Substituted indole compounds and methods for using them

Abstract

Substituted indole compounds are provided herein. In certain embodiments, the compounds are inhibitors of the alternative pathway of the complement system, in particular inhibitors of complement factor B (CFB). Also provided are compositions comprising the compounds and methods of using the same. The compounds provided are useful for treating, preventing or ameliorating diseases, conditions or disorders through inhibition of the alternative pathway of complement.

Description

[Technical Field]

[0001] Substituted indole compounds are provided herein. In certain embodiments, the compounds are inhibitors of alternative complement pathways, particularly complement factor B (CFB). Compositions containing these compounds and methods of using them are also provided. The provided compounds are useful for the treatment, prevention, or improvement of diseases, conditions, or disorders through inhibition of alternative complement pathways. [Background technology]

[0002] The complement system is a crucial component of the innate immune system, possessing two main functions: host defense against microbial pathogens and clearance of apoptotic cells. Since its initial discovery in the 1890s by Jules Bordet and Paul Ehrlich, more than a century of research on complement has revealed its diverse roles in immune responses, surveillance, homeostasis, and metabolism (Hajishengallis, Nat Immunol 2017 18:1288-1298; Sim, Immunobiology 2016 221(10):1037-1045; Ricklin, Nat Immunol 2010 11(9):785-797). The complement system contains numerous soluble proteins found in circulation and tissues as inactive enzyme precursors activated by serine protease cleavage. Complement activation is tightly regulated by plasma and membrane-bound regulators. Dysregulation of complement activity due to gene mutations, autoantibodies, or chronic inflammation is known to cause tissue damage in a variety of pathological conditions, including autoimmunity, inflammation, neurodegeneration, and widespread renal disease (Zipfel, Nat Rev Immunol 2009 9:729-749; Holers, Annu Rev Immunol 2014 32:433-459).

[0003] There are three activation pathways: the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP) (Merle, Front Immunol 2015 6:262). CP is activated by immunoglobulins (IgG and IgM) and immune complexes by binding C1q to the Fc domain (Botto, Annu Rev Immunol 2002 205:395-406). LP is activated by a group of proteins that bind to sugars on the surface of bacteria, such as mannose-binding lectins (MBLs) (Garred, Immunol Rev 2016 274(1):74-97). In contrast to the other two pathways, which require specific stimuli for activation, AP maintains low levels of activation in plasma through a spontaneous hydrolytic process called "tick-over" and can also be secondarily activated by the other two complement pathways (Lachmann, Adv Immunol 2009 104:115-149). AP forms a loop that rapidly self-amplifies unless inactivated by factor H and factor I. Three activation pathways generate protease complexes called "C3 convertases" (C3bBb and C4b2a) to cleave C3, forming C3bBbC3b as a C5 convertase. The terminal complement pathway assembles C5b with other complement proteins to form the C5b-9 membrane invasion complex (MAC), which mediates the lysis of pathogens or apoptotic cells (Bhakdi, Immunol Today 1991 12:318-320). Two soluble fragments of the C3 and C5 cleavage products, C3a and C5a (also called "anaphylatoxins"), are potent chemotacticants that trigger inflammatory responses via their receptors (Klos, Mol Immunol 2009 46(14):2753-2766).

[0004] Complement hyperactivation and renal deposition are observed in various chronic kidney diseases (CKDs), including atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), IgA nephropathy (IgAN), membranous nephropathy (MN), ANCA-associated vasculitis (AAV), focal segmental glomerulosclerosis (FSGS), and lupus nephritis (LN) (Harris, Semin Immunopathol 2018 40(1):125-140; Willows, Clin Med 2020 20(2):156-160). Preclinical and clinical evidence supports the role of complement, particularly AP, in disease onset and progression. Genetic defects in complement genes such as CFH, CFI, CFHR, CFB, C3, and MCP / CD46 have been directly linked to aHUS and C3G (Bu, J Am Soc Nephrol 2014 25(1):55-64; Marinozzi, J Am Soc Nephrol 2015 25:2053-2065; Xiao, Semin Thromb Hemost 2014 40(4):465-471). Complement activation by autoantibodies and immune complexes in the kidney leads to renal damage and contributes to the progression of several glomerular diseases (Corvillo, Front Immunol 2019 10:886; Marinozzi, J Am Soc Nephrol 2017 28(5):1603-1613; Seikrit, N Engl J Med 2018 379(25):2479-2481). Recent studies provide evidence of local renal production and activation of complement proteins in CKD, including IgAN and diabetic nephropathy (Muehlig, Front Immunol 2020 11:1833; Zhou, Clin J Am Soc Nephrol 2021 16(2):213-224; Kelly Am J Nephrol 2015 41:48-56). The kidneys are thought to be more susceptible to complement hyperactivation due to local complement production and their unique microenvironment (Thurman, Clin J Am Soc Nephrol 2020 11:1856).

[0005] Considerable effort has been devoted to the development of complement-targeted therapies. Eculizumab is a C5 monoclonal antibody approved for the treatment of aHUS. However, when tested in C3G, only a small fraction of patients with higher levels of C5b-9 (MAC) showed disease improvement. This is likely due to the contribution of activating fragments at the C3 level upstream of the terminal pathway (Vivarelli, Semin Thromb Hemost 2014 40(4):472-477). Several therapeutic agents targeting various complement pathways are currently under development, each with its own advantages and limitations (Zipfel, Front Immunol 2019 10:2166; Thurman, Kidney Int 2016 90(4):746-752). Nevertheless, there is still a need for potent therapeutic compounds that block both the C3 and C5 levels of the complement system.

[0006] As a major enzyme in AP, CFB provides a highly desirable target for blocking the central amplification loop and terminal complement pathway. Knocking out CFB has been shown to be protective in rodent models of C3G (Pickering, Nat Genet 2002 31(4):424-428), MN (Luo, Front Immunol 2018 9:1433), ANCA-associated vasculitis (Xiao, Am J Pathol 2007 170(1):52-64), LN (Watanabe, J Immunol 2000 164(2):786-794), and multiple renal impairment models (Thurman, Am J Physiol Renal Physiol 2012 302:F1529-F1536; Casiraghi, Am J Transplant 2017 17:2312-2325; Morigi, Sci Rep 2016 6:8445). Genetic deficiencies in CFB in these models resulted in reduced proteinuria, protection from renal impairment, and extended survival. Like many complement proteins, CFB circulates at high plasma concentrations of 300–400 μg / mL in its native form. Recently, the selective CFB inhibitor, iptacopan (LNP023), has been shown to bind to active CFB (Schubart Proc Natl Acad Sci US A.2019 116(16):7926-7931). In a phase II clinical trial in C3G, iptacopan demonstrated promising efficacy with reduced proteinuria after 12 weeks of treatment (Wong, J Am Soc Nephrol 2020 31:55A). However, variability in complement activity and patient response has also been observed, suggesting that very potent compounds with greater and more sustained complement inhibition in vivo may provide greater therapeutic effects in patients with C3G and broad-spectrum CKD. [Overview of the Initiative]

[0007] In certain embodiments, a compound of formula (I) or a pharmaceutically acceptable salt thereof is provided herein. In certain embodiments, the compound is an inhibitor of the alternative complement pathway. In certain embodiments, the compound is an inhibitor of complement factor B (CFB). In certain embodiments, the compounds provided herein will provide a therapeutic effect related to the inhibition of the alternative complement pathway or CFB, including treating or preventing certain autoimmune diseases or disorders, inflammatory diseases or disorders, metabolic diseases or disorders, neurological diseases or disorders, lung diseases, respiratory diseases or disorders, eye diseases, cardiovascular diseases, and kidney diseases. Complement-mediated kidney diseases include chronic kidney disease (CKD), diabetic nephropathy, glomerular kidney disease, complement C3 glomerulopathy (C3G), IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis (DDD), minimal change disease (MCD), paroxysmal nocturnal hemoglobinuria (PNH), ANCA-associated vasculitis, lupus nephritis, and polycystic kidney disease (PKD).

[0008] In certain embodiments, formula (I):

Chemical formula

[0009] Also provided are pharmaceutical compositions formulated for administration by appropriate routes and means, which contain one or more of the compounds provided herein or pharmaceutically acceptable salts thereof in a therapeutically effective concentration, and optionally include at least one pharmaceutical carrier.

[0010] In another embodiment, the present invention provides a method for treating a disease or disorder mediated by an alternative complement pathway, particularly by complement factor B, comprising administering to a subject having such disease or disorder a therapeutically effective amount of one or more compounds disclosed herein or pharmaceutically acceptable salts thereof or a pharmaceutical composition disclosed herein. In certain embodiments, the disease or disorder is chronic kidney disease (CKD), diabetic nephropathy, glomerulonephropathy, complement C3 glomerulopathy (C3G), IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis (DDD), minimal change nephropathy (MCD), paroxysmal nocturnal hemoglobinuria (PNH), ANCA-associated vasculitis, lupus nephritis, polycystic kidney disease (PKD), autosomal dominant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), end-stage renal disease (ESRD), acute kidney injury, or polycystic hepatic cysts.

[0011] Combination therapies are also provided, which involve using one or more compounds or compositions provided herein in combination with other pharmaceuticals for the treatment of the diseases and disorders described herein. These and other aspects of the subject matter described herein will become apparent from the following detailed description and drawings. [Brief explanation of the drawing]

[0012] [Figure 1] This shows the effect of therapeutic administration of compound A of formula I (oral administration at 30 mg / kg / day once daily (QD)) on the urinary protein-creatinine ratio (UPCR) in a rat model of membranous nephropathy (passive Heymann nephritis model or PHN) treated with anti-Fx1a. [Figure 2A] Figure 1 shows the kidney C3d deposition measured on day 14 of the same PHN rat study. [Figure 2B] Figure 1 shows complement factor Ba fragments in the urine measured on day 14 of the same PHN rat study. [Figure 3A] Figure 1 shows the urinary full-length complement factor B measured on day 14 of the PHN rat study. [Figure 3B] Figure 1 shows neutrophil gelatinase-binding lipocalin (NGAL-1) in the urine of the same PHN rat study on day 14. [Figure 4] Figure 1 shows the amount of kidney damage molecule 1 (KIM-1) in the urine of PHN rats on day 14. [Modes for carrying out the invention]

[0013] A.Definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art. If there are multiple definitions of a term herein, the definition in this section shall prevail unless otherwise specified.

[0014] When used herein, the term “approximately” is used to indicate that a number is being modified, and therefore encompasses a range of uncertainty of the number from 0% to 10%.

[0015] The term "alkyl," as used herein, refers to a saturated hydrocarbon chain that may be linear or branched, containing the indicated number of carbon atoms, or having an additional 1 to 10, 1 to 8, 1 to 6, 1 to 4, or 1 to 3 carbon atoms, which are bonded to the rest of the molecule by single bonds. In certain embodiments, the hydrocarbon chain is optionally deuterated. For example, C1-C3 alkyl indicates that the group may have 1 to 3 carbon atoms (including terminal values); C1-C6 alkyl indicates that the group may have 1 to 6 carbon atoms (including terminal values). In some embodiments, alkyl is a C1-C3 alkyl representing a linear or branched saturated monovalent hydrocarbon group having 1 to 3 carbon atoms. In some embodiments, alkyl is a C1-C6 alkyl representing a linear or branched saturated monovalent hydrocarbon group having 1 to 6 carbon atoms. Examples of alkyls, but not limited to, include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl.

[0016] The term "alkoxy," as used herein, refers to a group of the formula -OR unless otherwise specified, where R is an alkyl as defined herein. Alkoxys may be, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, n-pentoxy, 2-pentoxy, 3-pentoxy, or hexyloxy. Similarly, the term "alkylthio" refers to a group of the formula -S-(alkyl). The terms "haloalkoxy" and "haloalkylthio" refer to -O-(haloalkyl) and -S-(haloalkyl), respectively.

[0017] When used herein, the term "alkylsulfinyl" refers to the group of the formula -S(O)R unless otherwise specified, where R is alkyl as defined herein.

[0018] When used herein, the term "alkylsulfonyl" refers to the group of the formula -S(O)2R unless otherwise specified, where R is alkyl as defined herein.

[0019] As used herein, the term "aryl" is intended to mean any stable monocyclic or bicyclic carbocyclic ring having up to six members in each ring, unless otherwise specified, and at least one ring being aromatic. Examples of aryls include phenyl, naphthyl, tetrahydronaphthyl, indanyl, or biphenyl.

[0020] The term "azolyl" as used herein refers to a five-membered heteroaryl ring system containing at least one nitrogen atom, unless otherwise specified. Examples of azolyls include pyrrole, imidazole, pyrazole, thiazole, isothiazole, oxazole, isoxazole, thiadiazole, and oxadiazole.

[0021] The term "cycloalkyl," as used herein, refers to a monocyclic, bicyclic, tricyclic, or other polycyclic hydrocarbon group having the indicated number of ring carbon atoms or an additional 3 to 10 carbon atoms, and being fully saturated or partially unsaturated (i.e., non-aromatic), unless otherwise specified. Polycyclic cycloalkyls may be condensed, crosslinked, and / or spirocyclic systems. Examples of cycloalkyl groups, but not limited to, include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornyl, bicyclo[1.1.1]pentane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, spiro[3.3]heptane, and partially unsaturated hydrocarbon rings, such as cyclobutylene, cyclopentene, and cyclohexene. In some embodiments, the cycloalkyl is a monocyclic C3-C8 cycloalkyl.

[0022] The term "deuterium" as used herein, unless otherwise specified, is deuterium by the symbol D or 2This refers to the heavy isotope of hydrogen represented by H. When used herein, if a particular position in a compound is indicated as “deuterated” as having deuterium or having the prefix “jutero-”, it is understood that the compound is an isotopically enriched compound, and the presence of deuterium at that position in the compound is substantially higher than its natural abundance of 0.0156%, for example, at least 90% deuterium at that particular position.

[0023] As used herein, the term "deuteroalkyl" refers, unless otherwise specified, to an alkyl group in which one or more hydrogen atoms are substituted with deuterium in substantially greater abundance than its natural abundance, for example, at least 90% deuterium at a particular position.

[0024] The terms “enantiomerically pure” or “pure enantiomer” as used herein indicate that a compound contains a single enantiomer (excluding its corresponding non-superimal image) in greater than 75% by weight, greater than 80% by weight, greater than 85% by weight, greater than 90% by weight, greater than 91% by weight, greater than 92% by weight, greater than 93% by weight, greater than 94% by weight, greater than 95% by weight, greater than 96% by weight, greater than 97% by weight, greater than 98% by weight, greater than 98.5% by weight, greater than 99% by weight, greater than 99.2% by weight, greater than 99.5% by weight, greater than 99.6% by weight, greater than 99.7% by weight, greater than 99.8% by weight, or greater than 99.9% by weight. Certain embodiments described herein provide compounds that exist as pure enantiomers. Certain embodiments also provide pharmaceutical compositions containing the enantiomerically pure compounds described herein.

[0025] The terms “halo,” “halogen,” or “halogenated” as used herein refer to monovalent fluorine, chlorine, bromine, or iodine groups unless otherwise specified.

[0026] The term "haloalkyl," as used herein, refers to a monovalent alkyl group in which at least one hydrogen atom is substituted with a halogen, unless otherwise specified. In some embodiments, two or more hydrogen atoms (e.g., 2, 3, 4, 5, or 6) are substituted with halogens of independently selected proportions. In these embodiments, each hydrogen atom may be substituted with the same halogen (e.g., fluoro), or the hydrogen atoms may be substituted with a combination of different halogens (e.g., fluoro and chloro). "Haloalkyl" also includes alkyl moieties in which all hydrogens are substituted with halogens (sometimes referred to herein as perhaloalkyl, e.g., perfluoroalkyl, e.g., trifluoromethyl).

[0027] The term "cyano" as used herein refers to the -CN group unless otherwise specified.

[0028] The term "cyanoalkyl," as used herein, refers to an alkyl group in which one hydrogen atom of the alkyl group is substituted with a cyano group, unless otherwise specified herein.

[0029] The terms “heterocyclic,” “heterocyclyl,” or “heterocyclic” as used herein, unless otherwise specified, refer to stable 3-, 4-, 5-, 6-, or 7-membered monocyclic, stable 4-, 5-, 6-, or 7-membered monocyclic, or stable 6-, 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic heterocyclic systems comprising a carbon atom and at least one non-aromatic (i.e., saturated or partially unsaturated) ring consisting of 1 to 4, preferably up to 3, heteroatoms selected from the group consisting of N, O, and S, wherein the nitrogen and sulfur atoms may be optionally oxidized as N-oxides, sulfoxides, or sulfones, and the nitrogen atom may be optionally quaternized. Heterocyclic systems may be bonded via ring carbon atoms or, if possible, ring nitrogen atoms. Bicyclic heterocyclic systems may be condensed, bridged, and / or spiro-dicyclic systems. In some embodiments, the heterocyclyl is a monocyclic compound having 4 to 7, preferably 4 to 6, ring atoms (of which one or two are heteroatoms independently selected from the group consisting of N, O, and S). In some embodiments, the heterocyclyl is a monocyclic compound having 4 to 7, preferably 4 to 6, ring atoms (of which at least one heteroatom is N, and the second heteroatom is N, O, or S). In certain embodiments, the heterocyclyl is azetidine, pyrrolidine, piperidine, piperazine, morpholine, or thiomorpholine. In some embodiments, the heterocyclyl group is bicyclic, in which the first ring (bonding site to the rest of the molecule) is a saturated or partially saturated monocyclic heterocyclyl as described herein, and the second ring may be an aromatic or non-aromatic ring consisting of a carbon atom and 1 to 4, preferably up to 3, heteroatoms independently selected from the group consisting of N, O, and S, or the second ring may be a benzene ring, or a "cycloalkyl," or a "cycloalkenyl" as defined herein.Examples of such heterocyclic groups include, but are not limited to, azetidine, chroman, dihydrofuran, dihydropyran, dioxane, dioxolane, hexahydroazepine, imidazolidine, imidazoline, indoline, isochroman, isoindoline, isothiazolin, isothiazolidine, isoxazolidine, isoxazolidine, morpholine, oxazoline, oxazolidine, oxetane, piperazine, piperidine, dihydropyridine, tetrahydropyridine, dihydropyridazine, pyran, pyrazolidine, pyrazoline, pyrrolidine, pyrroline, tetrahydrofuran, tetrahydropyran, thiamorpholine, tetrahydrothiophene, thiazoline, thiazolidin, thiomorpholine, thiethane, thiolane, sulfolane, 1,3-dioxolane, 1,3-oxazolidine, 1,3-thia Examples include zolidine, tetrahydrothiopyran, tetrahydrotriazine, 1,3-dioxane, 1,4-dioxane, hexahydrotriazine, tetrahydro-oxazine, tetrahydropyrimidine, perhydroazepine, perhydro-1,4-diazepine, perhydro-1,4-oxazepine, 7-azabicyclo[2.2.1]heptane, 3-azabicyclo[3.2.0]heptane, 7-azabicyclo[4.1.0]heptane, 2,5-diazabicyclo[2.2.1]heptane, 2-oxa-5-azabicyclo[2.2.1]heptane, tropane, 2-oxa-6-azaspiro[3.3]heptane, dihydrobenzofuran, dihydrobenzimidazolyl, dihydrobenzoxazole, and dihydrobenzothiazolyl, as well as their N-oxides, sulfones, or sulfoxides.

[0030] When used herein, the term "heteroaryl" refers, unless otherwise specified, to a stable 5-membered, 6-membered, or 7-membered monocyclic—or stable 9-membered, or 10-membered fused bicyclic ring system comprising a carbon atom and at least one aromatic ring consisting of 1 to 4, preferably up to 3, heteroatoms selected from the group consisting of N, O, and S, wherein the nitrogen and sulfur heteroatoms or carbon atoms of the heteroaryl may be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. In the case of a bicyclic "heteroaryl," the first ring (the bond site to the rest of the molecule) is a monocyclic heteroaryl group as described herein, and the second ring does not need to be aromatic and does not need to contain heteroatoms. Therefore, a bicyclic "heteroaryl" includes, for example, a stable five- or six-membered monocyclic aromatic ring consisting of a carbon atom as defined above and one to four, preferably up to three, heteroatoms fused to a benzene ring, or a second monocyclic "heteroaryl," "heterocyclyl," "cycloalkyl," or "cycloalkenyl" as defined above. Examples of heteroaryl groups include, but are not limited to, benzimidazole, benzopyrazole, benzisothiazole, benzisoxazole, benzofuran, isobenzofuran, benzothiazole, benzothiophene, benzotriazole, benzoxazole, furan, furazan, imidazole, indazole, indole, indidine, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, phthalazine, pteridine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyridinone, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, benzimidazole, benzothiadiazole, isoindole, pyrrolopyridine, imidazopyridine, for example, imidazo[1,2-a]pyridine, pyrazolopyridine, pyrrolopyrimidine, and their N-oxides.

[0031] The term "oxo" refers to a carbonyl (C=O) group. When it is shown that a carbon atom is substituted with an oxo group, it is understood that two hydrogen atoms are removed from the carbon atom and replaced with =O. Similarly, when it is shown that a carbon atom is substituted with two groups and that it can be substituted with an "oxo" group, it is understood that the two substituents can come together to form an oxo group.

[0032] The term “subject” as used herein, unless otherwise specified, refers to any human or veterinary subject, including mammals such as mice, rats, cattle, sheep, pigs, rabbits, goats, horses, monkeys, dogs, cats, and humans (including neonates, infants, young, adolescent, adult, or elderly patients).

[0033] The term "thiol" refers to a group having the formula -SH.

[0034] The term "therapeutic dose" refers to an amount sufficient to produce a beneficial or desired clinical outcome. A therapeutic dose may be administered in one or more doses. A therapeutic dose is sufficient to alleviate, improve, stabilize, halt, slow or delay the progression of a disease.

[0035] Unless otherwise stated or specifically noted, substitutions, if present, may occur at any atom of an alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl group whose valence is permissible.

[0036] Unless otherwise specifically stated, if a compound may take on alternative tautomers or stereoisomers, all alternative isomers are intended to be included within the scope of the claimed subject matter. For example, unless otherwise specifically stated, the compounds provided herein may be stereoisomerically pure (e.g., a single enantiomer or diastereomer) or a mixture of stereoisomers, such as a racemic or diastereomer mixture.

[0037] The terms “to treat,” “to cure,” or “to treat” generally refer to controlling, alleviating, improving, slowing the progression of, and / or eliminating a specified condition after it has been established. In addition to its usual meaning, the terms “to prevent,” “to prevent,” or “prevent” also refer to delaying the onset of a specified condition or reducing the risk of developing it or the risk of processes that could lead to the condition and / or the risk of recurrence of the symptoms of the condition.

[0038] In any instance where there is a discrepancy between a chemical name and a chemical structure in the description herein, the chemical structure shall prevail.

[0039] B. Compound In a particular embodiment, formula (I): [ka] (In the formula, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; Z is NR 2 or CR 2a R 2b and; R 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R11 It is optionally replaced by; R 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; and R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b These, together with the carbon atoms to which they are bonded, form a cycloalkyl or heterocycline, and the cycloalkyl or heterocycline is composed of 1, 2, or 3 independently selected R 11 It is optionally replaced by; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3Alkoxy or Halo C 1~3 It is an alkoxy; R 7 These are haloalkyl, deuteroalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl, or haloalkyl; R 9 is a haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 , -S(O) t R 12 or -S(O) t NR 13 R 14 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by; Each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is alkylsulfinyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Forms cycloalkyl, 3- to 6-membered heterocyclyl, or oxo molecules, C 3~5 Cycloalkyl or 3- to 6-membered heterocyclyls are optionally substituted with one or two independently selected halos; R 12 is alkyl, deuteroalkyl, or haloalkyl; R 13 and R 14 Each of these is independently hydrogen, alkyl, deuteroalkyl or haloalkyl, or R 13 and R 14 Along with the nitrogen atom to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R u is a methylene, ethylene, or propylene linker that is optionally substituted with 1 to 6 independently selected halos; k is 0, 1, 2, or 3; t is either 1 or 2; m is 0, 1 or 2; and n is 0, 1, or 2, however, Z is NR 2 If so, m is 1, and n is 1 or 2; and Z is CR 2a R 2b And R 2a and R2b However, together with the carbon atoms to which they are bonded, they form a cycloalkyl group, and when m is 1, the cycloalkyl group has at least one R 11 (This will be replaced by...) Compounds of or pharmaceutically acceptable salts thereof are provided herein.

[0040] In a particular embodiment, formula (I): [ka] (In the formula, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; Z is NR 2 or CR 2a R 2b and; R 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -Ru -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; and R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b These, together with the carbon atoms to which they are bonded, form a cycloalkyl or heterocycline, and the cycloalkyl or heterocycline is composed of 1, 2, or 3 independently selected R 11 It is optionally replaced by; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 7 These are haloalkyl, deuteroalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R u-Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl, or haloalkyl; R 9 is a haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 , -S(O) t R 12 or -S(O) t NR 13 R 14 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by; Each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is an alkylsulfinyl; R 12 is alkyl, deuteroalkyl, or haloalkyl; R 13 and R 14 Each of these is independently hydrogen, alkyl, deuteroalkyl or haloalkyl, or R 13 and R 14 Along with the nitrogen atom to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R u is a methylene, ethylene, or propylene linker that is optionally substituted with 1 to 6 independently selected halos; k is 0, 1, 2, or 3; t is either 1 or 2; m is 0, 1 or 2; and n is 0, 1, or 2, however, Z is NR 2 If so, m is 1, and n is 1 or 2; and Z is CR 2a R 2b And R 2a and R 2b However, together with the carbon atoms to which they are bonded, they form a cycloalkyl group, and when m is 1, the cycloalkyl group has at least one R 11 (This will be replaced by...) Compounds of or pharmaceutically acceptable salts thereof are provided herein.

[0041] In a particular embodiment, formula (I): [ka] (In the formula, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; Z is NR2 or CR 2a R 2b and; R 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; and R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with, or 1, 2, or 3 independently selected R11 Forms heterocyclines that are optionally substituted; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 7 These are haloalkyl, deuteroalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl, or haloalkyl; R 9 is a haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 , -S(O) t R 12or -S(O) t NR 13 R 14 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by; Each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is alkylsulfinyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Forms cycloalkyl, 3- to 6-membered heterocyclyl, or oxo molecules, C 3~5 Cycloalkyl or 3- to 6-membered heterocyclyls are optionally substituted with one or two independently selected halos; R 12 is alkyl, deuteroalkyl, or haloalkyl; R 13 and R 14Each of these is independently hydrogen, alkyl, deuteroalkyl or haloalkyl, or R 13 and R 14 Along with the nitrogen atom to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R u is a methylene, ethylene, or propylene linker that is optionally substituted with 1 to 6 independently selected halos; k is 0, 1, 2, or 3; t is either 1 or 2; m is 0, 1 or 2; and n is 0, 1, or 2, where Z is NR 2 If this is the case, then m is 1, and n is either 1 or 2. Compounds of or pharmaceutically acceptable salts thereof are provided herein.

[0042] In a particular embodiment, formula (I): [ka] (In the formula, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; Z is NR 2 or CR 2a R 2b and; R 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -Ru -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; and R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with, or 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 7 These are haloalkyl, deuteroalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl, or haloalkyl; R 9 is a haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 , -S(O) t R 12 or -S(O) t NR 13 R 14 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by; Each R 11These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is an alkylsulfinyl; R 12 is alkyl, deuteroalkyl, or haloalkyl; R 13 and R 14 Each of these is independently hydrogen, alkyl, deuteroalkyl or haloalkyl, or R 13 and R 14 Along with the nitrogen atom to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R u is a methylene, ethylene, or propylene linker that is optionally substituted with 1 to 6 independently selected halos; k is 0, 1, 2, or 3; t is either 1 or 2; m is 0, 1 or 2; and n is 0, 1, or 2, where Z is NR 2 If this is the case, then m is 1, and n is either 1 or 2. Compounds of or pharmaceutically acceptable salts thereof are provided herein.

[0043] In a particular embodiment, formula (I): [ka] (In the formula, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; Z is NR 2 or CR 2a R 2b and; R 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; and R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with, or 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 7 These are haloalkyl, deuteroalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl, or haloalkyl; R 9 is, -R u-cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 , -S(O) t R 12 or -S(O) t NR 13 R 14 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by; Each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1--3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is an alkylsulfinyl; R 12 is alkyl, deuteroalkyl, or haloalkyl; R 13 and R 14Each of these is independently hydrogen, alkyl, deuteroalkyl or haloalkyl, or R 13 and R 14 Along with the nitrogen atom to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R u is a methylene, ethylene, or propylene linker that is optionally substituted with 1 to 6 independently selected halos; k is 0, 1, 2, or 3; t is either 1 or 2; m is 0, 1 or 2; and n is 0, 1, or 2, where Z is NR 2 If this is the case, then m is 1, and n is either 1 or 2. Compounds of or pharmaceutically acceptable salts thereof are provided herein.

[0044] In a particular embodiment, formula (II): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0045] In a particular embodiment, formula (IIa): [ka] A compound of formula (I) or a pharmaceutically acceptable salt thereof having (wherein j is 1 or 2, and when j is 1, R 11 The carbon atom bonded is a single R 11 If it has a substituent and j is 2, then R 11 The carbon atoms bonded to it are two independently selected R 11 A substituent is provided herein.

[0046] In a particular embodiment, formula (IIb): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0047] In a particular embodiment, formula (IIc): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0048] In a particular embodiment, formula (IId): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0049] In a particular embodiment, formula (IIe): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0050] In a specific embodiment, the expression (IIf): [ka] Compounds of formula (I) (wherein p is 1 or 2); or pharmaceutically acceptable salts thereof are provided herein. In certain embodiments, compounds of formula (IIf) (wherein each R 11 A compound of formula (I) or (IIf) is provided herein, independently of the other variables being halo and other variables being as described elsewhere in this specification for formula (I) or (IIf). In certain embodiments, a compound of formula (IIf) (wherein each R is a compound of formula (IIf)) is provided herein. 11(where is fluoro, and the other variables are as described elsewhere in this specification for formula (I) or (IIf)) is provided herein.

[0051] In a particular embodiment, formula (III): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0052] In a particular embodiment, formula (IIIa): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof (wherein n is 1 or 2) having the above are provided herein.

[0053] In a particular embodiment, formula (IV): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0054] In a particular embodiment, formula (IVa): [ka] Compounds of or pharmaceutically acceptable salts thereof are provided herein.

[0055] In a particular embodiment, formula (IVb): [ka] A compound of formula (I) having (wherein j is 1 or 2); or a pharmaceutically acceptable salt thereof is provided herein, and when j is 1, R 11The carbon atom bonded is a single R 11 If it has a substituent and j is 2, then R 11 The carbon atoms bonded to it are two independently selected R 11 It has substituents.

[0056] In a particular embodiment, formula (I): [ka] (In the formula, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; Z is NR 2 or CR 2a R 2b and; R 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -Ru -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; and R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 7 These are deuteroalkyl, heterocyclyl, or heteroaryl, and include haloalkyl, deuteroalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl, or haloalkyl; R 9 is a haloalkyl, -R u -cycloalkyl, -R u-heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)NR 13 R 14 , -S(O) t R 12 or -S(O) t NR 13 R 14 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by; Each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is alkylsulfinyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Forms cycloalkyl, 3- to 6-membered heterocyclyl, or oxo molecules, C 3~5 Cycloalkyl or 3- to 6-membered heterocyclyls are optionally substituted with one or two independently selected halos; R12 is alkyl, deuteroalkyl, or haloalkyl; R 13 and R 14 Each of these is independently hydrogen, alkyl, deuteroalkyl or haloalkyl, or R 13 and R 14 Along with the nitrogen atom to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R u is a methylene, ethylene, or propylene linker that is optionally substituted with 1 to 6 independently selected halos; k is 0, 1, 2, or 3; t is either 1 or 2; m is 0, 1 or 2; and n is 0, 1, or 2, however, Z is NR 2 If this is the case, then m is 1, and n is either 1 or 2. Compounds of or pharmaceutically acceptable salts thereof are provided herein.

[0057] In a particular embodiment, formula (I): [ka] (In the formula, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; Z is NR 2 or CR 2a R 2b and; R 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R14 or -S(O) t R 12 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; and R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 7 These are haloalkyl, deuteroalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl, or haloalkyl; R 9 is a haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)NR 13 R 14 , -S(O) t R 12 or -S(O) t NR 13 R 14 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by; Each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is alkylsulfinyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Forms cycloalkyl, 3- to 6-membered heterocyclyl, or oxo molecules, C 3~5 Cycloalkyl or 3- to 6-membered heterocyclyls are optionally substituted with one or two independently selected halos; R 12 is alkyl, deuteroalkyl, or haloalkyl; R 13 and R 14 Each of these is independently hydrogen, alkyl, deuteroalkyl or haloalkyl, or R 13 and R 14 Along with the nitrogen atom to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R u is a methylene, ethylene, or propylene linker that is optionally substituted with 1 to 6 independently selected halos; k is 0, 1, 2, or 3; t is either 1 or 2; m is 0, 1 or 2; and n is 0, 1, or 2, however, Z is NR 2 If this is the case, then m is 1, and n is either 1 or 2. Compounds of or pharmaceutically acceptable salts thereof are provided herein.

[0058] In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R) 11 This refers to Halo, Cyano, or Halo C 1~3 Compounds of formula (IIa) or (IVb) (wherein R is alkyl; other variables are as described elsewhere in this specification for each of formulas (IIa) and (IVb)) are provided herein. In certain embodiments, compounds of formula (IIa) or (IVb) (wherein R is alkyl; other variables are as described elsewhere in this specification for each of formulas (IIa) and (IVb)) are provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 This refers to Halo, Cyano, or Halo C 1~3 A alkyl group is provided herein, where j is 1 or 2, k is 0, and m and n are both 1.

[0059] In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R) 11 is fluoro, cyano, or fluoroC 1~3 Compounds of formula (IIa) or (IVb) (wherein R is alkyl; other variables are as described elsewhere in this specification for each of formulas (IIa) and (IVb)) are provided herein. In certain embodiments, compounds of formula (IIa) or (IVb) (wherein R is alkyl; other variables are as described elsewhere in this specification for each of formulas (IIa) and (IVb)) are provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is fluoro, cyano, or fluoroC 1~3 A alkyl group is provided herein, where j is 1 or 2, k is 0, and m and n are both 1.

[0060] In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R) 11A compound of formula (IIa) or (IVb) (wherein R is fluoro, cyano, -CHF2, or -CF3; other variables are as described elsewhere in this specification for each of formulas (IIa) and (IVb)) is provided herein. In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R is fluoro, cyano, -CHF2, or -CF3; other variables are as described elsewhere in this specification for each of formulas (IIa) and (IVb)) is provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 (where is fluoro, cyano, -CHF2 or -CF3; j is 1 or 2; k is 0; m and n are both 1) are provided herein.

[0061] In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R) 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11A compound of formula (IIa) or (IVb) (wherein R is 0 or 1; m and n are both 1) is provided herein. In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R is 0 or 1) is provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 (where is halo; j is 2; k is 0; m and n are both 1) are provided herein.

[0062] In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R) 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 A compound of formula (IIa) or (IVb) (wherein R is fluoro; j is 2; k is 0 or 1; m and n are both 1) is provided herein. In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R is fluoro; j is 2; k is 0 or 1; m and n are both 1) is provided herein. 1is hydrogen, fluoro or chloro; X is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is fluoro; j is 2; k is 0; m and n are both 1) are provided herein.

[0063] In certain embodiments, a compound of formula (IIa) or (IVb) wherein R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; R 3 is halo, cyano, C 1~3 alkyl or haloC 1~3 alkyl; R 4 is hydrogen, halo, cyano, C 1~3 alkyl or haloC 1~3 alkyl; R 5 is halo, C 1~3 alkyl, C 3~5 cycloalkyl, haloC 1~3 alkyl, haloC 1~3 alkoxy or C 1~3 alkoxy; R 6 is halo, cyano, C 1~3 alkyl, C 3~5 cycloalkyl, haloC 1~3 alkyl, C 1~3 alkoxy or haloC 1~3 alkoxy; R 11 is cyano; j is 1; k is 0 or 1; m and n are both 1) are provided herein.In certain embodiments, a compound of formula (IIa) or (IVb) wherein R 1 is hydrogen, fluoro or chloro; X is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6is methyl; R 11 (where is cyano; j is 1; k is 0; m and n are both 1) are provided herein.

[0064] In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R) 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 A compound of formula (IIa) or (IVb) (wherein R is -CHF2 or -CF3; j is 1; k is 0 or 1; m and n are both 1) is provided herein. In certain embodiments, a compound of formula (IIa) or (IVb) (wherein R is -CHF2 or -CF3; j is 1; k is 0 or 1; m and n are both 1) is provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 (where is -CHF2 or -CF3; j is 1; k is 0; m and n are both 1) are provided herein.

[0065] In a particular embodiment, formula (IVc): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0066] In a particular embodiment, equation (IVd): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0067] In a particular embodiment, formula (IVe): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0068] In a particular embodiment, equation (IVf): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0069] In certain embodiments, a compound of formula (IIc) or (IVf) (wherein R) 11 These are, independently, halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C1~3 Alkoxy, halo C 1~3 Alkoxy, C 1~3 Alkylthio, halo C 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or halo C 1~3 is alkylsulfinyl; or two Rs 11 groups, together with the carbon atom to which they are attached, form a C 3~5 cycloalkyl, 3- to 6-membered heterocyclyl or oxo; and the remaining variables are as described elsewhere in this specification for each of formulas (IIc) and (IVf)) are provided herein. In certain embodiments, a compound of formula (IIc) or (IVf) wherein R 11 is, independently of each other, halo, cyano, C 1~3 alkyl, dideutero C 1~3 alkyl, halo C 1~3 alkyl, cyano C 1~3 alkyl, hydroxy C 1~3 alkyl, C 1~3 alkoxy C 1~3 alkyl, halo C 1~3 alkoxy C 1~3 alkyl, hydroxyl, C 1~3 alkoxy, halo C 1~3 alkoxy, C 1~3 alkylthio, halo C 1~3 alkylthio, C 1~3 alkylsulfonyl, C 1~3 alkylsulfinyl or halo C 1~3 is alkylsulfinyl; and the remaining variables are as described elsewhere in this specification for each of formulas (IIc) and (IVf)) are provided herein.

[0070] In certain embodiments, a compound of formula (IIc) or (IVf) wherein R 11 is halo, C 1~3 alkyl, halo C 1~3Alkyl or hydroxyl compounds (other variables are as described elsewhere in this specification for each of formulas (IIc) and (IVf)) are provided herein. In certain embodiments, compounds of formula (IIc) or (IVf) or pharmaceutically acceptable salts thereof (wherein R is used) are provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 These are, independently, Halo and C. 1~3 Alkyl, Halo C 1~3 Compounds of formula (IIc) or (IVf) or pharmaceutically acceptable salts thereof (wherein R) are provided herein. In certain embodiments, compounds of formula (IIc) or (IVf) or pharmaceutically acceptable salts thereof are provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 These are, independently, Halo and C. 1~3 Alkyl, Halo C 1~3 Alkyl or hydroxyl compounds are provided herein.

[0071] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R) 11a C 1~3 Alkyl or Halo C 1~3 Alkyl; R 11b (where is hydroxyl, and the remaining variables are as described elsewhere in this specification for formulas (IIc) and (IVf)) are provided herein.

[0072] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R) 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 Each of them is independent of C 1~3 Alkyl, Halo C 1~3 The following are provided herein: alkyl or hydroxyl, the remaining variables are as described elsewhere herein for formulas (IIc) and (IVf). In certain embodiments, compounds of formula (IIc) or (IVf) or pharmaceutically acceptable salts thereof (wherein R is used). 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 Each of them is independent of C 1~3 Alkyl, Halo C 1~3 Alkyl or hydroxyl compounds are provided herein.

[0073] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R) 11a is methyl or trifluoromethyl, and R 11b A compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R is hydroxyl, and the remaining variables are as described elsewhere in this specification for formulas (IIc) and (IVf)) is provided herein. In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R is hydroxyl, and the remaining variables are as described elsewhere in this specification for formulas (IIc) and (IVf)) is provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is methyl or trifluoromethyl, and R 11b Compounds of formula (IIc) or (IVf) or pharmaceutically acceptable salts thereof (wherein R is hydroxyl) are provided herein. In certain embodiments, compounds of formula (IIc) or (IVf) or pharmaceutically acceptable salts thereof (wherein R is hydroxyl) are provided herein. 1is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is methyl or trifluoromethyl, and R 11b (where is hydroxyl) is provided herein.

[0074] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R) 11 Each of these is independently a halo; the remaining variables are as described elsewhere in this specification for formulas (IIc) and (IVf). In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R is the given R) is provided herein. 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 Each of them is independently a halo; k is 0, 1, 2, or 3; m is 0, 1 or 2; and n (where n is 0, 1, or 2) is provided herein.

[0075] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 is fluoro; k is 0, 1, 2, or 3; m is 0, 1 or 2; and Compounds of formula (IIc) or (IVf) are provided herein (wherein k is 0, m is 1; n is 1; other variables are as described elsewhere herein for formulas (IIc) and (IVf), respectively).

[0076] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R)11 A compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R is fluoro; the remaining variables are as described elsewhere in this specification for each of formulas (IIc) and (IVf) respectively) is provided herein. In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R is fluoro; the remaining variables are as described elsewhere in this specification for each of formulas (IIc) and (IVf) respectively) is provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 It is methyl, and R 11 A fluoro(which is provided herein) is provided herein.

[0077] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharmaceutically acceptable salt thereof (wherein R) 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 A fluoro(which is provided herein) is provided herein.

[0078] In a particular embodiment, formula (IVg): [ka] Compounds of formula (I), (IVb), or (IVc) having the above, or pharmaceutically acceptable salts thereof, are provided herein.

[0079] In a particular embodiment, formula (IVh): [ka] Compounds of formula (I), (IVb), or (IVc) having the above, or pharmaceutically acceptable salts thereof, are provided herein.

[0080] In a particular embodiment, formula (IVi): [ka] Compounds of formula (I), (IVb), or (IVc) having the above, or pharmaceutically acceptable salts thereof, are provided herein.

[0081] In certain embodiments, compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 11 These are independently halo, cyano, or halo-C 1~3 The compounds provided herein are alkyl; the remaining variables are as described elsewhere in this specification for formulas (IId), (IVg), (IVh), and (IVi). In certain embodiments, compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 11 This is cyano or halo C 1~3 The compounds provided herein are alkyl; the remaining variables are as described elsewhere in this specification for each of the formulas (IId), (IVg), (IVh), and (IVi). In certain embodiments, compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 11 is cyano or fluorocarbon 1~3 The compounds provided herein are alkyl; the remaining variables are as described elsewhere in this specification for each of the formulas (IId), (IVg), (IVh), and (IVi). In certain embodiments, compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 11 (wherein is cyano, -CHF2, or -CF3; the remaining variables are as described elsewhere in this specification for each of the formulas (IId), (IVg), (IVh), and (IVi)) are provided herein.

[0082] In certain embodiments, compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 1is hydrogen, fluoro, chloro, or methyl; X is N or CH; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 Alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 This is cyano or halo C 1~3 Compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 1 is hydrogen, fluoro, chloro, or methyl; X is N or CH; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 Alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 is cyano or fluorocarbon 1~3 Compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 1is hydrogen, fluoro, chloro, or methyl; X is N or CH; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 Alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 (wherein is cyano, -CHF2, or -CF3) are provided herein.

[0083] In certain embodiments, compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 It is methyl, and R 11 This is cyano or halo C 1~3 Compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 It is methyl, and R 11 is cyano or fluorocarbon 1~3Compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 It is methyl, and R 11 (wherein is cyano, -CHF2, or -CF3) are provided herein.

[0084] In certain embodiments, compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 This is cyano or halo C 1~3 Alkyl materials are provided herein.

[0085] In certain embodiments, compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is cyano or fluorocarbon 1~3 Alkyl materials are provided herein.

[0086] In certain embodiments, compounds of formula (IId), (IVg), (IVh), or (IVi) or pharmaceutically acceptable salts thereof (wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl;5 is methoxy or cyclopropyl; R 6 is methyl; R 11 (wherein is cyano, -CHF2, or -CF3) are provided herein.

[0087] In a particular embodiment, formula (IVj): [ka] Compounds of formula (I), (IVb), or (IVf) or pharmaceutically acceptable salts thereof having R are provided herein. In certain embodiments, compounds of formula (IIe) or (IVj) or pharmaceutically acceptable salts thereof (wherein R 11 (Each of these is independently a halo; the remaining variables are as described elsewhere in this specification for formulas (IIe) and (IVj)).

[0088] In certain embodiments, a compound of formula (IIe) or (IVj) or a pharmaceutically acceptable salt thereof (wherein R) 1 These are hydrogen, fluoro, chloro, or methyl; X is N or CH; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 Alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 Each of these is independently a halo) and is provided herein.

[0089] In certain embodiments, a compound of formula (IIe) or (IVj) or a pharmaceutically acceptable salt thereof (wherein R) 1 These are hydrogen, fluoro, chloro, or methyl; X is N or CH; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 Alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 A fluoro(which is provided herein) is provided herein.

[0090] In certain embodiments, a compound of formula (IIe) or (IVj) or a pharmaceutically acceptable salt thereof (wherein R) 11 A compound of formula (IIe) or (IVj) or a pharmaceutically acceptable salt thereof (wherein R is fluoro; the remaining variables are as described elsewhere in this specification for each of formulas (IIe) and (IVj) respectively) is provided herein. In certain embodiments, a compound of formula (IIe) or (IVj) or a pharmaceutically acceptable salt thereof (wherein R is fluoro 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 It is methyl, and R 11 Compounds of formula (IIe) or (IVj) or pharmaceutically acceptable salts thereof (wherein R is fluoro) are provided herein. In certain embodiments, compounds of formula (IIe) or (IVj) or pharmaceutically acceptable salts thereof are provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5is methoxy or cyclopropyl; R 6 is methyl; R 11 A fluoro(which is provided herein) is provided herein.

[0091] In a particular embodiment, equation (IVk): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof (wherein p is 1 or 2) having are provided herein. In certain embodiments, compounds of formula (IIf) or (IVk) or pharmaceutically acceptable salts thereof (wherein R 11 Each of the following is independently a halo, and the remaining variables are as described for formulas (IIf) and (IVk), respectively) provided herein. In certain embodiments, a compound of formula (IIf) or (IVk) or a pharmaceutically acceptable salt thereof (wherein R is the compound of formula (IIf) or (IVk) or a pharmaceutically acceptable salt thereof) is provided herein. 11 A compound of formula (IIf) or (IVk) or a pharmaceutically acceptable salt thereof (wherein R is fluoro, and the remaining variables are as described for formulas (IIf) and (IVk), respectively) is provided herein. In certain embodiments, a compound of formula (IIf) or (IVk) or a pharmaceutically acceptable salt thereof (wherein R is fluoro, and the remaining variables are as described for formulas (IIf) and (IVk), respectively) is provided herein. 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 Each of them is independently a halo; Compounds of formula (IIf) or (IVk) (wherein p is 1 or 2) are provided herein. In more specific embodiments, compounds of formula (IIf) or (IVk) (wherein R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 is fluoro; p (where p is 1 or 2) is provided herein.

[0092] In certain embodiments, a compound of formula (IIf) or (IVk) or a pharmaceutically acceptable salt thereof (wherein R) 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 It is methyl, and R 11 Compounds of formula (IIf) or (IVk) or pharmaceutically acceptable salts thereof (wherein R is fluoro) are provided herein. In certain embodiments, compounds of formula (IIf) or (IVk) or pharmaceutically acceptable salts thereof are provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl;5 is methoxy or cyclopropyl; R 6 is methyl; R 11 A fluoro(which is provided herein) is provided herein.

[0093] In a particular embodiment, formula (IVl): [ka] Compounds of formula (I), (IVa), (IVb), (IVf), or (IVj) having R, or pharmaceutically acceptable salts thereof (wherein R 11a and R 11b These are, independently, halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is alkylsulfinyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 The following are provided herein: forming cycloalkyl, 3- to 6-membered heterocyclyl or oxo; the remaining variables are as described elsewhere in this specification for each of formulas (I)(IVa), (IVb), (IVf), and (IVj).

[0094] In certain embodiments, a compound of formula (IVl) (wherein R 11a is Halo, Cyano, C 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C1~3 Alkyl or cyano C 1~3 alkyl; R 11b is halo, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 The alkylsulfinyl (the remaining variables are as described elsewhere in this specification for formula (IVl)) is provided herein.

[0095] In certain embodiments, a compound of formula (IVl) (wherein R 11a Hello, C 1~3 Alkyl or Halo C 1~3 It is alkyl, R 11b A compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R is a halo or hydroxyl, and the other variables are as described elsewhere in this specification for formula (IVl)) is provided herein. In certain embodiments, a compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R is a halo or hydroxyl, and the other variables are as described elsewhere in this specification for formula (IVl)) is provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a Hello, C 1~3 Alkyl or Halo C 1~3 It is alkyl, R 11b Compounds of formula (IVl) or pharmaceutically acceptable salts thereof (wherein R is a halo or hydroxyl) are provided herein. In certain embodiments, compounds of formula (IVl) or pharmaceutically acceptable salts thereof (wherein R is a halo or hydroxyl) are provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5is methoxy or cyclopropyl; R 6 is methyl; R 11a Hello, C 1~3 Alkyl or Halo C 1~3 It is alkyl, R 11b (where is a halo or hydroxyl) is provided herein.

[0096] In certain embodiments, a compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R) 11a C 1~3 Alkyl or Halo C 1~3 Alkyl; R 11b A compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R is hydroxyl, and the remaining variables are as described elsewhere in this specification for formula (IVl)) is provided herein. In certain embodiments, a compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R is hydroxyl, and the remaining variables are as described elsewhere in this specification for formula (IVl)) is provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a C 1~3 Alkyl or Halo C 1~3 It is alkyl, R 11b A compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R is hydroxyl, and the remaining variables are as described elsewhere in this specification for formula (IVl)) is provided herein. In certain embodiments, a compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R is hydroxyl, and the remaining variables are as described elsewhere in this specification for formula (IVl)) is provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a C 1~3 Alkyl or Halo C 1~3 It is alkyl, R 11b (where is hydroxyl) is provided herein.

[0097] In certain embodiments, a compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R) 11a is methyl or trifluoromethyl, and R 11b A compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R is hydroxyl, and the remaining variables are as described elsewhere in this specification for formula (IVl)) is provided herein. In certain embodiments, a compound of formula (IVl) or a pharmaceutically acceptable salt thereof (wherein R is hydroxyl, and the remaining variables are as described elsewhere in this specification for formula (IVl)) is provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is methyl or trifluoromethyl, and R 11b Compounds of formula (IVl) or pharmaceutically acceptable salts thereof (wherein R is hydroxyl) are provided herein. In certain embodiments, compounds of formula (IVl) or pharmaceutically acceptable salts thereof (wherein R is hydroxyl) are provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is methyl or trifluoromethyl, and R 11b (where is hydroxyl) is provided herein.

[0098] In certain embodiments, a compound of formula (IVl) (wherein R 11a is fluoro, and R 11b A compound of formula (IVl) is provided herein, where R is fluoro, and the other variables are as described elsewhere in this specification for formula (IVl). In certain embodiments, compounds of formula (I), (II), (IIa), (IIc), (IIe), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl) (wherein each R is fluoro) are provided herein. 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is either an alkylsulfinyl or has two R's 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Compounds of formula (I), (II), (IIa), (IIc), (IIe), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl) are provided herein (wherein each R is a cycloalkyl, 3- to 6-membered heterocycline, or oxo; other variables are described elsewhere in this specification for each of formulas (I), (II), (IIa), (IIc), (IIe), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl)), (IVa), (IVb), (IVf), (IVj), (IVk), and (IVl) (wherein each R is a cycloalkyl, 3- to 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 It is alkoxy; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5Compounds of formula (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl) are provided herein (wherein each R is a compound of a compound of formula (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl). In certain embodiments, compounds of formula (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl) (wherein each R is a compound of a compound of formula (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl) are provided herein. 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Halo C 1~3 Alkyl, hydroxyl, halo C 1~3 It is alkoxy; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Compounds of formula (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl) are provided herein (wherein each R is a cycloalkyl compound). In particular embodiments, compounds of formula (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl) are provided herein (wherein each R is a cycloalkyl compound). 11 These are independently fluoro, cyano, oxo, hydroxyl, methyl, -CHF2, -CF3 or -OCHF2, or two R 11The groups, together with the carbon atoms to which they are bonded, form cyclobutyl or oxo; other variables are described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), and (IVl)). In particular embodiments, compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl) (wherein each R) are provided herein. 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Halo C 1~3 Alkyl, hydroxyl, or halo C 1~3 The compounds provided herein are alkoxy; other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl). In particular embodiments, compounds of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl) (wherein each R is a compound of the formula). 11These are independently fluoro, cyano, oxo, hydroxyl, methyl, -CHF2, -CF3, or -OCHF2; the other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl) (wherein R 11 is Halo, Cyano, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 The compounds provided herein are alkyl; other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl) (wherein R 11 This refers to Halo, Cyano, or Halo C 1~3The compounds provided herein are alkyl; other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl) (wherein R 11 is fluoro, cyano, or fluoroC 1~3 The compounds provided herein are alkyl; other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl). In certain embodiments, compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl) (wherein R 11(wherein is fluoro, cyano, -CHF2, or -CF3; other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl)) are provided herein. In certain embodiments, compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl) (wherein R 11 (I) is a halo; the other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl)). In particular embodiments, compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl) (wherein R is a halo; the other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl) (wherein R is a halo). 11 (where is fluoro; other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl)). These are provided herein.

[0099] In a particular embodiment, equation (V): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having are provided herein.

[0100] In a particular embodiment, equation (VI): [ka] Compounds of formula (I), (II), or (IV) or pharmaceutically acceptable salts thereof having R are provided herein. In certain embodiments, compounds of formula (VI) (wherein R 3 R is a halo, cyano, alkyl, or haloalkyl; 4 is hydrogen, halo, C 1~3 Alkyl or Halo C 1~3 Alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 8 R is hydrogen, alkyl, or haloalkyl; 9 R is a cycloalkyl or heterocycline, and the cycloalkyl or heterocycline is 1, 2, or 3 independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 Compounds of formula (I) or (VI) (wherein R 8 R is hydrogen, alkyl, or haloalkyl; 9 is haloalkyl-R u -Cycloalkyl or cycloalkyl, -R u -Cycloalkyl or cycloalkyl is 1, 2, or 3 R 11 It is optionally replaced by each R 11 These are independently Halo or Halo C 1~3 Compounds of formula (I) or (VI) (wherein R is alkyl, and other variables are as described elsewhere in this specification for each of formulas (I) and (VI)) are provided herein. In certain embodiments, compounds of formula (I) or (VI) (wherein R is alkyl) are provided herein. 8 is hydrogen, C 1~3 Alkyl or Halo C 1~3 Alkyl; R 9 is Hello C 1~3 Alkyl-R u -C 3~5 Cycloalkyl or C 3~5 It is cycloalkyl, -R u -C 3~5 Cycloalkyl or C 3~5 Cycloalkyls have 1, 2, or 3 R 11 It is optionally replaced by each R 11 These are independently Halo or Halo C 1~3The following are provided herein: (the alkyl is the remaining variable, as is described elsewhere in this specification for each of formulas (I) and (VI)).

[0101] In certain embodiments, a compound of formula (I) or (VI) (wherein R) 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen, C 1~3 Alkyl or Halo C 1~3 Alkyl; R 9 is Hello C 1~3 Alkyl-R u -C 3~5 Cycloalkyl or C 3~5 It is cycloalkyl, -R u -C 3~5 Cycloalkyl or C 3~5 Cycloalkyls have 1, 2, or 3 R 11 It is optionally replaced by each R 11 These are independently Halo or Halo C 1~3 Compounds of formula (I) or (VI) (wherein R is alkyl; the remaining variables are as described elsewhere in this specification for each of formulas (I) and (VI)) are provided herein. In certain embodiments, compounds of formula (I) or (VI) (wherein R is alkyl; the remaining variables are as described elsewhere in this specification for each of formulas (I) and (VI)) are provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen, C 1~3 Alkyl or Halo C 1~3 Alkyl; R 9 is Hello C 1~3 Alkyl-R u -C 3~5 Cycloalkyl or C 3~5 It is cycloalkyl, -R u -C 3~5 Cycloalkyl or C3~5 Cycloalkyls have 1, 2, or 3 R 11 It is optionally replaced by each R 11 These are independently Halo or Halo C 1~3 The following are provided herein: (the alkyl is; the remaining variables are as described elsewhere in this specification for each of formulas (I) and (VI).

[0102] In certain embodiments, a compound of formula (I) or (VI) (wherein R) 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen, C 1~3 Alkyl or Halo C 1~3 Alkyl; R 9 is Hello C 1~3 Alkyl-R u -C 3~5 Cycloalkyl or C 3~5 It is cycloalkyl, -R u -C 3~5 Cycloalkyl or C 3~5 Cycloalkyls have 1, 2, or 3 R 11 It is optionally replaced by each R 11 These are independently Halo or Halo C 1~3 Compounds of formula (I) or (VI) (wherein R) are provided herein, which are alkyl; m and n are both 1, and k is 0. In certain embodiments, compounds of formula (I) or (VI) (wherein R) are provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen, C 1~3 Alkyl or Halo C 1~3 Alkyl; R 9 is Hello C 1~3 Alkyl-R u -C 3~5Cycloalkyl or C 3~5 It is cycloalkyl, -R u -C 3~5 Cycloalkyl or C 3~5 Cycloalkyls have 1, 2, or 3 R 11 It is optionally replaced by each R 11 These are independently Halo or Halo C 1~3 Alkyl compounds (wherein m and n are both 1 and k is 0) are provided herein. In certain embodiments, compounds of formula (I) or (VI) or pharmaceutically acceptable salts thereof (wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 (wherein is methyl; the remaining variables are as described elsewhere in this specification for each of formulas (I) and (VI)) are provided herein.

[0103] In certain embodiments, a compound of formula (I) or (VI) (wherein R) 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 R is hydrogen; 9 is -CH2CHF2, cyclopropylmethyl, cyclobutyl, or bicyclo[1.1.1]pentan-1-yl, or cyclopropylmethyl, cyclobutyl, or bicyclo[1.1.1]pentan-1-yl has 1, 2, or 3 R 11 It is optionally replaced by each R 11 Compounds of formula (I) or (VI) (wherein R is independently fluoromethyl; m and n are both 1, and k is 0) are provided herein. In certain embodiments, compounds of formula (I) or (VI) (wherein R is 0) are provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl;5 is methoxy or cyclopropyl; R 6 is methyl; R 8 R is hydrogen; 9 - is -CH2CHF2, cyclopropylmethyl, cyclobutyl, or bicyclo[1.1.1]pentan-1-yl, or cyclopropylmethyl, cyclobutyl, or bicyclo[1.1.1]pentan-1-yl has 1, 2, or 3 R 11 It is optionally replaced by each R 11 (where m and n are independently fluoro or trifluoromethyl; m and n are both 1, and k is 0) are provided herein.

[0104] In certain embodiments, a compound of formula (I) or (VI) (wherein R) 8 R is hydrogen, alkyl, or haloalkyl; 9 is, -R u -Cycloalkyl or cycloalkyl, -R u -Cycloalkyl or cycloalkyl is 1, 2, or 3 R 11 It is optionally replaced by each R 11 These are independently Halo or Halo C 1~3 Compounds of formula (I) or (VI) (wherein R is alkyl, and other variables are as described elsewhere in this specification for each of formulas (I) and (VI)) are provided herein. In certain embodiments, compounds of formula (I) or (VI) (wherein R is alkyl) are provided herein. 8 R is hydrogen, alkyl, or haloalkyl; 9 is, -R u -Cycloalkyl or cycloalkyl, -R u -Cycloalkyl or cycloalkyl is 1, 2, or 3 R 11 It is optionally replaced by each R 11 These are independently Halo or Halo C 1~3 Compounds of formula (I) or (VI) (wherein R is alkyl, and other variables are as described elsewhere in this specification for each of formulas (I) and (VI)) are provided herein. In certain embodiments, compounds of formula (I) or (VI) (wherein R is alkyl) are provided herein. 8 R is hydrogen, alkyl, or haloalkyl;9 A compound of formula (I) or (VI) is provided herein (wherein k is 0; m is 1; n is 1; the other variables are as described elsewhere herein for each of formulas (I) and (VI)). In certain embodiments, a compound of formula (I) or (VI) is provided herein (wherein k is 0; m is 1; n is 1; the other variables are as described elsewhere herein for each of formulas (I) and (VI)). In certain embodiments, a compound of formula (I) or (VI) is provided herein (wherein R 11 (where is fluoro, and the other variables are as described elsewhere in this specification for each of formulas (I) and (VI)) are provided herein. In a particular embodiment, formula (VIa): [ka] Compounds of formula (I), (II), (IV), (IVa), or (VI) or pharmaceutically acceptable salts thereof (wherein j is 1 or 2) having are provided herein. In certain embodiments, compounds of formula (VIa) or pharmaceutically acceptable salts thereof (wherein R 11 These are, independently, Halo, Cyano, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3It is alkylsulfinyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Forming a cycloalkyl group; where j is 1 or 2, the remaining variables are as described elsewhere in this specification for formula (VIa). In certain embodiments, a compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein R is provided) is provided herein. 11 These are, independently, Halo, Cyano, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is alkylsulfinyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 A compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein R is 1) is provided herein, forming a cycloalkyl group; j is 1; the remaining variables are as described elsewhere herein for formula (VIa). In certain embodiments, a compound of formula (VIa) or a pharmaceutically acceptable salt thereof is provided herein. 11 is Hello C 1~3 A compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein the formula, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; R 3is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 is Hello C 1~3 A compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 11 (where is trifluoromethyl; j is 1; k is 0; m is 1; n is 1) is provided herein.

[0105] In certain embodiments, a compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein R 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is Hello C 1~3 A compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein R is 0; where R is 1; where R is 1) is provided herein. In certain embodiments, a compound of formula (VIa) or a pharmaceutically acceptable salt thereof is provided herein. 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 (where is trifluoromethyl; j is 1; k is 0; m is 1; n is 1) is provided herein.

[0106] In certain embodiments, a compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein R 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 These are Halo, Cyano, and Halo C, each operating independently. 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is alkylsulfonyl; or two R11 The group, together with the carbon atoms to which they are bonded, C 3~5 A cycloalkyl group is provided herein, where j is 1 or 2, k is 0, m is 1, and n is 1.

[0107] In certain embodiments, a compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein R 11 Each of these is independently either fluoro, cyano, -CF3, -CHF2, -OCF3, or -S(O)2CH3, or two R 11 The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group; j is 1 or 2; the remaining variables are as described elsewhere in this specification for formula (VIa).

[0108] In certain embodiments, a compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein R 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 Each of these is independently either fluoro, cyano, -CF3, -CHF2, -OCF3, or -S(O)2CH3; or two R 11 The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group; j is 1 or 2, k is 0; m is 1, and n is 1) are provided herein.

[0109] In certain embodiments, a compound of formula (VIa) or a pharmaceutically acceptable salt thereof (wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11Each of these is independently either fluoro, cyano, -CF3, -CHF2, -OCF3, or -S(O)2CH3; or two R 11 The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group; j is 1 or 2, k is 0; m is 1, and n is 1) are provided herein.

[0110] In a particular embodiment, equation (VIb): [ka] Compounds of formula (I), (II), (IV), (IVa), or (VI) or pharmaceutically acceptable salts thereof having the above are provided herein.

[0111] In a particular embodiment, equation (VIc): [ka] Compounds of formula (I), (II), (IV), (IVa), or (VI) or pharmaceutically acceptable salts thereof having the above are provided herein.

[0112] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharmaceutically acceptable salt thereof (wherein R) 11 These are, independently, Halo, Cyano, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C1~3 Alkyl sulfinyl or halo C 1~3 It is alkylsulfinyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 A cycloalkyl compound is provided herein, the remaining variables being as described elsewhere in this specification for each of the formulas (VIb) and (VIc).

[0113] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharmaceutically acceptable salt thereof (wherein R) 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 These are Halo, Cyano, and Halo C, each operating independently. 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is alkylsulfonyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 The following are provided herein: forming a cycloalkyl; the remaining variables are as described elsewhere herein for each of formulas (VIb) and (VIc).

[0114] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharmaceutically acceptable salt thereof (wherein R) 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 These are Halo, Cyano, and Halo C, each operating independently. 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is alkylsulfonyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C3~5 A cycloalkyl group is provided herein.

[0115] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharmaceutically acceptable salt thereof (wherein R) 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 These are Halo, Cyano, and Halo C, each operating independently. 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is alkylsulfonyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 A cycloalkyl compound is provided herein; the remaining variables are as described elsewhere in this specification for formula (VIb) or (VIc).

[0116] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharmaceutically acceptable salt thereof (wherein R) 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 These are Halo, Cyano, and Halo C, each operating independently. 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is alkylsulfonyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 A cycloalkyl group is provided herein, where m is 1, n is 1, j is 1 or 2, and k is 0.

[0117] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharmaceutically acceptable salt thereof (wherein R)11 Each of these is independently either fluoro, cyano, -CF3, -CHF2, -OCF3, or -S(O)2CH3, or two R 11 The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group; j is 1 or 2; the remaining variables are as described elsewhere in this specification for each of the formulas (VIb) and (VIc).

[0118] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharmaceutically acceptable salt thereof (wherein R) 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 Each of these is independently either fluoro, cyano, -CF3, -CHF2, -OCF3, or -S(O)2CH3; or two R 11 The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group; m is 1; n is 1; j is 1 or 2; and k is 0. These are provided herein.

[0119] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharmaceutically acceptable salt thereof (wherein R) 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 Each of these is independently either fluoro, cyano, -CF3, -CHF2, -OCF3, or -S(O)2CH3; or two R 11 The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group; m is 1; n is 1; j is 1 or 2; and k is 0. These are provided herein.

[0120] In certain embodiments, compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc) (wherein each R) 11 These are independently: halo, cyano, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is alkylsulfinyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Forming cycloalkyl or oxo compounds; other variables are provided herein, as described elsewhere in this specification for each of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc).

[0121] In certain embodiments, compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc) (wherein each R) 11 These are independently, halo, cyano C 1~3 Alkyl, Halo C 1~3 Alkyl, hydroxyl, halo C 1~3 Alkoxy, C 1~3 Alkyl sulfonyl or halo C 1~3 It is alkylsulfonyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5Forming cycloalkyl or oxo compounds; other variables are provided herein, as described elsewhere in this specification for each of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc).

[0122] In certain embodiments, compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc) (wherein each R) 11 These are independently, halo, cyano C 1~3 Alkyl, Halo C 1~3 Alkyl, hydroxyl, halo C 1~3 Alkoxy or C 1~3 It is alkylsulfonyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Forming cycloalkyl or oxo compounds; other variables are provided herein, as described elsewhere in this specification for each of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc).

[0123] In certain embodiments, compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc) (wherein each R) 11 These are independently: halo, cyano, and C. 1~3 Alkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 The compounds provided herein are alkylsulfonyl compounds; other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc). In certain embodiments, compounds of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc) (wherein each R is an alkylsulfonyl compound). 11 is independently fluoro, cyano, -CHF2, -CF3, -OCF3, -OCHF2 or -S(O)2CH3; or two R 11The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group; other variables are described elsewhere in this specification for each of the formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc). In certain embodiments, compounds of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc) (wherein each R) are provided herein. 11 is independently fluoro, cyano, -CHF2, -CF3, -OCF3 or -S(O)2CH3; or two R 11 The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group, and other variables are described elsewhere in this specification for each of the formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc). In certain embodiments, compounds of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc) (wherein each R) are provided herein. 11 (These are independently fluoro, cyano, -CHF2, -CF3, -OCF3, or -S(O)2CH3; the other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc)) provided herein.

[0124] In a particular embodiment, formula (VII): [ka] Compounds of formula (I), (II), (IV), (VI), or (X) or pharmaceutically acceptable salts thereof (wherein q is 0, 1, 2, or 3) having are provided herein. In a particular embodiment, formula (VIIa): [ka] Compounds of formula (I), (II), (IV), (VI), or (X) or pharmaceutically acceptable salts thereof having are provided herein. In certain embodiments, compounds of formula (VII) or (VIIa) (wherein each R 11 These are independently known as Halo, Cyano, and Halo C. 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; k is 0; X is CH; R 1 R is hydrogen; the other variables are as described for formulas (I), (II), (IV), (VI), and (X), respectively) provided herein. In certain embodiments, compounds of formula (VII) or (VIIa) (wherein each R is hydrogen; the other variables are as described for formulas (I), (II), (VI), and (X), respectively) are provided herein. 11 is independently halo, cyano, haloalkyl, or hydroxyl; k is 0; X is CH; R 1 R is hydrogen; the other variables are as described for formulas (I), (II), (IV), (VI), and (X), respectively) provided herein. In more specific embodiments, compounds of formula (VII) or (VIIa) (wherein each R) are provided herein. 11 These are independently halo, cyano, or halo-C 1~3 It is alkyl; k is 0; X is CH; R 1 A is hydrogen; the other variables are as described for formulas (I), (II), (IV), (VI), and (X), respectively) provided herein. In more specific embodiments, compounds of formula (VII) or (VIIa) (wherein R) are provided herein. 4 R is hydrogen; 5 is methoxy; R 6 It is methyl, and X, R 1 , R 11 (and k are as described above) are provided herein.

[0125] In a particular embodiment, formula (VIII): [ka] Compounds of formula (I), (II), or (IV) or pharmaceutically acceptable salts thereof (wherein ring A is a cycloalkyl, heterocyclyl, aryl, or heteroaryl; q is 0, 1, 2, or 3; the other variables are as described for formulas (I), (II), and (IV), respectively) are provided herein. In certain embodiments, compounds of formula (VIII) (wherein ring A is a heterocyclyl or heteroaryl) are provided herein. In certain embodiments, compounds of formula (VIII) (wherein ring A is a heterocyclyl) are provided herein. In certain embodiments, compounds of formula (VIII) (wherein ring A is a heteroaryl) are provided herein. In certain embodiments, compounds of formula (VIII) (wherein ring A is a pyridinyl, pyrimidinyl, pyridadinyl, pyrazinyl, triazolyl, imidazolyl, thiazolyl, or pyrazolyl) are provided herein. In certain embodiments, compounds of formula (VIII) (wherein ring A is pyridinyl or pyrazolyl) are provided herein. In certain embodiments, compounds of formula (VIII) (wherein ring A is pyridinyl) are provided herein. In certain embodiments, compounds of formula (VIII) (wherein ring A is pyrazolyl) are provided herein. In certain embodiments, compounds of formula (VIII) (wherein ring A is azolyl) are provided herein. In certain embodiments, compounds of formula (VIII) (wherein X is CH and R 1 R is hydrogen; 4 R is hydrogen; 5 is methoxy; R 6 is methyl; each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 The alkylsulfinyl rings (where k is 0, q is 0, 1, 2, or 3, and ring A is as described above) are provided herein.

[0126] In a particular embodiment, equation (X): [ka] Compounds of formula (I) or pharmaceutically acceptable salts thereof having R are provided herein. In certain embodiments, compounds of formula (I) or (X) (wherein R 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, and alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R u and R 11 Compounds of formula (I) or (X) (wherein R) are provided herein, as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R) are provided herein. 2 C 1~6 Alkyl, Halo C 1~6 Alkyl, Jutero C 1~6 Alkyl, hydroxy C 1~6 Alkyl, C 1~6Alkoxy C 1~6 Alkyl, cyano C 1~6 Alkyl, -R u -C 3~6 Cycloalkyl, -R u -3-7 member heterocycline, C 3~6 Cycloalkyl, 3- to 7-membered heterocyclyl, or 5- to 10-membered heteroaryl, C 1~6 Alkyl, Halo C 1~6 Alkyl, Jutero C 1~6 Alkyl, hydroxy C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, cyano C 1~6 Alkyl, -R u -C 3~6 Cycloalkyl, -R u -3-7 member heterocycline, C 3~6 Cycloalkyl, 3- to 7-membered heterocyclyl, or 5- to 10-membered heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R u and R 11 Compounds of formula (I) or (X) (wherein R) are provided herein, as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R) are provided herein. 2 C 1~3 Alkyl, Halo C 1~3 Alkyl, Jutero C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, cyano C 1~3 Alkyl, -R u -C 3~6 Cycloalkyl, -R u -3-member to 6-member heterocycline, C 3~6 It is a cycloalkyl, 3- to 6-membered heterocyclyl, or 5- to 6-membered heteroaryl, C 1~3 Alkyl, Halo C 1~3 Alkyl, Jutero C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, cyano C1~3 Alkyl, -R u -C 3~6 Cycloalkyl, -R u -3-member to 6-member heterocycline, C 3~6 Cycloalkyl, 3- to 6-membered heterocyclyl, or 5- to 6-membered heteroaryl is one, two, or three independently selected R 11 It is optionally substituted in the base; R u and R 11 Compounds of formula (I) or (X) (wherein R) are provided herein, as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R) are provided herein. 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, cyanoalkyl, and -R u -Cycloalkyl or -R u - Heterocyclyl, alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, cyanoalkyl-R u -Cycloalkyl or -R u -Heterocyclines are R 11 It is optionally replaced by R 11 And other variables are as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R 2 C 1~3 Alkyl, Halo C 1~3 Alkyl, Jutero C 1~3 Alkyl, hydroxy C 1~3 Alkyl, cyano C 1~3 Alkyl, -R u -C 3~5 Cycloalkyl, -R u -3-membered to 5-membered heterocyclines, C 1~3 Alkyl, Halo C 1~3 Alkyl, Jutero C 1~3 Alkyl, hydroxy C 1~3 Alkyl, cyano C 1~3 Alkyl, -R u -C 3~5 Cycloalkyl, -R u -3-membered to 5-membered heterocyclines are independently selected R11 It is optionally substituted in the base, R 11 And other variables are as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R 2 These are haloalkyl, deuteroalkyl, and -R u -Cycloalkyl or -R u -Heterocyclyl, haloalkyl, deuteroalkyl, -R u -Cycloalkyl or -R u -Heterocyclines are independently selected R 11 It is optionally substituted in the base, R 11 And other variables are as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R 2 is Hello C 1~3 Alkyl, Jutero C 1~3 Alkyl, -R u -C 3~5 Cycloalkyl or -R u -3-member to 5-member heterocyclyl, Halo C 1~3 Alkyl, Jutero C 1~3 Alkyl, -R u -C 3~5 Cycloalkyl or -R u -3-membered to 5-membered heterocyclines are independently selected R 11 It is optionally substituted in the base, R 11 And other variables are as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R 2 is a haloalkyl or -R u -heterocyclyl, -R u -The heterocyclyl is optionally substituted with a halo selected independently; other variables are as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R 2 is Hello C1~3 Alkyl or -R u -3-member to 5-member heterocyclines, -R u -3-membered to 5-membered heterocyclyls are optionally substituted with independently selected halos; other variables are as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R 2 (wherein R is fluoroethyl or 3-fluorooxetane-3-yl)methyl; other variables are as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R is fluoroethyl or 3-fluorooxetane-3-yl) are provided herein. 2 A compound of formula (I) or (X) (wherein R is fluoroethyl; other variables are as described elsewhere in this specification for each of formulas (I) and (X)) is provided herein. In certain embodiments, a compound of formula (I) or (X) (wherein R is fluoroethyl; other variables are as described elsewhere in this specification for each of formulas (I) and (X)) is provided herein. 2 (wherein R is 3-fluorooxetane-3-yl)methyl; other variables are as described elsewhere in this specification for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X) (wherein R is 3-fluorooxetane-3-yl) are provided herein. 2 is alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl or cyanoalkyl, and alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl or cyanoalkyl is one R 11 It is optionally replaced by R 11 Compounds of formula (I) and (X) are provided herein, as described elsewhere in this specification. Furthermore, in certain embodiments, compounds of formula (X) (wherein X is CH and R) are provided herein. 1 is hydrogen, and R 4 R is hydrogen; 5 is methoxy; R 6 is methyl; each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is an alkyl sulfinyl; k is 0; R 2 (as described above) is provided herein.

[0127] In certain embodiments, a compound of formula (III), (IIIa), or formula (V) (wherein R) 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group which is optionally substituted with each R; 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 The alkylsulfinyl compounds (wherein R is described elsewhere in this specification for each of formulas (III), (IIIa), and (V)) are provided herein. In certain embodiments, compounds of formula (III), (IIIa), or (V) (wherein R is described elsewhere in this specification) are provided herein. 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 C is optionally replaced by3~6 Forming a cycloalkyl group, R 11 The formula (as described for formula (I)) is provided herein.

[0128] In certain embodiments, compounds of formula (I), (II), (IV), (IVa), (VI), or (X) (wherein m is 0 or 1; n is 0, 1, or 2, and other variables are as described elsewhere in this specification for each of formulas (I), (II), (IV), (IVa), (VI), and (X)) are provided herein. In certain embodiments, compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa), or (X) (wherein m is 1; n is 1, and the other variables are as described elsewhere in this specification for each of formulas (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa), and (X)) are provided herein. In certain embodiments, compounds of formulas (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa), or (X) are provided herein (wherein k is 0; m is 1; n is 1, and the other variables are as described elsewhere herein for each of formulas (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa), and (X)).

[0129] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with, or 1, 2, or 3 independently selected R 11 Forms a heterocycline which is optionally substituted; each R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0130] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with each R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0131] In certain embodiments, a compound of formula (I), (III), (IIIa), or (V) (wherein R) is used. 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 C is optionally replaced by 3~6 Forms a cycloalkyl group; each R 11 The formulas (III), (IIIa), and (V) are provided herein, as described elsewhere in this specification.

[0132] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a is, -Ru -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with, or 1, 2, or 3 independently selected R 11 Forms a heterocycline which is optionally substituted; R u , R 7 , R 8 , R 9 and R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0133] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with, or 1, 2, or 3 independently selected R 11 Forms a heterocycline which is optionally substituted; R 7 , R 8 , R 9 and R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0134] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a These are cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 C is replaced by 3~6 A cycloalkyl group is formed, or one, two, or three independently selected R groups. 11 It forms a 4-6 member heterocycline that is optionally substituted; R u , R 7 , R 8 , R 9 and R 11The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0135] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a These are cycloalkyl, heterocyclyl, and -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl or heterocyclyl is one, two or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 C is replaced by 3~6 A cycloalkyl group is formed, or one, two, or three independently selected R groups. 11 It forms a 4-6 member heterocycline that is optionally substituted; R 7 , R 8 , R 9 and R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0136] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a These are cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 C is replaced by 3~5 A cycloalkyl group is formed, or one, two, or three independently selected R groups. 11 It forms a 4-5 member heterocycline that is optionally substituted; R u , R 7 , R 8 , R 9 and R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0137] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2aand R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a heterocycline which is optionally substituted; R u , R 7 , R 8 , R 9 and R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0138] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a These are cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a heterocycline which is optionally substituted; R u , R 7 , R 8 , R 9 and R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0139] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2ais, -R u -Cycloalkyl or cycloalkyl, -R u -Cycloalkyl or cycloalkyl is 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0140] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a is, -R u -cycloalkyl, -R u - is a heterocyclyl, cycloalkyl, or heterocyclyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, or heterocyclyl is one, two, or three independently selected R 11 It is optionally replaced by; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0141] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a R is a cycloalkyl, heterocyclyl, aryl, or heteroaryl, and the cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a heterocycline which is optionally substituted; R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0142] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a R is a cycloalkyl, heterocyclyl, aryl, or heteroaryl, and the cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0143] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a is a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C1~3 Alkyl; R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0144] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a is a heteroaryl, and the heteroaryl is composed of 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0145] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a These are cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 It forms a 4-5 member heterocycline that is optionally substituted; R 7 , R 8, R 9 and R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0146] In certain embodiments, a compound of formula (I), (II), (IV), or (IVa) (wherein R) 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms cyclobutyl substituted with or forms oxetanyl; R 11 Compounds of formula (I), (II), (IV), and (IVa) are provided herein (as described elsewhere in this specification for each of them). In certain embodiments, compounds of formula (I), (II), (IV), or (IVa) (wherein R 2a and R 2b Along with the carbon atoms to which they are bonded, one or two R atoms 11 Forms cyclobutyl substituted with or forms oxetanyl; each R 11 is independently fluoro, cyano, -CHF2, -CF3, -OCF3 or -S(O)2CH3; or two R 11 The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group; m is 1; n is 1; and the other variables are as described elsewhere in this specification for each of the formulas (I), (II), (IV), and (IVa).

[0147] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a is -OR 7 , -SR 7 or -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3Alkyl; R 7 , R 8 , R 9 and R 11 The formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein, as described elsewhere in this specification.

[0148] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a is, -R u -Cycloalkyl, -OR 7 , -SR 7 or -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 7 is a haloalkyl or cycloalkyl; R 8 R is hydrogen; 9 is, -R u -Cycloalkyl or cycloalkyl, -R u -Cycloalkyl or cycloalkyl is 1, 2, or 3 independently selected R 11 Compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R is optionally substituted, and the remaining variables are as described elsewhere in this specification for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein. In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R is optionally substituted, and the remaining variables are as described elsewhere in this specification for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), or (V) are provided herein. 2a is, -R u -Cycloalkyl, -OR 7 , -SR 7 or -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 7is a haloalkyl or cycloalkyl; R 8 R is hydrogen; 9 is, -R u -Cycloalkyl or cycloalkyl, -R u -Cycloalkyl or cycloalkyl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; R 11 These are, independently, Halo or Halo C. 1~3 Compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R is alkyl; the remaining variables are as described elsewhere in this specification for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein. In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R is alkyl; the remaining variables are as described elsewhere in this specification for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), or (V) are provided herein. 2a cyclopropylmethyl, -OR 7 , -SR 7 or -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 7 is -CH2CF3 or cyclobutyl; R 8 is prime; R 9 This is cyclopropylmethyl or cyclobutyl, and cyclopropylmethyl or cyclobutyl has 1, 2, or 3 R 11 It is optionally replaced by each R 11 (is independently fluoro or trifluoromethyl, and the remaining variables are as described elsewhere in this specification for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V)) are provided herein. In certain embodiments, R 2b It is hydrogen.

[0149] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a is -OR 7 , -SR7 or -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 7 is -CH2CF3 or cyclobutyl; R 9 This is cyclopropylmethyl or cyclobutyl, and cyclopropylmethyl or cyclobutyl has 1, 2, or 3 R 11 It is optionally replaced by each R 11 (wherein it is independently fluoro or trifluoromethyl, and the remaining variables are as described elsewhere in this specification for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V)) are provided herein.

[0150] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 7 is, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 is, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is either optionally replaced by R 8 and R 9These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is an alkylsulfinyl; R u (wherein a methylene, ethylene, or propylene linker is optionally substituted with 1 to 6 independently selected halos) are provided herein.

[0151] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 7 R is a cycloalkyl, heterocyclyl, or heteroaryl, and the cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 R is a cycloalkyl, heterocyclyl, or heteroaryl, and the cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is either optionally replaced by R 8 and R9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 The heterocyclyl is optionally substituted with oxo, and each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is an alkylsulfinyl; R u (wherein a methylene, ethylene, or propylene linker is optionally substituted with 1 to 6 independently selected halos) are provided herein.

[0152] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 7 R is one, two, or three independently selected R 11 A cycloalkyl or heterocycline that is optionally substituted with; R 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 R is a cycloalkyl or heterocycline, and the cycloalkyl or heterocycline is 1, 2, or 3 independently selected R 11 It is either optionally replaced by R 8 and R 9These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by; R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 Alkyl sulfinyl compounds are provided herein.

[0153] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 7 is, -R u -Heterocyclyl or heterocyclyl, -R u -Heterocyclyl or heterocyclyl is 1, 2, or 3 independently selected R 11 It is optionally replaced by each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 Alkyl sulfinyl compounds are provided herein.

[0154] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 7 R is a haloalkyl group; 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 (which is a haloalkyl) are provided herein.

[0155] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 8 , R 9 and R 11 The formulas provided herein are as described for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0156] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 9 is 1, 2, or 3 R 11 -R is optionally replaced by u -It is a cycloalkyl, R 11Compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein (as described elsewhere in this specification for each of them). In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R 2a -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 9 R is one, two, or three independently selected R 11 A cycloalkyl that is optionally substituted with R 11 Compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), and (V) are provided herein (as described elsewhere in this specification for each of them). In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R 2a -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 9 (wherein is a cyclopropyl optionally substituted with one, two, or three fluoropolymers, the remaining variables being as described elsewhere in this specification for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V)) are provided herein.

[0157] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 is a haloalkyl, -R u -cycloalkyl, -R u-Heterocyclyl, cycloalkyl or heterocyclyl, haloalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, or heterocyclyl is one, two, or three independently selected R 11 It is optionally replaced by each R 11 These independently determine the halo, cyano, and C for each of equations (I), (II), (III), (IIIa), (IV), (IVa), and (V). 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 Alkyl sulfinyl compounds are provided herein.

[0158] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 is a haloalkyl, -R u - Heterocyclyl or heterocyclyl, haloalkyl, -R u -Heterocyclyl or heterocyclyl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; R 11 The formulas provided herein are as described for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0159] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2a is -OR 7 And; R 7 is a haloalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl or heterocyclyl, haloalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, or heterocyclyl is one, two, or three independently selected R 11 It is optionally replaced by; R 11 The formulas provided herein are as described for formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), respectively.

[0160] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R) 2b Compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R is hydrogen or methyl) are provided herein. In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IVa), or (V) (wherein R is hydrogen or methyl) are provided herein. 2b Compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), or (V) (wherein R is hydrogen) are provided herein. In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IVa), or (V) (wherein R is hydrogen) are provided herein. 2b (where is hydrogen, and the other variables are as described elsewhere in this specification for each of the formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V) respectively) are provided herein.

[0161] In certain embodiments, compounds of formula (I), (II), (IV), (IVa), (VI), or (X) (wherein m is 0, and the other variables are as described elsewhere in this specification for each of formulas (I), (II), (IV), (IVa), (VI), and (X)) are provided herein.

[0162] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein each R) are used. 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 The compounds provided herein are alkylsulfinyl compounds, the other variables being as described herein for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). In certain embodiments, compounds of formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein each R is an alkylsulfinyl compound). 11 These are independently: halo, cyano, and C. 1~3 Alkyl or Halo C 1~3The compounds provided herein are alkyl, and other variables are as described herein for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). In certain embodiments, compounds of formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein each R is alkyl). 11 These are independently halo, cyano, or halo-C 1~3 The compounds provided herein are alkyl, and other variables are as described herein for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). In certain embodiments, compounds of formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein each R is alkyl). 11 These are independently known as Halo, Cyano, and Halo C. 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy or Halo C 1~3 The following are provided herein: an alkoxy, with other variables as described herein for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). In a particular embodiment, each R 11 These are independently known as Halo, Cyano, and Halo C. 1~3 It is alkyl or hydroxyl.

[0163] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein each R) are used.11 These are independently halo, cyano, or halo-C 1~3 Alkyl, and other variables are provided herein as described herein for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). In a particular embodiment, each R 11 These are independently either halo or cyano.

[0164] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein each R) are used. 11 (The following are provided herein, independently of each of the following variables: fluoro, chloro, bromo, cyano, -CHF2, or -CF3, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). In a particular embodiment, each R 11 These are independently either Cl or cyano.

[0165] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein the nitrogen of indole is protected by a protecting group, and the other variables are as described elsewhere in this specification for each of formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X)) are provided herein. In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) are provided herein (wherein the nitrogen of indole is protected by Boc or p-toluenesulfonamide, and the other variables are as described elsewhere in this specification for each of formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X)).

[0166] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein k is 0, and the other variables are as described elsewhere in this specification for each of formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X)) are provided herein. In certain embodiments, compounds of formula (I), (Il), (IIa), (IIb), (IIc), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein k is 0, and the other variables are as described elsewhere in this specification for each of formulas (I), (Il), (IIa), (IIb), (IIc), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X)) are provided herein.

[0167] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein R, R) are used. 3 (wherein R is halo, methyl or -CF3, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X)) are provided herein. In certain embodiments, compounds of formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein R is a compound of the formulas (I, Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VIIa), (VIIII), (IX), or (X)) are provided herein. 3(where is methyl, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X)).

[0168] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein R, R) are used. 4 is hydrogen, halo, C 1~3 Alkyl or Halo C 1~3 Alkyl, and other variables are provided herein as described elsewhere in this specification for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). Furthermore, in certain embodiments, R 4 is hydrogen, fluoro, chloro, methyl, or -CF3. In a more specific embodiment, R 4 is hydrogen, fluoro, chloro, or methyl. In a more specific embodiment, R 4 It is hydrogen.

[0169] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein R, R) are used. 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl or C 1~3 The following are provided herein: (alkoxy; other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X)). In certain embodiments, R 5 These are chloro, bromo, methyl, cyclopropyl, or methoxy.

[0170] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein R, R) are used. 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl or C 1~3 The following are provided herein: (alkoxy; other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X)). In certain embodiments, R 6 These are chloro, bromo, cyano, methyl, cyclopropyl, or methoxy compounds.

[0171] In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein R, R) are used. 4 R is hydrogen or methyl; 5 is methoxy; R 6 (wherein is methyl, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X) respectively) are provided herein. Furthermore, in certain embodiments, R 4 R is hydrogen; 5 is methoxy, and R 6 is methyl. In certain embodiments, compounds of formula (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X) (wherein R is methyl). 4R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6 (wherein is methyl, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X)). In certain embodiments, compounds of formula (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X) (wherein R 1 is hydrogen, fluoro, or chloro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6(wherein is methyl, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X)). In certain embodiments, compounds of formula (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X) (wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, chloro, or methyl; 5 is methoxy or cyclopropyl; R 6(wherein is methyl, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X)). In certain embodiments, compounds of formula (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X) (wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 R is hydrogen, fluoro, or chloro; 5 is methoxy; R 6 (wherein is methyl, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X)).

[0172] In certain embodiments, a compound of formula (I), (Il), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VII), (VIIa), (VIII), (IX), or (X) (wherein R 1 (where is hydrogen; X is CH, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X)).

[0173] In certain embodiments, compounds of formula (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X) (wherein R 1 (where is hydrogen; X is CH, and the other variables are as described elsewhere in this specification for each of the formulas (I), (Il), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (III), (IIIa), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), and (X)).

[0174] In certain embodiments, pharmaceutical compositions are provided herein that comprise any of the compounds described herein (e.g., compounds of formula (I), (I), (Il), (IIa), (IIb), (IIc), (III), (IIIa), (IV), (IVa), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), (IVl), (IVm), (V), (VI), (VIa), (VIb), (IVc), (VII), (VIIa), (VIII), (IX), or (X)) or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

[0175] In a particular embodiment, the compound is of formula (I), 4-((2S,4S)-4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 1) 4-((2R,4R)-4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 2) 4-((2S,4S)-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; (Example 3) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (Example 4) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; (Example 5) 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; (±)-trans-4-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 6) 4-((2S,4S)-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 7) 4-((2S,4S)-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 8) 4-((2R,4R)-4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (Example 9) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid (Example 10) 4-((2R,4R)-4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (Example 11) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; (Example 12) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; (Example 13) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; (Example 14) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; (Example 15) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; (Example 16) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; 4-(-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; (Example 17) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; (Example 18) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 19) 4-((2R,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 20) 4-((2R,4R)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 21) 4-((2R,4R)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 22) 4-((2R,4R)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 23) 4-((2R,4R)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 24) 4-((2R,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidine-2-yl)benzoic acid; (Example 25) 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidine-2-yl)benzoic acid; 4-(1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 26) 4-((2R,4R)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidine-2-yl)benzoic acid; (Example 27) 4-((2R,4R)-1-((5-Methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-Methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 28) 4-((2R,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 29) 4-((2S,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((3R,5S)-1,1-difluoro-6-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; (Example 30) 4-((3S,5S)-1,1-difluoro-6-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid (or Example 30) 4-((3S,5R)-1,1-difluoro-6-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-((3R,5R)-1,1-difluoro-6-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-(1,1-difluoro-6-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; (±)-4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 31) (S)-4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 32) (R)-4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((5S,7S)-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; (Example 33) 4-((5R,7S)-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; (or Example 33) 4-((5R,7R)-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-((5S,7R)-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-((5S,7S)-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; (Example 34) 4-((5R,7S)-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; (or Example 34) 4-((5R,7R)-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-((5S,7R)-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-(5R,7S)-2,2-difluoro-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-8-azaspiro[4.5]decane-7-yl)benzoic acid; (Examples 35 or 36) 4-(5S,7S)-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-8-azaspiro[4.5]decane-7-yl)benzoic acid; (or Example 36 or 35) 4-(5S,7R)-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-(5R,7R)-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-8-azaspiro[4.5]decane-7-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-phenylpiperidine-2-yl)benzoic acid; (Example 37) 4-((2S,4S)-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-phenylpiperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-phenylpiperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-phenylpiperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-phenylpiperidine-2-yl)benzoic acid; 4-(4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-phenylpiperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(pyridine-2-yl)piperidine-2-yl)benzoic acid; (Example 38) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(pyridine-2-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(pyridine-2-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(pyridine-2-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(pyridine-2-yl)piperidine-2-yl)benzoic acid; 4-(2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azaspiro[3,4]octan-1-yl)benzoic acid; (Example 39) (S)-4-(2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid; (R)-4-(2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid; (R)-4-(2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; (Example 40) (S)-4-(2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; 4-(2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; 4-((2S,4S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 41) 4-((2R,4R)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidine-2-yl)benzoic acid; (Example 42) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 43) 4-((2S,4S)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 44) 4-((2R,4R)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (S)-4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 45) (R)-4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 46 or 47) 4-((2S,4r,6S)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 47 or 46) 4-((2S,4s,6R)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-((2R,4r,6R)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-(2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-((2R,4s,6S)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 48 or 49) 4-((2S,4r,6S)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 49 or 48) 4-((2S,4s,6R)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; (S)-4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)-2-fluorobenzoic acid; (Example 50) (R)-4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)-2-fluorobenzoic acid; 4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)-2-fluorobenzoic acid; (S)-4-(8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-8-azadhispiro[2.1.5 5 .1 3Undecane-7-yl benzoic acid; (Example 51) (R)-4-(8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-8-azadispiro[2.1.5 5 .1 3 Undecane-7-yl benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-8-azadhispiro[2.1.5 5 .1 3 Undecane-7-yl benzoic acid; (S)-4-(7-((3-chloro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2,2-difluoro-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 53) (R)-4-(7-((3-chloro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2,2-difluoro-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((3-chloro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2,2-difluoro-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (S)-4-(2,2-difluoro-7-((3-fluoro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 54) (R)-4-(2,2-difluoro-7-((3-fluoro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2,2-difluoro-7-((3-fluoro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-((2R,4s,6S)-2-cyano-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 52 or 55) 4-((2S,4r,6S)-2-cyano-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 55 or 52) 4-((2S,4s,6R)-2-cyano-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-cyano-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-cyano-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 56 or 57) 4-((2S,4r,6S)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 57 or 56) 4-((2S,4s,6R)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-((2R,4r,6R)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-(2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; (S)-4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 58) (R)-4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-((2R,4s,6S)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 59 or 60) 4-((2S,4r,6S)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 60 or 59) 4-((2S,4s,6R)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2S)-2-fluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 61) 4-((2R,4s,6S)-2-fluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 62 or 63) 4-((2S,4r,6S)-2-fluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Examples 62 or 63) 4-((2S,4s,6R)-2-fluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-fluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-fluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-((2R,4s,6S)-4-(2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 64) 4-((2S,4r,6S)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 64) 4-((2S,4s,6R)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-((2R,4r,6R)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-(2-hydroxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; (R)-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazine-2-yl)benzoic acid; (Example 65) (S)-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazine-2-yl)benzoic acid; (R)-4-(4-(2,2-difluoroethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; (Example 66) (S)-4-(4-(2,2-difluoroethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; 4-(4-(2,2-difluoroethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; (R)-4-(4-((3,3-difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; (Example 67) (S)-4-(4-((3,3-difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; 4-(4-((3,3-difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; (R)-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazine-2-yl)benzoic acid; (Example 68) (S)-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazine-2-yl)benzoic acid; (R)-4-(4-((3-fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; (Example 69) (S)-4-(4-((3-fluorooxetane-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; 4-(4-((3-fluorooxetane-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; (R)-4-(4-(2-fluoroethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; (Example 70) (S)-4-(4-(2-fluoroethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; 4-(4-(2-fluoroethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperazine-2-yl)benzoic acid; (±)-trans-4-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; (Example 71) 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; (Example 81) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidine-1-yl)piperidine-2-yl)benzoic acid; (Example 72) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(3-cyanoazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 73) 4-((2R,4R)-4-(3-cyanoazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(3-cyanoazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(3-cyanoazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(3-cyanoazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(3-(difluoromethyl)azetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 74) 4-((2R,4R)-4-(3-(difluoromethyl)azetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(3-(difluoromethyl)azetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(3-(difluoromethyl)azetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(3-(difluoromethyl)azetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((3-chloro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; (Example 75) 4-((2R,4R)-1-((3-chloro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((3-chloro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((3-chloro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((3-chloro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; (Example 76) 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(3-cyanoazetidine-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 77) 4-((2R,4R)-4-(3-cyanoazetidine-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(3-cyanoazetidine-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(3-cyanoazetidine-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(3-cyanoazetidine-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(5-azaspiro[2,3]hexane-5-yl)piperidine-2-yl)benzoic acid; (Example 78) 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(5-azaspiro[2,3]hexane-5-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(5-azaspiro[2,3]hexane-5-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(5-azaspiro[2,3]hexane-5-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-cyclopropyl-7-methyl-1H-indole-4-yl)methyl)-4-(5-azaspiro[2,3]hexane-5-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(methylsulfonyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; (Example 79) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(methylsulfonyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(methylsulfonyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(methylsulfonyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(methylsulfonyl)azetidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(3-fluoroazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 80) 4-((2R,4R)-4-(3-fluoroazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(3-fluoroazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(3-fluoroazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(3-fluoroazetidine-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-yloxy)piperidine-2-yl)benzoic acid; (Example 82) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-yloxy)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-yloxy)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-yloxy)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-yloxy)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 83) 4-((2R,4R)-4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 84) 4-((2R,4R)-4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidine-2-yl)benzoic acid; (Example 85) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidine-2-yl)benzoic acid; and 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidine-2-yl)benzoic acid Compounds selected from these are provided herein.

[0176] In certain embodiments, compounds of formula (I) selected from the group consisting of the compounds in Table A below, and pharmaceutically acceptable salts thereof are provided herein.

[0177] [Table 1]

[0178] Table 2

[0179] Table 3

[0180] Table 4

[0181] Table 5

[0182] Table 6

[0183] Table 7

[0184] Table 8

[0185] Table 9

[0186] Table 10

[0187] Table 11

[0188] Table 12

[0189] Table 13

[0190] Table 14

[0191] Table 15

[0192] Table 16

[0193] Table 17

[0194] Table 18

[0195] Table 19

[0196] Table 20

[0197] Table 21

[0198] Table 22

[0199] In certain embodiments, compounds of formula (I) selected from the group consisting of the compounds in Table B below, and pharmaceutically acceptable salts thereof are provided herein.

[0200] [Table 23]

[0201] [Table 24]

[0202] [Table 25]

[0203] [Table 26]

[0204] [Table 27]

[0205] [Table 28]

[0206] [Table 29]

[0207] [Table 30]

[0208] [Table 31]

[0209] [Table 32]

[0210] [Table 33]

[0211] [Table 34]

[0212] In certain embodiments, compounds of formula (I) selected from the group consisting of the compounds in Table C below, and pharmaceutically acceptable salts thereof are provided herein.

[0213] [Table 35]

[0214] [Table 36]

[0215] [Table 37]

[0216] [Table 38]

[0217] [Table 39]

[0218] [Table 40]

[0219] [Table 41]

[0220] [Table 42]

[0221] [Table 43]

[0222] [Table 44]

[0223] [Table 45]

[0224] In certain embodiments, compounds of formula (I) selected from the group consisting of the compounds in Table D below, and pharmaceutically acceptable salts thereof are provided herein.

[0225] [Table 46]

[0226] [Table 47]

[0227] [Table 48]

[0228] [Table 49]

[0229] [Table 50]

[0230] [Table 51]

[0231] [Table 52]

[0232] [Table 53]

[0233] [Table 54]

[0234] [Table 55]

[0235] In one embodiment, the compound of formula (I) is the following: 4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1-oxa-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-(9-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1-oxa-9-azaspiro[5.5]undecane-8-yl)benzoic acid; 4-(1,1-difluoro-6-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-(1-Methoxy-6-((5-Methoxy-7-methyl-1H-indole-4-yl)methyl)-6-Azaspiro[2.5]Octane-5-yl)benzoic acid; 4-(1,1-difluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(1-Methoxy-7-((5-Methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-(2-Methoxy-7-((5-Methoxy-7-methyl-1H-indole-4-yl)methyl)-7-Azaspiro[3.5]nonane-6-yl)benzoic acid; 4-(2-ethoxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(trifluoromethyl)piperidine-2-yl)benzoic acid; 4-(4-(difluoromethyl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-fluoro-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-methylpiperidine-2-yl)benzoic acid; 4-(4-ethyl-4-fluoro-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-fluoro-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-propylpiperidine-2-yl)benzoic acid; 4-((1R,3S,5S)-3-ethoxy-8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-8-azabicyclo[3.2.1]octan-1-yl)benzoic acid; 4-((2R,8R)-8-ethoxy-3-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-3-azabicyclo[3.2.1]octan-2-yl)benzoic acid; 4-((1R,4R,5R)-5-ethoxy-2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azabicyclo[2.2.2]octan-1-yl)benzoic acid; 4-((3R,5R)-5-ethoxy-2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azabicyclo[2.2.2]octan-3-yl)benzoic acid; 4-((2R,4R)-4-cyclopropoxy-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopentyloxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclobutylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopentyl methoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclohexylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetan-3-ylmethoxy)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((tetrahydrofuran-3-yl)methoxy)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-2-ylmethoxy)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((tetrahydrofuran-2-yl)methoxy)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((tetrahydro-2H-pyran-2-yl)methoxy)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((tetrahydro-2H-pyran-3-yl)methoxy)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((tetrahydro-2H-pyran-4-yl)methoxy)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(trifluoromethoxy)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(3-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-2-yl)benzoic acid; 4-(3-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-4-yl)benzoic acid; 4-(6-ethoxy-3-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-2-yl)benzoic acid; 4-(6-ethoxy-3-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-4-yl)benzoic acid; 4-((2R,4R)-4-(2,2-difluorocyclopropoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(2-fluoro-2-methylcyclopropoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(2,2-dimethylcyclopropoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(3,3-difluorocyclobutoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-acetamido-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-((2,2-difluorocyclopropyl)methoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-((2-fluoro-2-methylcyclopropyl)methoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-Methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2-methylcyclopropyl)methoxy)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-((2,2-dimethylcyclopropyl)methoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1-methylcyclopropoxy)piperidine-2-yl)benzoic acid; 4-(5-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)octahydrofluoro[3,2-c]pyridine-4-yl)benzoic acid; 4-((6S)-5-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)octahydrofluoro[3,2-c]pyridine-6-yl)benzoic acid; 4-(6-(((5S)-5-methoxy-7-methyloctahydro-1H-indole-4-yl)methyl)-2H-6l4-pyrano[3,2-c]pyridine-5-yl)benzoic acid; 4-(6-(((7S)-5-methoxy-7-methyloctahydro-1H-indole-4-yl)methyl)-2H-6l4-pyrano[3,2-c]pyridine-7-yl)benzoic acid; 4-((1R)-2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1,2,3,4-tetrahydro-2l4-isoquinoline-1-yl)benzoic acid; (S)-4-(5-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-5-azaspiro[2.5]octan-4-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-((6-fluoro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((6-chloro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-ethoxypiperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-((5-methoxy-6,7-dimethyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((7-cyclopropyl-5-methoxy-1H-indole-4-yl)methyl)-4-ethoxypiperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((7-cyano-5-methoxy-1H-indole-4-yl)methyl)-4-ethoxypiperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-((5-methoxy-7-(trifluoromethyl)-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-1-((7-(difluoromethyl)-5-methoxy-1H-indole-4-yl)methyl)-4-ethoxypiperidine-2-yl)benzoic acid; rac-4-((2R,4S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-(methyl-d3)-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-((3-fluoro-5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-3,7,8,9-tetrahydropyrano[3,2-e]indole-9-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-6,7,8,9-tetrahydro-3H-benzo[e]indole-9-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(5-methyl-1,6-dihydro-2H-fluoro[3,2-e]indole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-3,6,7,8-tetrahydrocyclopenta[e]indole-8-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-3,7,8,9-tetrahydrothiopyrano[3,2-e]indole-9-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-6,6-dioxide-3,7,8,9-tetrahydrothiopyrano[3,2-e]indole-9-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(6-methoxy-8-methyl-1,3,4,5-tetrahydrobenzo[cd]indole-5-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(6-methoxy-8-methyl-4,5-dihydro-1H-pyrano[2,3,4-cd]indole-5-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-3,7,8,9-tetrahydropyrano[3,2-e]indole-9-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-6,7,8,9-tetrahydro-3H-benzo[e]indole-9-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(5-methyl-1,6-dihydro-2H-fluoro[3,2-e]indole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-3,6,7,8-tetrahydrocyclopenta[e]indole-8-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-3,7,8,9-tetrahydrothiopyrano[3,2-e]indole-9-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-6,6-dioxide-3,7,8,9-tetrahydrothiopyrano[3,2-e]indole-9-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(6-methoxy-8-methyl-1,3,4,5-tetrahydrobenzo[cd]indole-5-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(6-methoxy-8-methyl-4,5-dihydro-1H-pyrano[2,3,4-cd]indole-5-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)-1-naphthoic acid; 5-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)quinoline-8-carboxylic acid; 8-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)quinoline-5-carboxylic acid; 8-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)imidazo[1,2-a]pyridine-5-carboxylic acid; 5-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid; 6-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid; rac-7-((2R,4S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)-2,3-dihydro-1H-indene-4-carboxylic acid; 7-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)-2,3-dihydrobenzofuran-4-carboxylic acid; (S)-3-(4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1,2,3,4-tetrahydroquinoline-7-yl)propanoic acid; (S)-2-((4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-1,2,3,4-tetrahydroquinoline-7-yl)oxy)acetic acid; 4-(9-((5-methoxy-7-(methyl-d3)-1H-indole-4-yl)methyl)-1-oxa-9-azaspiro[5.5]undecane-8-yl)benzoic acid; 4-(7-((5-methoxy-7-(methyl-d3)-1H-indole-4-yl)methyl)-1-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(8-((5-methoxy-7-(methyl-d3)-1H-indole-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; (4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)phenyl)phosphonic acid; rac-4-((2R,4S)-4-ethoxy-1-((5-methoxy-7-(methyl-d3)-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-((5-ethyl-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; N-hydroxy-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzamide; (4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)phenyl)boronic acid; Imino(4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)phenyl)(methyl)-16-sulfanone; (S)-4-(4,4-difluoro-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(5-ethoxy-2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azabicyclo[4.1.0]heptan-1-yl)benzoic acid; 4-(5-ethoxy-2-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2-azabicyclo[4.1.0]heptan-3-yl)benzoic acid; 4-(1-ethoxy-6-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-(1-ethoxy-7-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-7-azaspiro[3.5]nonane-6-yl)benzoic acid; Methyl 4-(4-(ethylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoate; 7-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)-2,3-dihydrobenzofuran-4-carboxylic acid; 8-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)imidazo[1,2-a]pyridine-5-carboxylic acid; 4-((2S)-3-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-2-yl)benzoic acid; 4-(((2R,4R)-2-(4-(2H-tetrazole-5-yl)phenyl)-4-(cyclopropylmethoxy)piperidine-1-yl)methyl)-5-methoxy-7-methyl-1H-indole; 5-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid; 4-(8-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-2,2-dimethyl-1-oxa-8-azaspiro[4.5]decane-7-yl)benzoic acid; 4-((2S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)-2-fluorobenzoic acid; and 4-[4-(ethylamino)-1-[(5-methoxy-7-methyl-1H-indole-4-yl)methyl]-2-piperidinyl]-2-fluorobenzoic acid; or Its stereoisomers and pharmaceutically acceptable salts Not a compound selected from the list.

[0236] In one embodiment, the compound of formula (I) is not a compound disclosed in PCT Publication No. International Publication No. 2022 / 028527 (which is incorporated herein by reference to exclude the compounds disclosed herein).

[0237] Any combination of the groups described above is conceivable for various variables in this specification. Therefore, throughout this specification, the groups and their substituents are selected by those skilled in the art to provide stable moieties and compounds.

[0238] The compounds of this disclosure include the compounds themselves and their salts. In the spirit of this disclosure, salts are preferably pharmaceutically acceptable salts of the compounds relating to this disclosure. This also includes salts that are not suitable for pharmaceutical use in themselves but can be used, for example, for the isolation or purification of the compounds relating to this disclosure. Salts may be formed, for example, between anions and positively charged substituents (e.g., aminos) in the compounds described herein. Suitable anions include chloride ions, bromide ions, iodide ions, sulfate ions, nitrate ions, phosphate ions, citrate ions, methanesulfonate ions, trifluoroacetate ions, and acetate ions. Similarly, salts may also be formed between cations and positively charged substituents (e.g., carboxylates) in the compounds described herein. Suitable cations include sodium ions, potassium ions, magnesium ions, calcium ions, and ammonium cations, such as tetramethylammonium ions.

[0239] As used herein, “pharmaceutically acceptable salt” means an acid or base addition salt, including, but not limited to, a base addition salt formed by a compound of formula (I) having an acidic moiety together with a pharmaceutically acceptable cation, such as sodium, potassium, magnesium, calcium, aluminum, lithium, and ammonium. A list of suitable salts can be found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418; SMBerge et al., “Pharmaceutical Salts”, J. Pharm. Sci. 1977, 66, 1-19; and “Pharmaceutical Salts: Properties, Selection, and Use. A Handbook”; Wermuth, CG and Stahl, PH (eds.), Verlag Helvetica Chimica Acta, Zurich, 2002 [ISBN 3-906390-26-8]; these are all incorporated herein by reference.

[0240] This disclosure also includes all suitable isotopic variants of the compounds relating to this disclosure, whether radioactive or not. An isotopic variant of a compound relating to this disclosure is understood to mean a compound in which at least one atom in the compound relating to this disclosure is replaced with another atom having the same atomic number but a different atomic mass from the atomic mass that normally or predominantly exists in nature.

[0241] Examples of isotopes that may be incorporated into the compounds relating to this disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, chlorine, bromine, and iodine, for example. 2 H (deuterium), 3 H (tritium), 13 C, 14 C, 15 N, 17 O, 18 O, 18 F, 36 Cl, 82 Br, 123 I, 124 I, 125 I, 129 I and 131 I. Certain isotopic variants of the compounds relating to this disclosure, particularly those incorporating one or more radioactive isotopes, may be useful, for example, for investigating the mechanism of action or the distribution of active compounds in the body. 3 H, 14 C and / or 18 Compounds labeled with 1F isotopes are suitable for this purpose. Furthermore, for example, the incorporation of deuterium isotopes may result in certain therapeutic effects, such as an extension of the half-life in the body or a reduction in the effective dose required, as a result of the compound's higher metabolic stability.

[0242] Therefore, certain embodiments provide isotopically enriched analogs of the compounds disclosed herein, such as deuterated analogs, to improve the pharmacokinetic (PK), pharmacodynamic (PD), and toxicity profiles of the compounds.

[0243] In some embodiments, hydrogen atoms in the compounds described herein may be substituted with deuterium atoms. In certain embodiments, “deuterated” when applied to a chemical group means a chemical group isotopically enriched with a substantially greater amount of deuterium than its natural abundance, for example, a chemical group that is at least 90% deuterium at a particular position, unless otherwise specified.

[0244] Isotope variants of the compounds relating to this disclosure can be prepared by using specific reagents and / or corresponding isotope modifications of the starting compounds therein, for example, by various methods including those described below and in the examples.

[0245] C. Formulations As used herein, the term “pharmaceutical composition” is intended to encompass products comprising the active ingredient and the inert component constituting the carrier, as well as any products arising directly or indirectly from any combination, complex formation or aggregation of any two or more components, from the dissociation of one or more components, or from one or more other types of reactions or interactions of components. Accordingly, the pharmaceutical compositions of the Disclosure include any compositions prepared by mixing the compounds of the Disclosure or their pharmaceutically acceptable salts and pharmaceutically acceptable carriers.

[0246] The term "pharmaceutically acceptable carrier" refers to a carrier or adjuvant that can be administered to a patient together with the compound of this disclosure or a pharmaceutically acceptable salt thereof, without impairing its pharmacological activity, and is non-toxic when administered in a dose sufficient to deliver a therapeutic amount of the compound.

[0247] The dosage administered depends on the compound formulation, route of administration, etc., and is generally determined experimentally, with inevitable variations depending on the target, host, and route of administration. Generally, the amount of the active compound in a unit dose of the formulation can be varied or adjusted between approximately 1 milligram (mg) and approximately 100 mg, or between approximately 1 mg and approximately 1000 mg, depending on the specific use. For convenience, the total daily dose may be divided and administered in several doses throughout the day.

[0248] Solid dosage forms of this pharmaceutical composition for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier, e.g., sodium citrate or dicalcium phosphate and / or a) fillers or bulking agents, e.g., starch, lactose, sucrose, glucose, mannitol and silicic acid; b) binders, e.g., carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and acacia; c) humectants, e.g., glycerol; d) disintegrants, e.g., agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) dissolution retarders, e.g., paraffin; f) absorption enhancers, e.g., quaternary ammonium compounds; g) wetting agents, e.g., cetyl alcohol and glycerol monostearate; h) absorbents, e.g., kaolin and bentonite clay; and i) lubricants, e.g., talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also include a buffering agent.

[0249] Similar types of solid pharmaceutical compositions can also be used as fillers in soft and rigid gelatin capsules, using excipients such as lactose or milk sugar and high molecular weight polyethylene glycol.

[0250] The solid dosage forms of this pharmaceutical composition, such as tablets, sugar-coated tablets, capsules, pills, and granules, may be prepared with coatings and shells, such as enteric coatings and other pharmaceutical coatings. They may optionally contain opacifying agents, and they may be formulated to selectively delay the release of the active ingredient only in specific parts of the intestinal tract, or preferentially in specific parts of the intestinal tract. Examples of embedding pharmaceutical compositions that may be used include polymers and waxes.

[0251] The active compound may, where appropriate, also be in the form of microencapsulated compounds accompanied by one or more of the excipients mentioned above.

[0252] Liquid dosage forms of this pharmaceutical composition for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compound, the liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizers and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol, and sorbitan fatty acid esters, as well as mixtures thereof.

[0253] In addition to the active compound, the suspension of this compound may contain suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methhydroxyl, bentonite, agar and tragacanth, and mixtures thereof.

[0254] The pharmaceutical compositions of this disclosure for injection include pharmaceutically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into solutions or dispersions for sterile injection immediately before use. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, and polyethylene glycol) and suitable mixtures thereof, vegetable oils (such as olive oil), and organic acid esters for injection such as ethyl oleate. Adequate fluidity can be maintained, for example, by the use of coating materials such as lecithin, and in the case of dispersions, by maintaining the required particle size and by the use of surfactants.

[0255] In addition to inert diluents, these pharmaceutical compositions may also contain adjuvants such as preservatives, humectants, emulsifiers, dispersants, sweeteners, flavorings, and fragrances. Prevention of microbial action can be ensured by including various antibacterial and antifungal agents, such as parabens, chlorobutanol, and phenolsorbic acid. The inclusion of isotonic agents such as sugars and sodium chloride may also be desirable. Sustained absorption of injectable pharmaceutical formulations can be achieved by including absorption-delaying agents such as aluminum monostearate and gelatin. Compounds can be incorporated into sustained-release or targeted delivery systems such as polymer matrices, liposomes, and microspheres. Such formulations may provide a more effective distribution of the compound.

[0256] Pharmaceutical compositions intended for injection can be sterilized, for example, by filtration through a bacterial-retaining filter or by incorporating a sterilizer in the form of a sterile solid pharmaceutical composition that can be dissolved or dispersed in sterile water or other sterile injection medium before use.

[0257] Dosage forms for topical administration of the compounds or pharmaceutical compositions of this disclosure include powders, patches, sprays, ointments, and inhalants. The active compound is mixed under sterile conditions with a pharmaceutically acceptable carrier and any preservatives, buffers, or propellants as needed.

[0258] The compounds and compositions described herein may be administered, for example, orally, parenterally (e.g., subcutaneously, intradermally, intravenously, or intramuscularly), topically, rectally, nasally, sublingually, or orally, every 4 to 120 hours, or in doses ranging from about 0.01 milligrams / kg to about 1000 mg / kg (e.g., about 0.01 to about 100 mg / kg, about 0.1 to about 100 mg / kg), depending on the requirements of the specific drug, dosage form, and / or route of administration. Other routes of administration include intestinal, intra-arterial, intraperitoneal, and subarachnoid administration. The interrelationships of doses for animals and humans (based on milligrams per square meter of body surface area) are described by Freireich et al., Cancer Chemother. Rep. 50, 219-244 (1966). Body surface area can be approximately determined from the patient's height and weight. See, for example, Scientific Tables, Geigy Pharmaceuticals, Ardsley, NY, 537 (1970). In certain embodiments, the composition is administered orally or by injection. The methods described herein assume the administration of a therapeutically effective amount of the compound or compound composition to achieve the desired or described effect. Typically, the pharmaceutical compositions of this disclosure would be administered about 1 to about 6 times per day, or alternatively, as continuous infusions. Such administration may be used for long-term or acute treatment.

[0259] Lower or higher doses than those listed above may be required. The specific dosage and treatment regimen for any particular patient will depend on a variety of factors, including the activity of the specific compound used, age, weight, overall health, sex, diet, timing of administration, excretion rate, drug combinations, severity and course of the disease, condition or symptom, the patient's predisposition to the disease, and the judgment of the treating physician.

[0260] The dosage form contains approximately 0.001 mg to approximately 2,000 mg (including approximately 0.001 mg to approximately 1,000 mg, approximately 0.001 mg to approximately 500 mg, and approximately 0.01 mg to approximately 250 mg) of a compound of formula (I) as defined anywhere herein or a salt thereof (e.g., a pharmaceutically acceptable salt). The dosage form may further contain a pharmaceutically acceptable carrier and / or further therapeutic agent.

[0261] Appropriate dose levels may be determined by any preferred method. Preferably, the active substance is administered at a frequency of 1 to 4 times per day in the case of topical administration, or less frequently when a drug delivery system is used. Nevertheless, the actual dose levels and time course of administration of the active ingredients in the pharmaceutical compositions of this disclosure may be varied to obtain an amount of the active ingredient that is effective in achieving the desired therapeutic response for a particular patient, composition, and method of administration without being unbearably toxic to the patient. In some cases, the dose may deviate from the prescribed amount, particularly depending on the patient's age, sex, weight, diet and overall health, route of administration, individual response to the active ingredient, nature of the formulation, and the time or interval at which administration is performed. Therefore, in some cases it may be sufficient to control the dose below the minimum amount described above, but in other cases it may exceed the upper limit described. In the case of higher doses, it may be desirable to divide them into multiple individual doses over the course of a day.

[0262] D.How to use Methods of using the compounds disclosed herein, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, for the treatment, prevention, or improvement of diseases or disorders mediated by or otherwise affected by complement alternative pathways are provided herein. In more specific embodiments, methods of using the compounds disclosed herein, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, for the treatment, prevention, or improvement of diseases or disorders mediated by or otherwise affected by complement factor B (CFB) are provided herein. In more specific embodiments, methods of using the compounds disclosed herein, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, for the treatment, prevention, or improvement of diseases or disorders mediated by or otherwise affected by the inhibition of complement alternative pathways are provided herein. In more specific embodiments, methods of using the compounds disclosed herein, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof, for the treatment, prevention, or improvement of diseases or disorders mediated by or otherwise affected by the inhibition of complement factor B are provided herein.

[0263] Known examples of complement-related diseases or disorders include neuropathy, multiple sclerosis, stroke, Guillain-Barré syndrome, traumatic brain injury, Parkinson's disease, impaired inappropriate or undesirable complement activation, hemodialysis complications, hyperacute allograft rejection, xenograft rejection, interleukin-2 induced toxicity during IL-2 therapy, inflammatory diseases, inflammation of autoimmune diseases, Crohn's disease, adult respiratory distress syndrome, thermal injuries including burns or frostbite, myocarditis, post-ischemic reperfusion, myocardial infarction, balloon angioplasty, post-pump syndrome during cardiopulmonary bypass or renal bypass, atherosclerosis, hemodialysis, renal ischemia, mesenteric artery reperfusion after aortic reconstruction, infection or sepsis, immune complex disorders and autoimmune diseases, rheumatoid arthritis, systemic lupus erythematosus (SLE), SLE nephritis, proliferative glomerulonephritis, hepatic fibrosis, hemolytic anemia, myasthenia gravis, tissue regeneration, and nerve regeneration. Furthermore, other known complement-related diseases include lung diseases and disorders, such as dyspnea, hemoptysis, ARDS, asthma, chronic obstructive pulmonary disease (COPD), emphysema, pulmonary embolism and infarction, pneumonia, fibrotic dust diseases, inert dust and minerals (e.g., silicon, carbon, beryllium and asbestos), pulmonary fibrosis, organic dust diseases, chemical injuries (caused by irritating gases and chemicals, such as chlorine, phosgene, sulfur dioxide, hydrogen sulfide, nitrogen dioxide, ammonia and hydrochloric acid), smoke pollution, heat injuries (e.g., burns, frostbite), asthma, allergies, bronchoconstriction, and hypersensitivity. Pneumonia, parasitic diseases, Goodpasture syndrome, pulmonary vasculitis, microimmune vasculitis, immune complex-associated inflammation; age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, macular edema, Behçet's uveitis, multifocal chorioretinitis, Vogt-Koyanagi-Harada syndrome, intermediate uveitis, scatter chorioretinitis, sympathetic ophthalmitis, ocular scarring pemphigoid, pemphigus ophthalmos, non-arteritic ischemic optic neuropathy, postoperative inflammation, and ocular diseases including retinal vein occlusion uveitis (including Behçet's disease and other subtypes of uveitis), and antiphospholipid antibody syndromes.

[0264] In certain embodiments, methods for treating kidney disease, chronic kidney disease, diabetic nephropathy, glomerulonephropathy, complement C3 glomerulopathy (C3G), IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis (DDD), minimal change nephropathy (MCD), paroxysmal nocturnal hemoglobinuria (PNH), ANCA-associated vasculitis, lupus nephritis, or polycystic kidney disease (PKD) are provided herein.

[0265] E. Embodiment Embodiment 1: Formula (I): [ka] (In the formula, R 1 These are hydrogen, fluoro, chloro, or methyl; X is either N or CH; Z is NR 2 or CR 2a R 2b and; R 2 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 or -S(O) t R 12 These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 2a is a haloalkyl, -R u -cycloalkyl, -R u-heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; and R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b These, together with the carbon atoms to which they are bonded, form a cycloalkyl or heterocycline, and the cycloalkyl or heterocycline is composed of 1, 2, or 3 independently selected R 11 It is optionally replaced by; R 3 is Halo, Cyano, C 1~3 Alkyl or Halo C 1~3 It is alkyl; R 4 These are hydrogen, halo, cyano, and C. 1~3 Alkyl or Halo C 1~3 It is alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 7 is a haloalkyl, -R u -cycloalkyl, -Ru -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl, or haloalkyl; R 9 is a haloalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 -C(O)NR 13 R 14 , -S(O) t R 12 or -S(O) t NR 13 R 14 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by; Each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is alkylsulfinyl; or Two R's 11 The group, together with the carbon atoms to which they are bonded, C 3~5 Forms cycloalkyl, 3- to 6-membered heterocyclyl, or oxo molecules, C 3~5 Cycloalkyl or 3- to 6-membered heterocyclyls are optionally substituted with one or two independently selected halos; R 12 is alkyl, deuteroalkyl, or haloalkyl; R 13 and R 14 Each of these is independently hydrogen, alkyl, deuteroalkyl or haloalkyl, or R 13 and R 14 Along with the nitrogen atom to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms heterocyclines that are optionally substituted; R u is a methylene, ethylene, or propylene linker that is optionally substituted with 1 to 6 independently selected halos; k is 0, 1, 2, or 3; t is either 1 or 2; m is 0, 1 or 2; and n is 0, 1, or 2, however, Z is NR 2 If so, m is 1, and n is 1 or 2; and Z is CR 2a R 2b And R 2a and R 2b However, together with the carbon atoms to which they are bonded, they form a cycloalkyl group, and when m is 1, the cycloalkyl group has at least one R 11 (This will be replaced by...) A compound of or a pharmaceutically acceptable salt thereof.

[0266] Embodiment 2: m is 0 or 1; n is 0, 1 or 2, where Z is NR 2 The compound according to Embodiment 1, wherein m is 1 and n is 1 or 2.

[0267] Embodiment 3: m is 0 or 1; and n is 0 or 1, provided that Z is NR 2 The compound according to Embodiment 1, in which case m is 1 and n is 1.

[0268] Embodiment 4: Formula (II): [ka] (wherein m is 0 or 1; n is 0 or 1; and X, R) 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 (and k are as described in Embodiment 1) A compound according to any one of Embodiments 1 to 3, or a pharmaceutically acceptable salt thereof, having the above characteristics.

[0269] Embodiment 5: Formula (III): [ka] (In the formula, X, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 (and k are as described in Embodiment 1) A compound according to any one of Embodiments 1 to 4, or a pharmaceutically acceptable salt thereof, having the above characteristics.

[0270] Embodiment 6: Formula (IV): [ka] (wherein m is 0 or 1; n is 0 or 1; and X, R) 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 (k, m, and n are as described in Embodiment 1) A compound according to any one of Embodiments 1 to 4, or a pharmaceutically acceptable salt thereof, having the above characteristics.

[0271] Embodiment 7: Formula (IVa): [ka] A compound according to any one of Embodiments 1 to 4, or a pharmaceutically acceptable salt thereof, having the above characteristics.

[0272] Embodiment 8: Formula (V): [ka] (In the formula, X, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6 (and k are as described in Embodiment 1) A compound according to any one of Embodiments 1 to 4, or a pharmaceutically acceptable salt thereof, having the above characteristics.

[0273] Embodiment 9: R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with, or 1, 2, or 3 independently selected R 11A compound according to any one of Embodiments 1 to 8, which forms a heterocycline that is optionally substituted.

[0274] Embodiment 10:R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 A compound according to any one of Embodiments 1 to 8, which forms a cycloalkyl group substituted with [a specific compound].

[0275] Embodiment 11: R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 C is optionally replaced by 3~6 The compound according to Embodiment 5 or 8, which forms a cycloalkyl group.

[0276] Embodiment 12: R 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with, or 1, 2, or 3 independently selected R 11A compound according to any one of Embodiments 1 to 8, which forms a heterocycline that is optionally substituted.

[0277] Embodiment 13: R 2a These are cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 Forms a cycloalkyl group substituted with, or 1, 2, or 3 independently selected R 11 A compound according to any one of Embodiments 1 to 8, which forms a heterocycline that is optionally substituted.

[0278] Embodiment 14: R 2a These are cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 C is replaced by 3~6A cycloalkyl group is formed, or one, two, or three independently selected R groups. 11 A compound according to any one of Embodiments 1 to 8, which forms a 4-6 membered heterocycline that is optionally substituted.

[0279] Embodiment 15: R 2a These are cycloalkyl, heterocyclyl, and -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl or heterocyclyl is one, two or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 C is replaced by 3~6 A cycloalkyl group is formed, or one, two, or three independently selected R groups. 11 A compound according to any one of Embodiments 1 to 8, which forms a 4-6 membered heterocycline that is optionally substituted.

[0280] Embodiment 16: R 2a These are cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2bAlong with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 C is replaced by 3~5 A cycloalkyl group is formed, or one, two, or three independently selected R groups. 11 A compound according to any one of Embodiments 1 to 8, which forms a 4-5 membered heterocycline that is optionally substituted.

[0281] Embodiment 17: R 2a is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 And, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 A compound according to any one of Embodiments 1 to 8, which forms a heterocycline that is optionally substituted.

[0282] Embodiment 18: R 2a These are cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 A compound according to any one of Embodiments 1 to 8, which forms a heterocycline that is optionally substituted.

[0283] Embodiment 19: R 2a is, -R u -Cycloalkyl or cycloalkyl, -R u -Cycloalkyl or cycloalkyl is 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 A compound according to any one of Embodiments 1 to 8, which is alkyl.

[0284] Embodiment 20:R 2a is, -R u -cycloalkyl, -R u - is a heterocyclyl, cycloalkyl, or heterocyclyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, or heterocyclyl is one, two, or three independently selected R 11 It is optionally replaced by; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 A compound according to any one of Embodiments 1 to 8, which is alkyl.

[0285] Embodiment 21: R 2a R is a cycloalkyl, heterocyclyl, aryl, or heteroaryl, and the cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 A compound according to any one of Embodiments 1 to 8, which forms a heterocycline that is optionally substituted.

[0286] Embodiment 22: R 2a R is a cycloalkyl, heterocyclyl, aryl, or heteroaryl, and the cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 A compound according to any one of Embodiments 1 to 8, which is alkyl.

[0287] Embodiment 23:R 2a is a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl is 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 A compound according to any one of Embodiments 1 to 8, which is alkyl.

[0288] Embodiment 24: R 2a is a heteroaryl, and the heteroaryl is composed of 1, 2, or 3 independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3A compound according to any one of Embodiments 1 to 8, which is alkyl.

[0289] Embodiment 25: R 2a These are cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 The cycloalkyl, heterocyclyl, aryl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Is it alkyl; or R 2a and R 2b Along with the carbon atoms to which they are bonded, there are 1, 2, or 3 independently selected R 11 It forms a 4-5 member heterocycline that is optionally substituted; R 7 , R 8 , R 9 and R 11 The compound is as described in Embodiment 1, or as described in any one of Embodiments 1 to 8.

[0290] Embodiment 26: R 2a is -OR 7 , -SR 7 or -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 7 , R 8 , R 9 and R 11 The compound is as described in Embodiment 1, or as described in any one of Embodiments 1 to 8.

[0291] Embodiment 27: R 2a is, -R u -Cycloalkyl, -OR7 , -SR 7 or -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 Alkyl; R 7 is a haloalkyl or cycloalkyl; R 8 R is hydrogen; 9 is, -R u -Cycloalkyl or cycloalkyl, -R u -Cycloalkyl or cycloalkyl is 1, 2, or 3 independently selected R 11 It is optionally replaced by; R 11 These are, independently, Halo or Halo C. 1~3 A compound according to any one of Embodiments 1 to 8, which is alkyl.

[0292] Embodiment 28: R 7 is, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl (where -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 (Optionally replaced by) 1, 2, or 3 independently selected R 11 A cycloalkyl or heterocycline that is optionally substituted with; R 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 is, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11It is either optionally replaced by R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is an alkylsulfinyl; R u The compound according to any one of embodiments 1 to 8, 12 to 18, 25 and 26, wherein is a methylene, ethylene, or propylene linker optionally substituted with 1 to 6 independently selected halos.

[0293] Embodiment 29: R 7 R is a cycloalkyl, heterocyclyl, or heteroaryl, and the cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 R is a cycloalkyl, heterocyclyl, or heteroaryl, and the cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is either optionally replaced by R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R11 The heterocyclyl is optionally substituted with oxo, and each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 It is an alkylsulfinyl; R u The compound according to any one of embodiments 1 to 8, 12 to 18, 25 and 26, wherein is a methylene, ethylene, or propylene linker optionally substituted with 1 to 6 independently selected halos.

[0294] Embodiment 30:R 7 R is one, two, or three independently selected R 11 A cycloalkyl or heterocycline that is optionally substituted with; R 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 R is a cycloalkyl or heterocycline, and the cycloalkyl or heterocycline is 1, 2, or 3 independently selected R 11 It is either optionally replaced by R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 A compound according to any one of embodiments 1 to 8, 12 to 18, 25 and 26, which is an alkyl sulfinyl.

[0295] Embodiment 31:R 7 is, -R u -Heterocyclyl or heterocyclyl, -R u -Heterocyclyl or heterocyclyl is 1, 2, or 3 independently selected R 11 It is optionally replaced by each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 A compound according to any one of embodiments 1 to 8, 12 to 18, 25 and 26, which is an alkyl sulfinyl.

[0296] Embodiment 32: R 7 R is a haloalkyl group; 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 The compound is a haloalkyl compound as described in any one of embodiments 1-8, 12-18, 25, and 26.

[0297] Embodiment 33:R2a -NR 8 R 9 And; R 2b is hydrogen, deuterium, halogen, C 1~3 Alkyl, Jutero C 1~3 Alkyl or Halo C 1~3 A compound that is alkyl, as described in any one of embodiments 1-8, 12-18, 25, and 26.

[0298] Embodiment 34: R 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 is a haloalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl or heterocyclyl, haloalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, or heterocyclyl is one, two, or three independently selected R 11 It is optionally replaced by each R 11 These are independently: halo, cyano, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 The compound according to embodiment 33, which is an alkyl sulfinyl.

[0299] Embodiment 35: R 8 R is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; 9 is a haloalkyl, -R u - Heterocyclyl or heterocyclyl, haloalkyl, -R u-Heterocyclyl or heterocyclyl is 1, 2, or 3 independently selected R 11 The compound according to Embodiment 33, which is optionally substituted with [the compound].

[0300] Embodiment 36: R 2a is -OR 7 And; R 7 is a haloalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl or heterocyclyl, haloalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, or heterocyclyl is one, two, or three independently selected R 11 It is optionally replaced by; R 11 The compound is as described in Embodiment 1, or any one of Embodiments 1-8, 12-18, 25, and 26.

[0301] Embodiment 37: R 2b The compound is one of any one of embodiments 1 to 8, 12 to 36, wherein is hydrogen or methyl.

[0302] Embodiment 38: R 2b The compound is hydrogen, as described in any one of embodiments 1 to 8, 12 to 37.

[0303] Embodiment 39: Formula (VI): [ka] (In the formula, X, R 1 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 (and k are as described for embodiments 1, 4, and 6, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiment 1, 4, or 6, having the above characteristics.

[0304] Embodiment 40:R 3 R is a halo, cyano, alkyl, or haloalkyl; 4 is hydrogen, halo, C 1~3 Alkyl or Halo C 1~3 Alkyl; R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkoxy or C 1~3 It is an alkoxy; R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, Halo C 1~3 Alkyl, C 1~3 Alkoxy or Halo C 1~3 It is an alkoxy; R 8 R is hydrogen, deuterium, alkyl, or haloalkyl; 9 R is a cycloalkyl or heterocycline, and the cycloalkyl or heterocycline is 1, 2, or 3 independently selected R 11 It is optionally replaced by; or R 8 and R 9 These, together with the nitrogen atom to which they are bonded, form a heterocyclyl or heteroaryl, and the heterocyclyl or heteroaryl consists of 1, 2, or 3 independently selected R 11 It is optionally replaced by each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, Halo C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 The compound according to Embodiment 39, wherein it is an alkylsulfinyl; k is 0, 1, or 2; m is 0 or 1; and n is 0, 1, or 2.

[0305] Embodiment 41: Formula (VIa): [ka] (wherein j is 1 or 2, and X, R) 1 , R 3 , R 4 , R 5 , R 6 , R 11 (k, m, and n are as described for Embodiments 1, 4, 6, and 39, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 39, having the above characteristics.

[0306] Embodiment 42: Formula (VII): [ka] (wherein q is 0, 1, 2 or 3, and X, R) 1 , R 3 , R 4 , R 5 , R 6 (and k are as described for Embodiment 1 or 4, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiment 1 or 4, having the above characteristics.

[0307] Embodiment 43: Formula (VIIa): [ka] A compound according to Embodiment 42 or a pharmaceutically acceptable salt thereof having the above.

[0308] Embodiment 44: Formula (VIII): [ka] (wherein the formula, ring A is cycloalkyl, heterocyclyl, aryl or heteroaryl; q is 0, 1, 2 or 3, and X, R)1 , R 3 , R 4 , R 5 , R 6 , R 11 (and k are as described for embodiments 1, 4, and 6, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiment 1, 4, or 6, having the above characteristics.

[0309] Embodiment 45: The compound according to Embodiment 44, wherein ring A is a heterocyclyl or heteroaryl.

[0310] Embodiment 46: The compound according to Embodiment 44, wherein ring A is a heteroaryl compound.

[0311] Embodiment 47: The compound according to Embodiment 44, wherein ring A is pyridinyl, pyrimidinyl, pyridadinyl, pyrazinyl, triazolyl, imidazolyl, thiazolyl, or pyrazolyl.

[0312] Embodiment 48: Ring A is pyridinyl or pyrazolyl; q is 0, 1, 2 or 3, and X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 The compound according to Embodiment 44, wherein k is as described in Embodiment 44.

[0313] Embodiment 49: Ring A is pyridinyl; q is 0, 1, 2 or 3, X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 The compound according to Embodiment 44, wherein k is as described in Embodiment 44.

[0314] Embodiment 50: Ring A is pyrazolyl; q is 0, 1, 2 or 3, and X, R 1 , R 3 , R 4 , R5 , R 6 , R 11 The compound according to Embodiment 44, wherein k is as described in Embodiment 44.

[0315] Embodiment 51: Ring A is azolyl; q is 0, 1, 2 or 3, X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 The compound according to Embodiment 44, wherein k is as described in Embodiment 44.

[0316] Embodiment 52: Formula (IX): [ka] (In the formula, q is 0, 1, 2 or 3, R 1 , R 3 , R 4 , R 5 , R 6 (and k are as described for embodiments 1, 4, and 6, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiment 1, 4, or 6, having the above characteristics.

[0317] Embodiment 53: Formula (X): [ka] (In the formula, m is 1; n is 1 or 2, X, R) 1 , R 2 , R 3 , R 4 , R 5 , R 6 (k, m, and n are as described in Embodiment 1) A compound according to Embodiment 1 or a pharmaceutically acceptable salt thereof having the above characteristics.

[0318] Embodiment 54: R 2These include alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, and -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl, and alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -Heterocyclyl, cycloalkyl, heterocyclyl, or heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R u and R 11 The compound described in Embodiment 53 is as described in Embodiment 1.

[0319] Embodiment 55:R 2 is alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl or cyanoalkyl, and alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl or cyanoalkyl is R 11 It is optionally replaced by; R 1 , R 3 , R 4 , R 5 , R 6 , R 11 , R 11 The compound according to Embodiment 53, wherein k, m, and n are as described in Embodiment 1.

[0320] Embodiment 56: R 2 C 1~6 Alkyl, Halo C 1~6 Alkyl, Jutero C 1~6 Alkyl, hydroxy C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, cyano C 1~6 Alkyl, -R u -C 3~6 Cycloalkyl, -R u -3-7 member heterocycline, C 3~6Cycloalkyl, 3- to 7-membered heterocyclyl, or 5- to 10-membered heteroaryl, C 1~6 Alkyl, Halo C 1~6 Alkyl, Jutero C 1~6 Alkyl, hydroxy C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, cyano C 1~6 Alkyl, -R u -C 3~6 Cycloalkyl, -R u -3-7 member heterocycline, C 3~6 Cycloalkyl, 3- to 7-membered heterocyclyl, or 5- to 10-membered heteroaryl is one, two, or three independently selected R 11 It is optionally replaced by; R 1 , R 3 , R 4 , R 5 , R 6 , R 11 The compound according to Embodiment 53, wherein k, m, and n are as described in Embodiment 1.

[0321] Embodiment 57: R 2 is Hello C 1~3 Alkyl or -R u -3-member to 5-member heterocyclines, -R u -3- to 5-membered heterocyclyls are arbitrarily substituted with independently selected halos; R 1 , R 3 , R 4 , R 5 , R 6 The compound according to Embodiment 53, wherein k, m, and n are as described in Embodiment 1.

[0322] Embodiment 58:R 2 (R) is fluoroethyl or 3-fluorooxetane-3-yl)methyl; 1 , R 3 , R 4 , R 5 , R 6 The compound according to Embodiment 53, wherein k, m, and n are as described in Embodiment 1.

[0323] Embodiment 59: Formula (IIa): [ka] (wherein j is 1 or 2; X, R) 1 , R 3 , R 4 , R 5 , R 6 , R 11 (k, m, and n are as described for Embodiments 1, 4, and 6, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiment 1, 4, or 6, having the above characteristics.

[0324] Embodiment 60: Formula (IIc): [ka] (In the formula, X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 (k, m, and n are as described for Embodiments 1, 4, and 6, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiment 1, 4, or 6, having the above characteristics.

[0325] Embodiment 61: Formula (IVb): [ka] (wherein j is 1 or 2; X, R) 1 , R 3 , R 4 , R 5 , R 6 , R 11 (and k are as described for embodiments 1, 4, 6, and 59, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0326] Embodiment 62: Formula (IIe): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 (This is described in detail for embodiments 1, 4, 6, and 59, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0327] Embodiment 63: Formula (IIf): [ka] (wherein p is 1 or 2; X, R) 1 , R 4 , R 5 , R 6 and R 11 (This is described in detail for Embodiments 1, 4, and 6, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiment 1, 4, or 6, having the above characteristics.

[0328] Embodiment 64: Formula (IVk): [ka] (wherein p is 1 or 2; X, R) 1 , R 4 , R 5 , R 6 and R 11 (This is described in detail for Embodiments 1, 4, and 6, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiment 1, 4, or 6, having the above characteristics.

[0329] Embodiment 65: Formula (IVf): [ka] (In the formula, X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 (and k are as described for embodiments 1, 4, 6, 59, and 60, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, 59, or 60, having the above characteristics.

[0330] Embodiment 66: Formula (IVj): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 (This is described for embodiments 1, 4, 6, 59, and 60, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, 59, or 60, having the above characteristics.

[0331] Embodiment 67: Formula (IIb): [ka] A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0332] Embodiment 68: m is 1; n is 1; X, R 1 , R 4 , R 5 , R 6 and R 11 The compound described in Embodiment 67 or a pharmaceutically acceptable salt thereof, as described in Embodiments 1, 4, 6, and 59, respectively.

[0333] Embodiment 69: Formula (IId): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 (This is described in detail for embodiments 1, 4, 6, and 59, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0334] Embodiment 70: Formula (IVc): [ka] (In the formula, X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 (k, m, and n are as described for Embodiments 1, 4, 6, and 59, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0335] Embodiment 71: Formula (IVg): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 (This is described in detail for embodiments 1, 4, 6, and 59, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0336] Embodiment 72: Formula (IVd): [ka] (In the formula, X, R 1 , R 3 , R4 , R 5 , R 6 , R 11 (k, m, and n are as described for Embodiments 1, 4, 6, and 59, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0337] Embodiment 73: Formula (IVe): [ka] (In the formula, X, R 1 , R 3 , R 4 , R 5 , R 6 , R 11 (k, m, and n are as described for Embodiments 1, 4, 6, and 59, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0338] Embodiment 74: Formula (IVh) [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 (This is described in detail for embodiments 1, 4, 6, and 59, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0339] Embodiment 75: Formula (IVi): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11(This is described in detail for embodiments 1, 4, 6, and 59, respectively.) A compound or pharmaceutically acceptable salt thereof according to Embodiments 1, 4, 6, or 59, having the above characteristics.

[0340] Embodiment 76: Each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Jutero C 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 It is alkoxy; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 A compound according to any one of Embodiments 1 to 75, which forms a cycloalkyl or oxo.

[0341] Embodiment 77: Each R 11 These are independently fluoro, cyano, oxo, hydroxyl, methyl, -CHF2, -CF3 or -OCHF2, or two R 11 The compound according to any one of Embodiments 1 to 75, wherein the groups, together with the carbon atoms to which they are bonded, form a cyclobutyl or oxo compound.

[0342] Embodiment 78: Each R 11 These are independently known as Halo, Cyano, and Halo C. 1~3 Alkyl, Halo C 1~3 Alkoxy or C 1~3 It is alkylsulfonyl; or two R 11 The group, together with the carbon atoms to which they are bonded, C 3~5 A compound according to any one of Embodiments 1 to 75 that forms a cycloalkyl group.

[0343] Embodiment 79: Each R 11 These are independently fluoro, cyano, -CF3, -CHF2, -OCF3 or -S(O)2CH3, or two R 11The groups, together with the carbon atoms to which they are bonded, form a cyclopropyl group; the compound according to any one of Embodiments 1 to 75.

[0344] Embodiment 80: Each R 11 These are independently: halo, cyano, oxo, and C. 1~3 Alkyl, Halo C 1~3 Alkyl, cyano C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy, Halo C 1~3 Alkoxy, C 1~3 Alkylthio, Halo C 1~3 Alkylthio, C 1~3 Alkyl sulfonyl, C 1~3 Alkyl sulfinyl or halo C 1~3 A compound according to any one of Embodiments 1 to 75, which is an alkyl sulfinyl.

[0345] Embodiment 81: Each R 11 These are independently known as Halo, Cyano, and Halo C. 1~3 Alkyl, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, Halo C 1~3 Alkoxy C 1~3 Alkyl, hydroxyl, C 1~3 Alkoxy or Halo C 1~3 A compound according to any one of Embodiments 1 to 75, which is an alkoxy.

[0346] Embodiment 82: Each R 11 These are independently halo, cyano, or halo-C 1~3 A compound according to any one of Embodiments 1 to 75, wherein the compound is alkyl or hydroxyl.

[0347] Embodiment 83: Each R 11 These are independently halo, cyano, or halo-C 1~3 A compound according to any one of Embodiments 1 to 75, wherein the compound is alkyl.

[0348] Embodiment 84: Each R 11The compound according to any one of Embodiments 1 to 75, wherein is independently F, Cl, Br, cyano, -CHF2, or -CF3.

[0349] Embodiment 85: Each R 11 The compound according to any one of Embodiments 1 to 75, wherein the compound is independently a halo or a cyano.

[0350] Embodiment 86: Each R 11 The compound according to any one of Embodiments 1 to 75, wherein is independently chloro or cyano.

[0351] Embodiment 87:R 11 The compound is a halo, as described in any one of Embodiments 1-76, 78, 80-83, or 85.

[0352] Embodiment 88:R 11 The compound is a fluoropolymer, as described in any one of embodiments 1 to 76, 78, 80 to 83, or 85.

[0353] Embodiment 89:R 11 This is cyano or halo C 1~3 A compound according to any one of embodiments 1 to 76, 78, or 80 to 83, wherein the compound is alkyl.

[0354] Embodiment 90:R 11 is Hello C 1~3 A compound according to any one of embodiments 1 to 76, 78, 80, or 89, which is alkyl.

[0355] Embodiment 91:R 11 Fluoroc 1~3 A compound according to any one of embodiments 1 to 76, 78, 80, or 89, which is alkyl.

[0356] Embodiment 92:R 11 The compound is one of any one of embodiments 1 to 76, 78, or 80 to 83, wherein the compound is cyano, -CHF2, or -CF3.

[0357] Embodiment 93:R11 The compound is -CF3, as described in any one of embodiments 1 to 76, 78, 80, or 89.

[0358] Embodiment 94: The compound according to any one of Embodiments 1 to 53, 59, 60, 61, 65, 67, 69, 70, 72, or 73, wherein k is 0.

[0359] Embodiment 95 k is a compound according to any one of Embodiments 1 to 53, 59, 60, 61, 65, 67, 69, 70, 72, or 73.

[0360] Embodiment 96: The compound according to any one of Embodiments 1, 4, 6, 7, 39, 41, 53, 59, 60, 61, 65, 67, 70, 72, or 73, wherein m is 1 and n is 1.

[0361] Embodiment 97:R 3 The compound according to Embodiment 96, wherein is halo, methyl, or -CF3.

[0362] Embodiment 98:R 3 The compound according to Embodiment 97, wherein the compound is methyl.

[0363] Embodiment 99:R 4 is hydrogen, halo, C 1~3 Alkyl or Halo C 1~3 A compound according to any one of Embodiments 1 to 98, which is alkyl.

[0364] Embodiment 100:R 4 The compound according to any one of Embodiments 1 to 99, wherein is hydrogen, fluoro, chloro, methyl, or -CF3.

[0365] Embodiment 101:R 4 The compound according to any one of Embodiments 1 to 100, wherein is hydrogen, fluoro, chloro, or methyl.

[0366] Embodiment 102:R 4The compound is hydrogen, as described in any one of Embodiments 1 to 101.

[0367] Embodiment 103:R 5 Hello, C 1~3 Alkyl, C 3~5 Cycloalkyl or C 1~3 A compound according to any one of embodiments 1 to 102, which is an alkoxy.

[0368] Embodiment 104: R 5 The compound according to any one of Embodiments 1 to 103, wherein is chloro, bromo, methyl, cyclopropyl, or methoxy.

[0369] Embodiment 105:R 6 is Halo, Cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl or C 1~3 A compound according to any one of embodiments 1 to 104, which is an alkoxy.

[0370] Embodiment 106:R 6 The compound is one of any one of Embodiments 1 to 105, wherein is chloro, bromo, cyano, methyl, cyclopropyl, or methoxy.

[0371] Embodiment 107:R 4 R is hydrogen or methyl; 5 is methoxy, and R 6 The compound according to any one of embodiments 1 to 106, wherein is methyl.

[0372] Embodiment 108:R 4 R is hydrogen; 5 is methoxy, and R 6 The compound is methyl, as described in any one of Embodiments 1 to 107.

[0373] Embodiment 109:R 1 A compound according to any one of Embodiments 1 to 108, wherein is hydrogen and X is CH.

[0374] Embodiment 110: 4-((2S,4S)-4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 1) 4-((2R,4R)-4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(4-fluoro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 2) 4-((2S,4S)-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(4-bromo-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; (Example 3) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (Example 4) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; (Example 5) 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazole-1-yl)piperidine-2-yl)benzoic acid; (±)-trans-4-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 6) 4-((2S,4S)-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(2H-indazole-2-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 7) 4-((2S,4S)-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(4-(difluoromethyl)-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 8) 4-((2R,4R)-4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-chloro-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (Example 9) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid (Example 10) 4-((2R,4R)-4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(4-cyano-1H-pyrazole-1-yl)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (Example 11) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazole-1-yl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; (Example 12) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; (Example 13) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(2-oxopyrrolidine-1-yl)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; (Example 14) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; (Example 15) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; (Example 16) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; 4-(-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(sulfamoylamino)piperidine-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; (Example 17) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; (Example 18) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)-4-(oxetane-3-ylamino)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 19) 4-((2R,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 20) 4-((2R,4R)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4S)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; (Example 21) 4-((2R,4R)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2S,4R)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-((2R,4S)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indole-4-yl)methyl)piperidine-2-yl)benzoic acid; 4-(4-(bicyclo[1.1.1...

Claims

1. the below described: 【Chemistry 11-1】 A compound of or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. A pharmaceutical composition containing the following:

3. A pharmaceutical composition according to claim 2, for use in pharmaceuticals.

4. The invention described in claim 2, for use in the treatment of diseases or disorders related to complement factor B (CFB). A pharmaceutical composition.

5. The aforementioned disease or disorder is an autoimmune disease or disorder, an inflammatory disease or disorder, a metabolic disease or disorder. Harm, neurological disorders or disabilities, lung diseases, respiratory diseases or disabilities, eye diseases, cardiovascular diseases, and kidney diseases A pharmaceutical composition according to claim 4, selected from the patient.

6. The aforementioned disease or disorder is age-related macular degeneration, geographic atrophy, focal segmental glomerulosclerosis (FS) The pharmaceutical composition according to claim 4, selected from GS and diabetic nephropathy.

7. A pharmaceutical composition according to claim 2, for use in the treatment of age-related macular degeneration.

8. A pharmaceutical composition according to claim 2, for use in the treatment of geographic atrophy.

9. A pharmaceutical composition according to claim 2, for use in the treatment of diabetic nephropathy.

10. A pharmaceutical compound according to claim 2 for use in the treatment of focal segmental glomerulosclerosis (FSGS). Finished product.

11. For the manufacture of pharmaceuticals for the treatment of diseases or disorders related to complement factor B (CFB), The compound described in claim 1 or a pharmaceutically acceptable salt thereof, or any of claims 2 to 10. Use of the pharmaceutical composition described.

12. The aforementioned disease or disorder is age-related macular degeneration, geographic atrophy, focal segmental glomerulosclerosis (FS) The use according to claim 11, selected from GS and diabetic nephropathy.

13. The use according to claim 11, wherein the disease or disorder is age-related macular degeneration.

14. The use according to claim 11, wherein the disease or disorder is geographic atrophy.

15. Claim 11, wherein the disease or disorder is focal segmental glomerulosclerosis (FSGS). Use.

16. The use according to claim 11, wherein the disease or disorder is diabetic nephropathy.

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