Inhibitors of solute carrier family 6A member 19 (SLC6A19) and their usage

Abstract

This document provides compounds of formula (I) or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m, R 1 R 2 R 3 R 5 R 6 R 7 R 8 R 9 and R 10 As defined elsewhere in this document. Methods for preparing compounds of formula (I) are also provided herein. Methods for inhibiting SLC6A19 and for treating SLC6A19-mediated diseases, conditions, or disorders in individuals in need are also provided herein. (I)

Description

Cross-reference of related applications

[0001] This application claims priority to U.S. Provisional Application No. 63 / 535,282, filed August 29, 2023, and U.S. Provisional Application No. 63 / 572,752, filed April 1, 2024, the entire contents of each of which are incorporated herein by reference. Background Technology

[0002] Solute carrier family 6A member 19 (SLC6A19) (also known as B0AT1) is a sodium-dependent neutral amino acid (NAA) transporter that is primarily expressed on the apical membrane of kidney and intestinal epithelial cells (Fairweather et al.). J. Biol. Chem (2015) 290, 24308-24325). In the intestine, surface expression of SLC6A19 depends on the chaperone protein ACE2 to promote amino acid uptake (Singer et al.). Am. J. Physiol. Gastrointest. Liver Physiol (2012)303, G686-G695). In the kidney, SLC6A19 requires TMEM27 for surface expression to reabsorb amino acids (Verrey et al.). Arch. Eur. J. Physiol. (2009) 458, 53-60).

[0003] Phenylketonuria (PKU) is caused by mutations in phenylalanine hydroxylase (PAH), a key enzyme in the metabolism of phenylalanine (Phe) into tyrosine (Tyr) (both NAAs). PKU patients accumulate Phe toxicity in their blood and other tissues, leading to neurological changes (Scriver CR). Hum. Mutat (2007) 28, 831-843). Treatment options for PKU include strict protein restriction with poor compliance and two FDA-approved drugs (Palynziq and Kuvan, both limited to a subgroup of patients); a large number of unmet medical needs remain (Strisciuglio et al.). Metabolites (2014) 4, 1007-1017; Gentile et al. Mol. Genet. and Metab. (2010) 99, S64-S67). Since PKU symptoms result from the systemic accumulation of Phe, inhibiting SLC6A19 to limit intestinal absorption of Phe and its reuptake in the kidneys may be a feasible way to treat PKU. Indeed, in mouse models of PKU, loss of SLC6A19 significantly increased urinary Phe excretion and significantly reduced plasma Phe, and normalized neurotransmitter levels (Belanger et al.). JCI Insight (2018) 3, e121762).

[0004] The prevalence of chronic kidney disease (CKD) is rising rapidly, with an estimated 15% of the adult population in the United States suffering from CKD (CDC 2021). Loss-of-function splicing (c.1173+2T>G) in SLC6A19 has been reported (Sveinbjornsson G. et al.). Hum. Mol. Genet. (2014) 23, 6935-6943) and the association between missense (D173N) variants and CKD prevention (Sinnott-Amstrong N. et al.) Nat. Genet. (2021) 53, 185-194).

[0005] Metabolic syndrome and related diseases, such as diabetes, are a global epidemic. It is estimated that one-third of adults in the United States have metabolic syndrome (Saklayen M.). Curr Hypertens Rep (2018) 20, 12). Mice lacking SLC6A19 exhibit numerous improved metabolic outcomes, including resistance to weight gain on a high-fat diet, improved glucose tolerance and insulin sensitivity, and increased energy expenditure (Jiang et al.). Mol. Metab. (2015) 4, 406-417). These positive results may be due to increased secretion of FGF21 and GLP-1 (two hormones that play important roles in regulating energy metabolism) (Geng et al.). Nat Rev Endo (2020) 16, 654-667; Baggio et al. Mol Metab (2021) 46). Therefore, inhibiting SLC6A19 may be an effective way to treat metabolic diseases.

[0006] In humans, loss of function of the SLC6A19 biallelic gene leads to a rare disease called Hartnup disorder, which is mostly asymptomatic in well-nourished patients (Seow et al. Nat. Genet. (2004) 36, 1003-1007. Azmanov et al. Hum. Mutat. (2008) 29, 1217-1221). Because NAA tryptophan is essential for nicotinamide synthesis, patients with Hartnup disorder may experience niacin deficiency and related symptoms, including dermatitis, photosensitivity, and psychosis, but these symptoms are well managed with niacin supplementation (Hashmi et al.). StatPearls (2021)). Similarly, mice with complete SLC6A19 deletion can survive and be fertile (Jiang et al.). Mol. Metab. (2015) 4, 406-417). Therefore, inhibiting SLC6A19 is considered a feasible treatment approach.

[0007] Treatments for these types of diseases / conditions are still needed. Summary of the Invention

[0008] In one respect, this paper provides compounds of formula (I): (I), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 4-10 aryl heteroaryl groups are optionally mediated by one or more R groups. 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 C 1-6 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0009] In some embodiments of the compound of formula (I): (I), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing. m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0010] In one respect, this paper provides compounds of formula (IA): (IA), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 3 R 5 R 6 R 7 R 8 and R 9 As defined elsewhere in this document.

[0011] In one respect, this paper provides compounds of formula (IB): (IB), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 2 R 3 R 5 R 6 R 7 R 9 R 10 And ring A as defined elsewhere in this document.

[0012] In one respect, this paper provides compounds of formula (IC): (IC), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m , p R 3a R 1 R 5 R 6 R 7 R 8 and R 9 As defined elsewhere in this document.

[0013] In one respect, this paper provides compounds of formula (ID): (ID), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m , q , r R 3a R 5 R 6 R 7 R 8 and R 9 As defined elsewhere in this document.

[0014] In one respect, compounds of formula (IE) are provided: (IE), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein R 1 R 3 R 5 R 6 R 7 R 8 and R 9 As defined elsewhere in this document.

[0015] In one respect, this paper provides compounds of formula (IF): (IF), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 5 R 6 R 7 R 8 and R 9 As defined elsewhere in this document.

[0016] In one respect, this paper provides compounds of formula (IG): (IG), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 4 R 5 R 6 R 7 R 8 and R 9 As defined elsewhere in this document.

[0017] In one respect, this paper provides compounds of formula (IH): (IH), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m , s , t R 3 R 5 R 6 R 7 R 9 R 8a Y 1 Y 2 Y 3 Y 4 and Y 5 As defined elsewhere in this document.

[0018] In one aspect, this document provides pharmaceutical compositions comprising (i) a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and (ii) one or more pharmaceutically acceptable excipients.

[0019] In one aspect, this document provides a method for regulating SLC6A19 in cells, the method comprising exposing cells to (i) an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0020] In one aspect, this document provides a method for inhibiting SLC6A19 in cells, the method comprising exposing cells to (i) an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0021] In one aspect, this document provides a method for regulating SLC6A19 in the cells of an individual in need, the method comprising administering to the individual an effective amount of (i) a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0022] In one aspect, this document provides a method for treating an individual in need of an SLC6A19-mediated disease, condition, or disorder, the method comprising administering to the individual an effective amount of (i) a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0023] In another variation, this document provides a method for treating an individual in need of SLC6A19-mediated disease, condition, or disorder, the method comprising administering to the individual (i) a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. In some embodiments, a therapeutically effective amount of the compound or pharmaceutical composition is administered.

[0024] In one aspect, this document provides a kit comprising: (i) an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients; and (ii) instructions for use in treating an SLC6A19-mediated disease, condition, or disorder in an individual in need.

[0025] In another variation, this document provides a kit comprising: (i) a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients; and (ii) instructions for use in treating an SLC6A19-mediated disease, condition, or ailment in an individual of need. In some embodiments, the kit comprises a therapeutically effective amount of the compound or pharmaceutical composition.

[0026] In some respects, this document provides methods for preparing compounds of formula (I) or any embodiment or variation thereof (e.g., compounds of formula (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4), (I-A5), (I-A6), (IB), (IC), (I-C1), (I-C2), (I-C3), (I-C4), (ID), (I-D1), (IE), (IF), (IG) or (IH)), or their stereoisomers or tautomers or pharmaceutically acceptable salts thereof. Detailed Implementation

[0027] "Individual" refers to a mammal and includes both humans and non-human mammals. Examples of individuals include (but are not limited to) mice, rats, hamsters, guinea pigs, rabbits, cats, dogs, goats, sheep, cattle, and humans. In some implementations, an individual refers to a human.

[0028] As used in this article, the "about" parameter or value includes and describes the parameter or value itself. For example, "about X" includes and describes X itself.

[0029] "Treatment" is a means of achieving a beneficial or desired outcome (including clinical outcomes). A beneficial or desired outcome may include one or more of the following: reducing one or more symptoms arising from a disease or condition; reducing the severity of a disease or condition; slowing or preventing the development of one or more symptoms associated with a disease or condition (e.g., stabilizing a disease or condition, preventing or delaying the worsening or progression of a disease or condition); and alleviating a disease, for example, by causing the remission of clinical symptoms (e.g., improving the disease state, enhancing the effect of another medication, delaying the progression of the disease, improving quality of life, and / or prolonging survival).

[0030] As used herein, “delay” the progression of a disease or condition means to postpone, impede, slow, delay, stabilize, and / or postpone the progression of the disease or condition. The length of this delay can vary depending on the individual’s medical history and / or treatment. It will be apparent to those skilled in the art that a sufficient or significant delay can effectively cover prevention, as the individual will not exhibit symptoms of the disease or condition.

[0031] As used herein, the terms "therapeutic effective amount" or "effective amount" mean the amount of the disclosed compound or its pharmaceutical salt sufficient to achieve therapeutic effect when administered to an individual. As understood in the art, an "effective amount" can be one or more doses, for example, a single dose or multiple doses may be required to achieve the desired therapeutic endpoint. An effective amount may be considered in the context of administration of one or more therapeutic agents, and a single agent may be considered to be administered in an effective amount if the desired or beneficial result can be achieved or has been achieved in combination with one or more other agents.

[0032] As used herein, “unit dosage form” refers to a physically discrete unit suitable as a unit dose, each unit containing a predetermined amount of active ingredient or compound in a pharmaceutically acceptable carrier.

[0033] As used herein, “pharmaceutically acceptable” means a material that is biologically or otherwise desirable, such as a material that can be incorporated into a pharmaceutical composition administered to an individual without causing significant undesirable biological effects.

[0034] As used herein, the term "alkyl" refers to an unbranched or branched saturated monovalent hydrocarbon chain. As used herein, alkyl groups have 1-20 carbon atoms (i.e., C64-C64).1-20 Alkyl groups), 1-16 carbons (i.e., C164-C165) 1-16 Alkyl groups), 1-12 carbons (i.e., C46) 1-12 Alkyl groups), 1-10 carbons (i.e., C46) 1-10 Alkyl groups), 1-8 carbons (i.e., C46) 1-8 Alkyl groups), 1-6 carbons (i.e., C16-C65) 1-6 Alkyl groups), 1-4 carbons (i.e., C46) 1-4 Alkyl groups or 1-3 carbons (i.e., C46) 1-3 Alkyl groups. Examples of alkyl groups include (but are not limited to) methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and 3-methylpentyl. When an alkyl residue having a specific number of carbon atoms is named by its chemical name or molecular formula, all positional isomers having that number of carbon atoms may be covered—for example, "butyl" includes n-butyl, sec-butyl, isobutyl, and tert-butyl; and "propyl" includes n-propyl and isopropyl. Certain commonly used alternative names may be used, and these names will be understood by those skilled in the art. For example, a divalent group such as a divalent "alkyl" may be called an "alkylene".

[0035] As used herein, the term "alkenyl" refers to a branched or unbranched monovalent hydrocarbon chain comprising at least one carbon-carbon double bond. As used herein, alkenyl groups have 2–20 carbons (i.e., C60 ... 2-20 alkenyl), 2-16 carbons (i.e., C 2-16 alkenyl), 2-12 carbons (i.e., C10), 2-12 alkenyl), 2-10 carbons (i.e., C10), 2-10 alkenyl), 2-8 carbons (i.e., C10), 2-8 alkenyl), 2-6 carbons (i.e., C10), 2-6 alkenyl), 2-4 carbons (i.e., C10), 2-4 Alkenyl) or 2-3 carbons (i.e., C) 2-3 Alkenyl groups. Examples of alkenyl groups include (but are not limited to) vinyl, propenyl, propenyl-1,2-butadienyl, and 1,3-butadienyl. When an alkenyl residue having a specific number of carbon atoms is named by its chemical name or molecular formula, all positional isomers having that number of carbon atoms can be covered—for example, "propenyl" includes both propenyl and propenyl-2-olefin. Certain commonly used alternative names may be used, and these names will be understood by those skilled in the art. For example, a divalent group such as a divalent "alkenyl" may be called an "alkenylene".

[0036] As used herein, the term "alkynyl" refers to a branched or unbranched monovalent hydrocarbon chain comprising at least one carbon-carbon triple bond. As used herein, an alkynyl group has 2–20 carbons (i.e., C60 ... 2-20 alkynyl group), 2-16 carbons (i.e., C16-C26)2-16 alkynyl group), 2-12 carbons (i.e., C12-C22) 2-12 alkynyl group), 2-10 carbons (i.e., C10-C20) 2-10 alkynyl group), 2-8 carbons (i.e., C10-C20) 2-8 alkynyl group), 2-6 carbons (i.e., C10-C20) 2-6 alkynyl group), 2-4 carbons (i.e., C10-C20) 2-4 (alkynyl group) or 2-3 carbons (i.e., C10) 2-3 (Alynyl). Examples of alkynyl groups include (but are not limited to) ethynyl, propynyl-1-propynyl, propynyl-2-propynyl, butynyl-1-propynyl, butynyl-2-propynyl, and butynyl-3-propynyl. When an alkynyl residue with a specific number of carbon atoms is named by its chemical name or molecular formula, all positional isomers with that number of carbon atoms can be covered—for example, "propynyl" includes both propynyl-1-propynyl and propynyl-2-propynyl. Certain commonly used alternative names may be used, and these names will be understood by those skilled in the art. For example, a divalent group such as a divalent "alkynyl" may be called an "alkynylene".

[0037] As used herein, the term "alkoxy" refers to the -O-alkyl moiety. Examples of alkoxy groups include (but are not limited to) methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexyloxy, and 1,2-dimethylbutoxy.

[0038] As used herein, the term "aryl" refers to a fully unsaturated carbocyclic moiety. The term "aryl" encompasses both monocyclic and polycyclic fused-ring moieties. As used herein, aryl encompasses, for example, 6 to 20 cyclic carbon atoms (i.e., C646-C646). 6-20 aryl), 6 to 16 ring carbon atoms (i.e., C 6-16 aryl), 6 to 12 ring carbon atoms (i.e., C 6-12 aryl group or 6 to 10 ring carbon atoms (i.e., C46, ​​C56, C6 ... 6-10 The aryl ring moiety. Examples of aryl moiety include (but are not limited to) phenyl, naphthyl, fluorenyl, and anthracene.

[0039] As used herein, the term "cycloalkyl" refers to a saturated or partially unsaturated carbocyclic moiety. The term "cycloalkyl" encompasses both monocyclic and polycyclic moietyes, wherein the polycyclic moiety may be fused, branched, or spirocyclic. A cycloalkyl group comprises a cycloalkenyl group, wherein the cyclic moiety includes at least one cyclic double bond. A cycloalkyl group comprises any polycyclic carbocyclic moiety containing at least one non-aromatic ring, regardless of its connection point with other parts of the molecule. As used herein, a cycloalkyl group comprises, for example, 3 to 20 cyclic carbon atoms (i.e., C64 ... 3-20 cycloalkyl groups), 3 to 16 cyclic carbon atoms (i.e., C164 ...64646646466646666666666666666666666666666 3-16 cycloalkyl groups), 3 to 12 cyclic carbon atoms (i.e., C12+ ... 3-12 cycloalkyl groups), 3 to 10 cyclic carbon atoms (i.e., C14 and C24). 3-10cycloalkyl groups), 3 to 8 cyclic carbon atoms (i.e., C1646-C ... 3-8 cycloalkyl groups), 3 to 6 cyclic carbon atoms (i.e., C164-C ... 3-6 cycloalkyl groups or 3 to 5 cyclic carbon atoms (i.e., C1646-C ... 3-5 The cycloalkyl ring. Monocyclic cycloalkyl ring moiety includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic groups include, for example, bicyclic [2.2.1]heptyl, bicyclic [2.2.2]octyl, adamantyl, norbornyl, naphthyl, 7,7-dimethyl-bicyclic [2.2.1]heptyl, etc. In addition, cycloalkyl also includes spirocycloalkyl ring moiety (e.g., spiro[2.5]octyl, spiro[4.5]decyl, or spiro[5.5]undecyl).

[0040] As used herein, the term "halogen" refers to an atom occupying Group VIIA of the periodic table and including fluorine (fluorinyl), chlorine (chloroyl), bromine (bromoyl), and iodine (iodoyl). Additionally, terms such as "halogenated alkyl" refer to both monohalogenated and polyhalogenated alkyl groups. For example, the term "C1-C4 haloalkyl" refers to trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, difluoromethyl, etc.

[0041] As used herein, the term "heteroaryl" refers to an aromatic (fully unsaturated) ring moiety comprising one or more ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heteroaryl" includes both monocyclic and polycyclic fused-ring moieties. As used herein, heteroaryls include, for example, 5 to 20 ring atoms (i.e., 5-20-membered heteroaryls), 5 to 16 ring atoms (i.e., 5-16-membered heteroaryls), 5 to 12 ring atoms (i.e., 5-12-membered heteroaryls), 5 to 10 ring atoms (i.e., 5-10-membered heteroaryls), 5 to 8 ring atoms (i.e., 5-8-membered heteroaryls), or 5 to 6 ring atoms (i.e., 5-6-membered heteroaryls). Any monocyclic or polycyclic aromatic ring moiety comprising one or more ring heteroatoms is considered a heteroaryl, regardless of its connection points to other parts of the molecule (i.e., the heteroaryl moiety may be connected to other parts of the molecule through any ring carbon or any ring heteroatom of the heteroaryl moiety). Examples of heteroaryl groups include (but are not limited to) acridinel, benzimidazolyl, benzothiazolyl, benzoindolyl, benzofuranyl, benzothiazolyl, benzothiadiazolyl, benzonaphthofuranyl, benzooxazolyl, benzothienyl (benzothienyl, benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[l,2-a]pyridyl, carbazole, cenolinyl, dibenzofuranyl, dibenzothienyl, furanyl, and isothiazolyl. Imidazolyl, indazole, indolyl, indazole, isoindolyl, isoquinolinyl, isoxazolyl, naphridinyl, oxadiazolyl, oxazolyl, 1-oxopyridinyl, 1-oxopyrimidinyl, 1-oxopyrazinyl, 1-oxopyridazinyl, phenazinyl, phthalazinyl, pteridinyl, purine, pyrroleyl, pyrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxolinyl, quinolinyl, quininecycloyl, isoquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, and triazinyl. Examples of fused heteroaryl rings include (but are not limited to) benzo[d]thiazolyl, quinolinyl, isoquinolinyl, benzo[b]thiophene, indazole, benzo[d]imidazolyl, pyrazolo[1,5-a]pyridyl, and imidazo[1,5-a]pyridyl, wherein the heteroaryl group may be linked via any ring of the fused system.

[0042] As used herein, the term "heterocyclic group" refers to a saturated or partially unsaturated cyclic moiety comprising one or more cyclic heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The term "heterocyclic group" includes both monocyclic and polycyclic moieties, wherein the polycyclic moieties can be fused, bridged, or spirocyclic. Any non-aromatic monocyclic or polycyclic moieties comprising at least one cyclic heteroatom are considered heterocyclic groups, regardless of their connection points to other parts of the molecule (i.e., the heterocyclic group moieties can be connected to other parts of the molecule through any cyclic carbon or any cyclic heteroatom of the heterocyclic group moieties). Furthermore, the term "heterocyclic group" is intended to cover any polycyclic moieties comprising at least one cyclic heteroatom, wherein the polycyclic moieties include at least one non-aromatic ring, regardless of their connection points to other parts of the molecule. As used herein, heterocyclic groups include, for example, 3 to 20 ring atoms (i.e., 3-20 membered heterocyclic groups), 3 to 16 ring atoms (i.e., 3-16 membered heterocyclic groups), 3 to 12 ring atoms (i.e., 3-12 membered heterocyclic groups), 3 to 10 ring atoms (i.e., 3-10 membered heterocyclic groups), 3 to 8 ring atoms (i.e., 3-8 membered heterocyclic groups), 3 to 6 ring atoms (i.e., 3-6 membered heterocyclic groups), 3 to 5 ring atoms (i.e., 3-5 membered heterocyclic groups), 5 to 8 ring atoms (i.e., 5-8 membered heterocyclic groups), or 5 to 6 ring atoms (i.e., 5-6 membered heterocyclic groups). Examples of heterocyclic groups include, for example, azirrobutyl, azirrophenyl, benzo[b][l,4]dioxetyl, 1,4-benzodioxetyl, benzopyranyl, benzodioxetyl, benzopyranone, benzofuranone, dioxetyl, dihydropyranyl, hydrogenpyranyl, thiophenyl[l,3]dithiaalkyl, decahydroisoquinolinyl, furanone, imidazolinyl, imidazolinyl, indololinyl, indazinyl, isoindolyl Linyl, isothiazolyl, isoxazolyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolyl, ethylene oxide, oxacyclobutyl, phenothiazinyl, phenotoxazinyl, piperidinyl, piperazinyl, 4-piperidinoneyl, pyrrolidinyl, pyrazolyl, quininecycloyl, thiazolyl, tetrahydrofuranyl, tetrahydropyranyl, trithiaalkyl, tetrahydroquinolinyl, thiophenyl (i.e., thienyl), thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. Examples of spiroheterocyclic rings include (but are not limited to) bicyclic and tricyclic systems, such as oxabicyclo[2.2.2]octyl, 2-oxa-7-azaspiro[3.5]nonyl, 2-oxa-6-azaspiro[3.4]octyl, and 6-oxa-1-azaspiro[3.3]heptyl. Examples of fused heterocyclic rings include (but are not limited to) 1,2,3,4-tetrahydroisoquinolinyl, 4,5,6,7-tetrahydrothieno[2,3-c]pyridyl, indololinyl, and isoindololinyl, wherein the heterocyclic group may be linked via any ring of the fused system.

[0043] As used in this article, the term "oxo group" refers to the =O part.

[0044] As used herein, the terms “optional” and “optionally” mean that the event or situation described below may or may not occur, and that the description includes both the scenario in which the event or situation occurs and the scenario in which the event or situation does not occur. Thus, the term “optionally substituted” implies that any one or more (e.g., 1, 2, 1 to 5, 1 to 3, 1 to 2, etc.) hydrogen atoms on a specified atom or part or group may or may not be substituted by atoms or parts or groups other than hydrogen. By way of example and not limitation, the phrase “methyl group optionally substituted with one or more chlorines” encompasses the -CH3, -CH2Cl, -CHCl2, and -CCl3 moieties.

[0045] It should be understood that the aspects and implementation schemes described herein as "including" include implementation schemes that are "composed of" and "substantially composed of".

[0046] As used herein, the term "pharmaceutically acceptable salt" for a given compound refers to a salt that retains the biological efficacy and properties of the given compound and is biologically or otherwise desirable. "Pharmaceutically acceptable salt" includes, for example, salts formed with inorganic acids and salts formed with organic acids. Furthermore, if the compound described herein is obtained as an acid addition salt, the free base can be obtained by alkalizing a solution of the acidic salt. Conversely, if the product is a free base, an addition salt, and especially a pharmaceutically acceptable addition salt, it can be produced according to the conventional procedure for preparing acid addition salts from basic compounds by dissolving the free base in a suitable organic solvent and treating the solution with acid. See, for example, [link to relevant documentation]. Handbook of Pharmaceutical Salts Properties, Selection, and Use,The International Union of Pure and Applied Chemistry, John Wiley & Sons (2008), is incorporated herein by reference in its entirety. Those skilled in the art will recognize the various synthetic methods that can be used to prepare non-toxic, pharmaceutically acceptable addition salts. Pharmaceutically acceptable acid addition salts can be prepared from inorganic or organic acids. Salts derived from inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc. Salts derived from organic acids include, for example, acetates, propionates, gluconates, glycolates, pyruvates, oxalates, malates, malonates, succinates, maleates, fumarates, tartrates, citrates, benzoates, cinnamates, amygdalinates, methanesulfonates, ethanesulfonates, p-toluenesulfonates, salicylates, trifluoroacetates, etc. Similarly, pharmaceutically acceptable base addition salts can be prepared from inorganic or organic bases. Salts derived from inorganic bases include (by way of example only) sodium, potassium, lithium, aluminum, ammonium, calcium, and magnesium salts. Salts derived from organic bases include (but are not limited to) salts of primary, secondary, and tertiary amines. Specific examples of suitable amines include (by way of example only) isopropylamine, trimethylamine, diethylamine, tri(isopropyl)amine, tri(n-propyl)amine, ethanolamine, 2-dimethylaminoethanol, piperazine, piperidine, morpholine, N-ethylpiperidine, etc.

[0047] Isotopically labeled forms of the compounds illustrated herein can be prepared. The isotopically labeled compounds have the structures illustrated herein, except that one or more atoms are replaced by atoms having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, for example, […]. 2 H, 3 H, 11 C 13 C 14 C 13 N、 15 N、 15 O、 17 O、 18 O、 31 P, 32 P, 35 S, 18 F, 36 Cl、 123 I and 125 I. In some embodiments, a compound of formula (I) is provided, wherein one or more hydrogen atoms are replaced by deuterium or tritium.

[0048] Some of the compounds described herein can exist as tautomers. The tautomers exist in equilibrium. For example, compounds containing amides can exist in equilibrium with imine tautomers. Regardless of the type of tautomer shown, and regardless of the equilibrium nature between the tautomers, those skilled in the art will understand that the compounds disclosed herein include both amides and imine tautomers. Therefore, for example, it should be understood that compounds containing amides include their imine tautomers. Similarly, it should be understood that compounds containing imines include their amide tautomers.

[0049] This article also provides prodrugs or pharmaceutically acceptable salts of the compounds illustrated herein. A prodrug is a compound that can be administered to an individual and release, in vivo, the parent drug compound illustrated herein. It should be understood that prodrugs can be prepared by modifying functional groups on the parent drug compound in a manner that causes the modification to cleave in vitro or in vivo to release the parent drug compound. See, for example, Rautio, J., Kumpulainen, H., Heimbach, T. et al., Prodrugs: design and clinical applications. Nat Rev Drug Discov 7, 255-270 (2008), which is incorporated herein by reference in its entirety.

[0050] The compounds disclosed herein, or pharmaceutically acceptable salts thereof, may contain an asymmetric center, thereby producing enantiomers, diastereomers, and other stereoisomers, which can be defined according to the absolute stereochemical definition (…). R )-or( S (or, for amino acids, defined as (D)- or (L)-). This disclosure is intended to include all such possible isomers as well as their racemic and optically pure forms, and mixtures thereof in any proportion. Optically active (+) and (-), ( R )-and( S (D)- and (L)- isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques such as chromatography and / or fractional crystallization. Conventional techniques for preparing / separating individual enantiomers include chiral synthesis from suitable optically pure precursors, or resolution of racemic mixtures (or racemic mixtures of salts or derivatives) using, for example, chiral high-performance liquid chromatography (HPLC) and chiral supercritical fluid chromatography (SFC). When the compounds described herein contain olefinic double bonds or other geometrically asymmetric centers, this disclosure is intended to include E and Z geometrical isomers unless otherwise stated. Similarly, cis- and trans- are used in their conventional sense to describe relative spatial relationships.

[0051] "Stereoisomers" are compounds with different three-dimensional structures formed by identical atoms bonded by the same bonds but not interchangeable. This disclosure covers various stereoisomers and mixtures thereof, and includes "enantiomers," which are two stereoisomers whose structures are non-overlapping mirror images of each other. "Diadiaomers" are stereoisomers having at least two asymmetric atoms but not being mirror images of each other.

[0052] When a given structure with two stereocenters exists in enantiomeric and / or diastereomeric forms, the wedge-shaped and / or dashed bonds indicate that the composition is primarily composed of a single isomer with known relative and absolute stereochemistry (e.g., )constitute.

[0053] When a given structure has enantiomeric and / or diastereomeric forms, the flat key (key) indicates that all stereoisomeric forms of the drawn structure can exist, for example... .

[0054] When a given structure exists in enantiomeric and / or diastereomeric forms, the composition comprises at least 90% by weight, and an asterisk indicates a single enantiomer or diastereomer having an unknown relative or absolute stereochemistry, for example... .

[0055] When a given structure has the potential for both cis and trans configurations and its composition comprises at least 90% by weight, an asterisk (*) indicates a single unknown cis or trans configuration, for example... .

[0056] compound In one respect, this paper provides compounds of formula (I): (I), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 C1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 4-10 aryl heteroaryl groups are optionally mediated by one or more R groups. 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 C 1-6 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R3x C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0057] In some embodiments of the compound of formula (I): (I), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing. m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0058] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, m Integers between 1 and 2; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, -N(R) 4 2. 4-6 membered heteroaryl or 4-6 membered heterocyclic group, wherein R 3 C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or 4-6 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 The 4-6 aryl heteroaryl group is optionally mediated by one or more R 3x replace; The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-3 Alkyl, 4-6 membered heteroaryl, 4-6 membered heterocyclic or C 3-6 cycloalkyl, wherein R 4 C 1-3 Alkyl or C 3-6 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or C 1-3 Halogenated alkyl groups, wherein R 5 and R 7 C 1-3 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 C 1-3 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-6 cycloalkyl, C 6-10 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-6 cycloalkyl, C 6-10 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 3a C 1-3 Alkyl, C 1-3 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3breplace, R 4a C 1-3 Alkyl, C 1-3 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-3 Alkyl, C 1-3 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 3x For OH, -CN, halogen, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 3x C 1-3 Alkyl, C 1-3 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-3 Alkyl or C 1-3 Alkyl group.

[0059] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, m Integers between 1 and 2; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R3 C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 cycloalkyl, -N(R) 4 )2 or 4-6 membered heterocyclic groups, in which R 3 C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 cycloalkyl or 4-6 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 3-6 cycloalkyl, wherein R 4 C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 3-6 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-6 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or C 1-3 Halogenated alkyl groups, wherein R 5 and R 7 C 1-3 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-6 cycloalkyl, C 6-10 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-6 cycloalkyl, C 6-10 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups, -OC 1-3 Halogenated alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-3 Alkyl, C 1-3 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-3 Alkyl, C 1-3 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-3 Alkyl, C 1-3 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-3 Alkyl or C 1-3 Alkyl group.

[0060] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, (I), Or a pharmaceutically acceptable salt of its stereoisomers, tautomers, or any of the foregoing. m Integers from 1 to 4; R1 It is -NH-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 4-10 aryl heteroaryl groups are optionally mediated by one or more R groups. 3x replace; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 C 1-6 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0061] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, m Integers from 1 to 4; R 1 It is -NH-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 It is a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group, wherein R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3a R 4a and R 8a Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0062] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, m Integers from 1 to 4; R 1 It is -NH-; R 2 For H; R 3 C 1-6 Alkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently H or C 1-6 alkyl, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl or C 1-6 Alkoxy or C 1-6 Halogenated alkyl groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8It is a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group, wherein R 8 The 3-10 heterocyclic or 5-10 heteroaryl group is optionally mediated by one or more R groups. 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl)2, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D or a halogen group.

[0063] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, m Integers from 1 to 4; R1 It is -NH-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0064] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, m Integers between 1 and 2; R 1 It is -NH-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 C 1-6 Alkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 4-10 aryl heteroaryl groups are optionally mediated by one or more R groups. 3x replace The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl or 4-10 membered heterocyclic group; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl or C 1-6 Alkoxy or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 C 1-6 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8 It is a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group, wherein R 8 The 3-10 heterocyclic or 5-10 heteroaryl group is optionally mediated by one or more R groups. 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 3x C 1-6 Alkyl; and R 3b R 4b and R 8b Each can be independently a D, -OH, or a halogen group.

[0065] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, m Integers between 1 and 2; R 1 It is -NH-; R 2 For H; R 3 C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 cycloalkyl, -N(R)4 )2 or 4-6 membered heterocyclic groups, in which R 3 C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 cycloalkyl or 4-6 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 3-6 cycloalkyl, wherein R 4 C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 3-6 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-6 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or C 1-3 Halogenated alkyl groups, wherein R 5 and R 7 C 1-3 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-6 cycloalkyl, C 6-10 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-6 cycloalkyl, C 6-10 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0066] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, m Integers from 1 to 4; R 1 It is -NH-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4)2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 It is a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group, wherein R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3a R 4a and R 8a Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0067] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, m Integers from 1 to 4; R 1 It is -NH-; R 2 For H; R 3 C 1-6 Alkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently H or C 1-6 alkyl, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl or C 1-6 Alkoxy or C 1-6 Halogenated alkyl groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8 It is a 3-10 membered heterocyclic group or a 5-10 membered heteroaryl group, wherein R 8 The 3-10 heterocyclic or 5-10 heteroaryl group is optionally mediated by one or more R groups. 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl)2, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or -OC3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3a R 4a and R 8a Each is independently a D or a halogen group.

[0068] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0069] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , and In some implementation schemes, by The representatives are selected from the following groups: and In some implementation schemes, by The representatives are selected from the following groups: , , , , , , and .

[0070] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , , , , , and .

[0071] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: and .

[0072] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , , , , , , , , , , and .

[0073] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representative part is .

[0074] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , , and .

[0075] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representative part is .

[0076] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , and .

[0077] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , and .

[0078] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representative part is .

[0079] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , , , , , , , , and .

[0080] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 , , , , , , , , , , , , , , , , , , , , , , and In some implementation schemes, by The representatives are selected from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0081] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0082] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0083] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0084] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representatives are selected from the following groups: , , , , , , , and In some implementation schemes, by The representatives are selected from the following groups: , , , , , , , , , and .

[0085] In some embodiments of the compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, a pharmaceutically acceptable salt thereof, by The representative part is .

[0086] In some embodiments of a compound of formula (I) or its stereoisomers or tautomers or any of the foregoing, R 1 It can be -NH-, -O-, or -S-. In some implementations, R 1 For -O-. In some implementations, R1 For -S-. In some implementations, R 1 It is -NH-.

[0087] In one respect, this article provides compounds of formula (I), such as compounds of formula (IA): (IA), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 3 R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I).

[0088] In some embodiments of compounds of formula (I) or (IA), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, m It is an integer between 1 and 4. In some implementations, m It is an integer between 1 and 2. In some implementations, m The value is 1. In some implementations, m The value is 2. In some implementations, m The value is 3. In some implementation schemes, m The value is 4.

[0089] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 4-10 aryl heteroaryl groups are optionally mediated by one or more R groups. 3x Replacement, subject to the condition that R 3 When R is a 4-10 quinone heteroaryl group, 1 For -NH-. In some implementations, R 3 C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, -N(R)4 )2, 4-6 membered heteroaryl or 4-6 membered heterocyclic group, wherein R 3 C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or 4-6 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 The 4-6 aryl heteroaryl group is optionally mediated by one or more R 3x Replacement, subject to the condition that R 3 When R is a 4-6 member heteroaryl group, 1 It is -NH-.

[0090] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, where R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replacement. In some implementations, R 3 C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 cycloalkyl, -N(R) 4 )2 or 4-6 membered heterocyclic groups, where R 3 C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 cycloalkyl or 4-6 membered heterocyclic groups optionally via one or more R 3a Replacement. In some implementations, R 3 C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 cycloalkyl, -N(R) 4 )2 or 4-6 membered heterocyclic groups.

[0091] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 For optional access via one or more R 3a Replacement C 1-6 Alkyl group. In some embodiments, R 3 C 1-3Alkyl group. In some embodiments, R 3 It is methyl, ethyl, or isopropyl. In some embodiments, R 3 It is methyl. In some embodiments, R 3 It is ethyl. In some embodiments, R 3 It is isopropyl.

[0092] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 For optional access via one or more R 3a Replacement C 1-6 Alkyl; R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Each time it appears, it is independently -OH, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Replacement C 1-3 Alkyl; R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 3a C 1-3 Alkyl, C 1-3 Alkoxy, 4-6 membered heterocyclic group, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Each time it appears, it is independently of D, -OH, halogen, or C. 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Replacement C 1-3 Alkyl; R 3a -OH, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl) 2, 4-10 heteroaryl, 4-10 heterocyclic or C 3-10 cycloalkyl, wherein R 3a C 1-6 Alkoxy or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and R 3b It is an -OH or halogen group. In some embodiments, R 3 Choose from the following groups: , , , , , , , , , , , , , , , , , , and .

[0093] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 For optional access via one or more R 3a Replacement C1-6 Alkyl; R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Each time it appears, it is independently -OH, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Replacement C 1-3 Alkyl; R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups, -OC 1-3 Halogenated alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heterocyclic groups, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Each time it appears, it is independently of D, -OH, halogen, or C. 1-3 Alkyl or C 1-3Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Replacement C 1-3 Alkyl; and R 3a For -OH. In some implementations, R 3 for .

[0094] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 For optional access via one or more R 3a Replacement C 3-10 cycloalkyl; R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Each time it appears, it is independently -OH, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Replacement C 3-6 cycloalkyl; R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 3a C 1-3 Alkyl, C 1-3 Alkoxy, 4-6 membered heterocyclic group, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Each time it appears, it is independently of D, -OH, halogen, or C. 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Replacement C 3-10 cycloalkyl; R 3a -OH, -CN, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl) 2 or 4-10 heteroaryl, wherein R 3a C 1-6 Alkyl groups are optionally oxidized via one or more R groups. 3b Replace; and R 3b It is a halogenated group. In some implementations, R 3 Choose from the following groups: , , , , , , , , , , , , and .

[0095] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 For optional access via one or more R 3a Replacement C 3-10 cycloalkyl, R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Each time it appears, it is independently -OH, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Replacement C 3-6 cycloalkyl; R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups, -OC 1-3 Halogenated alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heterocyclic groups, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Each time it appears, it is independently of D, -OH, halogen, or C. 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Replacement C 3-6 Cycloalkyl, and R 3a Halogenated or C 1-3 Alkyl group. In some embodiments, R3 For optional via one or more halogen groups or C 1-3 Alkyl-substituted C 3-6 Cycloalkyl. In some embodiments, R 3 For optional passage via one or more C 1-3 Alkyl-substituted cyclopropyl. In some embodiments, R 3 for In some implementations, R 3 For optional access via one or more R 3a Replacement C 3-6 Cycloalkyl, and R 3a It is a halogenated group. In some implementations, R 3 C that is optionally substituted with one or more Br, Cl, I or F 3-6 Cycloalkyl. In some embodiments, R 3 It is a cyclopropyl group optionally substituted with one or more Br, Cl, I, or F. In some embodiments, R 3 for In some implementations, R 3 Choose from the following groups: and In some embodiments of compounds of formula (I) or (IA), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 3 -N(R) 4 )2, and each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace; R 4a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 4a C1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace; and each R 4b Each time it appears, it is independently -OH, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 -N(R) 4 )2, and each R 4 Independently for H and C 1-3 Alkyl, 4-6 membered heteroaryl, 4-6 membered heterocyclic or C 3-6 cycloalkyl, wherein R 4 C 1-3 Alkyl or C 3-6 cycloalkyl groups are optionally cyclic to one or more R 4a Replace; R 4a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 4a C 1-3 Alkyl, C 1-3 Alkoxy, 4-6 membered heterocyclic group, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 4b Replace; and each R 4b Each time it appears, it is independently of D, -OH, halogen, or C. 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 3 -N(R) 4 )2, and each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl groups optionally via one or more R 4aReplace; R 4a Each time it appears, it is independently -OH, -CN, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 Choose from the following groups: , , , , , , , , , , , , , , , , and .

[0096] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 -N(R) 4 )2, and each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 Cycloalkyl. In some embodiments, R 3 -N(R) 4 )2, and each R 4 Independently for H and C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments, R 3 -N(R) 4 )2, and each R 4 Independently H or C 1-3 alkyl.

[0097] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 -N(R) 4 )2, and two R 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 4a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace; and each R 4b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 -N(R) 4 )2, and two R 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-6 membered heterocyclic groups, R 4a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups, -OC 1-3 Halogenated alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heterocyclic groups, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R b Replace; and each R b Each time it appears, it is independently of D, -OH, halogen, or C. 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 3 -N(R) 4 )2, and two R4 Together with the N atom it is attached to, it forms a 4-6 membered heterocyclic group. In some embodiments, R 3 for .

[0098] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 For optional access via one or more R 3a Substituted 4-10 membered heterocyclic groups; R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Substituted 4-6 membered heterocyclic groups, R 3a Independently -OH, oxo group, -CN, halogen group, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 3a C1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Substituted 4-10 membered heterocyclic groups; R 3a Each time it appears, it is independently -OH, -CN, or C. 1-6 Alkyl group. In some embodiments, R 3 Choose from the following groups: , , , , , , , , , , , , , , , , , , , and .

[0099] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 For optional access via one or more R 3a Substituted 4-10 membered heterocyclic groups; R 3a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3a Substituted 4-6 membered heterocyclic groups, R 3a Independently -OH, oxo group, -CN, halogen group, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups, -OC 1-3 Halogenated alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heterocyclic groups, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 3 It is a 4-6 membered heterocyclic group. In some implementations, R 3 It is a 4-6 membered heterocyclic group. In some implementations, R 3 Choose from the following groups: , and .

[0100] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 For optional access via one or more R 3a Replacement C 1-3 Alkoxy; R 3aEach time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 C 1-3 Alkyl group. In some embodiments, R 3 for .

[0101] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 3 For optional access via one or more R 3x Substituted 4-10 heteroaryl groups; R 3x Each time it appears, it is independently -OH, -CN, halogen, or C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3x Substituted 4-6 heteroaryl groups, R 3x Independently -OH, -CN, halogen, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 3x C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 3b Replace; and each R 3b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 3 For optional access via one or more R 3x Substituted 4-10 heteroaryl groups; R 3x It is C independently each time it appears. 1-6 Alkyl group. In some embodiments, R 3 Choose from the following groups: , , , , , , , , , , , , , , , and .

[0102] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Haloalkyl, wherein R 5 and R 7 C 1-6 Each alkyl group is independently and optionally substituted with one or more halogen groups or CN, and R 5 and R 7 C 1-6 Each alkoxy group is optionally substituted with one or more halogen groups independently. In some embodiments, R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or C 1-3 Haloalkyl, wherein R 5 and R 7 C 1-3 Each alkyl group is independently and optionally substituted with one or more halogen groups or CN, and R 5 and R 7 C 1-3 Each alkoxy group is optionally substituted with one or more halogen groups independently. In some embodiments, R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Halogenated alkyl groups, and R 5 and R 7 C 1-3 Each alkoxy group is optionally substituted with one or more halogen groups independently. In some embodiments, R 5 and R 7 Each is independently represented by H. In some implementations, R... 5 and R 7 One of them is H, and R 5 and R 7 The other one is independently a halogen group, -CN, or C. 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Halogenated alkyl groups.

[0103] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Haloalkyl, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted independently with one or more halogen groups or CN. In some embodiments, R 5 and R 7 Each is independently H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or C 1-3 Haloalkyl, wherein R 5 and R 7 C 1-3 Each alkyl group is optionally substituted independently with one or more halogen groups or CN. In some embodiments, R 5 and R 7 Each is independently H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Halogenated alkyl groups. In some embodiments, R 5 and R 7 Each is independently represented by H. In some implementations, R... 5 and R 7 One of them is H, and R 5 and R 7 The other one is independently a halogen group, C 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Halogenated alkyl groups.

[0104] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 6 and R 9 Each is independently an H or a halogen group. In some embodiments, R 6 and R 9 Each is independently H, F, or Cl. In some implementations, R 6 and R 9 Each is independently represented by H. In some implementations, R... 6 and R 9 Each is an independent halogen group. In some implementations, R 6 and R9 Each is independently F or Cl. In some implementations, R 6 and R 9 One of them is H, and R 6 and R 9 The other component is a halogen group. In some implementations, R... 6 and R 9 One of them is H, and R 6 and R 9 The other one is F or Cl.

[0105] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 membered heterocyclic or 5-20 membered heteroaryl, wherein each R 8 Optionally via one or more R 8a Replace; R 8a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 8 C 3-6 cycloalkyl, C 6-12 aryl, 3-6 membered heterocyclic or 5-10 membered heteroaryl, wherein each R 8 Optionally via one or more R 8a Replace; R 8a Independently -OH, oxo group, -CN, halogen group, C 1-3Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3 Alkyl group.

[0106] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 membered heterocyclic or 5-20 membered heteroaryl, wherein each R 8 Optionally via one or more R 8a Replace; R 8a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8bIndependently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 8 C 3-6 cycloalkyl, C 6-12 aryl, 3-6 membered heterocyclic or 5-10 membered heteroaryl, wherein each R 8 Optionally via one or more R 8a Replace; R 8a Independently -OH, oxo group, -CN, halogen group, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups, -OC 1-3 Halogenated alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heterocyclic groups, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Each time it appears, it is independently of D, -OH, halogen, or C. 1-3 Alkyl or C 1-3 Alkyl group.

[0107] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 8 C 3-10 Cycloalkyl. In some embodiments, R 8 For optional access via one or more R 8a Replacement C 3-10 cycloalkyl, R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 8 For optional access via one or more R 8a Replacement C 3-6 cycloalkyl; R 8a Independently -OH, oxo group, -CN, halogen group, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3 Alkyl group.

[0108] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 8 C 3-10 Cycloalkyl. In some embodiments, R 8 For optional access via one or more R 8a Replacement C 3-10 cycloalkyl, R 8a Independently -OH, oxo group, -CN, halogen group, C1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R b Each time it appears, it is independently of D, -OH, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 8 C 3-6 Cycloalkyl.

[0109] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 8 C 6-12 Aryl. In some implementations, R 8 For optional access via one or more R 8a Replacement C 6-12 Aryl, R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8bReplace; and each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 8 For optional access via one or more R 8a Replacement C 6-10 Aryl; R 8a Independently -OH, oxo group, -CN, halogen group, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 8 for .

[0110] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 8 C 6-12 Aryl. In some implementations, R 8 For optional access via one or more R 8a Replacement C 6-12 Aryl, R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R b Each time it appears, it is independently of D, -OH, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 8 C 3-6 Cycloalkyl.

[0111] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 8 It is a 3-10 membered heterocyclic group. In some implementations, R 8 For optional access via one or more R 8a Substituted 3-10 membered heterocyclic groups, R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 8 For optional access via one or more R 8a Substituted 3-10 membered heterocyclic groups, R 8a Independently -OH, oxo group, -CN, halogen group, C1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 8 For optional access via one or more R 8a Substituted 3-10 membered heterocyclic groups, R 8a Independently an oxo group, a halogen group, or a C group 1-6 Alkyl group. In some embodiments, R 8 Choose from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , and .

[0112] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R8 It is a 3-10 membered heterocyclic group. In some implementations, R 8 For optional access via one or more R 8a Substituted 3-10 membered heterocyclic groups; R 8a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Each time it appears, it is independently of D, -OH, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group.

[0113] In some implementation schemes, R 8 It is a 3-6 membered heterocyclic group. In some implementations, R 8 For optional access via one or more R 8a Substituted 3-6 membered heterocyclic groups; R 8a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups, -OC 1-3 Halogenated alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heterocyclic groups, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC3-6 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 8 For optional access via one or more R 8a Substituted 3-10 membered heterocyclic groups; and R 8a It is independently a halogen or C group each time it appears. 1-3 Alkyl group. In some embodiments, R 8 Choose from the following groups: , , , , , , , and In some implementations, R 8 Choose from the following groups: , , , , , , , , , and In some embodiments of compounds of formula (I) or (IA), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 8 It is a 3-10 quinone heteroaryl group. In some implementations, R 8 For optional access via one or more R 8a Substituted 3-10 heteroaryl groups, R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 8 For optional access via one or more R 8a Substituted 3-10 heteroaryl groups; R 8a Independently -OH, oxo group, -CN, halogen group, C 1-3 Alkyl, C 2-4 alkenyl, C 1-3 Alkoxy, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2、-C(O)C 1-3 Alkyl group, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heteroaryl, 4-6 membered heterocyclic, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3 Alkyl group. In some embodiments, R 8 For optional access via one or more R 8a Substituted 3-10 heteroaryl groups, R 8a Independently -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl)2, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl or C1-6 Alkyl groups are optionally oxidized via one or more R groups. 8b Replace; and each R 8b It can be D, -OH, or a halogen group independently. In some embodiments, R 8 Choose from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0114] In some embodiments of a compound of formula (I) or (IA), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, R 8 It is a 5-20 quinone heteroaryl group. In some implementation schemes, R 8 For optional access via one or more R8a Substituted 5-20 heteroaryl groups; R 8a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Each time it appears, it is independently of D, -OH, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 8 For optional access via one or more R 8a Substituted 5-10 heteroaryl groups; R 8a Each time it appears, it is independently -OH, oxo group, -CN, halogen group, or C. 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups, -OC 1-3 Halogenated alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-3 Alkyl), -C(O)N(C 1-3 Alkyl) 2, 4-6 membered heterocyclic groups, C 3-6 cycloalkyl or -OC 3-6 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-6 membered heterocyclic C 3-6 cycloalkyl or -OC 3-6 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Independently D, -OH, halogen, C 1-3 Alkyl or C 1-3Alkyl group. In some embodiments, R 8 For optional access via one or more R 8a Substituted 5-10 heteroaryl groups; R 8a Each time it appears, it is independently -CN, halogen, or C. 1-3 Alkyl, C 1-3 Alkoxy, -C(O)NH2 or C 3-6 cycloalkyl, wherein R 8a C 1-6 Alkyl groups are optionally oxidized via one or more R groups. 8b Replace; and each R 8b It is either a D or a halogen group each time it appears. In some implementations, R... 8 Choose from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and In some implementations, R 8 Choose from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0115] In one respect, this article provides compounds of formula (I) or (IA), such as compounds of formula (I-A1): (I-A1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 3 R 5 R 7 and R 8 As defined for compounds of formula (I).

[0116] In one respect, this article provides compounds of formula (I) or (IA), such as compounds of formula (I-A2): (I-A2), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m, R3, R6, R7 and R8 are as defined for compounds of formula (I).

[0117] In one respect, this article provides compounds of formula (I) or (IA), such as compounds of formula (I-A3): (I-A3), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m, R3, R6, R7 and R8 are as defined for compounds of formula (I).

[0118] In some embodiments of compounds of formula (I) or (IA), such as compounds of formula (I-A3), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 7 H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Haloalkyl, wherein R 7 C 1-6 The alkyl group is optionally substituted with one or more halogen groups or CN; and R 9 It is an H or halogen group. In some embodiments, R 7 H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or C 1-3 Haloalkyl, wherein R 7 C 1-3 The alkyl group is optionally substituted with one or more halogen groups or CN; and R 9 It is an H or halogen group. In some embodiments, R 7 H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Haloalkyl; and R9 It is an H or halogen group. In some embodiments, R 7 For H; and R 9 It is an H or halogen group. In some embodiments, R 7 It is a halogroup; and R 9 It is a halogen group.

[0119] In one respect, this article provides compounds of formula (I) or (IA), such as compounds of formula (I-A4): (I-A4), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 3 R 5 and R 8 As defined for compounds of formula (I).

[0120] In one respect, this article provides compounds of formula (I) or (IA), such as compounds of formula (I-A5): (I-A5), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 3 and R 7 As defined for compounds of formula (I).

[0121] In some embodiments of compounds of formula (I) or (IA), such as compounds of formula (I-A5), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 7 H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Haloalkyl, wherein R 7 C 1-6 The alkyl group is optionally substituted with one or more halogen groups or CN. In some embodiments, R 7 H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or C 1-3 Haloalkyl, wherein R 7 C 1-3 The alkyl group is optionally substituted with one or more halogen groups or CN. In some embodiments, R 7 H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or C 1-3Halogenated alkyl groups. In some embodiments, R 7 Halogenated, C 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Halogenated alkyl groups. In some embodiments, R 7 It is a halogenated group. In some implementations, R 7 For F. In some implementations, R 7 For Cl. In some implementations, R 7 C 1-6 Alkyl group. In some embodiments, R 7 C 1-3 Alkyl group. In some embodiments, R 7 It is methyl. In some embodiments, R 7 It is ethyl. In some embodiments, R 7 It is isopropyl. In some embodiments, R 7 C 1-6 Alkyl group. In some embodiments, R 7 C 1-3 Alkyl group. In some embodiments, R 7 It is methoxylated. In some embodiments, R 7 C 1-6 Halogenated alkyl groups. In some embodiments, R 7 C 1-3 Halogenated alkyl groups. In some embodiments, R 7 It is CF3.

[0122] In one respect, this article provides compounds of formula (I) or (IA), such as compounds of formula (I-A6): (I-A6), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 3 and R 8 As defined for compounds of formula (I).

[0123] In one respect, this article provides compounds of formula (I), such as compounds of formula (IB): (IB), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m、 R 2 R 3 R 5 R 6 R 7 R 9 and R10 As defined for compounds of formula (I); and ring A is optionally mediated by one or more R a Substituted 5-10 membered heteroaryl or 5-10 membered heterocyclic group; each R a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R b Replace; and each R b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group. In some embodiments, R 2 R 3 R 5 R 6 R 7 R 9 and R 10 As defined for compounds of formula (I); and ring A is optionally mediated by one or more R a Replacement C 6-20 Aryl, 5-10 membered heteroaryl or 5-10 membered heterocyclic; each R a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10cycloalkyl, wherein R a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R b Replace; and each R b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkyl group.

[0124] In some embodiments of the (IB) compound or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, ring A is... , , , , , or ;in V 1 V 2 V 3 V 4 V 5 and V 6 Each can be independently -N-, -NH-, -S-, -O-, or -CH-; W 1 W 2 W 3 W 4 and W 5 Each can be independently -N- or -CH-; X 1 X 2 X 3 X 4 and X 5 Each can be independently -N-, -NH-, -S-, -O-, -CH-, or -CH2-; Z 1 Z 2 Z 3 Z 4 and Z 5 Each can be independently -N-, -S-, -O-, -CH-, or -CH2-; v and v 1 Each is an independent integer between 0 and 7; w Integers between 0 and 6; x Integers between 0 and 5; and z and z1 Each is an integer from 0 to 8.

[0125] In some embodiments of the (IB) compound or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, ring A is... , , or ;in V 1 and V 2 Each can be independently -N-, -NH-, -S-, -O-, or -CH-; W 1 W 2 W 3 and W 4 Each can be independently -N- or -CH-; X 1 X 2 X 3 X 4 and X 5 Each can be independently -N-, -NH-, -S-, -O-, -CH-, or -CH2-; Z 1 Z 2 Z 3 and Z 4 Each can be independently -N-, -S-, -O-, or -CH-; v Integers between 0 and 7; w Integers between 0 and 6; x Integers between 0 and 5; and z Integers between 0 and 8.

[0126] In some embodiments of the (IB) compound or its stereoisomers or tautomers or pharmaceutically acceptable salts thereof, ring A is... , , or ;in V 1 and V 2 Each can be independently -N-, -NH-, -S-, -O-, or -CH-; W 1 W 2 W 3 and W 4 Each can be independently -N- or -CH-; X 1 X 2X 3 X 4 and X 5 Each can be independently -N-, -NH-, -S-, -O-, -CH-, or -CH2-; Z 1 Z 2 Z 3 Z 4 and Z 5 Each can be independently -N-, -S-, -O-, -CH-, or -CH2-; v Integers between 0 and 7; w Integers between 0 and 6; x Integers between 0 and 5; and z Integers between 0 and 8.

[0127] In some embodiments of compounds of formula (I), (IA), or (IB), or their stereoisomers or tautomers, the compound is a compound of the following formula: (I-B1) (I-B2) (I-B3) (I-B4) (I-B5) or (I-B6), of which V 1 V 2 V 3 V 4 V 5 and V 6 Each can be independently -N-, -NH-, -S-, -O-, or -CH-; W 1 W 2 W 3 W 4 and W 5 Each can be independently -N- or -CH-; X 1 X 2 X 3 X 4 and X 5 Each can be independently -N-, -NH-, -S-, -O-, -CH-, or -CH2-; Z 1 Z 2 Z 3 Z 4 and Z 5Each can be independently -N-, -S-, -O-, -CH-, or -CH2-; v and v 1 Each is an independent integer between 0 and 7; w Integers between 0 and 6; x Integers between 0 and 5; and z and z 1 Each compound is an integer from 0 to 8. In some embodiments, the compound is a compound of formula (I-B1). In some embodiments, the compound is a compound of formula (I-B2). In some embodiments, the compound is a compound of formula (I-B3). In some embodiments, the compound is a compound of formula (I-B4). In some embodiments, the compound is a compound of formula (I-B5). In some embodiments, the compound is a compound of formula (I-B6).

[0128] In some embodiments of compounds of formula (I), (IA), or (IB), or their stereoisomers or tautomers, the compound is a compound of the following formula: (I-B1) (I-B2) (I-B3) or (I-B4), of which V 1 and V 2 Each can be independently -N-, -NH-, -S-, -O-, or -CH-; W 1 W 2 W 3 and W 4 Each can be independently -N- or -CH-; X 1 X 2 X 3 X 4 and X 5 Each can be independently -N-, -NH-, -S-, -O-, -CH-, or -CH2-; Z 1 Z 2 Z 3 and Z 4 Each can be independently -N-, -S-, -O-, or -CH-; v Integers between 0 and 7; w Integers between 0 and 6; x Integers between 0 and 5; and z The value is an integer between 0 and 8. In some embodiments, the compound is a compound of formula (I-B1). In some embodiments, the compound is a compound of formula (I-B2). In some embodiments, the compound is a compound of formula (I-B3). In some embodiments, the compound is a compound of formula (I-B4).

[0129] In some embodiments of compounds of formula (I), (IA), or (IB), or their stereoisomers or tautomers, the compound is a compound of the following formula: (I-B1-i) (I-B2-i) (I-B3-i) or (I-B4-i), where V 1 and V 2 Each can be independently -N-, -NH-, -S-, -O-, or -CH-; W 1 W 2 W 3 and W 4 Each can be independently -N- or -CH-; X 1 X 2 X 3 X 4 and X 5 Each can be independently -N-, -NH-, -S-, -O-, -CH-, or -CH2-; Z 1 Z 2 Z 3 and Z 4 Each compound is independently -N-, -S-, -O-, or -CH-. In some embodiments, the compound is a compound of formula (I-B1-i). In some embodiments, the compound is a compound of formula (I-B2-i). In some embodiments, the compound is a compound of formula (I-B3-i). In some embodiments, the compound is a compound of formula (I-B4-i).

[0130] In one respect, this article provides compounds of formula (I), such as compounds of formula (IC): (IC), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m , p R 3a R 1R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I); and p Integers between 0 and 5.

[0131] In some embodiments of compounds of formula (I), such as compounds of formula (IC), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, p It can be 0 or 1. In some implementations, p It is 0. In some implementation schemes, p The value is 1.

[0132] In one respect, this article provides compounds of formula (I) or (IC), such as compounds of formula (I-C1): (I-C1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 3a R 1 R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I).

[0133] In some embodiments of compounds of formula (I) or (IC), such as compounds of formula (I-C1), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 1 It is -NH-.

[0134] In one respect, this article provides compounds of formula (I), (IA), or (IC), such as compounds of formula (I-C2): (I-C2), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 3a R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I). In some embodiments of compounds of formula (I), (IA), or (IC), such as compounds of formula (I-C2), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, R 3aHalogenated or C 1-6 Alkyl group. In some embodiments, R 3a Halogenated or C 1-3 Alkyl group. In some embodiments, R 3a C 1-3 Alkyl group. In some embodiments, R 3a For CH3. In some implementations, R 3a It is a halogenated group. In some implementations, R 3a It can be Br, Cl, F, or I. In some implementations, R 3a It is F.

[0135] In some embodiments of compounds of formula (I), (IA), or (IC), such as compounds of formula (I-C2), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, X is -O-, and R 3a C 1-6 Alkyl group. In some embodiments, X is -O-, and R... 3a C 1-3 Alkyl group. In some embodiments, X is -O-, and R... 3a It is a methyl group.

[0136] In one respect, this paper provides compounds of formula (I-C3): (I-C3), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I).

[0137] In one respect, this paper provides compounds of formula (I-C4): (I-C4), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I).

[0138] In one respect, this article provides compounds of formula (I) or (IA), such as compounds of formula (ID): (ID), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m , q , r R 3a R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I); q It is an integer between 1 and 7; and r Integers between 0 and 18.

[0139] In some embodiments of compounds of formula (I), such as compounds of formula (ID), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, q It is an integer from 1 to 3. In some implementations, q The value is 1. In some implementations, q The value is 2. In some implementations, q The value is 3.

[0140] In one respect, this article provides compounds of formula (I), (IA), or (ID), such as compounds of formula (I-D1): (I-D1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m , r R 3a R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I); and r Integers between 0 and 6.

[0141] In one aspect, compounds of formula (I) are provided, such as compounds of formula (IE): (IE), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein R 1 R 3 R 5 R 6 R 7 R 8 and R 9 As defined elsewhere in this document.

[0142] In one respect, this paper provides compounds of formula (IF): (IF), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I).

[0143] In one respect, this paper provides compounds of formula (IG): (IG), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m R 4 R 5 R 6 R 7 R 8 and R 9 As defined for compounds of formula (I).

[0144] In some embodiments of compounds of formula (I), such as compounds of formula (IG), or their stereoisomers or tautomers or pharmaceutically acceptable salts thereof, each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 Cycloalkyl. In some embodiments, each R 4 Independently for H and C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 3-6 Cycloalkyl. In some embodiments, each R 4 Independently H or C 1-3 Alkyl group. In some embodiments, one R 4 For H and another R 4 C 1-3 Alkyl group. In some embodiments, one R 4 For H and another R 4 It is a methyl group.

[0145] In one respect, this paper provides compounds of formula (IH): (IH), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein m , s ,t R 3 R 5 R 6 R 7 R 9 R 8a Y 1 Y 2 Y 3 Y 4 and Y 5 As defined for compounds of formula (I); Y 1 Y 2 Y 3 Y 4 and Y 5 Each can be independently -C-, -CH-, -CH2-, -N-, -NH-, -S-, or -O-; s Integers between 0 and 6; t It is 1 or 2; and Represents a single or double bond. In some implementations of formula (IH), t The value is 1. In some implementations of formula (IH), t For 2. In some embodiments of formula (IH), Y has 1 To Y 5 The ring is aryl or heteroaryl. In some embodiments of formula (IH), it has Y 1 To Y 5 The ring is aryl. In some embodiments of formula (IH), Y has 1 To Y 5 The ring is C6 aryl. In some embodiments of formula (IH), Y has 1 To Y 5 The ring is a heteroaryl group. In some embodiments of formula (IH), it has a Y ring. 1 To Y 5 The ring is a 6-membered heteroaryl group. In some embodiments of formula (IH), Y... 1 To Y 5 The ring is pyridyl or pyrazinyl. In some embodiments of formula (IH), it has Y 1 To Y 5 The ring is pyridinyl. In some embodiments of formula (IH), it has a Y ring. 1 To Y 5 The ring is pyrazinyl.

[0146] In some embodiments of compounds of formula (I), such as compounds of formula (IH), or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, m Integers between 1 and 2; nX is an integer between 0 and 2; X is -O-, -S-, or -C(R) 12a (R) 12b -, -N(H)- or -N(C)- 1-6 alkyl)-; R 3 C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 cycloalkyl, -N(R) 4 )2 or 4-6 membered heterocyclic groups, where each R 3 Optionally via one or more R 3a Replace; each R 4 Independently for H and C 1-3 Alkyl, C 1-3 Halogenated alkyl or C 3-6 cycloalkyl, or two R 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-6 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-3 Alkyl, C 3-6 cycloalkyl or C 1-3 Haloalkyl, wherein R 5 and R 7 C 1-3 Each alkyl group is optionally substituted independently with one or more halogen groups or CN; R 6 and R 9 Each is independently an H or a halo group; R 11a and R 11b Each independently is H or C 1-3 Alkyl, R 11a and R 11b One of them is H or C 1-6 Alkyl, and R 11a and R 11b The other one in R 12a Or R 12b One of them together forms C 3-10 cycloalkyl; R 12a and R 12b Each independently is H or C 1-3 Alkyl, or R 12a and R 12b One of them is H or C 1-3 Alkyl, and R 12a and R 12b The other one in R 11a Or R 11b Together they form C 3-6 cycloalkyl; each R 8a Independently -OH, oxo group, -CN, halogen group, C1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl groups, -OC 1-3 Halogenated alkyl groups, -NH2, -NH(C) 1-3 alkyl), -N(C) 1-3 Alkyl) 2, 4-6 membered heterocyclic groups or C 3-6 cycloalkyl, wherein R a C 1-3 Alkyl, C 1-3 Alkoxy, 4-6 membered heterocyclic group or C 3-6 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and each R 8b Each time it appears, it is independently -OH, halogen, or C. 1-3 Alkyl or C 1-3 Alkoxy; Y 1 Y 2 Y 3 Y 4 and Y 5 Each can be independently -C-, -CH-, -CH2-, -N-, -NH-, -S-, or -O-; s Integers between 0 and 6; t It is 1 or 2; and It represents a single bond or a double bond.

[0147] In some embodiments of compounds of formula (I), such as compounds of formula (IH), or their stereoisomers or tautomers or pharmaceutically acceptable salts thereof, the compound is a compound of the following formula: (IHai) (IHa-ii) (IHa-iii) (IHa-iv) (IHav) or (IHa-vi). In some implementations, t It is 0. In some implementation schemes, t The value is 1.

[0148] In some embodiments of compounds of formula (I), such as compounds of formula (IH), or their stereoisomers or tautomers or pharmaceutically acceptable salts thereof, the compound is a compound of the following formula: (IHbi) (IHb-ii), (IHb-iii) or (IHb-iv), of which q It is an integer between 1 and 7; and r It is an integer between 0 and 18. In some implementations, t It is 0. In some implementation schemes, t The value is 1. In some implementations, t =1, and Y 5 For -C-. In some implementations, t Y is 1 5 For -C-, Y 1 Y 2 Y 3 and Y 4 Any one of them is -N-, -NH-, -S-, or -O- and Y 1 Y 2 Y 3 and Y 4 The other component is independently -C-, -CH-, or -CH2-. In some implementations, t Y is 1 5 For -C-, Y 1 Y 2 Y 3 and Y 4 Any two of them are -N-, -NH-, -S-, or -O- and Y 1 Y 2 Y 3 and Y 4 The other one in each is independently -C-, -CH-, or -CH2-.

[0149] In some embodiments of a compound of formula (I), any variation thereof, or an embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, is selected from Table 1. In some embodiments of a compound of formula (I), any variation thereof, or an embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, is selected from compounds 1-83 of Table 1. In some embodiments of a compound of formula (I), any variation thereof, or an embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, the compound, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, is selected from compounds 1-90 of Table 1.

[0150] Using ChemDraw ®Professional software version 17.1.1.0 or Collaborative Drug Discovery (CDD) CDD Vault 3 Update generates the compound names of all intermediates and compounds included in Table 1.

[0151] A Knime workflow is created to retrieve structures from the internal ChemAxon Compound Registry, generate specification SMILES using the RDKit Canon SMILES node, remove stereochemistry using the ChemAxon / Infocom MolConverter node, and name the structures using the ChemAxon / Infocom Naming node. The following indicates the versions and extensions of the Knime Analytics Platform utilized in the workflow: Knime Analytics Platform 4.2.2 RDKit Knime Integration 4.0.1.v 202006261025 (This extension includes the RDKit CanonSMILES node) ChemAxon / Infocom Marvin Extensions Feature 4.3.0v202100 (This extension includes the MolConverter node) ChemAxon / Infocom JChem Extensions Feature 4.3.0v202100 (This extension includes namenodes) Table 1

[0152] In some embodiments, this document provides a compound of formula (I), any variation thereof or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: N-((5-chloro-6-(6-methoxypyridin-3-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(1H-pyrrolo[3,2-b]pyridin-2-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5'-chloro-1H,1'H-[2,6'-biindole]-2'-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(5-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-methoxypyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(6-methoxypyridazin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(2-methoxypyrimidin-5-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-(dimethylamino)pyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(5-(difluoromethoxy)pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-(trifluoromethoxy)pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(pyrazolo[1,5-a]pyridin-5-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(pyrazolo[1,5-a]pyridin-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-fluoro-6-(6-methoxypyridazin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-fluoro-6-(5-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)-2-hydroxypropionamide; N-((5-fluoro-6-(6-methoxypyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)oxetane-3-carboxamide; N-((5-fluoro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)tetrahydrofuran-2-carboxamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)tetrahydrofuran-3-carboxamide; N-((5-chloro-6-(5-cyclopropylpyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)oxetane-2-carboxamide; N-((5-chloro-6-(3-fluoropyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(1-methyl-1H-pyrazol-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(isoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(4-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methylpyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-cyclopropylpyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((6-(5-methoxypyrazin-2-yl)-5-(trifluoromethyl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(2-methoxypyridin-4-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-methoxy-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methylthiazo-2-yl)-1H-indol-2-yl)methyl)acetamide; 5-(2-(acetamidomethyl)-5-chloro-1H-indol-6-yl)pyrazin-2-carboxamide; N-((5-chloro-6-(imidazo[1,2-a]pyrazin-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-fluoroisoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(5-chlorothiazo-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(4-fluoroisoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(3-methyl-1H-pyrazol-1-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(imidazo[2,1-b]thiazo-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(3-cyclopropyl-1H-pyrazol-1-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxy-6-methylpyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(1-methyl-1H-benzo[d]imidazol-5-yl)-1H-indol-2-yl)methyl)acetamide; N-((5'-chloro-1-methyl-1H,1'H-[5,6'-biindole]-2'-yl)methyl)acetamide; N-((5-chloro-6-(2,3-dihydrobenzo[b][1,4]dioxane-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(2,2-difluorobenzo[d][1,3]dioxacyclopenten-5-yl)-1H-indol-2-yl)methyl)acetamide; N-((6-(benzo[d][1,3]dioxacyclopenten-5-yl)-5-chloro-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(imidazo[1,2-a]pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(1-cyclopropyl-1H-imidazol-4-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-ethyl-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-methoxypyrimidin-4-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-(dimethylamino)pyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-cyclopropoxypyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-(trifluoromethoxy)pyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-(difluoromethoxy)pyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-(difluoromethoxy)pyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((6-(5-methoxypyrazin-2-yl)-5-methyl-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(imidazo[1,2-a]pyrimidin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrimidin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-(methoxy-d3)pyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-cyanopyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-chloroisoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(1-oxo-isoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)propionamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)-1-fluorocyclopropane-1-carboxamide; 1-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)-3-methylurea; N-((6-(benzo[b]thiophen-6-yl)-5-chloro-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-7-fluoro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)azacyclobutane-1-carboxamide; N-((5-chloro-6-(2-methylthiazo-4-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(pyridazin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-methylpyridazin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-fluoro-5-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-{[6-(3a,5-diaza-2-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,7-diaza-5-indanyl)-2-indolyl]methyl}acetamide; N-{[6-(1,4,7a-triaza-6-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-({5-chloro-6-[6-(ethylamino)-3-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(2,4-diaza-2H-inden-2-yl)-2-indolyl]methyl}trifluoromethoxyacetamide; N-{[5-chloro-6-(1-methyl-1H-1,2,3-triazol-4-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-fluoro-2-isoindolinyl)-2-indolyl]methyl}trifluoromethoxyacetamide; N-{[5-chloro-6-(5-fluoro-2-isoindolinyl)-2-indolyl]methyl}-1-fluorocyclopropaneformamide; N-{[6-(2,3a-diaza-5-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[6-(1,3,3a-triaza-5-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3-fluoro-4-methoxyphenyl)-2-indolyl]methyl}acetamide; 1-{[5-chloro-6-(5-fluoro-2-isoindolinyl)-2-indolyl]methyl}-3-methylurea; N-{[5-chloro-6-(6-indololinyl)-2-indolyl]methyl}acetamide; N-({5-chloro-6-[6-(hydroxymethyl)-3-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(2-methyl-5-pyrimidinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(4-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-indololinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}3,3-difluorolactic acid; N-{[5-chloro-6-(1,7-diaza-1H-inden-5-yl)-2-indolyl]methyl}acetamide; N-[(5-chloro-1H,1'H-6,6'-biindol-2-yl)methyl]acetamide; N-{[5-chloro-6-(6-cyano-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}(2-oxetane)acetamide; N-{[5-chloro-6-(6-ethoxy-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}2-methoxycyclopropaneformamide; 1-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}urea; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}-3-hydroxy-3-oxetaneformamide; N-{[6-(5-amino-6-fluoro-2-pyridyl)-5-chloro-2-indolyl]methyl}acetamide; 3-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1-cyclopropyl-1-methylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}difluoromethoxyacetamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-methyl-1-(1-methylcyclopropyl)urea; N-({6-[5-(1-azacyclobutane)-6-fluoro-2-pyridyl]-5-chloro-2-indolyl}methyl)acetamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-cyclopropyl-1-methylurea; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}-2-methyl-2-oxetaneformamide; 3-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1-methyl-1-(1-methylcyclopropyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}2-difluoromethoxypropionamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-4-morpholine carboxamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}3-methoxypropionamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-(dimethylamino)cyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}1-methoxycyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}trifluoromethoxyacetamide; 3-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1-(1-methylcyclopropyl)urea; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}methoxyacetamide; Methyl carbamate {[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}carbamate; N-{[5-chloro-6-(2-fluoro-4-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(2-cyclopropyl-5-pyrimidinyl)-2-indolyl]methyl}acetamide; Methyl carbamate {[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}carbamate; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-(methylamino)cyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}2-methoxypropionamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}2-methoxybutyramide; N-{[5-cyano-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}acetamide; 3-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1,1-dimethylurea; N-{[5-chloro-6-(5,6-difluoro-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methyl-3-pyridyl)-2-indolyl]methyl}acetamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(1-methylcyclopropyl)urea; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1,1-dimethylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-difluoromethoxycyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-(2-pyridyl)cyclopropaneformamide; N-({5-chloro-6-[6-fluoro-5-(methylamino)-2-pyridyl]-2-indolyl}methyl)1-hydroxycyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1-hydroxycyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-cyanocyclopropaneformamide; N-({5-chloro-6-[5-(ethylamino)-6-fluoro-2-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(5-fluoro-6-methyl-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-2-pyridyl)-2-indolyl]methyl}acetamide; N-{[3,5-dichloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}3-hydroxypropionamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-oxa-6-aza-6-spiro[3.3]heptaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-aminocyclopropaneformamide; N-({5-chloro-6-[6-chloro-5-(methylamino)-2-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-6-oxa-1-aza-1-spiro[3.3]heptaneformamide; N-({5-chloro-6-[6-fluoro-5-(methylamino)-2-pyridyl]-2-indolyl}methyl)-1-azacyclobutanecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-oxa-6-aza-6-spiro[3.3]heptaneformamide; N-({6-[5-(1-azacyclobutane)-2-pyrazinyl]-5-chloro-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-hydroxy-1-azacyclobutaneformamide; N-({5-chloro-6-[5-(dimethylamino)-6-fluoro-2-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(1,4-diaza-5-indanyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}methoxyacetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}3-hydroxycyclobutaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}2-methoxycyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}3-methoxypropionamide; 6-{5-chloro-2-[(3-methylureido)methyl]-6-indolyl}-2-fluoro-3-(methylamino)pyridine; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-methoxycyclopropaneformamide; 1-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-3-methylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-methyl-4-pyrazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-(dimethylamino)cyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}trifluoromethoxyacetamide; 1-{[5-chloro-6-(6-methoxy-3-pyridyl)-2-indolyl]methyl}-3-methylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-4-morpholine carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(2-oxetane)acetamide; 1-{[5-chloro-6-(5-methoxy-2-pyridyl)-2-indolyl]methyl}-3-methylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1,3-oxazol-5-carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-isoxazolecarboxamide; 3-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureido)cyclobutanol; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(2,2-difluoroethyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-4-pyridazine carboxamide; 3-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureido)propionitrile; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(3-isoxazolyl)acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}2-hydroxybutyramide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-pyridazine carboxamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(2-methoxyethyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-azacyclobutaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-perhydro-3-furfurylamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1,3-oxazol-4-carboxamide; 1-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-(perhydro-3-furanyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-cyano-1-azacyclobutaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}2-hydroxy-3-methylbutyramide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(methylamino)acetamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(4-isoxazolyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-hydroxy-3-methyl-1-azacyclobutaneformamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(3-oxetane)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}hydroxyacetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-cyanocyclobutaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-cyano-3-oxetaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-cyanocyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-methyl-3-isoxazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-hydroxycyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-pyrazole carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-oxabicyclo[2.1.1]hexane-1-carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-oxabicyclo[2.1.1]hexane-4-carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}3-fluorolactamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1,3-thiazolyl-2-carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-(methylamino)cyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-pyrazinecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}2-methoxypropionamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-pyrimidinecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-4-pyrimidinecarboxamide; N-({5-chloro-6-[6-fluoro-5-(methylamino)-2-pyridyl]-2-indolyl}methyl)acetamide; 1-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-methyl-5-pyrazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}difluoromethoxyacetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(3-oxetane)acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-methyl-4-imidazolium carboxamide; N-({5-chloro-6-[6-(methylamino)-3-pyridazinyl]-2-indolyl}methyl)acetamide; N-({5-chloro-6-[5-fluoro-6-(methylamino)-3-pyridyl]-2-indolyl}methyl)acetamide; N-{[6-(5-acetyl-2-pyrazinyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(2,4-diaza-2-indanyl)-2-indolyl]methyl}-1-pyrrolidinecarboxamide; N-{[5-chloro-6-(5-methyl-3-isoxazolyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-perhydro-2-furfurylamide; N-{[5-chloro-6-(5-isopropenyl-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-({5-chloro-6-[6-(methylamino)-3-pyridyl]-2-indolyl}methyl)acetamide; N-({5-chloro-6-[5-(methylamino)-2-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-fluoro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-methylcyclopropaneformamide; N-{[5-chloro-6-(5-vinyl-2-pyrazinyl)-2-indolyl]methyl}-1-methylcyclopropaneformamide; N-{[5-chloro-6-(5-isopropenyl-2-pyrazinyl)-2-indolyl]methyl}1-methylcyclopropaneformamide; N-{[5-chloro-6-(2-methyl-1,3-oxazol-4-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-oxazol-5-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,4-dioxa-5,8-diaza-2,3-dihydro-6-naphthyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-quinoxalinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-vinyl-2-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,4-dioxa-5-aza-2,3-dihydro-7-naphthyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-dioxa-4-aza-6-indenyl)-2-indolyl]methyl}acetamide; N-({5-chloro-6-[5-(methylamino)-2-pyrazinyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(1,4-dioxa-5-aza-2,3-dihydro-6-naphthyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-oxazol-2-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(4-methyl-1,3-oxazol-2-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3-isothiazolyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3-thia-1,5-diaza-6-indenyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-dioxa-4-aza-5-indenyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1-thia-7-aza-2-indenyl)-2-indolyl]methyl}acetamide; N-{[6-(1,3a-diaza-4,5,6,7-tetrahydro-2-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-dioxa-5-aza-6-indenyl)-2-indolyl]methyl}acetamide; N-{[6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-({5-chloro-6-[5-(hydroxymethyl)-2-pyrazinyl]-2-indolyl}methyl)acetamide; N-({5-fluoro-6-[5-(trifluoromethyl)-2-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-fluoro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}acetamide; N-({6-[5-(difluoromethyl)-2-pyridyl]-5-fluoro-2-indolyl}methyl)acetamide; N-({5-fluoro-6-[5-(trifluoromethyl)-2-pyrazinyl]-2-indolyl}methyl)acetamide; N-({5-chloro-6-[6-(difluoromethyl)-3-pyridazinyl]-2-indolyl}methyl)acetamide; N-{[6-(1-benzofuran-6-yl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-fluoro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}lactic acid; N-{[6-(1-benzothiophen-5-yl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,4-diazabicyclo[3.3.0]oct-2,4-dien-3-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-fluoro-6-methoxy-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-ethyl-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(4-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3,4-dihydro-2H-1,4-benzoxazin-6-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-vinyl-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-2,4-diaza-2-indanyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-ethoxy-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-{[6-(1-benzofuran-5-yl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-thiazo-4-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1-methyl-1,4-diaza-1H-inden-5-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1-methyl-1,6-diaza-1H-inden-5-yl)-2-indolyl]methyl}acetamide; N-{[6-(1,3-benzothiazo-2-yl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(4-methyl-1,3-thiazo-2-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(4-thia-1,6-diazabicyclo[3.3.0]oct-2,5,7-trien-3-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3-methyl-5-isoxazolyl)-2-indolyl]methyl}acetamide; 2-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureido)cyclobutanol; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-perhydro-2-furfurylamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-methyl-2-oxetaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}2-cyanocyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-hydroxy-1-pyrrolidinecarboxamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(3,3-difluoropropyl)urea; 2-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureido)ethanol; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-isoxazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-pyrazole carboxamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-cyclopropylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-methyl-1,3-oxazol-4-carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-piperazine carboxamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(3-isoxazolyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-methyl-5-isoxazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-hydroxy-3-oxetaneformamide; N-{[5-chloro-6-(3-methyl-1,2-benzisoxazol-5-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3-methyl-1,2-benzisoxazol-6-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-methylcyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}-1-pyrrolidinecarboxamide; and N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}-1-azacyclobutanecarboxamide; N-{[5-methoxy-6-(6-methoxy-3-pyridazinyl)-2-indolyl]methyl}lactic acid; N-{[5-methoxy-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}lactic acid; N-{[5-methoxy-6-(6-methoxy-3-pyridazinyl)-2-indolyl]methyl}acetamide; N-{[5-methoxy-6-(6-methoxy-3-pyridazinyl)-2-indolyl]methyl}methoxyacetamide; N-{[5-methoxy-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}3,3-difluoropropionamide; N-{[5-methoxy-6-(6-methoxy-3-pyridazinyl)-2-indolyl]methyl}3,3-difluoropropionamide; N-{[5-methoxy-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}methoxyacetamide; N-{[5-methoxy-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}lactic acid; 1-{[5-methoxy-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-methylurea; 3-{[5-methoxy-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1,1-dimethylurea; N-{[5-chloro-6-(5-cyclopropyl-2-pyridinyl)-2-indolyl]methyl}acetamide; N-{[6-(5-methoxy-2-pyrazinyl)-5-trifluoromethoxy-2-indolyl]methyl}2-methylpropionamide; and N-{[5-(cyanomethyl)-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}acetamide, Or any variation or implementation thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof.

[0153] In some embodiments, this document provides a compound of formula (I), any variation thereof or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: N-((5-chloro-6-(6-methoxypyridin-3-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(1H-pyrrolo[3,2-b]pyridin-2-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5'-chloro-1H,1'H-[2,6'-biindole]-2'-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(5-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-methoxypyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(6-methoxypyridazin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(2-methoxypyrimidin-5-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-(dimethylamino)pyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(5-(difluoromethoxy)pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-(trifluoromethoxy)pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(pyrazolo[1,5-a]pyridin-5-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(pyrazolo[1,5-a]pyridin-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-fluoro-6-(6-methoxypyridazin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-fluoro-6-(5-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; (S)-N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)-2-hydroxypropionamide; N-((5-fluoro-6-(6-methoxypyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; (R)-N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)-2-hydroxypropionamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)oxetane-3-carboxamide; N-((5-fluoro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; (S)-N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)tetrahydrofuran-2-carboxamide; (S)-N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)tetrahydrofuran-3-carboxamide; N-((5-chloro-6-(5-cyclopropylpyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; (S)-N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)oxetane-2-carboxamide; (R)-N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)oxetane-2-carboxamide; N-((5-chloro-6-(3-fluoropyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(1-methyl-1H-pyrazol-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(isoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(4-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methylpyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-cyclopropylpyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((6-(5-methoxypyrazin-2-yl)-5-(trifluoromethyl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(2-methoxypyridin-4-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-methoxy-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methylthiazo-2-yl)-1H-indol-2-yl)methyl)acetamide; 5-(2-(acetamidomethyl)-5-chloro-1H-indol-6-yl)pyrazin-2-carboxamide; N-((5-chloro-6-(imidazo[1,2-a]pyrazin-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-fluoroisoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(5-chlorothiazo-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(4-fluoroisoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)-1-methylcyclopropane-1-carboxamide; N-((5-chloro-6-(1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(3-methyl-1H-pyrazol-1-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(imidazo[2,1-b]thiazo-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(3-cyclopropyl-1H-pyrazol-1-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxy-6-methylpyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(1-methyl-1H-benzo[d]imidazol-5-yl)-1H-indol-2-yl)methyl)acetamide; N-((5'-chloro-1-methyl-1H,1'H-[5,6'-biindole]-2'-yl)methyl)acetamide; N-((5-chloro-6-(2,3-dihydrobenzo[b][1,4]dioxane-6-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(2,2-difluorobenzo[d][1,3]dioxacyclopenten-5-yl)-1H-indol-2-yl)methyl)acetamide; N-((6-(benzo[d][1,3]dioxacyclopenten-5-yl)-5-chloro-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(imidazo[1,2-a]pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(1-cyclopropyl-1H-imidazol-4-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-ethyl-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-methoxypyrimidin-4-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-(dimethylamino)pyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-cyclopropoxypyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-(trifluoromethoxy)pyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-(difluoromethoxy)pyridin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-(difluoromethoxy)pyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((6-(5-methoxypyrazin-2-yl)-5-methyl-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(imidazo[1,2-a]pyrimidin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrimidin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-(methoxy-d3)pyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-cyanopyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-chloroisoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(1-oxo-isoindoline-2-yl)-1H-indoline-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)propionamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)-1-fluorocyclopropane-1-carboxamide; 1-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)-3-methylurea; N-((6-(benzo[b]thiophen-6-yl)-5-chloro-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-7-fluoro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)azacyclobutane-1-carboxamide; N-((5-chloro-6-(2-methylthiazo-4-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(pyridazin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-methylpyridazin-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(6-fluoro-5-methoxypyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(oxazol-4-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(isoxazo-3-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(5-methyloxazol-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(2-methyloxazol-5-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(thieno[3,2-b]pyridin-2-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-chloro-6-(2,3-dihydro-[1,4]dioxane-hexeno[2,3-c]pyridin-7-yl)-1H-indol-2-yl)methyl)acetamide; N-((5-fluoro-6-(5-methoxypyrazin-2-yl)-1H-indol-2-yl)methyl)propionamide; N-{[6-(3a,5-diaza-2-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,7-diaza-5-indanyl)-2-indolyl]methyl}acetamide; N-{[6-(1,4,7a-triaza-6-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-({5-chloro-6-[6-(ethylamino)-3-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(2,4-diaza-2H-inden-2-yl)-2-indolyl]methyl}trifluoromethoxyacetamide; N-{[5-chloro-6-(1-methyl-1H-1,2,3-triazol-4-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-fluoro-2-isoindolinyl)-2-indolyl]methyl}-1-fluorocyclopropaneformamide; N-{[5-chloro-6-(5-fluoro-2-isoindolinyl)-2-indolyl]methyl}trifluoromethoxyacetamide; N-{[6-(2,3a-diaza-5-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[6-(1,3,3a-triaza-5-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3-fluoro-4-methoxyphenyl)-2-indolyl]methyl}acetamide; 1-{[5-chloro-6-(5-fluoro-2-isoindolinyl)-2-indolyl]methyl}-3-methylurea; N-{[5-chloro-6-(6-indololinyl)-2-indolyl]methyl}acetamide; N-({5-chloro-6-[6-(hydroxymethyl)-3-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(2-methyl-5-pyrimidinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(4-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(S)-3,3-difluorolactic acid; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(R)-3,3-difluorolactic acid; N-{[5-chloro-6-(5-indololinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3,3-difluorolactic acid; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}[(S)-2-oxetane]acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}[(R)-2-oxetane]acetamide; N-{[5-chloro-6-(1,7-diaza-1H-inden-5-yl)-2-indolyl]methyl}acetamide; N-[(5-chloro-1H,1'H-6,6'-biindol-2-yl)methyl]acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}2-oxetane]acetamide; N-{[5-chloro-6-(6-cyano-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-ethoxy-3-pyridyl)-2-indolyl]methyl}acetamide; trans-N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl} 2-methoxycyclopropaneformamide; trans-N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}(1R,2R)-2-methoxycyclopropaneformamide; trans-N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}(1S,2S)-2-methoxycyclopropaneformamide; 1-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}urea; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}-3-hydroxy-3-oxetaneformamide; N-{[6-(5-amino-6-fluoro-2-pyridyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}-(R)-2-methyl-2-oxetaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}-(S)-2-methyl-2-oxetaneformamide; 3-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1-cyclopropyl-1-methylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}difluoromethoxyacetamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-methyl-1-(1-methylcyclopropyl)urea; N-({6-[5-(1-azacyclobutane)-6-fluoro-2-pyridyl]-5-chloro-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(R)-2-difluoromethoxypropionamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-cyclopropyl-1-methylurea; 3-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1-methyl-1-(1-methylcyclopropyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(S)-2-difluoromethoxypropionamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-4-morpholine carboxamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}3-methoxypropionamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-(dimethylamino)cyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}1-methoxycyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}trifluoromethoxyacetamide; 3-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1-(1-methylcyclopropyl)urea; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-(S)-perhydro-2-furfurylamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}methoxyacetamide; Methyl carbamate {[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}carbamate; N-{[5-chloro-6-(2-fluoro-4-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(2-cyclopropyl-5-pyrimidinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}(R)-2-methoxypropionamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(S)-2-methoxybutyramide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(R)-2-methoxybutyramide; Methyl carbamate {[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}carbamate; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-(methylamino)cyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(R)-2-methoxybutyramide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(S)-2-methoxybutyramide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}(S)-2-methoxypropionamide; 3-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1,1-dimethylurea; N-{[5-cyano-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5,6-difluoro-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methyl-3-pyridyl)-2-indolyl]methyl}acetamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(1-methylcyclopropyl)urea; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1,1-dimethylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-difluoromethoxycyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-(2-pyridyl)cyclopropaneformamide; N-({5-chloro-6-[6-fluoro-5-(methylamino)-2-pyridyl]-2-indolyl}methyl)1-hydroxycyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-1-hydroxycyclopropaneformamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-cyanocyclopropaneformamide; N-({5-chloro-6-[5-(ethylamino)-6-fluoro-2-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(5-fluoro-6-methyl-3-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-2-pyridyl)-2-indolyl]methyl}acetamide; N-{[3,5-dichloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}3-hydroxypropionamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-oxa-6-aza-6-spiro[3.3]heptaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-aminocyclopropaneformamide; N-({5-chloro-6-[6-chloro-5-(methylamino)-2-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-6-oxa-1-aza-1-spiro[3.3]heptaneformamide; N-({5-chloro-6-[6-fluoro-5-(methylamino)-2-pyridyl]-2-indolyl}methyl)-1-azacyclobutanecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-oxa-6-aza-6-spiro[3.3]heptaneformamide; N-({6-[5-(1-azacyclobutane)-2-pyrazinyl]-5-chloro-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-hydroxy-1-azacyclobutaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}[(R)-2-oxetane]acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}[(S)-2-oxetane]acetamide; (1S,2R)-2-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureo)cyclobutanol; N-({5-chloro-6-[5-(dimethylamino)-6-fluoro-2-pyridyl]-2-indolyl}methyl)acetamide; trans-N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(1R,2R)-2-methoxycyclopropaneformamide; trans-N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(1S,2S)-2-methoxycyclopropaneformamide; N-{[5-chloro-6-(1,4-diaza-5-indanyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(1r,3r)-3-hydroxycyclobutaneformamide; (1R,2S)-2-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureo)cyclobutanol; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}methoxyacetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(1s,3s)-3-hydroxycyclobutaneformamide; trans-N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(-2-methoxycyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}3-methoxypropionamide; cis-N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(1R,2S)-2-methoxycyclopropaneformamide; cis-N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(1S,2R)-2-methoxycyclopropaneformamide; trans-N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(1R,2R)-2-cyanocyclopropaneformamide; trans-N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(1S,2S)-2-cyanocyclopropaneformamide; 6-{5-chloro-2-[(3-methylureido)methyl]-6-indolyl}-2-fluoro-3-(methylamino)pyridine; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-methoxycyclopropaneformamide; 1-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-3-methylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(2-oxetane)acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-methyl-4-pyrazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-(dimethylamino)cyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}trifluoromethoxyacetamide; 1-{[5-chloro-6-(6-methoxy-3-pyridyl)-2-indolyl]methyl}-3-methylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-4-morpholine carboxamide; 1-{[5-chloro-6-(5-methoxy-2-pyridyl)-2-indolyl]methyl}-3-methylurea; N-{[5-chloro-6-(3-methyl-1,2-benzisoxazol-6-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3-methyl-1,2-benzisoxazol-5-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-hydroxy-3-oxetaneformamide; (1S,2S)-2-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureo)cyclobutanol; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-methyl-5-isoxazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-methyl-2-oxetaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-(R)-perhydro-2-furfurylamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-(R)-2-methyl-2-oxetaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-(S)-2-methyl-2-oxetaneformamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(3-isoxazolyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-piperazine carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-methyl-1,3-oxazol-4-carboxamide; trans-N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(-2-cyanocyclopropaneformamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-cyclopropylurea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1,3-oxazol-5-carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-isoxazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-(R)-3-hydroxy-1-pyrrolidinecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-pyrazole carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-isoxazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-(S)-3-hydroxy-1-pyrrolidinecarboxamide; 2-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureido)ethanol; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(3,3-difluoropropyl)urea; (1s,3s)-3-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureo)cyclobutanol; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(2,2-difluoroethyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-4-pyridazine carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(S)-2-hydroxybutyramide; 3-(3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}ureido)propionitrile; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(3-isoxazolyl)acetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(R)-2-hydroxybutyramide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-pyridazine carboxamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(2-methoxyethyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-(R)-2-azacyclobutaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-(R)-perhydro-3-furfurylamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1,3-oxazol-4-carboxamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-[(R)-perhydro-3-furanyl]urea; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-[(S)-perhydro-3-furanyl]urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-cyano-1-azacyclobutaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(S)-2-hydroxy-3-methylbutyramide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(methylamino)acetamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(4-isoxazolyl)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-hydroxy-3-methyl-1-azacyclobutaneformamide; 3-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-(3-oxetane)urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}hydroxyacetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-cyanocyclobutaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-3-cyano-3-oxetaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-cyanocyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-methyl-3-isoxazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-hydroxycyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-pyrazole carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(S)-3-fluorolactamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-oxabicyclo[2.1.1]hexane-1-carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-oxabicyclo[2.1.1]hexane-4-carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(R)-3-fluorolactic acid; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1,3-thiazolyl-2-carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(S)-2-methoxypropionamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}1-(methylamino)cyclopropaneformamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-2-pyrazinecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(R)-2-methoxypropionamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-5-pyrimidinecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-4-pyrimidinecarboxamide; N-({5-chloro-6-[6-fluoro-5-(methylamino)-2-pyridyl]-2-indolyl}methyl)acetamide; 1-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}urea; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-methyl-5-pyrazolecarboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}difluoromethoxyacetamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}-1-methyl-4-imidazolium carboxamide; N-{[5-chloro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(3-oxetane)acetamide; N-({5-chloro-6-[6-(methylamino)-3-pyridazinyl]-2-indolyl}methyl)acetamide; N-({5-chloro-6-[5-fluoro-6-(methylamino)-3-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}-1-azacyclobutanecarboxamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}-1-pyrrolidinecarboxamide; N-{[6-(5-acetyl-2-pyrazinyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(2,4-diaza-2-indanyl)-2-indolyl]methyl}-1-pyrrolidinecarboxamide; N-{[5-chloro-6-(5-methyl-3-isoxazolyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridyl)-2-indolyl]methyl}-(R)-perhydro-2-furfurylamide; N-{[5-chloro-6-(5-isopropenyl-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-({5-chloro-6-[6-(methylamino)-3-pyridyl]-2-indolyl}methyl)acetamide; N-({5-chloro-6-[5-(methylamino)-2-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-fluoro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-methylcyclopropaneformamide; N-{[5-chloro-6-(5-vinyl-2-pyrazinyl)-2-indolyl]methyl}-1-methylcyclopropaneformamide; N-{[5-chloro-6-(5-isopropenyl-2-pyrazinyl)-2-indolyl]methyl}1-methylcyclopropaneformamide; N-{[5-chloro-6-(2-methyl-1,3-oxazol-4-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-oxazol-5-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,4-dioxa-5,8-diaza-2,3-dihydro-6-naphthyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-vinyl-2-pyridyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-quinoxalinyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3-methyl-5-isoxazolyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,4-dioxa-5-aza-2,3-dihydro-7-naphthyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-dioxa-4-aza-6-indenyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}1-methylcyclopropaneformamide; N-{[5-chloro-6-(1,4-dioxa-5-aza-2,3-dihydro-6-naphthyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-oxazol-2-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(4-methyl-1,3-oxazol-2-yl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(3-isothiazolyl)-2-indolyl]methyl}acetamide; N-({5-chloro-6-[5-(methylamino)-2-pyrazinyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(3-thia-1,5-diaza-6-indenyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-dioxa-4-aza-5-indenyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1-thia-7-aza-2-indenyl)-2-indolyl]methyl}acetamide; N-{[5-chloro-6-(1,3-dioxa-5-aza-6-indenyl)-2-indolyl]methyl}acetamide; N-{[6-(1,3a-diaza-4,5,6,7-tetrahydro-2-indenyl)-5-chloro-2-indolyl]methyl}acetamide; N-{[6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}acetamide; N-({5-chloro-6-[5-(hydroxymethyl)-2-pyrazinyl]-2-indolyl}methyl)acetamide; N-({5-fluoro-6-[5-(trifluoromethyl)-2-pyridyl]-2-indolyl}methyl)acetamide; N-{[5-fluoro-6-(6-fluoro-5-methoxy-2-pyridinyl)-2-indolyl]methyl}acetamide; N-({6-[5-(difluoromethyl)-2-pyridyl]-5-fluoro-2-indolyl}methyl)acetamide; N-({5-fluoro-6-[5-(trifluoromethyl)-2-pyrazinyl]-2-indolyl}methyl)acetamide; N-{[5-chloro-6-(5-cyclopropyl-2-pyridinyl)-2-indolyl]methyl}acetamide; N-({5-chloro-6-[6-(difluoromethyl)-3-pyridazinyl]-2-indolyl}methyl)acetamide; and N-{[5-fluoro-6-(5-methoxy-2-pyrazinyl)-2-indolyl]methyl}(R)-lactic acid; Or any variation or implementation thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof.

[0154] Treatment This document provides a method for regulating SLC6A19 in cells, the method comprising exposing cells to (i) an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0155] This document provides a method for inhibiting SLC6A19 in cells, the method comprising exposing cells to (i) a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. In some embodiments, the individual is a human.

[0156] This document provides a method for reducing systemic amino acid levels in an individual in need, the method comprising administering to the individual (i) an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. In some embodiments, the amino acid is phenylalanine, tyrosine, glutamine, or glycine. In some embodiments, systemic levels of phenylalanine, tyrosine, glutamine, or glycine are reduced in the individual after treatment. In some embodiments, levels of phenylalanine, tyrosine, glutamine, or glycine are reduced by at least 10%, at least 20%, at least 30%, or at least 50% after administration of the compound.

[0157] This article provides a method for treating an individual in need of SLC6A19-mediated disease, condition, or disorder, the method comprising administering to the individual (i) an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. In some implementations, the SLC6A19-mediated disease, condition, or disorder is selected from the group consisting of: phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, metabolic disease, hyperphenylalaninemia, tyrosinemia (type I, II, or III), nonketotic hyperglycinemia, isovaleric acidemia, methylmalonic acidemia, propionic acidemia, maple syrup diabetes mellitus, DNAJC12 deficiency, urea cycle disorder, hyperammonemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity-related disorders, and neurodevelopmental disorders and autism spectrum disorders. In some implementations, the SLC6A19-mediated disease, condition, or disorder is phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, or metabolic disease. In some implementations, the SLC6A19-mediated disease, condition, or disorder is phenylketonuria (PKU). In some implementations, the SLC6A19-mediated disease, condition, or disorder is chronic kidney disease (CKD). In some embodiments, the SLC6A19-mediated disease, condition, or disorder is a metabolic disease. In some embodiments, the SLC6A19-mediated disease, condition, or disorder is metabolic syndrome. In some embodiments, the SLC6A19-mediated disease, condition, or disorder is associated with abnormal levels of amino acids. In some embodiments, the SLC6A19-mediated disease, condition, or disorder is associated with a genetic defect in phenylalanine hydroxylase.

[0158] This document provides a method for treating an individual in need of SLC6A19-mediated disease, condition, or disorder, the method comprising administering to the individual (i) a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or (ii) a pharmaceutical composition comprising a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients. In some implementations, the SLC6A19-mediated disease, condition, or disorder is selected from the group consisting of: phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, metabolic disease, hyperphenylalaninemia, tyrosinemia (type I, II, or III), nonketotic hyperglycinemia, isovaleric acidemia, methylmalonic acidemia, propionic acidemia, maple syrup diabetes mellitus, DNAJC12 deficiency, urea cycle disorder, hyperammonemia, diabetes mellitus, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity-related disorders, and neurodevelopmental disorders and autism spectrum disorders. In some implementations, the SLC6A19-mediated disease, condition, or disorder is phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, or metabolic disease. In some implementations, the SLC6A19-mediated disease, condition, or disorder is phenylketonuria (PKU). In some implementations, the SLC6A19-mediated disease, condition, or disorder is chronic kidney disease (CKD). In some embodiments, the SLC6A19-mediated disease, condition, or disorder is a metabolic disease. In some embodiments, the SLC6A19-mediated disease, condition, or disorder is metabolic syndrome. In some embodiments, the SLC6A19-mediated disease, condition, or disorder is associated with abnormal levels of amino acids. In some embodiments, the SLC6A19-mediated disease, condition, or disorder is associated with a genetic defect in phenylalanine hydroxylase. In some embodiments, the individual is a human being.

[0159] This document provides a compound of formula (I), any variation thereof or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), any variation thereof or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients for regulating SLC6A19 in cells.

[0160] This document provides a compound of formula (I), any variation thereof or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), any variation thereof or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients for inhibiting SLC6A19 in cells.

[0161] This document provides a compound of formula (I), any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof, for reducing systemic levels of phenylalanine, tyrosine, glutamine, or glycine in individuals of need, said pharmaceutical composition comprising a compound of formula (I), any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0162] This document provides for the treatment of SLC6A19-mediated diseases, conditions, or disorders in individuals of need, including a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0163] This document provides a compound of formula (I), any variation thereof or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), any variation thereof or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients for manufacturing a medicament for regulating SLC6A19 in cells.

[0164] This document provides a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients for manufacturing a medicament for inhibiting SLC6A19 in cells.

[0165] This document provides for the manufacture of a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or one or more pharmaceutically acceptable excipients, for the manufacture of a medicament for reducing systemic levels of phenylalanine, tyrosine, glutamine, or glycine in an individual of need.

[0166] This document provides for the treatment of SLC6A19-mediated diseases, conditions, or disorders in individuals of need, including a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

[0167] In some embodiments, the compounds provided herein inhibit SLC6A19 at concentrations less than 10 µM, less than 1 µM, less than 0.5 µM, less than 0.1 µM, less than 0.010 µM, or less than 0.001 µM. In some embodiments, the compounds provided herein inhibit SLC6A19 at concentrations of 1-10 µM, 0.01 to 1 µM, or 0.01 to 10 µM.

[0168] In some embodiments, the compound has an IC50 of less than 10 nM, less than 10 µM, less than 1 µM, less than 0.5 µM, or less than 0.1 µM. 50 In some embodiments, the compounds provided herein have IC50 values ​​of 1 to 10 nM, 1 to 10 µM, 0.01 to 1 µM, 0.01 to 10 µM, 0.001 to 0.01 µM, or 0.001 to 0.010 µM. 50 .

[0169] In some implementations, the individual receiving treatment is a minor or infant. In some implementations, the individual is under 10 years of age, under 9 years of age, under 8 years of age, under 7 years of age, under 6 years of age, under 5 years of age, under 4 years of age, under 3 years of age, under 2 years of age, or under 1 year of age. In some implementations, the individual is a person.

[0170] In some implementations, the individual has abnormal levels of amino acids. In some implementations, SLC6A19-mediated diseases, conditions, or disorders are associated with a genetic defect in phenylalanine hydroxylase. In some implementations, the individual is a human being.

[0171] In some implementation schemes of the foregoing, the application is oral.

[0172] medicine box This disclosure also provides a pharmaceutical kit for implementing the methods disclosed herein. The kit may include a compound as described herein and suitable for packaging, or a pharmaceutically acceptable salt thereof. The kit may include one or more containers comprising any of the compounds described herein. In one aspect, the kit contains a compound of this disclosure or a pharmaceutically acceptable salt thereof, and a label and / or instructions for use of the compound to treat the disease or condition described herein. The kit may include a unit dosage form of the compound.

[0173] This document provides a kit comprising (i) an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, and (ii) instructions for use in treating an SLC6A19-mediated disease, condition, or disorder in an individual in need. This document also provides a kit comprising (i) a pharmaceutical composition comprising an effective amount of a compound of formula (I), or any variation thereof or embodiment thereof, or a stereoisomer thereof or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients; and (ii) instructions for use in treating an SLC6A19-mediated disease, condition, or disorder in an individual in need. In some embodiments, the individual is a person.

[0174] This document provides a kit comprising (i) a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and (ii) instructions for use in treating an SLC6A19-mediated disease, condition, or disorder in an individual in need. This document also provides a kit comprising (i) a pharmaceutical composition comprising a compound of formula (I), any variation or embodiment thereof, a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients; and (ii) instructions for use in treating an SLC6A19-mediated disease, condition, or disorder in an individual in need. In some embodiments, the individual is a person.

[0175] Articles are also provided, wherein the articles comprise a pharmaceutically acceptable salt of a compound of formula (I) as set forth elsewhere herein, or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or any of the foregoing, contained in a suitable container. Articles are also provided comprising pharmaceutical compositions comprising a pharmaceutically acceptable salt of a compound of formula (I) as set forth elsewhere herein, or any variation or embodiment thereof, or a stereoisomer or tautomer thereof, or any of the foregoing, contained in a suitable container. The container may be a vial, can, ampoule, pre-filled syringe, or intravenous bag.

[0176] Preparation method This disclosure also provides methods for preparing the compounds of the present invention. In some aspects, methods are provided for preparing compounds (I), (IA), (I-A1), (I-A2), (I-A3), (I-A4), (I-A5), (I-A6), (IB), (I-B1), (I-B2), (I-B3), (I-B4), (IC), (I-C1), (I-C2), (I-C3), (I-C4), (ID), (I-D1), (IE), (IF), (IG) or (IH) of the present invention, or their stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing.

[0177] In some embodiments, the method for preparing a pharmaceutically acceptable salt of a compound of formula (I) or its stereoisomers or tautomers or any of the foregoing includes: (a) Make the compound of formula (I-1): (I-1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Q 1 It is a halogenated group; PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -N-, -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 C 1-6 Alkyl, C 1-6Alkoxy, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 4-10 aryl heteroaryl groups are optionally mediated by one or more R groups. 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 C 1-6 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 10 For H; R 3a and R 4a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace, and R 3b and R 4b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; With compound of formula (I-2): (I-2), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Y 1It is boric acid or borate ester; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; Each R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and Each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkoxy; The reaction is carried out in the presence of a coupling agent to provide a compound of formula (I-3): (I-3), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 4-10 aryl heteroaryl groups are optionally mediated by one or more R groups. 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 C 1-6 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x C1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace, and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; Subsequently, (b) Optionally, the compound of formula (I-3) is contacted with a deprotecting agent; To provide compounds of formula (I).

[0178] In some embodiments, the method for preparing a pharmaceutically acceptable salt of a compound of formula (I) or its stereoisomers or tautomers or any of the foregoing includes: (a) Make the compound of formula (I-1): (I-1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Q 1 It is a halogenated group; PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -N-, -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 C 1-6Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; With compound of formula (I-2): (I-2), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Y 1 It is boric acid or borate ester; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; Each R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and Each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkoxy; The reaction is carried out in the presence of a coupling agent to provide a compound of formula (I-3): (I-3), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; Subsequently, (b) Optionally, the compound of formula (I-3) is contacted with a deprotecting agent; To provide compounds of formula (I).

[0179] In some implementations, the protecting group is absent.

[0180] In some embodiments, the protecting group is a sulfonyl group. In some embodiments, the protecting group is SO2Ph. In some embodiments, the protecting group is SO2Ph(CH3).

[0181] In some embodiments, the compound of formula (I-1) is an aryl halide, and the compound of formula (I-2) is a borate ester or boric acid. In some embodiments, the borate ester is pinacol borate ester. In some embodiments, the reaction is Suzuki coupling. In some embodiments, the coupling agent includes a catalyst. In some embodiments, the catalyst is Pd(dppf)Cl2·CH2Cl2, Pd(PPh3)4, chloro[(di(1-adamantyl)-N-butylphosphine)-2-(2-aminobiphenyl)]palladium(II) or [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloromethane.

[0182] In some embodiments, the coupling agent also includes a base. In some embodiments, the base is potassium carbonate, cesium carbonate, or sodium carbonate.

[0183] In some embodiments, the coupling agent includes one or more agents selected from the group consisting of palladium catalysts, phosphine ligands, and bases.

[0184] In some embodiments, the deprotecting agent includes an acid. In some embodiments, the acid is HCl, TFA, or barbituric acid.

[0185] In some embodiments, the deprotecting agent includes a base. In some embodiments, the base is potassium carbonate.

[0186] In some embodiments, the method for preparing a pharmaceutically acceptable salt of formula (I) or (I') compound or its stereoisomers or tautomers or any of the foregoing includes: (a) Make the compound of formula (II-1): (II-1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Q 3 For H; PG is absent or has a protecting group; m Integers from 1 to 4; R 1a It can be -N-, -NH-, -O-, or -S-; R 2 For H; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; With compound of formula (II-2): (II-2), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Y 3 It is a -C(O)OH or -C(O)- halogroup; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and R 34-10 aryl heteroaryl groups are optionally mediated by one or more R groups. 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -N- or -NH-; and Each R 3a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace; R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace, and Each R 3bIndependently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkoxy; The reaction is carried out in the presence of a coupling agent to provide a compound of formula (I-3): (I-3), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and R 3 4-10 aryl heteroaryl groups are optionally mediated by one or more R groups. 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace, and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; Subsequently, (b) Optionally, the compound of formula (I-3) is contacted with a deprotecting agent; To provide compounds of formula (I).

[0187] In some embodiments, the method for preparing a pharmaceutically acceptable salt of formula (I) or (I') compound or its stereoisomers or tautomers or any of the foregoing includes: (a) Make the compound of formula (II-1): (II-1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Q 3 For H; PG is absent or has a protecting group; m Integers from 1 to 4; R 1a It can be -N-, -NH-, -O-, or -S-; R 2 For H; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; With compound of formula (II-2): (II-2), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Y 3 It is a -C(O)OH or -C(O)- halogroup; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a Replace, and Each R 3a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, Each R 3b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkoxy; The reaction is carried out in the presence of a coupling agent to provide a compound of formula (I-3): (I-3), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Cycloalkyl or 4-10 membered heterocyclic groups optionally via one or more R 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 C 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 C 3-10 cycloalkyl, C 6-20 Aryl, 3-10 heterocyclic or 5-10 heteroaryl, optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3breplace, R 4a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a C 1-6 Alkyl, C 1-6 Alkoxy, 4-10 membered heterocyclic group, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; Subsequently, (b) Optionally, the compound of formula (I-3) is contacted with a deprotecting agent; To provide compounds of formula (I).

[0188] In some implementations, the protecting group is absent.

[0189] In some embodiments, the protecting group is a sulfonyl group. In some embodiments, the protecting group is SO2Ph. In some embodiments, the protecting group is SO2Ph(CH3).

[0190] In some embodiments, the deprotecting agent includes an acid. In some embodiments, the acid is HCl, TFA, or barbituric acid.

[0191] In some embodiments, the deprotecting agent includes a base. In some embodiments, the base is potassium carbonate. In some embodiments, the compound of formula (II-1) is an amine, and the compound of formula (II-2) is a carboxylic acid. In some embodiments, the coupling agent includes HATU. In some embodiments, the coupling agent further includes a base. In some embodiments, the base is a tertiary amine. In some embodiments, the base is DIEA. In some embodiments, the coupling agent includes EDCI, HOBt, and tertiary amine bases (e.g., DIEA or N-methylimidazole). In some embodiments, the coupling agent includes hexafluorophosphate chloride-N,N,N′,N′-tetramethylformamidinium and N-methylimidazole.

[0192] Listed implementation schemes Implementation Scheme 1. A compound of formula (I): (I), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8bEach is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

[0193] Implementation Scheme 2. The compound of Implementation Scheme 1, wherein the compound is a compound of formula (IA): (IA), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing.

[0194] Implementation Scheme 3. A compound as described in Implementation Scheme 1 or 2, wherein the compound is a compound of formula (IB): (IB), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: ring A is a 5-10 membered heteroaryl or a 5-10 membered heterocyclic group, wherein each of the 5-10 membered heteroaryl or 5-10 membered heterocyclic group is optionally irradiated by one or more R a replace.

[0195] Implementation Scheme 4. A compound of any one of Implementation Schemes 1-3, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m It is an integer between 1 and 2.

[0196] Implementation Scheme 5. A compound of any one of Implementation Schemes 1-4, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m The value is 1.

[0197] Implementation Scheme 6. A compound of any one of Implementation Schemes 1-5, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 C 1-3 Alkyl, C 1-3 Haloalkyl, C 3-6 cycloalkyl, -N(R) 4 )2 or 4-6 membered heterocyclic groups, where each R 3 Optionally via one or more R 3a replace.

[0198] Implementation Scheme 7. A compound of any one of Implementation Schemes 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 C 1-3 alkyl.

[0199] Implementation Scheme 8. A compound of any one of Implementation Schemes 1-7, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 It is a methyl group.

[0200] Implementation Scheme 9. A compound of any one of Implementation Schemes 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 For optional access via one or more R 3a Replacement C 1-3 alkyl.

[0201] Implementation Scheme 10. A compound of any one of Implementation Schemes 1-6 or 9, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein R 3 for .

[0202] Implementation Scheme 11. A compound of any one of Implementation Schemes 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 For optional access via one or more R 3a Replacement C 3-6 Cycloalkyl.

[0203] Implementation Scheme 12. A compound of any one of Implementation Schemes 1-6 or 11, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein R 3 For optional via one or more halogen groups or C 1-3 Alkyl-substituted C 3-6 Cycloalkyl.

[0204] Implementation Scheme 13. A compound of any one of Implementation Schemes 1-6 or 11-12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein R 3 Choose from the following groups: and .

[0205] Implementation Scheme 14. A compound of any one of Implementation Schemes 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 -N(R) 4 )2, where each R 4 Independently H or C 1-3 alkyl.

[0206] Implementation Scheme 15. A compound of any one of Implementation Schemes 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 For optional access via one or more R 3a Substituted 4-6 membered heterocyclic groups.

[0207] Implementation Scheme 16. A compound of any one of Implementation Schemes 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 -N(R) 4 )2, where two R 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 3a Substituted 4-6 membered heterocyclic groups.

[0208] Implementation Scheme 17. A compound of any one of Implementation Schemes 1-6 or 16, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein R 3 for .

[0209] Implementation Scheme 18. A compound of any one of Implementation Schemes 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 For optional access via one or more R 3a Substituted 4-6 membered heterocyclic groups.

[0210] Implementation Scheme 19. A compound of any one of Implementation Schemes 1-6 or 18, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein R 3 Choose from the following groups: , and .

[0211] Implementation Scheme 20. A compound of any one of Implementation Schemes 1-19, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 5 and R 7 Each is independently H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl or C 1-3 Haloalkyl, wherein R 5 and R 7 The C mentioned 1-3 Each alkyl group is optionally substituted independently with one or more halogen groups or CN.

[0212] Implementation Scheme 21. A compound of any one of Implementation Schemes 1-20, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 5 and R 7 Each is independently H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Halogenated alkyl groups.

[0213] Implementation Scheme 22. A compound of any one of Implementation Schemes 1-21, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 5 and R 7 Each is independently represented by H.

[0214] Implementation Scheme 23. A compound of any one of Implementation Schemes 1-21, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 5 and R 7 One of them is H, and R 5 and R 7 The other one is independently a halogen group, C 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Halogenated alkyl groups.

[0215] Implementation Scheme 24. A compound of any one of Implementation Schemes 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 and R 9 Each can be an H or a halogen group independently.

[0216] Implementation Scheme 25. A compound of any one of Implementation Schemes 1-24, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 and R 9 Each can be H, F, or Cl independently.

[0217] Implementation Scheme 26. A compound of any one of Implementation Schemes 1-25, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 and R 9 Each is independently represented by H.

[0218] Implementation Scheme 27. A compound of any one of Implementation Schemes 1-25, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein R 6 and R 9 One of them is H, and R 6 and R9 The other one is F or Cl.

[0219] Implementation Scheme 28. A compound of any one of Implementation Schemes 1-27, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 For optional access via one or more R 8a Substituted 3-10 membered heterocyclic groups.

[0220] Implementation Scheme 29. A compound of any one of Implementation Schemes 1-28, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 Choose from the following groups: , , , , , , , and .

[0221] Implementation Scheme 30. A compound of any one of Implementation Schemes 1-27, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 For optional access via one or more R 8a Substituted 5-10 heteroaryl groups.

[0222] Implementation Scheme 31. A compound of any one of Implementation Schemes 1-27 or 30, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein R 8 For optional access via one or more R 8a Substituted 5-10 aryl groups, wherein each R 8a Independently -CN, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, -C(O)NH2 or C 3-6 cycloalkyl, wherein R 8a The C mentioned 1-6 Alkyl groups are optionally oxidized via one or more R groups. 8b Replace; and each R 8b It can be D or a halogen group independently.

[0223] Implementation Scheme 32. A compound of any one of Implementation Schemes 1-27 or 30-31, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein R 8 Choose from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0224] Implementation Scheme 33. A compound of any one of Implementation Schemes 1-27 or 30-32, wherein said compound is of formula (IH): (IH), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein s Integers between 0 and 6; t It is 1 or 2; and It represents a single bond or a double bond.

[0225] Implementation Scheme 34. The compound of Implementation Scheme 33, wherein the compound has the following formula: (IHbi) (IHb-ii), (IHb-iii) or (IHb-iv), or a stereoisomer or tautomer or a pharmaceutically acceptable salt thereof.

[0226] Implementation Scheme 35. The compound of Implementation Scheme 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from compounds 1-83 of Table 1.

[0227] Implementation Scheme 36. A method for preparing a compound of formula (I) as defined in any one of Implementation Schemes 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, comprising: (a) Make the compound of formula (I-1): (I-1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Q 1 It is a halogenated group; PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -N-, -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; With compound of formula (I-2): (I-2), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Y 1 It is boric acid or borate ester; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; Each R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a The C mentioned 1-6Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and Each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkoxy; The reaction is carried out in the presence of a coupling agent to provide a compound of formula (I-3): (I-3), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; Subsequently, (b) Optionally, the compound of formula (I-3) is contacted with a deprotecting agent; To provide compounds of formula (I).

[0228] Implementation Scheme 37. The method of Implementation Scheme 35, wherein the coupling agent comprises a palladium catalyst, a phosphine ligand, and / or a base.

[0229] Implementation Scheme 38. A method for preparing a compound of formula (I) as defined in any one of Implementation Schemes 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, said method comprising: (a) Make the compound of formula (I-1): (I-1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Q 1 It is a halogenated group; PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -N-, -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; With compound of formula (I-2): (I-2), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Y 1 It is boric acid or borate ester; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; Each R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and Each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkoxy; The reaction is carried out in the presence of a coupling agent to provide a compound of formula (I-3): (I-3), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups or the C 3-10cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; Subsequently, (b) Optionally, the compound of formula (I-3) is contacted with a deprotecting agent; To provide compounds of formula (I).

[0230] Implementation Scheme 39. The method of any one of Implementation Schemes 36-38, wherein the protecting group is a sulfonyl group.

[0231] Implementation Scheme 40. The method of any one of Implementation Schemes 36-39, wherein the deprotecting agent comprises an alkali.

[0232] Implementation Scheme 41. A pharmaceutical composition comprising (i) a compound as described in any one of Implementation Schemes 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and (ii) one or more pharmaceutically acceptable excipients.

[0233] Implementation Scheme 42. A method for regulating SLC6A19 in cells, the method comprising exposing the cells to a composition comprising a compound as described in any one of Implementation Schemes 1-35 or a stereoisomer or tautomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in Implementation Scheme 41.

[0234] Implementation Scheme 43. A method for inhibiting SLC6A19 in cells, the method comprising exposing the cells to a composition comprising a compound as described in any one of Implementation Schemes 1-35 or a stereoisomer or tautomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in Implementation Scheme 41.

[0235] Implementation Scheme 44. A method for reducing systemic phenylalanine, tyrosine, glutamine, or glycine levels in an individual in need, the method comprising administering to the individual a compound as described in any of Implementation Schemes 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in Implementation Scheme 41.

[0236] Implementation Scheme 45. A method for treating an individual in need of an SLC6A19-mediated disease, condition, or disorder, the method comprising administering to the individual a compound as described in any of Implementation Schemes 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in Implementation Scheme 41.

[0237] Implementation Scheme 46. The method of Implementation Scheme 45, wherein the disease, condition or disorder is selected from the group consisting of: phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, metabolic disease, hyperphenylalanineemia, tyrosinemia (type I, II or III), nonketotic hyperglycineemia, isovaleric acidemia, methylmalonic acidemia, propionic acidemia, maple syrup diabetes, DNA JC12 deficiency, urea cycle disorder, hyperammonemia, diabetes, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity-related conditions, and neurodevelopmental disorders and autism spectrum disorders.

[0238] Implementation Scheme 47. The method of Implementation Scheme 45 or 46, wherein the disease, condition or disorder is selected from the group consisting of: phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome and metabolic diseases.

[0239] Implementation scheme 48. The method of implementation scheme 45, wherein the disease, symptom or ailment is related to abnormal levels of amino acids.

[0240] Implementation Scheme 49. The method of Implementation Scheme 45 or 46, wherein the disease, symptom or ailment is related to a genetic defect of phenylalanine hydroxylase.

[0241] Implementation scheme 50. The method of any one of implementation schemes 45-49, wherein the individual is a person.

[0242] Implementation Scheme 51. The method of any one of Implementation Schemes 45-50, wherein a therapeutically effective amount of the compound is administered.

[0243] Implementation Scheme 52. A pillbox comprising (i) a compound as described in any of Implementation Schemes 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in Implementation Scheme 41, and (ii) instructions for use in treating an SLC6A19-mediated disease, condition, or ailment in an individual in need.

[0244] Implementation scheme 53. A medicine box as described in implementation scheme 52, wherein the disease, symptom or ailment is related to abnormal levels of amino acids.

[0245] Implementation scheme 54. A medicine box as described in implementation scheme 52 or 53, wherein the disease, symptom or ailment is related to a genetic defect of phenylalanine hydroxylase.

[0246] Implementation Scheme 55. The medicine box of Implementation Scheme 52 or 53, wherein the disease, condition or disorder is selected from the group consisting of: phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, metabolic disease, hyperphenylalanineemia, tyrosinemia (type I, II or III), nonketotic hyperglycemia, isovaleric acidemia, methylmalonic acidemia, propionic acidemia, maple syrup diabetes, DNA JC12 deficiency, urea cycle disorder, hyperammonemia, diabetes, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity-related conditions, and neurodevelopmental disorders and autism spectrum disorders.

[0247] Implementation Scheme 56. A kit as described in any of Implementation Schemes 52-55, wherein the individual has a genetic defect of phenylalanine hydroxylase.

[0248] Implementation Scheme B-1. A compound of any one of Implementation Schemes 1-28, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 Choose from the following groups: , , , , , , , , , and .

[0249] Implementation Scheme B-2. A compound of any one of Implementation Schemes 1-27 or 30-31, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 Choose from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

[0250] Implementation Scheme B-3. The compound of Implementation Scheme 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from compounds 1-90 in Table 1.

[0251] Example The following synthetic reaction schemes detailed in the schemes and examples illustrate only some methods for synthesizing the disclosed compounds or embodiments or aspects thereof. As will be apparent to those skilled in the art, various modifications can be made to these synthetic reaction schemes.

[0252] The starting materials and intermediates of the synthetic reaction scheme can be separated and purified (as needed) using conventional techniques, including (but not limited to) filtration, distillation, crystallization, and chromatography. These materials can be characterized using conventional methods, including physical constants and spectral data.

[0253] Although certain exemplary embodiments are illustrated and described herein, the compounds disclosed herein or any variations thereof or embodiments may be prepared using appropriate starting materials in accordance with the methods generally described herein and / or by means of methods available to those skilled in the art.

[0254] Synthesis Examples As illustrated in the schemes and examples below, in certain exemplary embodiments, compounds of formula (I) as set forth elsewhere herein, or any variation or embodiment thereof, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts of any of the foregoing, are prepared according to general procedures. The general and other methods described below, known to synthetic chemists in the art, can be applied to all formulas, variations, embodiments, and substances set forth herein.

[0255] In some embodiments, this document provides methods for preparing a compound of formula (I) or a stereoisomer or tautomer or a pharmaceutically acceptable salt thereof, according to any one of schemes 1-8.

[0256] plan Option 1 Compound S1-4 can be prepared according to Scheme 1. S1-1 is reacted with pinacol boronic acid ester S1-2 in hot DMF in the presence of a palladium catalyst (e.g., [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloromethane complex) to obtain S1-3. The indole N-sulfonyl protecting group can be removed by heating in an aqueous methanol solution with a base (e.g., potassium carbonate) to obtain compound S1-4.

[0257] Option 2 Compound S2-5 can be prepared according to Scheme 2. S2-1 is reacted with boric acid (e.g., S2-2) in hot dioxane in the presence of a palladium catalyst (e.g., [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloromethane complex) and an inorganic base (e.g., potassium carbonate) via Suzuki coupling to give S2-3. Treatment with a protic acid (e.g., TFA) in a solvent (e.g., DCM) yields S2-4. The indole N-sulfonyl protecting group can be removed by heating in an aqueous methanol solution with a base (e.g., potassium carbonate) to obtain compound S2-5.

[0258] Option 3 Compound S3-4 can be prepared according to Scheme 3. S3-1 and pinacol boronic acid ester S3-2 are subjected to Suzuki coupling in hot dioxane in the presence of a palladium catalyst (e.g., [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloromethane complex) and an inorganic base (e.g., potassium carbonate) to yield S3-3. The indole N-sulfonyl protecting group can be removed by heating in an aqueous methanol solution with a base (e.g., potassium hydroxide) to obtain compound S3-4.

[0259] Option 4 Compound S4-7 can be prepared according to Scheme 7. S4-1 is reacted with bis(pinacolyl)diboron in hot dioxane under a palladium catalyst (e.g., [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloromethane complex) and an inorganic base (e.g., potassium acetate) to give S4-2. S4-2 is then subjected to Suzuki coupling by heating an aryl or heteroaryl halide (e.g., S4-3) in an aqueous solution of dioxane under a palladium catalyst (e.g., chloro[di(1-adamantyl)-N-butylphosphine)-2-(2-aminobiphenyl)]palladium(II)) and an inorganic base (e.g., potassium carbonate) to give S4-4. The indole N-sulfonyl protecting group can be removed by heating in THF under TBAF to give S4-5. The N-Boc group is removed by treatment with a protic acid (e.g., HCl) in EtOAc to give S4-6. The S4-6 compound is coupled with the acid S4-7 in a solvent (e.g., DCM) in the presence of HATU and DIEA to obtain the compound of formula S4-8.

[0260] Option 5 Compound S5-3 can be prepared according to Scheme 5. S5-3 is obtained by Suzuki coupling of S5-1 aryl or heteroaryl halide (e.g., S5-2) with a palladium catalyst (e.g., chloro[di(1-adamantyl)-N-butylphosphine)-2-(2-aminobiphenyl)]palladium(II)) and an inorganic base (e.g., potassium carbonate) in a hot aqueous solution of dioxane.

[0261] Option 6 Compound S6-3 can be prepared according to Scheme 6. S6-1 and carboxylic acid S6-2 are coupled in a solvent (e.g., acetonitrile) in the presence of hexafluorophosphate chloride-N,N,N′,N′-tetramethylformamidinium and N-methylimidazolium to obtain compound S6-3.

[0262] Option 7 Compound S7-3 can be prepared according to Scheme 7. S7-1 is coupled with carboxylic acid S7-2 in a solvent (e.g., ethanol) in the presence of EDCI, HOBt and N-methylimidazole to obtain compound S7-3.

[0263] Option 8 Compound S8-5 can be prepared according to Scheme 8. S8-1 is reacted with aryl or heteroaryl tributyltinane (e.g., S8-2) by heating in a solvent (e.g., dioxane) under a catalyst (e.g., tetrakis(triphenylphosphine)palladium(0)) to obtain S8-3. The N-Boc protecting group is removed by treatment with HCl in a solvent (e.g., EtOAc) to obtain S8-4. The reaction with acetic anhydride and DIEA in a solvent (e.g., DCM) yields compound S8-5.

[0264] Option 9 Compound S9-2 can be prepared according to Scheme 9. Compound S9-1 is obtained by heating in a solvent (e.g., dioxane) and then subjecting it to Stieler coupling with an aryl or heteroaryl tributyltinane in the presence of a catalyst (e.g., tetra(triphenylphosphine)palladium(0)).

[0265] Option 10 Compound S10-2 can be prepared according to scheme 10. Compound S10-1 (wherein R...) is prepared by heating in a mixed solvent system (e.g., dioxane / water). 12 The compound of formula S10-2 can be obtained by Suzuki coupling of a hydrogen or protecting group (e.g., phenylsulfonyl) with an aryl or heteroaryl halide in the presence of a catalyst (e.g., tetra(triphenylphosphine)palladium(0)) and a base (e.g., K2CO3), which may or may not require additional deprotection or functional group manipulation under standard conditions.

[0266] Option 11 Compound S11-4 can be prepared according to Scheme 11. Compound S11-1 is subjected to Suzuki coupling with an aryl or heteroaryl halide in the presence of a catalyst (e.g., Pd(dppf)Cl2) and a base (e.g., K2CO3) by heating in a mixed solvent system (e.g., dioxane / water) to obtain compound S11-2. The amino group is deprotected using a reagent (e.g., HCl in EtOAc) to obtain compound S11-3. The free amino group is acylated using an acyling agent (e.g., carboxylic anhydride) to obtain compound S11-4.

[0267] Option 12 Compound S12-2 can be prepared according to Scheme 12. Using reagents (e.g., S12-2, where R...) 3 and R 13 It may be individually alkyl or hydrogen or wherein R 3 and R 13 The S12-1 compound is reacted in a solvent (e.g., DCM) in the presence of a base (e.g., DIEA) to give the S12-3 compound.

[0268] Option 13 Compound S13-3 can be prepared according to scheme 13. Using reagents (e.g., S13-2, where R...) 3 and R 13 It may be individually alkyl or hydrogen or wherein R 3 and R 13 The S13-1 compound is reacted in a solvent (e.g., DMF) in the presence of CDI and a base (e.g., DIEA) to give the S13-3 compound.

[0269] Intermediate A-1: ​​6-bromo-[1,3]dioxacyclopentenyl[4,5- c Synthesis of pyridine Step a: K₂CO₃ (1.59 g, 11.5 mmol, 2.0 eq) and (chloromethoxy)ethane (815 mg, 8.62 mmol, 1.50 eq) were added dropwise to a solution of 6-bromopyridin-3-ol (1.00 g, 5.75 mmol, 1.00 eq) in DMF (4 mL) at 0 °C. The reaction mixture was then heated to room temperature. After 6 h, the reaction mixture was quenched by adding H₂O (15 mL). The resulting mixture was then extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography to give 2-bromo-5-(ethoxymethoxy)pyridine. LC-MS (ESI) m / z: [M + H] + C8H 10 Calculated value of BrNO2: 232.0; Experimental value: 232.1.

[0270] Step b: 2 M LDA (2.37 mL, 4.74 mmol, 1.10 eq) in anhydrous THF (10 mL) was added dropwise to a solution of 2-bromo-5-(ethoxymethoxy)pyridine (1.00 g, 4.31 mmol, 1.00 eq) in anhydrous THF (10 mL) at -65 °C. After 1 h at -65 °C, a solution of diisopropyl borate (891 mg, 4.74 mmol, 1.10 eq) in THF (5 mL) was added dropwise. The reaction mixture was heated to -15 °C. After 3 h, 30 wt% H₂O₂ (977 mg, 8.62 mmol, 2.00 eq) was added dropwise. The reaction mixture was then heated to room temperature. After 1.5 h, the reaction mixture was quenched by adding H₂O (15 mL). The resulting mixture was extracted using EtOAc (3 × 20 mL). The combined organic layers were washed with saturated aqueous Na₂SO₃ solution (2 × 20 mL) and brine (20 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography to give 2-bromo-5-(ethoxymethoxy)pyridine-4-ol. LC-MS (ESI) m / z: [M + H] + C8H 10 Calculated value of BrNO3: 248.0; Experimental value: 248.1.

[0271] Step c: 4 M HCl (5 mL, 20.0 mmol, 10.0 eq) in MeOH was added to a solution of 2-bromo-5-(ethoxymethoxy)pyridin-4-ol (510 mg, 2.1 mmol, 1.00 eq) in MeOH (3.0 mL). After 2 h, the reaction mixture was concentrated under reduced pressure to give 6-bromopyridin-3,4-diol hydrochloride. LC-MS (ESI) m / z: [M + H] + Calculated value of C5H4BrNO2: 190.0; Experimental value: 189.8.

[0272] Step d: Cs₂CO₃ (971 mg, 2.98 mmol, 1.50 eq) and chloroiodomethane (526 mg, 2.98 mmol, 1.50 eq) were added to a solution of 6-bromopyridine-3,4-diol hydrochloride (450 mg, 1.99 mmol, 1.00 eq) in DMF (15.0 mL). The reaction mixture was then heated to 60 °C. After 2 h, the reaction mixture was cooled to room temperature and quenched by adding H₂O (10 mL). The resulting mixture was extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine (3 × 10 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography to give 6-bromo-[1,3]dioxacyclopenteno[4,5-c]pyridine. LC-MS (ESI) m / z: [M + H] + Calculated value of C6H4BrNO2: 201.9; Experimental value: 202.1.

[0273] Intermediate A-2: 6-chlorothiazo[5,4-] c Synthesis of pyridine Step a: Benzoyl isothiocyanate (9.44 g, 57.8 mmol, 3.0 eq) was added dropwise to a solution of 5-bromo-2-chloropyridin-4-amine (4.0 g, 19.3 mmol, 1.00 eq) in acetone (40 mL). After 16 h, the reaction mixture was concentrated under reduced pressure. The residue was ground with n-heptane (3 mL) for 20 min and then collected by vacuum filtration to obtain N -((5-bromo-2-chloropyridin-4-yl)thiocarbamoyl)benzamide.

[0274] Step b: To N1-(5-bromo-2-chloropyridin-4-yl)thiocarbamoyl)benzamide (6.00 g, 16.2 mmol, 1.00 eq) was dissolved in MeOH (60 mL) with 6 M sodium hydroxide aqueous solution (5.4 mL, 32.4 mmol, 2.0 eq). The reaction mixture was then heated to 75 °C. After 4 h, the reaction mixture was cooled to room temperature and quenched by adding saturated NH4Cl aqueous solution (20 mL). The resulting precipitate was collected by vacuum filtration. The filter cake was washed with H2O (2 × 20 mL) and DCM (20 mL). The filter cake was then dried under reduced pressure to give 1-(5-bromo-2-chloropyridin-4-yl)thiourea. LC-MS (ESI) m / z: [M + H] + Calculated value of C6H5BrClN3S: 265.9; Experimental value: 266.1.

[0275] Step c: L-proline (863 mg, 7.50 mmol, 2.0 eq), Cs₂CO₃ (2.44 g, 7.5 mmol, 2.0 eq), and CuI (71.5 mg, 0.38, 0.1 eq) were added to a solution of 1-(5-bromo-2-chloropyridin-4-yl)thiourea (1.00 g, 3.75 mmol, 1.00 eq) in DMSO (5.0 mL). The reaction mixture was then heated to 70 °C. After 2 h, the reaction mixture was cooled to room temperature and quenched by pouring into H₂O (10 mL). The resulting precipitate was collected by vacuum filtration. The filter cake was washed with H₂O (10 mL) and then dried under reduced pressure to give 6-chlorothiazo[5,4-c]pyridin-2-amine. LC-MS (ESI) m / z: [M + H] + Calculated value of C6H4ClN3S: 186.0; Experimental value: 185.8.

[0276] Step d: Amyl nitrite (1.89 g, 16.2 mmol, 5.00 eq) was added to a solution of 6-chlorothiazo[5,4-c]pyridine-2-amine (600 mg, 3.23 mmol, 1.00 eq) in THF (6.0 mL). The reaction mixture was then heated to 85 °C. After 4 h, the reaction mixture was cooled to room temperature and quenched by pouring into H2O (5 mL). The resulting mixture was extracted with EtOAc (3 × 5 mL). The combined organic layers were washed with brine (2 × 10 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude residue obtained was purified by column chromatography to give 6-chlorothiazo[5,4-c]pyridine. LC-MS (ESI) m / z: [M + H] +Calculated value of C6H3ClN2S: 171.0; Experimental value: 171.2.

[0277] Intermediate A-3: 6-bromo-2,3-dihydro-[1,4]dioxane-[2,3-] b Synthesis of pyrazine Step a: 60% sodium hydride (3.84 g, 95.9 mmol, 2.00 eq) was added fractionally to a solution (63 mL) of ethane-1,2-diol at 0 °C. After 30 min, 5-bromo-6-chloropyrazine-2-amine (10.0 g, 47.9 mmol, 1.00 eq) was added fractionally. The reaction mixture was then heated to 140 °C. After 1 h, the reaction mixture was cooled to room temperature and quenched by adding ice water (50.0 mL). The resulting mixture was then extracted with EtOAc (2 × 50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude residue was ground with EtOAc (12 mL) for 10 min. The solid was collected by vacuum filtration and dried under reduced pressure to give 2-((6-bromo-4-iodopyridin-3-yl)oxy)ethane-1-ol. LC-MS (ESI) m / z: [M + H] + Calculated value of C6H8BrN3O2: 234.0; Experimental value: 234.2.

[0278] Step b: A solution of 2-((6-bromo-4-iodopyridin-3-yl)oxy)ethane-1-ol (4.10 g, 17.5 mmol, 1.00 eq) in (dimethoxymethyl)dimethylamine (12 mL) was heated to 50 °C. After 1 h, the reaction solution was cooled to room temperature and quenched by adding ice water (25 mL). The resulting mixture was extracted with EtOAc (2 × 20 mL). The combined organic layers were washed with brine (15 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude residue obtained was ground with EtOAc (15 mL) for 10 min. The solid was collected by vacuum filtration and dried under reduced pressure to obtain ( E )- N -(5-bromo-6-(2-hydroxyethoxy)pyrazin-2-yl)- N , N -Dimethylformamidinium. LC-MS (ESI) m / z: [M + H] + C9H 13 Calculated value of BrN4O2: 289.0; Experimental value: 288.8.

[0279] Step c: Add to toluene (310 mL) ( E )- N -(5-bromo-6-(2-hydroxyethoxy)pyrazin-2-yl)- N , N - Dimethylformamidin (3.10 g, 10.7 mmol, 1.00 eq) was added to Cs₂CO₃ (10.4 g, 32.1 mmol, 3.00 eq), Pd(OAc)₂ (240 mg, 1.1 mmol, 0.1 eq), and BINAP (1.34 g, 2.14 mmol, 0.20 eq). The sealed reaction vessel was evacuated and refilled three times with nitrogen, then heated to 90 °C. After 16 h, the reaction mixture was cooled to room temperature and quenched by pouring into H₂O (30 mL). The resulting mixture was extracted with EtOAc (3 × 30 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude residue obtained was purified by column chromatography and preparative HPLC to obtain ( E )- N -(2,3-dihydro-[1,4]dioxanehexeno[2,3-b]pyrazin-6-yl)- N , N - Dimethylformamidinium. LC-MS (ESI) m / z: [M + 2H] + C9H 12 Calculated value of N4O2: 209.1; Experimental value: 209.1.

[0280] Step d: Add (12 mL) of EtOH to ( E )- N -(2,3-dihydro-[1,4]dioxanehexeno[2,3-b]pyrazin-6-yl)- N , N Ethane-1,2-diamine (380 mg, 6.32 mmol, 2.19 eq) was added dropwise to dimethylformamidin (1.2 g, 2.88 mmol, 1.00 eq). The reaction mixture was then heated to 80 °C. After 12 h, the reaction mixture was cooled to room temperature and quenched by pouring into H₂O (20 mL). The resulting mixture was extracted with EtOAc (3 × 10 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude residue obtained was purified by preparative HPLC to give 2,3-dihydro-[1,4]dioxane-[2,3-b]pyrazin-6-amine. LC-MS (ESI) m / z: [M + H] +Calculated value of C6H7N3O2: 154.1; Experimental value: 154.0.

[0281] Step e: At 0 °C, a solution of 40% HBr aqueous solution (1 mL, 7.37 mmol, 5.9 eq) and NaNO2 (128 mg, 1.86 mmol, 1.5 eq) in H2O (1 mL) was added to a solution of 2,3-dihydro-[1,4]dioxane-[2,3-b]pyrazin-6-amine (190 mg, 1.24 mmol, 1.00 eq) in H2O (0.5 mL). After 5 minutes, CuBr (355 mg, 2.48 mmol, 2.00 eq) was added in a single addition. After 1 h, the reaction solution was heated to room temperature and quenched by pouring into H2O (2 mL). The resulting mixture was extracted with EtOAc (3 × 3 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude residue was purified by preparative HPLC to give 6-bromo-2,3-dihydro-[1,4]dioxane-[2,3-b]pyrazine. LC-MS (ESI) m / z: [M + H] + Calculated value of C6H5BrN2O2: 217.0; Experimental value: 217.2.

[0282] Intermediate A-4: N -((6-acetyl-5-chloro-1-(phenylsulfonyl)-1 H Synthesis of 1-indol-2-yl)methyl)acetamide Step a: N -((6-Bromo-5-chloro-1-(phenylsulfonyl)-1 HA mixture of indole-2-yl)methyl)acetamide (1.50 g, 3.40 mmol, 1.00 eq) and tributyl(1-ethoxyvinyl)stanane (2.45 g, 6.79 mmol, 2.00 eq) in dioxane (10 mL) was degassed and purged three times with N2, followed by the addition of Pd(PPh3)2Cl2 (238 mg, 339 µmol, 0.10 eq). The reaction mixture was then heated to 90 °C and stirred for 16 h. The reaction mixture was then cooled to 23 °C and quenched by the addition of an aqueous HCl solution (1 M, 5 mL). The resulting mixture was extracted with EtOAc (3 × 15 mL). The combined organic extracts were washed with brine (3 × 15 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude residue obtained was milled at 23 °C with MTBE (10 mL) for 30 min to obtain N -((6-acetyl-5-chloro-1-(phenylsulfonyl)-1 H (-Indole-2-yl)methyl)acetamide. LC-MS (ESI): m / z: [M + H] + C 19 H 17 ClN2O 4- Calculated value of S: 405.1; Experimental value: 405.1.

[0283] Intermediate A-5: N -((6-Bromo-5-chloro-1-(phenylsulfonyl)-1 H -indol-2-yl)methyl)-λ 5 Synthesis of chloromethylamine Step a: Four reactions were performed in parallel. Acetic acid (41.6 mL, 726.0 mmol, 3.0 eq) was added dropwise to a solution of 3-bromo-4-chloroaniline (50.0 g, 242.0 mmol, 1.00 eq) in DCM (270.0 mL), followed by dropwise addition of NIS (76.3 g, 339.0 mmol, 1.40 eq.) in MeOH (270 mL) over 1 h. After 5 h, the four reaction solutions were combined for further processing. The reaction mixture was quenched by adding H2O (2.0 L). The resulting mixture was then extracted with EtOAc (3 × 2.0 L). The combined organic layers were washed with brine (3 × 1.0 L), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude residue obtained was purified by column chromatography to give 5-bromo-4-chloro-2-iodoaniline. LC-MS(ESI) m / z: [M + H] +Calculated value of C6H4BrClIN: 331.8; Experimental value: 331.9.

[0284] Step b: To a solution of 5-bromo-4-chloro-2-iodoaniline (118.0 g, 355.0 mmol, 1.00 eq) in DMF (1.0 L), tert-butyl propionate (55.1 g, 355 mmol, 1.0 eq), TEA (247 mL, 1.78 mol, 5.00 eq), CuI (13.5 g, 71.0 mmol, 0.20 eq), and bis(triphenylphosphine)palladium(II) dichloride (7.5 g, 10.7 mmol, 0.03 eq) were added. The sealed reaction vessel was evacuated and refilled three times with nitrogen. After 2 h at room temperature, the reaction solution was quenched by pouring into ice water (2.0 L). The resulting mixture was extracted using EtOAc (3 × 1.0 L). The combined organic layers were washed with brine (3 × 1.0 L), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography to give tert-butyl (3-(2-amino-4-bromo-5-chlorophenyl)prop-2-yn-1-yl)carbamate. LC-MS (ESI) m / z: [M - C₄H₁₉₂H] + C 14 H 16 Calculated value of BrClN2O2: 303.0; Experimental value: 302.8.

[0285] Step c: Pyridine (49.4 mL, 611.0 mmol, 2.0 eq) was added dropwise to a solution of (3-(2-amino-4-bromo-5-chlorophenyl)prop-2-yn-1-yl)carbamate (110.0 g, 305 mmol, 1.00 eq) in DCM (1.0 L) at 0 °C, followed by dropwise addition of benzenesulfonyl chloride (39.0 mL, 305 mmol, 1.00 eq). The reaction mixture was then heated to room temperature. After 1 h, the reaction mixture was quenched by pouring it into ice water (2.0 L). The resulting biphasic mixture was extracted using EtOAc (3 × 1.0 L). The combined organic layers were washed with brine (3 × 1.0 L), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to give tert-butyl (3-(4-bromo-5-chloro-2-(phenylsulfonamido)phenyl)prop-2-yn-1-yl)carbamate, which was used without further purification. LC-MS (ESI) m / z: [M + Na] + C 20 H 20 Calculated value of BrClN2O4S: 521.0; Experimental value: 521.0.

[0286] Step d: CuCl (4.46 g, 45.0 mmol, 0.15 eq) and Cs₂CO₃ (14.7 g, 45.0 mmol, 0.15 eq) were added to a solution of (3-(4-bromo-5-chloro-1-(phenylsulfonyl)phenyl)prop-2-yn-1-yl)carbamate (150.0 g, 300.0 mmol, 1.00 eq) in MeCN (1.5 L). The sealed reaction vessel was evacuated and refilled three times with nitrogen. After 3 h at room temperature, the reaction solution was quenched by pouring into ice water (2.0 L). The resulting biphasic mixture was extracted with EtOAc (3 × 1.0 L). The combined organic layers were washed with brine (3 × 1.0 L), dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give ((6-bromo-5-chloro-1-(phenylsulfonyl)-1-yl)carbamate. H 2-Indole-2-yl)methyl)carbamate tert-butyl ester, used without any further purification. LC-MS (ESI) m / z: [M - C4H9+ 2H] + C 20 H 20 Calculated value of BrClFN2O4S: 442.9; Experimental value: 443.1.

[0287] Step e: At 0°C, to ((6-bromo-5-chloro-1-(phenylsulfonyl)-1) H tert-butyl indo-2-yl)methyl)carbamate (59.0 g, 118.0 mmol, 1.00 eq) was added fractionally to a solution of EtOAc (10 mL) with 4 M HCl (500 mL, 2.0 mol, 16.9 eq). The reaction mixture was then heated to room temperature. After 1 h, the reaction mixture was concentrated under reduced pressure to obtain... N -((6-Bromo-5-chloro-1-(phenylsulfonyl)-1 H -indol-2-yl)methyl)-λ 5 -Chloromethylamine, which was used without further purification. LC-MS (ESI) m / z: [M+H] + C 15 H 12 Calculated value of BrClN2O2S: 398.9; Experimental value: 399.1.

[0288] Example S-1: N -((5-Chloro-7-Fluoro-6-(5-Methoxypyrazin-2-yl)-1 H Synthesis of -indol-2-yl)methyl)acetamide (compound 78) Step a: 1-Chloroprene-2,5-dione (10.3 g, 77.3 mmol, 1.05 eq) was added to a solution of 3-bromo-2-fluoroaniline (14.0 g, 73.7 mmol, 1.00 eq) in DMF (70.0 mL). After addition, the reaction mixture was heated to 70 °C and stirred for 1 h. The reaction mixture was then cooled to 0 °C and quenched by adding H2O (100 mL). The resulting mixture was then extracted with EtOAc (3 × 60 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give 3-bromo-4-chloro-2-fluoroaniline, which was used without further purification.

[0289] Step b: 1-Iodopyrrolidine-2,5-dione (22.5 g, 100.0 mmol, 1.50 eq) and BF3•Et2O (9.48 g, 66.8 mmol, 1.00 eq) were added to a solution of 3-bromo-4-chloro-2-fluoroaniline (15.0 g, 66.8 mmol, 1.00 eq) in DCM (80 mL) at 0 °C. After 1 h, the reaction mixture was quenched with water (100 mL) and then heated to room temperature. The resulting biphasic mixture was extracted with EtOAc (3 × 100 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude residue obtained was purified by column chromatography to give 3-bromo-4-chloro-2-fluoro-6-iodoaniline.

[0290] Step c: To a solution of 3-bromo-4-chloro-2-fluoro-6-iodoaniline (6.90 g, 19.6 mmol, 1.00 eq) in DMF (70 mL), tert-butyl propionate (3.67 g, 23.6 mmol, 1.20 eq), TEA (9.96 g, 98.4 mmol, 5.00 eq), CuI (750 mg, 3.94 mmol, 0.20 eq), and bis(triphenylphosphine)palladium(II) dichloride (1.38 g, 1.97 mmol, 0.10 eq) were added. The sealed reaction vessel was evacuated and refilled three times with nitrogen. After 1 h at room temperature, the reaction solution was quenched with water (30 mL). The resulting mixture was extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography to give tert-butyl (3-(2-amino-4-bromo-5-chloro-3-fluorophenyl)prop-2-yn-1-yl)carbamate. LC-MS (ESI) m / z: [M + H] + C 14 H 16 Calculated value of BrClFN2O2: 377.0; Experimental value: 377.1.

[0291] Step d: Cu(OAc)₂•H₂O (1.56 mmol, 7.81 mL, 0.50 eq) was added to a solution of (3-(2-amino-4-bromo-5-chloro-3-fluorophenyl)prop-2-yn-1-yl)carbamate (5.90 g, 15.6 mmol, 1.00 eq) in 1,2-DCE (60 mL). The reaction mixture was then heated to 100 °C. After 3 h, the reaction mixture was cooled to room temperature and quenched by pouring into H₂O (40 mL). The biphasic solution was then extracted with EtOAc (3 × 50 mL). The combined organic extracts were washed with brine (2 × 50 mL), dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The obtained crude residue was purified by column chromatography to give ((6-bromo-5-chloro-7-fluoro-1-yl)carbamate. H 2-Indole-2-yl)methyl)tert-butyl carbamate. LC-MS (ESI) m / z: [M - C4H9+ 2H] + C 14 H 16 Calculated value of BrClFN2O2: 320.9; Experimental value: 321.0.

[0292] Step e: At 0°C, to ((6-bromo-5-chloro-7-fluoro-1) H4 M HCl was added dropwise to a solution of tert-butyl indo-2-yl)methyl)carbamate (2.00 g, 5.30 mmol, 1.00 eq) in EtOAc (10 mL) to a solution of tert-butyl in EtOAc (20 mL, 80.00 mmol, 15.10 eq). The reaction mixture was then heated to room temperature. After 1 h, the reaction mixture was concentrated under reduced pressure to give (6-bromo-5-chloro-7-fluoro-1-yl)carbamate. H (-Indole-2-yl)methylamine hydrochloride, used without further purification. LC-MS (ESI) m / z: [M-NH2] + Calculated value of C9H8BrClFN2: 259.9; Experimental value: 260.0.

[0293] Step f: To (6-bromo-5-chloro-7-fluoro-1) H DIEA (1.32 g, 10.1 mmol, 2.00 eq) and acetic anhydride (728 mg, 7.13 mmol, 1.40 eq) were added dropwise to a solution of 16 mL of indole-2-yl)methylamine hydrochloride (1.60 g, 5.10 mmol, 1.00 eq) in THF. After 1 h, the reaction mixture was quenched by pouring into 10 mL of H₂O. The reaction mixture was extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with brine (10 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure. The crude residue was purified by column chromatography to obtain N -((6-bromo-5-chloro-7-fluoro-1 H (-Indole-2-yl)methyl)acetamide. LC-MS (ESI) m / z: [M + H] + C 11 H 10 Calculated value of BrClFN2O: 319.0; Experimental value: 319.0.

[0294] Step g: Perform two reactions in parallel. To N -((6-bromo-5-chloro-7-fluoro-1 H2-Methoxy-5-(tributyltinyl)acetamide (640 mg, 1.13 mmol, 1.00 eq) and Pd(PPh3)4 (145.0 mg, 0.13 mmol, 0.20 eq) were added to a solution of 2-indo-2-yl)methyl)acetamide (640 mg, 1.25 mmol, 2.00 eq) in dioxane (2.0 mL). The s...

Claims

1. A compound of formula (I): (I)， Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 The C mentioned 1-6 Alkyl, the C 1-6 Alkoxy, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a Replace, and R 3 The 4-10 heteroaryl group is optionally derived from one or more R 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 alkyl or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 The C mentioned 1-6 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace, and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

2. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein: m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 cycloalkyl, -N(R) 4 )2 or 4-10 membered heterocyclic groups, of which R 3 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a replace; Each R 4 Independently for H and C 1-6 Alkyl, C 1-6 Halogenated alkyl or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl, the C 1-6 Halogenated alkyl groups or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a Replace, or Two Rs 4 Together with the N atom it is attached to, it forms an optional structure via one or more R atoms. 4a Substituted 4-10 membered heterocyclic groups; R 5 and R 7 Each is independently H, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heterocyclic groups, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkyl group.

3. The compound of claim 1, wherein the compound is a compound of formula (IA): (I-A), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing.

4. The compound according to any one of claims 1-3, wherein the compound is a compound of formula (IB): (I-B), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Ring A is C 6-20 aryl, 5-10 membered heteroaryl or 5-10 membered heterocyclic, wherein the C 6-20 Aryl, the 5-10 membered heteroaryl, or the 5-10 membered heterocyclic group are each optionally irradiated by one or more R a replace.

5. The compound of any one of claims 1-4, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein... m It is an integer between 1 and 2.

6. The compound of any one of claims 1-4, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein... m The value is 1.

7. The compound of any one of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 C 1-3 alkyl.

8. The compound of any one of claims 1-7, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 It is a methyl group.

9. The compound of any one of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 For optional access via one or more R 3a Replacement C 1-3 alkyl.

10. The compound of any one of claims 1-6 or 9, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 for , , , , , , , , , , , , , , , , , , or .

11. The compound of any one of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 For optional access via one or more R 3a Replacement C 3-6 Cycloalkyl.

12. The compound of any one of claims 1-6 or 11, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 For optional access via one or more R 3a Replacement C 3-6 cycloalkyl; R 3a -OH, -CN, halogen, C 1-6 Alkyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 alkyl) 2 or 4-10 heteroaryl, wherein R 3a The C mentioned 1-6 Alkyl groups are optionally oxidized via one or more R groups. 3b Replace; and R 3b It is a halogen group.

13. The compound of any one of claims 1-6 or 11-12, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 Choose from the following groups: , , , , , , , , , , , , and .

14. The compound of any one of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 -N(R) 4 )2, where each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 Alkyl groups optionally via one or more R 4a Replace; R 4a Each time it appears, it is independently -OH, -CN, halogen, or C. 1-6 Alkyl or C 1-6 Alkyl group.

15. The compound of any one of claims 1-6 and 14, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 Choose from the following groups: , , , , , , , , , , , , , , , , and .

16. The compound of any one of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 For optional access via one or more R 3a Substituted 4-6 membered heterocyclic groups.

17. The compound of any one of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 For optional access via one or more R 3a Substituted 4-10 membered heterocyclic groups; R 3a Each time it appears, it is independently -OH, -CN, or C. 1-6 alkyl.

18. The compound of any one of claims 1-6 and 17, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 Choose from the following groups: , , , , , , , , , , , , , , , , , , , and .

19. The compound of any one of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 C 1-3 Alkyl group.

20. The compound of any one of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 It is a methoxy group.

21. The compound of any one of claims 1-6, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 Optionally via one or more R 3x Substituted 4-10 heteroaryl groups; R 3x It is C independently each time it appears. 1-6 alkyl.

22. The compound of any one of claims 1-6 and 21, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 3 Choose from the following groups: , , , , , , , , , , , , , , , and .

23. The compound of any one of claims 1-22, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 5 and R 7 Each is independently H, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Halogenated alkyl groups.

24. The compound of any one of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 5 and R 7 Each is independently represented by H.

25. The compound of any one of claims 1-23, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 5 and R 7 One of them is H, and R 5 and R 7 The other one is a halogen group, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 The C mentioned 1-6 Each alkoxy group may be independently and optionally substituted with one or more halogen groups.

26. The compound of any one of claims 1-25, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 and R 9 Each is independently represented by H.

27. The compound of any one of claims 1-25, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 6 and R 9 One of them is H, and R 6 and R 9 The other one is F or Cl.

28. The compound of any one of claims 1-27, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 For optional access via one or more R 8a Substituted 3-10 membered heterocyclic groups.

29. The compound of any one of claims 1-28, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 Choose from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , and .

30. The compound of any one of claims 1-27, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 For optional access via one or more R 8a Substituted 5-10 heteroaryl groups.

31. The compound of any one of claims 1-27 or 30, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 For optional access via one or more R 8a Substituted 5-10 aryl groups, wherein each R 8a Independently -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl)2, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a The C mentioned 1-6 alkyl or the C 1-6 Alkyl groups are optionally oxidized via one or more R groups. 8b Replace; and each R 8b It can be D, -OH, or a halogen group independently.

32. The compound of any one of claims 1-27 or 30-31, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein R 8 Choose from the following groups: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and .

33. The compound according to any one of claims 1-27 or 30-32, wherein the compound has the formula (IH): (I-H), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein s Integers from 0 to 6; t It is 1 or 2; and It represents a single bond or a double bond.

34. The compound of claim 33, wherein the compound has the following formula: (IHbi) (IHb-ii), (IHb-iii) or (IHb-iv), or its stereoisomers or tautomers, or a pharmaceutically acceptable salt of any of the foregoing.

35. The compound of claim 1, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from compounds 1-339 of Table 1.

36. A method for preparing a compound of formula (I) as defined in any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, the method comprising: (a) Make the compound of formula (I-1): (I-1)， Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Q 1 It is a halogenated group; PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -N-, -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 The C mentioned 1-6 Alkyl, the C 1-6 Alkoxy, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a Replace, and R 3 The 4-10 heteroaryl group is optionally derived from one or more R 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 alkyl or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 The C mentioned 1-6 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 10 For H; R 3a and R 4a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace, and R 3b and R 4b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; With compound of formula (I-2): (I-2)， Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Y 1 It is boric acid or borate ester; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; Each R 8a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b Replace; and Each R 8b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkoxy; The reaction is carried out in the presence of a coupling agent to provide a compound of formula (I-3): (I-3)， Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 The C mentioned 1-6 Alkyl, the C 1-6 Alkoxy, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a Replace, and R 3 The 4-10 heteroaryl group is optionally derived from one or more R 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 alkyl or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is independently and optionally substituted with one or more -CN groups, and R 5 and R 7 The C mentioned 1-6 Each alkoxy group is independently and optionally substituted with one or more halogen groups; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace, and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; Subsequently, (b) Optionally, the compound of formula (I-3) is contacted with a deprotecting agent; To provide compounds of formula (I).

37. The method of claim 35, wherein the coupling agent comprises a palladium catalyst, a phosphine ligand, and / or a base.

38. A method for preparing a pharmaceutically acceptable salt of a compound of formula (I) as defined in any one of claims 1-35, or a stereoisomer or tautomer thereof, or any of the foregoing, the method comprising: (a) Make the compound of formula (II-1): (II-1), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Q 3 For H; PG is absent or has a protecting group; m Integers from 1 to 4; R 1a It can be -N-, -NH-, -O-, or -S-; R 2 For H; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 alkyl or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; R 10 For H; R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; With compound of formula (II-2): (II-2), Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: Y 3 It is a -C(O)OH or -C(O)- halogroup; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 The C mentioned 1-6 Alkyl, the C 1-6 Alkoxy, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a Replace, and R 3 The 4-10 heteroaryl group is optionally derived from one or more R 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -N- or -NH-; and Each R 3a Independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace; R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace, and Each R 3b Independently D, -OH, halogen, C 1-6 Alkyl or C 1-6 Alkoxy; The reaction is carried out in the presence of a coupling agent to provide a compound of formula (I-3): (I-3)， Or its stereoisomers or tautomers, or pharmaceutically acceptable salts of any of the foregoing, wherein: PG is absent or has a protecting group; m Integers from 1 to 4; R 1 It can be -NH-, -O-, or -S-; R 2 For H; R 3 C 1-6 Alkyl, C 1-3 Alkoxy, C 3-10 cycloalkyl, -N(R) 4 )2, 4-10 membered heteroaryl or 4-10 membered heterocyclic group, wherein R 3 The C mentioned 1-6 Alkyl, the C 1-6 Alkoxy, the C 3-10 cycloalkyl groups or the 4-10 membered heterocyclic groups optionally via one or more R groups 3a Replace, and R 3 The 4-10 heteroaryl group is optionally derived from one or more R 3x replace, The constraint is that when R 3 When R is a 4-10 quinone heteroaryl group, 1 It is -NH-; Each R 4 Independently for H and C 1-6 Alkyl, 4-10 membered heteroaryl, 4-10 membered heterocyclic or C 3-10 cycloalkyl, wherein R 4 The C mentioned 1-6 alkyl or the C 3-10 cycloalkyl groups are optionally cyclic to one or more R 4a replace; R 5 and R 7 Each can be independently H, halogen, -CN, or C. 1-6 Alkyl, C 1-6 Alkoxy, C 3-10 cycloalkyl or C 1-6 Halogenated alkyl groups, wherein R 5 and R 7 The C mentioned 1-6 Each alkyl group is optionally substituted with one or more -CN groups independently; R 6 and R 9 Each can be an H or a halogen group independently; R 8 C 3-10 cycloalkyl, C 6-20 aryl, 3-10 heterocyclic or 5-10 heteroaryl, among which R 8 The C mentioned 3-10 cycloalkyl, the C 6-20 Aryl, the 3-10 membered heterocyclic group or the 5-10 membered heteroaryl group optionally via one or more R 8a replace; R 10 For H; R 3a R 4a and R 8a Each can be independently -OH, oxo group, -CN, halogen group, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2、-C(O)C 1-6 Alkyl group, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b replace, R 4a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 4b Replace, and R 8a The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 8b replace; R 3x -OH, -CN, halogen, C 1-6 Alkyl, C 2-6 alkenyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups, -OC 1-6 Halogenated alkyl groups, -NH2, -NH(C) 1-6 alkyl), -N(C) 1-6 Alkyl)2, -C(O)NH2, -C(O)NH(C 1-6 Alkyl), -C(O)N(C 1-6 Alkyl) 2, 4-10 membered heteroaryl, 4-10 membered heterocyclic, C 3-10 cycloalkyl or -OC 3-10 cycloalkyl, wherein R 3x The C mentioned 1-6 Alkyl, the C 1-6 alkoxy group, the 4-10 membered heterocyclic group, the C 3-10 cycloalkyl or -OC 3-10 cycloalkyl groups are optionally cyclic to one or more R 3b Replace, and R 3b R 4b and R 8b Each is independently a D, -OH, halogen group, or C group. 1-6 Alkyl or C 1-6 Alkoxy; Subsequently, (b) Optionally, the compound of formula (I-3) is contacted with a deprotecting agent; To provide compounds of formula (I).

39. The method of any one of claims 36-38, wherein the protecting group is a sulfonyl group.

40. The method of any one of claims 36-39, wherein the deprotecting agent comprises an alkali.

41. A pharmaceutical composition comprising (i) a compound as described in any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, and (ii) one or more pharmaceutically acceptable excipients.

42. A method for regulating SLC6A19 in cells, the method comprising exposing the cells to a composition comprising a compound as described in any one of claims 1-35 or a stereoisomer or tautomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 41.

43. A method for inhibiting SLC6A19 in cells, the method comprising exposing the cells to a composition comprising a compound as described in any one of claims 1-35 or a stereoisomer or tautomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 41.

44. A method for reducing systemic phenylalanine, tyrosine, glutamine, or glycine levels in an individual in need, the method comprising administering to the individual a compound as described in any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 41.

45. A method of treating an individual with an SLC6A19-mediated disease, condition, or disorder, the method comprising administering to the individual a compound as described in any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 41.

46. ​​The method of claim 45, wherein the disease, condition, or disorder is selected from the group consisting of: phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, metabolic disease, hyperphenylalanineemia, tyrosinemia (type I, II, or III), nonketotic hyperglycemia, isovaleric acidemia, methylmalonic acidemia, propionic acidemia, maple syrup diabetes, DNA JCl2 deficiency, urea cycle disorder, hyperammonemia, diabetes, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity-related disorders, and neurodevelopmental disorders and autism spectrum disorders.

47. The method of claim 45 or 46, wherein the disease, condition or disorder is selected from the group consisting of phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome and metabolic diseases.

48. The method of any one of claims 45-47, wherein the disease, condition or ailment is chronic kidney disease (CKD).

49. The method of claim 45, wherein the disease, symptom, or ailment is related to abnormal levels of amino acids.

50. The method of claim 45 or 46, wherein the disease, symptom, or ailment is related to a genetic defect in phenylalanine hydroxylase.

51. The method of any one of claims 45-50, wherein the individual is a person.

52. The method of any one of claims 45-51, wherein a therapeutically effective amount of the compound is administered.

53. A pillbox comprising (i) a compound as described in any one of claims 1-35 or a stereoisomer or tautomer thereof or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described in claim 41, and (ii) instructions for use in treating an SLC6A19-mediated disease, condition or disorder in an individual in need.

54. The medicine box of claim 53, wherein the disease, symptom, or ailment is related to abnormal levels of amino acids.

55. The medicine box as claimed in claim 53 or 54, wherein the disease, symptom, or ailment is related to a genetic defect of phenylalanine hydroxylase.

56. The medicine box as claimed in claim 53 or 54, wherein the disease, condition, or disorder is selected from the group consisting of: phenylketonuria (PKU), chronic kidney disease (CKD), metabolic syndrome, metabolic disease, hyperphenylalanineemia, tyrosinemia (type I, II, or III), nonketotic hyperglycemia, isovaleric acidemia, methylmalonic acidemia, propionic acidemia, maple syrup diabetes, DNA JC12 deficiency, urea cycle disorder, hyperammonemia, diabetes, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, obesity-related disorders, and neurodevelopmental disorders and autism spectrum disorders.

57. The pillbox according to any one of claims 53-56, wherein the individual has a genetic defect of phenylalanine hydroxylase.

58. The compound of any one of claims 1-35, or its stereoisomer or tautomer or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 41, for regulating SLC6A19 in cells.

59. The compound of any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 41, for inhibiting SLC6A19 in cells.

60. The compound of any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 41, for reducing systemic phenylalanine, tyrosine, glutamine, or glycine levels in an individual in need.

61. The compound of any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 41, for the treatment of an individual in need of an SLC6A19-mediated disease, condition, or disorder.

62. Use of the compound of any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 41, for the manufacture of a medicament for regulating SLC6A19 in cells.

63. Use of the compound of any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 41, for the manufacture of a medicament for inhibiting SLC6A19 in cells.

64. Use of the compound of any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 41, for the manufacture of a medicament for reducing systemic phenylalanine, tyrosine, glutamine, or glycine levels in an individual in need.

65. Use of the compound of any one of claims 1-35, or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 41, for the manufacture of a medicament for treating an individual in need of SLC6A19-mediated disease, condition, or disorder.

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