O)OR.

54. A compound as described in any one of claims 1 to 46, or a pharmaceutically acceptable salt thereof, wherein each R G1 Independently selected from fluoro, chloro, methyl and -C(O)OH.

55. The compound of claim 44 or a pharmaceutically acceptable salt thereof, wherein R 5A12 A single instance is represented by 1 R G1 Substituents: phenyl substituted.

56. A compound as described in any one of claims 1 to 45 and 55, or a pharmaceutically acceptable salt thereof, wherein R G1 It is -C(O)OR.

57. The compound of claim 56 or a pharmaceutically acceptable salt thereof, wherein R G1 It is -C(O)OH.

58. A compound as described in any one of claims 1 to 57, or a pharmaceutically acceptable salt thereof, wherein n is 0 or 1.

59. The compound of any one of claims 1 to 3, 5 to 40 and 44 to 58, wherein the compound of formula I is a compound of formula IV: or a pharmaceutically acceptable salt thereof, wherein: Ring B is a 3- to 7-membered saturated or partially unsaturated monocyclic carbocyclyl, a 5- to 10-membered saturated or partially unsaturated bicyclic carbocyclyl, a phenyl, an 8- to 10-membered bicyclic aryl, a 3- to 7-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 10-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, a 5- to 6-membered monocyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, or an 8- to 10-membered bicyclic heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; and m is 0, 1, 2, 3, 4, 5 or 6.

60. The compound of claim 59 or a pharmaceutically acceptable salt thereof, wherein: L 5 For divalent C 1-3 aliphatic, which is optionally substituted by 1, 2, 3 or 4 independently selected R L5A Substituent substitution; or L 5 and an L A -R A The 3- to 16-membered saturated or partially unsaturated monocyclic carbocyclyl, the 5- to 16-membered saturated or partially unsaturated bicyclic carbocyclyl, the 3- to 16-membered saturated or partially unsaturated monocyclic heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur, or the 5- to 16-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein each of the 3- to 16-membered monocyclic carbocyclyl, the 5- to 16-membered bicyclic carbocyclyl, the 3- to 16-membered monocyclic heterocyclyl and the 5- to 16-membered bicyclic heterocyclyl is independently optionally substituted by 1, 2, 3, 4, 5 or 6 R AG Substituent substitution.

61. A compound as described in any one of claims 1 to 3, 7 to 10 and 30 to 58, wherein the compound is a compound of formula V: or a pharmaceutically acceptable salt thereof, wherein z is 0, 1, 2 or 3.

62. The compound of claim 1 or 2, wherein the compound is a compound of formula VI: or a pharmaceutically acceptable salt thereof.

63. The compound of claim 1 or 2, wherein the compound is a compound of formula VII: or a pharmaceutically acceptable salt thereof, wherein z is 0, 1, 2 or 3.

64. The compound of claim 1 or 2, wherein the compound is selected from: 2-((1-(4,7-dimethyl-5-oxo-4,5-dihydropyrazolo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(4,7-dimethyl-5-oxo-3-phenyl-4,5-dihydropyrazolo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; and 2-((1-(4,7-dimethyl-5-oxo-3-vinyl-4,5-dihydropyrazolo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; or a pharmaceutically acceptable salt thereof.

65. The compound of claim 1 or 2, wherein the compound is selected from: 2-((1-(4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(4,7-dimethyl-5-oxo-3-(pyridin-2-yl)-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(3,4,7-trimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 6-Methyl-3-((1-(3,4,7-trimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)picolinic acid; 2-((1-(7-chloro-3-ethyl-4-methyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(7-chloro-4-methyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(7-chloro-3,4-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(7-chloro-4-ethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(7-chloro-3,4-diethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,2-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(4,7-dimethyl-5-oxo-4,5-dihydro-[1,2,4]triazolo[1,5-a]quinazolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(3,4,7-trimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(3,4,7-trimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)picolinic acid; 2-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)picolinic acid; 3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-methylpicolinic acid; 2-((1-(4-ethyl-3,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(4-ethyl-3,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)picolinic acid; 2-((1-(3,4-diethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(3,4-diethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-5-fluorobenzoic acid; 3-((1-(3,4-diethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-methylpicolinic acid; 2-((1-(4,7-dimethyl-5-oxo-2-propyl-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(4,7-dimethyl-5-oxo-2-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(4,7-dimethyl-5-oxo-2-phenethyl-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(2-(2-fluoropyridin-4-yl)-4,7-dimethyl-5-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; 2-((1-(4,7-dimethyl-5-oxo-2-(pyrimidin-5-yl)-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; 6-Chloro-3-((1-(4,7-dimethyl-5-oxo-2-(o-tolyl)-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)picolinic acid; 2-[1-(3-Methoxy-5,8-dimethyl-6-oxo-benzo[c][1,8]naphthyridin-10-yl)ethylamino]benzoic acid; 2-[1-[3-(Dimethylamino)-5,8-dimethyl-6-oxo-benzo[c][1,8]naphthyridin-10-yl]ethylamino]benzoic acid; 2-[1-[3-(2-methoxyethoxy)-5,8-dimethyl-6-oxo-benzo[c][1,8]naphthyridin-10-yl]ethylamino]benzoic acid; and 2-((1-(7-chloro-3,4-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)benzoic acid; or a pharmaceutically acceptable salt thereof.

66. The compound of claim 1 or 2, wherein the compound is selected from: 2-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)benzoic acid; 6-Methyl-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)picolinic acid; 2-((1-(3,8-dimethyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)benzoic acid; and 6-Chloro-3-((1-(3,8-dimethyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)picolinic acid; or a pharmaceutically acceptable salt thereof.

67. The compound of claim 1 or 2, wherein the compound is selected from: 2-ethyl-3,6-dimethyl-8-((6-methyl-[2,4'-bipyridinyl]-3-yl)amino)-8,9-dihydrobenzo[de]pyrazolo[4,5,1-ij][1,7]naphthyridin-4(3H)-one; 9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide; 9-(1-((6-chloro-2-(pyrimidin-4-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(pyrimidin-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridyl]-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-N,N-dimethylbenzamide; 4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)benzoic acid; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-ethyl-4,7-dimethyl-9-(1-((6-methyl-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-ethyl-4,7-dimethyl-9-(1-((6-methyl-2-(1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-ethyl-4,7-dimethyl-9-(1-((6-methyl-2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 4-(3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-methylpyridin-2-yl)-2-fluoro-N-methylbenzamide; 3-ethyl-9-(1-((2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)phenyl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((2-(4-acetylpiperazin-1-yl)phenyl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((2-(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)phenyl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(4-(2,2-difluoroethyl)-3-ethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(3-cyclopentyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(3-isopropyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(7-chloro-3-ethyl-4-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(7-chloro-3-(cyclopropylmethyl)-4-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-3-propyl-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-3-(tetrahydrofuran-3-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(3-(2-methoxyethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(3-(cyclopropylmethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(3-ethyl-4-methyl-5-oxo-7-(trifluoromethyl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(3,8-dimethyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 3-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 9-(1-((2-(1H-tetrazolyl-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-(1-methylpiperidin-4-yl)picolinamide; 6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-(pyridin-4-yl)picolinamide; 6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-methoxypicolinamide; 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)-2-hydroxyethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; and 9-(1-((2-(4-acetylpiperazin-1-yl)-6-chloropyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; or a pharmaceutically acceptable salt thereof.

68. The compound of claim 1 or 2, wherein the compound is selected from: 9-(1-((6-chloro-2-(1-methyl1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 5-(5-chloro-2-((1-(4,7-dimethyl-3-(1-methylazetidin-3-yl)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)phenyl)-N-methylpicolinamide; 9-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-indazol-5-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylazetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyethyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-cyclopropylazetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-((S)-2-hydroxypropyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-((R)-2-hydroxypropyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxy-2-methylpropyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2,2-difluoroethyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 2-(3-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)azetidin-1-yl)acetonitrile; 3-(3-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)azetidin-1-yl)propanenitrile; 3-(1-acetylazetidin-3-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)azetidine-1-carboxylic acid methyl ester; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methylsulfonyl)azetidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(1-acetylazetidin-3-yl)-9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-((1-(3-(1-acetylazetidin-3-yl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-chloro-N-methyl-[2,3'-bipyridine]-6'-carboxamide; 3-(1-acetylazetidin-3-yl)-9-(1-((6-chloro-2-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyacetyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(dimethylglycyl)azetidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-3-((S)-1-methylpyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-((1-acetylpiperidin-4-yl)methyl)-9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 4-((9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)methyl)-N,N-dimethylpiperidine-1-carboxamide; 4-((9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)methyl)-N-ethylpiperidine-1-carboxamide; 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-3-((1-(2,2-difluoroethyl)pyrrolidin-3-yl)methyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-hydroxyethyl)-4,7-dimethylimidazo[1,5-a]quinazolin-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(pyridin-3-yl)imidazo[1,5-a]quinazolin-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-methylpyridin-3-yl)imidazo[1,5-a]quinazolin-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(pyrimidin-5-yl)imidazo[1,5-a]quinazolin-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-methylpyridin-4-yl)imidazo[1,5-a]quinazolin-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-methylpyridin-3-yl)imidazo[1,5-a]quinazolin-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(pyrimidin-5-yl)imidazo[1,5-a]quinazolin-5(4H)-one; 4-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-3-yl)-N-methylpicolinamide; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 3-(azetidine-1-carbonyl)-9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethylimidazo[1,5-a]quinazolin-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(3-hydroxyazetidine-1-carbonyl)-4,7-dimethylimidazo[1,5-a]quinazolin-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-N,N,7-trimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 9-(1-((6-chloro-2-(3-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 9-(1-((6-chloro-2-(4-cyano-2-fluorophenyl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 9-(1-((6-chloro-2-(4-cyanophenyl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 9-(1-((6-chloro-2-morpholinylpyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 9-(1-((4-fluoro-2-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 9-(1-((6-chloro-2-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 9-(1-((6-chloro-2-(1,3-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-N,N,4,7-tetramethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carboxamide; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpiperidin-4-yl)imidazo[1,5-a]quinazolin-5(4H)-one; 3-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethylimidazo[1,5-a]quinazolin-5(4H)-one; 4-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydroimidazo[1,5-a]quinazolin-3-yl)piperidine-1-carboxylic acid ethyl ester; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpiperidin-4-yl)imidazo[1,5-a]quinazolin-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-ethylpyrrolidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyethyl)pyrrolidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-3-(1-methylpyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyethyl)pyrrolidin-3-yl)-7-methyl-4-(methyl-d3)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridyl]-3-yl)amino)ethyl)-3-(1-isopropylpyrrolidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2,2-difluoroethyl)pyrrolidin-3-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2,2-difluoroethyl)pyrrolidin-3-yl)-7-methyl-4-(methyl-d3)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 2-(3-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidin-1-yl)acetonitrile; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-3-(1-(2-hydroxyethyl)pyrrolidin-3-yl)-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-3-(1-(2-hydroxy-2-methylpropyl)pyrrolidin-3-yl)-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-3-(1-isopropylpyrrolidin-3-yl)-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-(1-(methylsulfonyl)pyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(1-acetylpyrrolidin-3-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidine-1-carboxylic acid methyl ester; 3-(9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridyl]-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)-N,N-dimethylpyrrolidine-1-carboxamide; 3-(3-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidin-1-yl)propionitrile; 3-(3-(9-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidin-1-yl)propionitrile; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxyacetyl)pyrrolidin-3-yl)-7-methyl-4-(methyl-d3)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(dimethylglycyl)pyrrolidin-3-yl)-7-methyl-4-(methyl-d3)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-3-(1-(1-methyl-1H-pyrazol-5-carbonyl)pyrrolidin-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 1-(3-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)pyrrolidine-1-carbonyl)cyclopropane-1-carbonitrile; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-methylpiperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-ethylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(2-methyltetrazol-5-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1,3,4-oxadiazol-2-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 5-[6-Chloro-3-[1-[4,7-dimethyl-3-(1-methyl-4-piperidinyl)-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-N-methyl-pyridine-2-carboxamide; 3-[6-chloro-3-[1-[4,7-dimethyl-3-(1-methyl-4-piperidinyl)-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-4H-1,2,4-oxadiazol-5-one; 9-[1-[[6-chloro-2-(1,3-dimethylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-6-oxo-3-pyridinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(4-hydroxy-1-piperidinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(3-fluoro-4-pyridinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(3-pyridinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 5-[3-[1-[4,7-dimethyl-3-(1-methyl-4-piperidinyl)-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-6-methyl-2-pyridinyl]-N-methyl-pyridine-2-carboxamide; 9-[1-[[6-chloro-2-(1-methyl-2-oxo-4-pyridinyl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxy-2-methyl-propyl)-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-[(2R)-2-hydroxypropyl]-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-[(2S)-2-hydroxypropyl]-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2-hydroxy-2-methylpropyl)piperidin-4-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxyethyl)-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-((1-methyl-1H-imidazol-2-yl)methyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(oxetan-3-yl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-[4-[9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-3-yl]-1-piperidinyl]propionitrile; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(1-(2,2-difluoroethyl)piperidin-4-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methylsulfonyl-4-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 4-[9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-3-yl]piperidine-1-carboxylic acid methyl ester; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-(1-cyclopropylsulfonyl-4-piperidinyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 4-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)-N,N-dimethylpiperidine-1-carboxamide; 3-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 4,7-dimethyl-9-(1-((6-methyl-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(methylsulfonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methylsulfonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methylsulfonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(quinolin-6-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methylsulfonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxyacetyl)-4-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 1-(4-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-3-yl)piperidine-1-carbonyl)cyclopropane-1-carbonitrile; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(1-methyl-1H-pyrazole-5-carbonyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(1-(dimethylglycyl)piperidin-4-yl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(1-(methyl-L-prolyl)piperidin-4-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4-methyl-3-(1-methylpiperidin-4-yl)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinoline-7-carbonitrile; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-2-(tetrahydro-2H-pyran-4-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-2-(tetrahydro-2H-pyran-4-yl)-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-2-(1-methylpiperidin-4-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 2-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-2-(1-(2-hydroxyethyl)piperidin-4-yl)-7-methyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(4-(9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-5-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-2-yl)piperidin-1-yl)propanenitrile; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-2-(1-methylazetidin-3-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-2-(1-methylpiperidin-4-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-2-(1-isopropylpiperidin-4-yl)-4,7-dimethyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-2-(1-methylpiperidin-4-yl)-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 2-(1-acetylpiperidin-4-yl)-9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 4-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-2-yl)piperidine-1-carboxylic acid ethyl ester; 4-(9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]isoquinolin-2-yl)-N,N-dimethylpiperidine-1-carboxamide; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-2-(1-(2,2-difluoroethyl)piperidin-4-yl)-4,7-dimethyl-2,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-[6-chloro-3-[1-[7-methyl-5-oxo-3-[(3S)-tetrahydrofuran-3-yl]-4-(trideuteratedmethyl)pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-4H-1,2,4-oxadiazol-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-7-methyl-4-(methyl-d3)-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(6-chloro-3-((1-(4-ethyl-7-methyl-5-oxo-3-((S)-tetrahydrofuran-3-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2'-methyl-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-((S)-tetrahydrofuran-3-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 6-chloro-3-((1-(4-ethyl-7-methyl-5-oxo-3-((S)-tetrahydrofuran-3-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-methyl-[2,3'-bipyridine]-6'-carboxamide; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-cyclopropyl-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-6-oxo-3-pyridinyl)-3-pyridinyl]amino]ethyl]-4-cyclopropyl-3-ethyl-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-Chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-3-ethyl-7-methyl-4-tetrahydrofuran-3-yl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-3-ethyl-4-(2-hydroxyethyl)-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one; 4-(6-chloro-3-(((3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)methyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide; 9-(1-((6-chloro-2-(3-methyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(6-chloro-3-((1-(3-ethyl-7-methyl-4-(methyl-d3)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(4-methyl-4H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,3-triazol-5-yl)pyridin-3-yl)amino)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 4-(6-chloro-3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)benzoic acid; 3-ethyl-4,7-dimethyl-9-(1-((6-methyl-2-(3-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2'-methyl-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(pyrimidin-5-yl)pyridin-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-ethyl-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 6-chloro-3-((1-(4-(2,2-difluoroethyl)-3-ethyl-7-methyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-methyl-[2,3'-bipyridine]-6'-carboxamide; 9-[1-[[2-(1-acetyl-4-piperidinyl)-6-chloro-3-pyridinyl]amino]ethyl]-3-ethyl-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 4-(6-chloro-3-((1-(3-(2-hydroxyethyl)-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(4-hydroxypiperidin-1-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(quinolin-6-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1-methyl-1H-indazol-5-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 3-(2-hydroxyethyl)-4,7-dimethyl-9-(1-((6-methyl-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-(pyrimidin-5-yl)pyridin-3-yl)amino)ethyl)-3-(2-hydroxyethyl)-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 5-[6-Chloro-3-[1-[3-(2-hydroxyethyl)-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-N-methyl-pyridine-2-carboxamide; 9-[1-[[6-chloro-2-(1-methyl-6-oxo-3-pyridinyl)-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-2-oxo-4-pyridinyl)-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(2-methoxy-4-pyridinyl)-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-4-piperidinyl)-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[2-(1-acetyl-4-piperidinyl)-6-chloro-3-pyridinyl]amino]ethyl]-3-(2-hydroxyethyl)-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4-(2,2-difluoroethyl)-3-(2-hydroxyethyl)-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one; 5-[6-Chloro-3-[1-[4-(2,2-difluoroethyl)-3-(2-hydroxyethyl)-7-methyl-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethylamino]-2-pyridinyl]-N-methyl-pyridine-2-carboxamide; 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4-ethyl-3-(2-hydroxyethyl)-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[(6-chloro-2-morpholinyl-3-pyridinyl)amino]ethyl]-4-ethyl-3-(2-hydroxyethyl)-7-methyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(2-morpholinoethyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-morpholinylethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-3'-fluoro-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-4,7-dimethyl-3-(2-(4-methylpiperazin-1-yl)ethyl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 4-(6-chloro-3-((1-(4,7-dimethyl-3-(2-morpholinylethyl)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide; 4-(6-chloro-3-((1-(4,7-dimethyl-3-(2-(4-methylpiperazin-1-yl)ethyl)-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide; 9-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-4-(2,2-difluoroethyl)-3-(2-(5,6-dihydro-[1,2,4]triazolo[1,5-a]pyrazin-7(8H)-yl)ethyl)-7-methyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4-ethyl-7-methyl-3-(2-pyridinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-(1-((6-chloro-2-morpholinylpyridin-3-yl)amino)ethyl)-4-ethyl-7-methyl-3-(pyridin-2-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 6-chloro-3-((1-(4-ethyl-7-methyl-5-oxo-3-(pyridin-2-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-N-methyl-[2,3'-bipyridine]-6'-carboxamide; 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-3-(pyridin-2-yl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,7-dimethyl-3-(pyridin-2-yl)-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4-ethyl-7-methyl-3-(3-pyridinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(2-pyridinylmethyl)pyrazolo[3,4-c]isoquinolin-5-one; 3-(6-chloro-3-((1-(4,7-dimethyl-5-oxo-3-(pyridin-2-ylmethyl)-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-3-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methyl-1,2,4-triazol-3-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxyethyl)-3-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-3-(1-methyl-3-piperidinyl)pyrazolo[3,4-c]isoquinolin-5-one; 9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-3-[1-(2-hydroxyethyl)-3-piperidinyl]-4,7-dimethyl-pyrazolo[3,4-c]isoquinolin-5-one; 3-[9-[1-[[6-chloro-2-(1-methylpyrazol-4-yl)-3-pyridinyl]amino]ethyl]-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-3-yl]piperidine-1-carboxylic acid methyl ester; 5-[6-chloro-3-[1-[4,7-dimethyl-3-(1-methyl-4-piperidinyl)-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethoxy]-2-pyridinyl]-N-methyl-pyridine-2-carboxamide; 5-[3-[1-[3-(1-acetyl-4-piperidinyl)-4,7-dimethyl-5-oxo-pyrazolo[3,4-c]isoquinolin-9-yl]ethoxy]-6-chloro-2-pyridinyl]-N-methyl-pyridine-2-carboxamide; 10-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(3-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-3-(hydroxymethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-3-((dimethylamino)methyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(4-hydroxypiperidin-1-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 1-(6-chloro-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)-N-methylpiperidine-4-carboxamide; 10-(1-((2-(4-acetylpiperazin-1-yl)-6-chloropyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 3-(6-chloro-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 10-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2'-methyl-[2,4'-bipyridyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-[2,3'-bipyridyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-1'-methyl-6'-oxo-1',6'-dihydro-[2,3'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 4-(6-chloro-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)-2-fluoro-N-methylbenzamide; 6-Chloro-N-methyl-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)-[2,3'-bipyridine]-6'-carboxamide; 10-(1-((6-chloro-6'-methoxy-[2,3'-bipyridyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2'-methoxy-[2,4'-bipyridinyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2'-(dimethylamino)-[2,4'-bipyridyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(quinolin-6-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1-methyl-1H-indazol-5-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 2-Fluoro-N-methyl-4-(6-methyl-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)benzamide; 8-methyl-10-(1-((6-methyl-2-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)pyridin-3-yl)amino)ethyl)-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-6-methylpyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((2',6-dimethyl-[2,4'-bipyridyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((2-(1-cyclopropyl-1H-pyrazol-4-yl)-6-methylpyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 7-(6-chloro-3-((1-(8-methyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)pyridin-2-yl)hexahydro-3H-oxazolo[3,4-a]pyrazin-3-one; 10-(1-((6-chloro-2-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)pyridin-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-6'-((dimethylamino)methyl)-[2,3'-bipyridyl]-3-yl)amino)ethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 3-(3-((1-(3,8-dimethyl-6-oxo-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-10-yl)ethyl)amino)-6-methylpyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 8-methyl-10-(1-((6-methyl-2-(2-methyl-2H-tetrazolyl-5-yl)pyridin-3-yl)amino)ethyl)-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 3-(3-((1-(3-ethyl-4,7-dimethyl-5-oxo-4,5-dihydro-3H-pyrazolo[3,4-c]isoquinolin-9-yl)ethyl)amino)-6-methylpyridin-2-yl)-1,2,4-oxadiazol-5(4H)-one; 10-(1-((6-chloro-2-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(1,3,4-oxadiazol-2-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(2-methyl-2H-tetrazol-5-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; 10-(1-((6-chloro-2-(2-methyl-1-oxoisoindolin-5-yl)pyridin-3-yl)amino)-2-hydroxyethyl)-8-methyl-4,5-dihydro-3H,6H-2,2a,5a-triazavinylanthracen-6-one; and 9-(1-((6-chloro-2-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)amino)-2-(4-methylpiperazin-1-yl)ethyl)-3-ethyl-4,7-dimethyl-3,4-dihydro-5H-pyrazolo[3,4-c]isoquinolin-5-one; or a pharmaceutically acceptable salt thereof.

69. A pharmaceutical composition comprising a compound according to any one of claims 1 to 68 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

70. A method for inhibiting PI3Kα, the method comprising administering to a subject a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 68 or a pharmaceutical composition according to claim 69.

71. The method of claim 70, or a pharmaceutically acceptable salt thereof, wherein the method selectively inhibits PI3Kα relative to other PI3K isoforms.

72. The method of claim 70 or 71, or a pharmaceutically acceptable salt thereof, wherein the method selectively inhibits mutant PI3Kα relative to wild-type PI3Kα.

73. A method of treating a disease, disorder or condition associated with PI3Kα, the method comprising administering to a subject in need thereof a compound of any one of claims 1 to 68 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 69.

74. The method of claim 73, wherein the disease, disorder or condition is associated with mutant PI3Kα.

75. A method of treating cancer, comprising administering to a subject in need thereof a compound of any one of claims 1 to 68 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 69.

76. The method of claim 75, wherein the cancer is selected from breast cancer, brain cancer, prostate cancer, endometrial cancer, gastric cancer, leukemia, lymphoma, sarcoma, colorectal cancer, lung cancer, ovarian cancer, skin cancer, and head and neck cancer.

77. The method of claim 76, wherein the disease or condition is CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal nevus, scoliosis / skeletal and spinal syndrome) or PIK3CA-associated overgrowth syndrome (PROS).

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