Substituted indole compounds and methods of use thereof

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 the alternative pathway of the complement system, particularly 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. [Background technology]

[0002] The complement system is a key component of the innate immune system with two major functions: host defense against microbial pathogens and clearance of apoptotic cells. Since its initial discovery in the 1890s by Jules Bordet and Paul Ehrlich, over a century of research on complement has revealed its diverse roles in immune response, 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 comprises a number of soluble proteins found in the circulation and tissues as inactive zymogens that are activated upon serine protease cleavage. Complement activation is tightly regulated by plasma and membrane-bound regulators. Dysregulation of complement activity by genetic mutations, autoantibodies or chronic inflammation has been shown to cause tissue damage in a variety of pathological conditions, including autoimmune, inflammatory, neurodegenerative and a wide range of renal diseases (Zipfel, Nat Rev Immunol 2009 9:729-749; Holers, Annu Rev Immunol 2014 32:433-459).

[0003] There are three activation pathways: classical pathway (CP), lectin pathway (LP) and 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 lectin (MBL) (Garred, Immunol Rev 2016 274(1):74-97). In contrast to the other two pathways, which require specific stimuli for activation, AP maintains a low level of activation in plasma through a natural hydrolysis process called "tickover" 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 factors H and I. The three activation pathways generate protease complexes called "C3 convertases" (C3bBb and C4b2a) to cleave C3 and form C3bBbC3b as C5 convertase. The terminal complement pathway assembles C5b with other complement proteins to form the C5b-9 membrane attack complex (MAC), which mediates the lysis of pathogens or apoptotic cells (Bhakdi, Immunol Today 1991 12:318-320). Two soluble fragments of C3 and C5 cleavage products, C3a and C5a (also called "anaphylatoxins"), are potent chemoattractants that trigger inflammatory responses through their receptors (Klos, Mol Immunol 2009 46(14):2753-2766).

[0004] Complement hyperactivation and renal deposition are observed in a variety of chronic kidney diseases (CKD), 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 a role for complement, particularly AP, in disease development and progression. Genetic defects in complement genes such as CFH, CFI, CFHR, CFB, C3 and MCP / CD46 have been directly associated with 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 injury and contributes to disease progression in multiple 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 have provided evidence of renal local production and activation of complement proteins in CKD, such as IgAN and diabetic kidney disease (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). Local production of complement and the unique microenvironment in the kidneys are thought to make the kidneys more prone to complement hyperactivation (Thurman, Clin J Am Soc Nephrol 2020 11:1856).

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

[0006] As the key enzyme of the AP, CFB provides a highly desirable target for blocking the central amplification loop and the 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 injury 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 deficiency of CFB in these models resulted in reduced proteinuria, protection from kidney damage and prolonged survival. Like many complement proteins, CFB circulates in its native form at high plasma concentrations of 300-400 μg / mL. Recently, a selective CFB inhibitor, iptacopan (LNP023), was 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 was also observed, indicating that highly potent compounds with greater and more sustained complement inhibition in vivo may confer greater therapeutic benefit to patients with C3G and extensive CKD. Summary of the Invention

[0007] In certain embodiments, provided herein is a compound of formula (I) or a pharma- ceutically acceptable salt thereof. 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 therapeutic benefits 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, pulmonary diseases, respiratory diseases or disorders, ophthalmic diseases, cardiovascular diseases, and renal 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 nephropathy (MCD), paroxysmal nocturnal hemoglobinuria (PNH), ANCA-associated vasculitis, lupus nephritis, and polycystic kidney disease (PKD).

[0008] In certain embodiments, the compound of formula (I): [ka] (In the formula, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; Z is NR 2 or CR 2a R 2b and; R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 , -C(O)NR 13 R 14 Or -S(O) t R 12and 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 optionally replaced with; R 2a is 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 one, two or three independently selected R 11 Optionally substituted with; and R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 is alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl or heterocyclyl, the cycloalkyl or heterocyclyl being selected from one, two or three independently selected R 11 optionally replaced with; R 3 is halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 7 is haloalkyl, deuteroalkyl, -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 optionally replaced with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 optionally substituted with; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R11 optionally replaced with; Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or The Two R's 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 cycloalkyl, 3- to 6-membered heterocyclyl or oxo, 3~5 cycloalkyl or 3- to 6-membered heterocyclyl is optionally substituted with 1 or 2 independently selected halo; R 12 is alkyl, deuteroalkyl or haloalkyl; R 13 and R 14 are each independently hydrogen, alkyl, deuteroalkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached, one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo; k is 0, 1, 2 or 3; t is 1 or 2; m is 0, 1 or 2; and n is 0, 1 or 2, provided that Z is NR 2 when m is 1 and n is 1 or 2; and Z is CR 2a R 2b m is 1, and R 2a and R 2b When, together with the carbon atom to which they are attached, form a cycloalkyl, the cycloalkyl must contain at least one R 11 (Replaced by or a pharma- ceutically acceptable salt thereof.

[0009] Also provided are pharmaceutical compositions formulated for administration by a suitable route and means, containing a therapeutically effective concentration of one or more of the compounds provided herein, or pharma- ceutically acceptable salts thereof, and optionally including at least one pharmaceutical carrier.

[0010] In another aspect, provided herein is a method of treating a disease or disorder mediated by the alternative complement pathway, particularly complement factor B, comprising administering to a subject having such a disease or disorder a therapeutically effective amount of one or more compounds disclosed herein or pharma- ceutical acceptable salts thereof, or a pharmaceutical composition disclosed herein. In certain embodiments, the disease or disorder is 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 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 failure (ESRD), acute kidney injury, or polycystic liver.

[0011] Also provided are combination therapies using one or more compounds or compositions provided herein in combination with other pharmaceutical agents for the treatment of the diseases and disorders described herein. These and other aspects of the subject matter described herein will become evident upon reference to the following detailed description and drawings. [Brief description of the drawings]

[0012] [Figure 1] FIG. 1 shows the effect of therapeutic administration of compound A of formula I (administered orally at 30 mg / kg / day once daily (QD)) on urinary protein-to-creatinine ratio (UPCR) in a rat model of membranous nephropathy (passive Heymann nephritis model or PHN) treated with anti-Fx1a. [Figure 2A] 1 shows renal C3d deposition measured on day 14 of the same PHN rat study shown in FIG. [Figure 2B] FIG. 2 shows urinary complement factor Ba fragments measured on day 14 of the same PHN rat study shown in FIG. 1. [Figure 3A] FIG. 1 shows urinary full-length complement factor B measured on day 14 of the PHN rat study. [Figure 3B] FIG. 2 shows urinary neutrophil gelatinase-binding lipocalin (NGAL-1) on day 14 of the same PHN rat study shown in FIG. [Figure 4] FIG. 1 shows kidney injury molecule 1 (KIM-1) in urine on day 14 of the PHN rat study. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] A.Definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In the event that there are a plurality of definitions for terms herein, those in this section prevail unless stated otherwise.

[0014] As used herein, when used to indicate modifying a numerical value, the term "about" encompasses a numerical uncertainty range of 0% to 10% of the numerical value.

[0015] The term "alkyl," as used herein, unless otherwise indicated, refers to a saturated hydrocarbon chain, which may be linear or branched, containing the indicated number of carbon atoms, or alternatively having 1-10, 1-8, 1-6, 1-4, or 1-3 carbon atoms, and attached to the remainder of the molecule by a single bond. In certain embodiments, the hydrocarbon chain is optionally deuterated. For example, C 1 ~C 3 Alkyl indicates that the group may have 1 to 3 (including the terminal values) carbon atoms; 1 ~C 6 Alkyl indicates that the group can have 1 to 6 (including terminal values) carbon atoms. In one embodiment, alkyl is C , which represents a linear or branched, saturated monovalent hydrocarbon group having 1 to 3 carbon atoms. 1 ~C 3 In one embodiment, alkyl is C 1 , which represents a linear or branched saturated monovalent hydrocarbon radical having 1 to 6 carbon atoms. 1 ~C 6 Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl.

[0016] The term "alkoxy", as used herein, unless otherwise indicated, refers to a group of formula -OR, where R is alkyl as defined herein. Alkoxy can 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 formula -S-(alkyl). The terms "haloalkoxy" and "haloalkylthio" refer to -O-(haloalkyl) and -S-(haloalkyl), respectively.

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

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

[0019] The term "aryl", as used herein, unless otherwise indicated, is intended to mean any stable monocyclic or bicyclic carbocyclic ring of up to six members in each ring, in which at least one ring is aromatic. Examples of aryl include phenyl, naphthyl, tetrahydronaphthyl, indanyl, or biphenyl.

[0020] The term "azolyl," as used herein, unless otherwise indicated, refers to a 5-membered heteroaryl ring system containing at least one nitrogen atom. Examples of azolyls include pyrrole, imidazole, pyrazole, thiazole, isothiazole, oxazole, isoxazole, thiadiazole, and oxadiazole.

[0021] The term "cycloalkyl", as used herein, unless otherwise indicated, refers to a monocyclic, bicyclic, tricyclic or other polycyclic hydrocarbon group having the indicated number of ring carbon atoms, or else having 3 to 10 carbon atoms, that is fully saturated or partially unsaturated (i.e., non-aromatic). Polycyclic cycloalkyls can be fused, bridged and / or spiro ring systems. Cycloalkyl groups include, but are not limited to, 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 certain embodiments, cycloalkyl refers to a monocyclic C 3 ~C8 It is cycloalkyl.

[0022] The term "deuterium" as used herein, unless otherwise indicated, shall be taken as having the symbol D or 2 H refers to a heavy isotope of hydrogen, represented by H. As used herein, when a particular position in a compound is designated as having deuterium or having the prefix "deutero-", it is understood that the compound is an isotopically enriched compound, where the presence of deuterium at that position in the compound is substantially greater than its natural abundance of 0.0156%, e.g., at least 90% deuterium at the particular position.

[0023] The term "deuteroalkyl," as used herein, unless otherwise indicated, refers to an alkyl group in which one or more hydrogen atoms of the alkyl have been replaced with deuterium in an abundance substantially greater than its natural abundance, e.g., at least 90% deuterium at a particular position.

[0024] The term "enantiomerically pure" or "pure enantiomer" as used herein indicates that a compound comprises more than 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 98.5%, 99%, 99.2%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9% by weight of a single enantiomer (excluding its corresponding non-superimposable mirror image). Certain embodiments described herein provide compounds that exist as pure enantiomers. Certain embodiments also provide pharmaceutical compositions comprising the enantiomerically pure compounds described herein.

[0025] The terms "halo," "halogen," or "halide," as used herein, unless otherwise indicated, refer to a monovalent fluorine, chlorine, bromine, or iodine radical.

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

[0027] The term "cyano," as used herein, unless otherwise indicated, refers to a --CN group.

[0028] The term "cyanoalkyl," as used herein, unless otherwise indicated, refers to an alkyl group, as defined herein, in which one hydrogen atom of the alkyl has been replaced with a cyano group.

[0029] The terms "heterocycle", "heterocyclyl" or "heterocyclic" as used herein, unless otherwise indicated, refer to a stable 3-, 4-, 5-, 6- or 7-membered monocyclic-, a stable 4-, 5-, 6- or 7-membered monocyclic- or a stable 6-, 7-, 8-, 9-, 10-, 11- or 12-membered bicyclic heterocyclic ring system containing at least one non-aromatic (i.e., saturated or partially unsaturated) ring consisting of carbon atoms and 1 to 4, preferably up to 3, heteroatoms selected from the group consisting of N, O and S, in which the nitrogen and sulfur atoms may be optionally oxidized as N-oxides, sulfoxides or sulfones, and the nitrogen atoms may be optionally quaternized. The heterocycles may be bonded via ring carbon atoms or ring nitrogen atoms, where possible. Bicyclic heterocyclic ring systems may be fused, bridged and / or spiro bicyclic ring systems. In certain embodiments, the heterocyclyl is monocyclic having 4 to 7, preferably 4 to 6, ring atoms, one or two of which are heteroatoms independently selected from the group consisting of N, O, and S. In certain embodiments, the heterocyclyl is monocyclic having 4 to 7, preferably 4 to 6, ring atoms, at least one of which is N and a second of which is N, O, or S. In certain embodiments, the heterocyclyl is azetidine, pyrrolidine, piperidine, piperazine, morpholine, or thiomorpholine. In certain embodiments, a heterocyclyl group is bicyclic, in which the first ring (the point of attachment to the remainder of the molecule) is a saturated or partially saturated monocyclic heterocyclyl as described herein and the second ring can be an aromatic or non-aromatic ring consisting of carbon atoms and 1 to 4, preferably up to 3, heteroatoms independently selected from the group consisting of N, O and S, or the second ring can 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, isothiazolidine, isoxazoline, isoxazolidine, morpholine, oxazoline, oxazolidine, oxetane, piperazine, piperidine, dihydropyridine, tetrahydropyridine, dihydropyridazine, pyran, pyrazolidine, pyrazoline, pyrrolidine, pyrroline, tetrahydrofuran, tetrahydropyran, thiamorpholine, tetrahydrothiophene, thiazoline, thiazolidine, thiomorpholine, thietane, thiolane, sulfolane, 1,3-dioxolane, 1,3-oxazolidine, 1,3-thia 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 and their N-oxides or sulfones or sulfoxides.

[0030] The term "heteroaryl," as used herein, unless otherwise indicated, refers to a stable 5-, 6-, or 7-membered monocyclic- or a stable 9- or 10-membered fused bicyclic ring system containing at least one aromatic ring consisting of carbon atoms and from 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 "heteroaryl," which is a bicyclic group, the first ring (the point of attachment to the remainder of the molecule) is a monocyclic heteroaryl group as described herein, and the second ring need not be aromatic or contain a heteroatom. Thus, a bicyclic "heteroaryl" includes, for example, a stable 5- or 6-membered monocyclic aromatic ring consisting of carbon atoms and one to four, preferably up to three, heteroatoms, as defined immediately above, fused to a benzene ring, or a second monocyclic "heteroaryl" or "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, indolizine, 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, such as imidazo[1,2-a]pyridine, pyrazolopyridine, pyrrolopyrimidine, and N-oxides thereof.

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

[0032] The term "subject", as used herein, unless otherwise indicated, refers to any human or veterinary subject, including mammals, e.g., mice, rats, cows, sheep, pigs, rabbits, goats, horses, monkeys, dogs, cats and humans (including neonatal, infant, juvenile, adolescent, adult or geriatric patients).

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

[0034] The term "therapeutically effective amount" is an amount sufficient to effect beneficial or desired clinical results. A therapeutically effective amount may be administered in one or more administrations. A therapeutically effective amount is an amount sufficient to palliate, ameliorate, stabilize, halt, slow or retard the progression of a disease state.

[0035] Unless otherwise stated or specifically stated, it is understood that, if present, substitution can occur at any atom of an alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl group, valence allowing.

[0036] Unless specifically stated otherwise, in cases where a compound can take on alternative tautomeric or stereoisomeric forms, all alternative isomers are intended to be encompassed within the scope of the claimed subject matter. For example, unless specifically stated otherwise, the compounds provided herein can be stereomerically pure (e.g., a single enantiomer or diastereomer) or can be a mixture of stereoisomers, such as a racemic or diastereomeric mixture.

[0037] The terms "treating," "treat," or "treatment" generally refer to controlling, alleviating, ameliorating, slowing the progression of, and / or eliminating the specified condition after the condition has been established. In addition to its ordinary meaning, the terms "preventing," "prevent" or "prevention" also refer to delaying the onset of the specified condition or reducing the risk of developing or of processes that may lead to the condition and / or the risk of recurrence of the symptoms of the condition.

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

[0039] B. Compound In certain embodiments, the compound of formula (I): [ka] (In the formula, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; Z is NR 2 or CR 2a R 2b and; R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -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 and alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is one, two or three independently selected R11 optionally replaced with; R 2a -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 one, two or three independently selected R 11 Optionally substituted with; and R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 is alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl or heterocyclyl, the cycloalkyl or heterocyclyl being selected from one, two or three independently selected R 11 optionally replaced with; R 3 is halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is alkoxy; R 6 is halo, cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, C 1~3Alkoxy or haloC 1~3 is alkoxy; R 7 is haloalkyl, deuteroalkyl, -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 optionally replaced with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 optionally substituted with; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 optionally replaced with; Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 cycloalkyl, 3- to 6-membered heterocyclyl or oxo, 3~5 cycloalkyl or 3- to 6-membered heterocyclyl is optionally substituted with 1 or 2 independently selected halo; R 12 is alkyl, deuteroalkyl or haloalkyl; R 13 and R 14 are each independently hydrogen, alkyl, deuteroalkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached, one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo; k is 0, 1, 2 or 3; t is 1 or 2; m is 0, 1 or 2; and n is 0, 1 or 2, provided that Z is NR 2 when m is 1 and n is 1 or 2; and Z is CR 2a R 2b and R 2a and R2b together with the carbon atom to which they are attached form a cycloalkyl, and when m is 1, the cycloalkyl is 11 (Replaced by or a pharma- ceutically acceptable salt thereof.

[0040] In certain embodiments, the compound of formula (I): [ka] (In the formula, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; Z is NR 2 or CR 2a R 2b and; R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -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 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 optionally replaced with; R 2a -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 one, two or three independently selected R 11 Optionally substituted with; and R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 is alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl or heterocyclyl, the cycloalkyl or heterocyclyl being selected from one, two or three independently selected R 11 optionally replaced with; R 3 is halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 7 is haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl; haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R uHeterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is one, two or three independently selected R 11 optionally replaced with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 optionally substituted with; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 optionally replaced with; Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; R 12 is alkyl, deuteroalkyl or haloalkyl; R 13 and R 14 are each independently hydrogen, alkyl, deuteroalkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached, one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo; k is 0, 1, 2 or 3; t is 1 or 2; m is 0, 1 or 2; and n is 0, 1 or 2, provided that Z is NR 2 when m is 1 and n is 1 or 2; and Z is CR 2a R 2b and R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl, and when m is 1, the cycloalkyl is 11 (Replaced by or a pharma- ceutically acceptable salt thereof.

[0041] In certain embodiments, the compound of formula (I): [ka] (In the formula, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; Z is NR2 or CR 2a R 2b and; R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -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 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 optionally replaced with; R 2a -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 one, two or three independently selected R 11 Optionally substituted with; and R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 is alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 or one, two or three independently selected R11 forming a heterocyclyl optionally substituted with; R 3 is halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 7 is haloalkyl, deuteroalkyl, -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 optionally replaced with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 optionally substituted with; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 optionally replaced with; Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 cycloalkyl, 3- to 6-membered heterocyclyl or oxo, 3~5 cycloalkyl or 3- to 6-membered heterocyclyl is optionally substituted with 1 or 2 independently selected halo; R 12 is alkyl, deuteroalkyl or haloalkyl; R 13 and R 14are each independently hydrogen, alkyl, deuteroalkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached, one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo; k is 0, 1, 2 or 3; t is 1 or 2; m is 0, 1 or 2; and n is 0, 1 or 2, provided that Z is NR 2 then m is 1 and n is 1 or 2. or a pharma- ceutically acceptable salt thereof.

[0042] In certain embodiments, the compound of formula (I): [ka] (In the formula, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; Z is NR 2 or CR 2a R 2b and; R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -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 and alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -Ru -cycloalkyl, -R u Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is one, two or three independently selected R 11 optionally replaced with; R 2a -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 one, two or three independently selected R 11 Optionally substituted with; and R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 is alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 or one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R 3 is halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 7 is haloalkyl, deuteroalkyl, -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 optionally replaced with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 optionally substituted with; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 optionally replaced with; Each R 11are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; R 12 is alkyl, deuteroalkyl or haloalkyl; R 13 and R 14 are each independently hydrogen, alkyl, deuteroalkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached, one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo; k is 0, 1, 2 or 3; t is 1 or 2; m is 0, 1 or 2; and n is 0, 1 or 2, provided that Z is NR 2 then m is 1 and n is 1 or 2. or a pharma- ceutically acceptable salt thereof.

[0043] In certain embodiments, the compound of formula (I): [ka] (In the formula, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; Z is NR 2 or CR 2a R 2b and; R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -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 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 optionally replaced with; R 2a -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 one, two or three independently selected R 11 Optionally substituted with; and R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3is alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 or one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R 3 is halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 7 is haloalkyl, deuteroalkyl, -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 optionally replaced with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 -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 optionally substituted with; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 optionally replaced with; Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1--3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; R 12 is alkyl, deuteroalkyl or haloalkyl; R 13 and R 14are each independently hydrogen, alkyl, deuteroalkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached, one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo; k is 0, 1, 2 or 3; t is 1 or 2; m is 0, 1 or 2; and n is 0, 1 or 2, provided that Z is NR 2 then m is 1 and n is 1 or 2. or a pharma- ceutically acceptable salt thereof.

[0044] In certain embodiments, the compound of formula (II): [ka] Provided herein are compounds of formula (I) having the formula:

[0045] In certain embodiments, the compound of formula (IIa): [ka] or a pharma- ceutically acceptable salt thereof, wherein j is 1 or 2, and when j is 1, R 11 The carbon atom bonded to a single R 11 When j is 2, R 11 The carbon atom bonded to is selected from two independently selected R 11 substituted) are provided herein.

[0046] In certain embodiments, the compound of formula (IIb): [ka] Provided herein are compounds of formula (I) having the formula:

[0047] In certain embodiments, the compound of formula (IIc): [ka] Provided herein are compounds of formula (I) having the formula:

[0048] In certain embodiments, the compound of formula (IId): [ka] Provided herein are compounds of formula (I) having the formula:

[0049] In certain embodiments, the compound of formula (IIe): [ka] Provided herein are compounds of formula (I) having the formula:

[0050] In certain embodiments, the formula (IIf): [ka] Provided herein is a compound of formula (I), wherein p is 1 or 2; or a pharma- ceutically acceptable salt thereof. In certain embodiments, a compound of formula (IIf), wherein each R 11 is independently halo, and the other variables are as described elsewhere herein for formula (I) or (IIf). In certain embodiments, compounds of formula (IIf), 11is fluoro, and the other variables are as described elsewhere herein for formula (I) or (IIf) as provided herein.

[0051] In certain embodiments, the compound of formula (III): [ka] Provided herein are compounds of formula (I) having the formula:

[0052] In certain embodiments, the compound of formula (IIIa): [ka] Provided herein are compounds of formula (I) having the formula:

[0053] In certain embodiments, the compound of formula (IV): [ka] Provided herein are compounds of formula (I) having the formula:

[0054] In certain embodiments, the compound of formula (IVa): [ka] or a pharma- ceutically acceptable salt thereof.

[0055] In certain embodiments, the compound of formula (IVb): [ka] or a pharma- ceutically acceptable salt thereof, wherein when j is 1, R 11The carbon atom bonded to a single R 11 When j is 2, R 11 The carbon atom bonded to is selected from two independently selected R 11 It has a substituent.

[0056] In certain embodiments, the compound of formula (I): [ka] (In the formula, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; Z is NR 2 or CR 2a R 2b and; R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -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 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 optionally replaced with; R 2a -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 one, two or three independently selected R 11 Optionally substituted with; and R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 is alkyl; R 3 is halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 7 is deuteroalkyl, heterocyclyl or heteroaryl; haloalkyl, deuteroalkyl, -R u -cycloalkyl, -R u Heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl is one, two or three independently selected R 11 optionally replaced with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 optionally substituted with; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 optionally replaced with; Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 cycloalkyl, 3- to 6-membered heterocyclyl or oxo, 3~5 cycloalkyl or 3- to 6-membered heterocyclyl is optionally substituted with 1 or 2 independently selected halo; R12 is alkyl, deuteroalkyl or haloalkyl; R 13 and R 14 are each independently hydrogen, alkyl, deuteroalkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached, one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo; k is 0, 1, 2 or 3; t is 1 or 2; m is 0, 1 or 2; and n is 0, 1 or 2, provided that Z is NR 2 then m is 1 and n is 1 or 2. or a pharma- ceutically acceptable salt thereof.

[0057] In certain embodiments, the compound of formula (I): [ka] (In the formula, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; Z is NR 2 or CR 2a R 2b and; R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, heteroaryl, -C(O)R 12 , -C(O)NR 13 R14 Or -S(O) t R 12 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 optionally replaced with; R 2a -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 one, two or three independently selected R 11 Optionally substituted with; and R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 is alkyl; R 3 is halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is alkoxy; R 6 is halo, cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3Alkyl, C 1~3 Alkoxy or haloC 1~3 is alkoxy; R 7 is haloalkyl, deuteroalkyl, -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 optionally replaced with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 optionally substituted with; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 optionally replaced with; Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 cycloalkyl, 3- to 6-membered heterocyclyl or oxo, 3~5 cycloalkyl or 3- to 6-membered heterocyclyl is optionally substituted with 1 or 2 independently selected halo; R 12 is alkyl, deuteroalkyl or haloalkyl; R 13 and R 14 are each independently hydrogen, alkyl, deuteroalkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached, one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo; k is 0, 1, 2 or 3; t is 1 or 2; m is 0, 1 or 2; and n is 0, 1 or 2, provided that Z is NR 2 then m is 1 and n is 1 or 2. or a pharma- ceutically acceptable salt thereof.

[0058] In certain embodiments, a compound of formula (IIa) or (IVb), 11 is halo, cyano or haloC 1~3 and the other variables are as described elsewhere herein for each of formulas (IIa) and (IVb). In certain embodiments, compounds 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 6 is methyl; R 11 is halo, cyano or haloC 1~3 is alkyl; j is 1 or 2; k is 0; m and n are both 1), as provided herein.

[0059] In certain embodiments, a compound of formula (IIa) or (IVb), 11 is fluoro, cyano or fluoroC 1~3 and the other variables are as described elsewhere herein for each of formulas (IIa) and (IVb). In certain embodiments, compounds 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 6 is methyl; R 11 is fluoro, cyano or fluoroC 1~3 is alkyl; j is 1 or 2; k is 0; m and n are both 1), as provided herein.

[0060] In certain embodiments, a compound of formula (IIa) or (IVb), 11 -Fluoro, cyano, -CHF 2 or -CF 3and the other variables are as described elsewhere herein for each of formulas (IIa) and (IVb). 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 6 is methyl; R 11 -Fluoro, cyano, -CHF 2 or -CF 3 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), 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 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 11is halo; j is 2; k is 0 or 1; m and n are both 1. In certain embodiments, provided herein is a compound of formula (IIa) or (IVb), where 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 6 is methyl; R 11 is halo; j is 2; k is 0; m and n are both 1), as provided herein.

[0062] In certain embodiments, a compound of formula (IIa) or (IVb), 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 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 11 is fluoro; j is 2; k is 0 or 1; m and n are both 1. In certain embodiments, provided herein is a compound of formula (IIa) or (IVb), where R 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), 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 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 11 is cyano; j is 1; k is 0 or 1; m and n are both 1. In certain embodiments, provided herein is a compound of formula (IIa) or (IVb), where 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 is cyano; j is 1; k is 0; m and n are both 1), as provided herein.

[0064] In certain embodiments, a compound of formula (IIa) or (IVb), 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 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 11 -CHF 2 or -CF 3

[0033] In certain embodiments, provided herein is 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 6 is methyl; R 11 -CHF 2 or -CF 3j is 1; k is 0; m and n are both 1), as provided herein.

[0065] In certain embodiments, the compound of formula (IVc): [ka] Provided herein are compounds of formula (I) having the formula:

[0066] In certain embodiments, the compound of formula (IVd): [ka] Provided herein are compounds of formula (I) having the formula:

[0067] In certain embodiments, the compound of formula (IVe): [ka] Provided herein are compounds of formula (I) having the formula:

[0068] In certain embodiments, the compound of formula (IVf): [ka] Provided herein are compounds of formula (I) having the formula:

[0069] In certain embodiments, a compound of formula (IIc) or (IVf), 11 are each independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 and R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , R 26 , R 27 , R 28 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , R 37 , R 38 , R 40 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 11 are each independently halo, cyano, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; and the remainder of the variables are as described elsewhere herein for each of formulas (IIc) and (IVf), as provided herein.

[0070] In certain embodiments, a compound of formula (IIc) or (IVf), 11 Halo, C 1~3 Alkyl, haloC 1~3Provided herein is a compound of formula (IIc) or (IVf), or a pharma- ceutically acceptable salt thereof, wherein R is alkyl or hydroxyl, and the other variables are as described elsewhere herein for each of formulas (IIc) and (IVf). In certain embodiments, a compound of formula (IIc) or (IVf), or a pharma- ceutically acceptable salt thereof, wherein R is alkyl or hydroxyl, and the other variables are as described elsewhere herein for each of formulas (IIc) and (IVf), is provided herein. 1 is 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 are each independently halo, C 1~3 Alkyl, haloC 1~3 Provided herein is a compound of formula (IIc) or (IVf) or a pharma- ceutically acceptable salt thereof, wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 are each independently halo, C 1~3 Alkyl, haloC 1~3 alkyl or hydroxyl) are provided herein.

[0071] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharma- ceutically acceptable salt thereof, 11a is C 1~3 Alkyl or haloC 1~3 R is alkyl; 11b is hydroxyl, and the remainder of the variables are as described elsewhere herein for formulas (IIc) and (IVf) as provided herein.

[0072] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen, fluoro or chloro; X ​​is CH; R 4is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 are each independently 1~3 Alkyl, haloC 1~3 Provided herein is a compound of formula (IIc) or (IVf), or a pharma- ceutically acceptable salt thereof, wherein R is alkyl or hydroxyl, and the remainder of the variables are as described elsewhere herein for formula (IIc) and (IVf). In certain embodiments, a compound of formula (IIc) or (IVf), or a pharma- ceutically acceptable salt thereof, wherein R is alkyl or hydroxyl, and the remainder of the variables are as described elsewhere herein for formula (IIc) and (IVf), is provided herein. 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 are each independently 1~3 Alkyl, haloC 1~3 alkyl or hydroxyl) are provided herein.

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

[0074] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharma- ceutically acceptable salt thereof, 11 and each independently is halo; the remaining variables are as described elsewhere herein for formulas (IIc) and (IVf). In certain embodiments, provided herein is a compound of formula (IIc) or (IVf) or a pharma- ceutically acceptable salt thereof, 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 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 11 are each independently a halo; k is 0, 1, 2 or 3; m is 0, 1 or 2; and and n is 0, 1 or 2) are provided herein.

[0075] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharma- ceutically acceptable salt thereof, 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 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 11 is fluoro; k is 0, 1, 2 or 3; m is 0, 1 or 2; and and n is 0, 1, or 2. In certain embodiments, provided herein are compounds of formula (IIc) or (IVf), where k is 0, m is 1; n is 1; and the other variables are as described elsewhere herein for each of formulas (IIc) and (IVf).

[0076] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharma- ceutically acceptable salt thereof,11 is fluoro; the remaining variables are as described elsewhere herein for each of formulas (IIc) and (IVf). In certain embodiments, a compound of formula (IIc) or (IVf) or a pharma- ceutically acceptable salt thereof, 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 6 is methyl, R 11 is fluoro) are provided herein.

[0077] In certain embodiments, a compound of formula (IIc) or (IVf) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen or fluoro; 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) are provided herein.

[0078] In certain embodiments, the compound of formula (IVg): [ka] Provided herein are compounds of Formula (I), (IVb) or (IVc), or a pharma- ceutically acceptable salt thereof, having the formula:

[0079] In certain embodiments, the compound of formula (IVh): [ka] Provided herein are compounds of Formula (I), (IVb) or (IVc), or a pharma- ceutically acceptable salt thereof, having the formula:

[0080] In certain embodiments, the compound of formula (IVi): [ka] Provided herein are compounds of Formula (I), (IVb) or (IVc), or a pharma- ceutically acceptable salt thereof, having the formula:

[0081] In certain embodiments, a compound of formula (IId), (IVg), (IVh) or (IVi) or a pharma- ceutically acceptable salt thereof, 11 are independently halo, cyano or haloC 1~3 and the remaining variables are as described elsewhere herein for formulas (IId), (IVg), (IVh) and (IVi). In certain embodiments, provided herein is a compound of formula (IId), (IVg), (IVh) or (IVi), or a pharma- ceutically acceptable salt thereof, wherein R 11 Cyano or haloC 1~3 and the remaining variables are as described elsewhere herein for each of formulas (IId), (IVg), (IVh), and (IVi). In certain embodiments, provided herein is a compound of formula (IId), (IVg), (IVh), or (IVi), or a pharma- ceutically acceptable salt thereof, wherein R 11 Cyano or fluoro C 1~3 and the remaining variables are as described elsewhere herein for each of formulas (IId), (IVg), (IVh), and (IVi). In certain embodiments, provided herein is a compound of formula (IId), (IVg), (IVh), or (IVi), or a pharma- ceutically acceptable salt thereof, wherein R 11 is cyano, -CHF 2 or -CF 3 and the remaining variables are as described elsewhere herein for each of formulas (IId), (IVg), (IVh) and (IVi) as provided herein.

[0082] In certain embodiments, a compound of formula (IId), (IVg), (IVh) or (IVi) or a pharma- ceutically acceptable salt thereof,1 is hydrogen, fluoro, chloro or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 R is alkyl; 5 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 Cyano or haloC 1~3 Provided herein is a compound of formula (IId), (IVg), (IVh) or (IVi), or a pharma- ceutically acceptable salt thereof, wherein R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 R is alkyl; 5 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 Cyano or fluoro C 1~3 Provided herein is a compound of formula (IId), (IVg), (IVh) or (IVi), or a pharma- ceutically acceptable salt thereof, wherein R 1is hydrogen, fluoro, chloro or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 R is alkyl; 5 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, -CHF 2 or -CF 3 ) is provided herein.

[0083] In certain embodiments, a compound of formula (IId), (IVg), (IVh) or (IVi) or a pharma- ceutically acceptable salt thereof, 1 is 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 Cyano or haloC 1~3 Provided herein is a compound of formula (IId), (IVg), (IVh) or (IVi), or a pharma- ceutically acceptable salt thereof, 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 6 is methyl, R 11 Cyano or fluoro C 1~3Provided herein is a compound of formula (IId), (IVg), (IVh) or (IVi), or a pharma- ceutically acceptable salt thereof, 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 6 is methyl, R 11 is cyano, -CHF 2 or -CF 3 ) is provided herein.

[0084] In certain embodiments, a compound of formula (IId), (IVg), (IVh) or (IVi) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 Cyano or haloC 1~3 alkyl) are provided herein.

[0085] In certain embodiments, a compound of formula (IId), (IVg), (IVh) or (IVi) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 Cyano or fluoro C 1~3 alkyl) are provided herein.

[0086] In certain embodiments, a compound of formula (IId), (IVg), (IVh) or (IVi) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen or fluoro; X ​​is CH; R 4is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is cyano, -CHF 2 or -CF 3 ) is provided herein.

[0087] In certain embodiments, the compound of formula (IVj): [ka] Provided herein is a compound of formula (I), (IVb) or (IVf) or a pharma- ceutically acceptable salt thereof, having the formula: 11 are each independently halo; the remaining variables are as described elsewhere herein for formulas (IIe) and (IVj), as provided herein.

[0088] In certain embodiments, a compound of formula (IIe) or (IVj) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 R is alkyl; 5 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 and each independently is halo.

[0089] In certain embodiments, a compound of formula (IIe) or (IVj) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 R is alkyl; 5 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 fluoro) are provided herein.

[0090] In certain embodiments, a compound of formula (IIe) or (IVj) or a pharma- ceutically acceptable salt thereof, 11 is fluoro; the remaining variables are as described elsewhere herein for each of formulas (IIe) and (IVj). In certain embodiments, a compound of formula (IIe) or (IVj) or a pharma- ceutically acceptable salt thereof (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 6 is methyl, R 11 In certain embodiments, provided herein is a compound of formula (IIe) or (IVj), or a pharma- ceutically acceptable salt thereof, wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is fluoro) are provided herein.

[0091] In certain embodiments, the compound of formula (IVk): [ka] Provided herein is a compound of formula (I) or a pharma- ceutically acceptable salt thereof, wherein p is 1 or 2. In certain embodiments, a compound of formula (IIf) or (IVk) or a pharma- ceutically acceptable salt thereof, wherein R 11 and each independently is halo, and the remaining variables are as described for formula (IIf) and (IVk), respectively. In certain embodiments, a compound of formula (IIf) or (IVk) or a pharma- ceutically acceptable salt thereof, wherein R 11 is fluoro, and the remaining variables are as described for formula (IIf) and (IVk), respectively. In certain embodiments, a compound of formula (IIf) or (IVk) or a pharma- ceutically acceptable salt thereof (wherein R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is alkoxy; R 6 is halo, cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, C 1~3 Alkoxy or haloC 1~3is alkoxy; R 11 are each independently a halo; and p is 1 or 2. In a further particular embodiment, a compound of formula (IIf) or (IVk) is provided herein, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 11 is fluoro; and p is 1 or 2).

[0092] In certain embodiments, a compound of formula (IIf) or (IVk) or a pharma- ceutically acceptable salt thereof, 1 is 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 In certain embodiments, provided herein is a compound of formula (IIf) or (IVk), or a pharma- ceutically acceptable salt thereof, wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 is fluoro) are provided herein.

[0093] In certain embodiments, the compound of formula (IVl): [ka] or a pharma- ceutically acceptable salt thereof, 11a and R 11b are each independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 and forming cycloalkyl, 3- to 6-membered heterocyclyl, or oxo; the remainder of the variables are as described elsewhere herein for each of formulas (I), (IVa), (IVb), (IVf), and (IVj) as provided herein.

[0094] In certain embodiments, a compound of formula (IVl), 11a is halo, cyano, C 1~3 Alkyl, deutero-C1~3 Alkyl, haloC 1~3 Alkyl or cyano C 1~3 Alkyl; R 11b Halo, hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; and the remainder of the variables are as described elsewhere herein for formula (IVl), as provided herein.

[0095] In certain embodiments, a compound of formula (IVl), 11a Halo, C 1~3 Alkyl or haloC 1~3 is alkyl, R 11b is halo or hydroxyl, and the other variables are as described elsewhere herein for formula (IVl). In certain embodiments, a compound of formula (IVl) or a pharma- ceutically acceptable salt thereof, 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 6 is methyl; R 11a Halo, C 1~3 Alkyl or haloC 1~3 is alkyl, R 11b Provided herein is a compound of formula (IVl) or a pharma- ceutically acceptable salt thereof, wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R5 is methoxy or cyclopropyl; R 6 is methyl; R 11a Halo, C 1~3 Alkyl or haloC 1~3 is alkyl, R 11b is halo or hydroxyl) are provided herein.

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

[0097] In certain embodiments, a compound of formula (IVl) or a pharma- ceutically acceptable salt thereof, 11a is methyl or trifluoromethyl, R 11b is hydroxyl, and the remaining variables are as described elsewhere herein for formula (IVl). In certain embodiments, provided herein is a compound of formula (IVl) or a pharma- ceutically acceptable salt thereof, 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 6 is methyl; R 11a is methyl or trifluoromethyl, R 11b Provided herein is a compound of formula (IVl) or a pharma- ceutically acceptable salt thereof, wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11a is methyl or trifluoromethyl, R 11b is hydroxyl) are provided herein.

[0098] In certain embodiments, a compound of formula (IVl), 11a is fluoro and R 11b is fluoro, and other variables are as described elsewhere herein for formula (IVl). In certain embodiments, a compound of formula (I), (II), (IIa), (IIc), (IIe), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl), wherein each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 and the other variables are as described elsewhere herein for each of formulas (I), (II), (IIa), (IIc), (IIe), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), and (IVl). In certain embodiments, compounds of formula (I), (II), (IIa), (IIc), (IIe), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl), wherein each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5and the other variables are as described elsewhere herein for each 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 11 are independently halo, cyano, oxo, C 1~3 Alkyl, haloC 1~3 Alkyl, Hydroxyl, HaloC 1~3 or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 and the other variables are as described elsewhere herein for each of formulas (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl). In certain embodiments, a compound of formula (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), or (IVl), wherein each R 11 are independently fluoro, cyano, oxo, hydroxyl, methyl, -CHF 2 , -CF 3 or -OCHF 2 or two R 11and the other variables are as described elsewhere herein for each of formulas (I), (II), (IIa), (IIc), (IIe), (IIf), (IV), (IVa), (IVb), (IVf), (IVj), (IVk), and (IVl). In certain embodiments, a compound of formula (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 11 are independently halo, cyano, oxo, C 1~3 Alkyl, haloC 1~3 Alkyl, hydroxyl or haloC 1~3 and the other variables are as described elsewhere herein for each of formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl). In certain embodiments, a compound of formula (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 11 are independently fluoro, cyano, oxo, hydroxyl, methyl, -CHF 2 , -CF 3 or -OCHF 2and the other variables are as described elsewhere herein for each of formula (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, a compound of formula (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, deutero-C 1~3 Alkyl or haloC 1~3 and the other variables are as described elsewhere herein for each of 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, a compound of formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), wherein R 11 is halo, cyano or haloC 1~3and the other variables are as described elsewhere herein for each of 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, a compound of formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), where R 11 is fluoro, cyano or fluoroC 1~3 and the other variables are as described elsewhere herein for each of 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, a compound of formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), or (IVl), where R 11 -Fluoro, cyano, -CHF 2 or -CF 3and the other variables are as described elsewhere herein for each of 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 formula (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk), and (IVl), where R 11 is halo; and the other variables are as described elsewhere herein for each of 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, a compound of formula (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; and the other variables are as described elsewhere herein for each of formulas (I), (II), (IIa), (IIb), (IIc), (IId), (IIe), (IIf), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (IVg), (IVh), (IVi), (IVj), (IVk) and (IVl) as provided herein.

[0099] In certain embodiments, the compound of formula (V): [ka] Provided herein are compounds of formula (I) having the formula:

[0100] In certain embodiments, the compound of formula (VI): [ka] Provided herein is a compound of formula (I), (II) or (IV) having the formula: 3 is halo, cyano, alkyl or haloalkyl; R 4 is hydrogen, halo, C 1~3 Alkyl or haloC 1~3 R is alkyl; 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, 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 8 is hydrogen, alkyl or haloalkyl; R 9 is cycloalkyl or heterocyclyl, and the cycloalkyl or heterocyclyl is selected from one, two, or three independently selected R 11 or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 k is 0, 1 or 2; m is 0 or 1; and n is 0, 1 or 2. In certain embodiments, provided herein are compounds of formula (I) or (VI), where R 8 is hydrogen, alkyl or haloalkyl; R 9 is haloalkyl-R u -cycloalkyl or cycloalkyl, -R u -cycloalkyl or cycloalkyl is one, two or three R 11 each R 11 are independently halo or haloC 1~3 Provided herein are compounds of formula (I) or (VI), where R is alkyl and the other variables are as described elsewhere herein for each of formulas (I) and (VI). In certain embodiments, compounds of formula (I) or (VI), where R is 8 is hydrogen, C 1~3 Alkyl or haloC 1~3 R is alkyl; 9 is HaroC 1~3 Alkyl-R u -C 3~5 Cycloalkyl or C 3~5 cycloalkyl, -R u -C 3~5 Cycloalkyl or C 3~5 Cycloalkyl can have one, two or three R 11 each R 11 are independently halo or haloC 1~3and alkyl, and the remainder of the variables are as described elsewhere herein for each of formulas (I) and (VI).

[0101] In certain embodiments, a compound of formula (I) or (VI), 1 is 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 8 is hydrogen, C 1~3 Alkyl or haloC 1~3 R is alkyl; 9 is HaroC 1~3 Alkyl-R u -C 3~5 Cycloalkyl or C 3~5 cycloalkyl, -R u -C 3~5 Cycloalkyl or C 3~5 Cycloalkyl can have one, two or three R 11 each R 11 are independently halo or haloC 1~3 and the remaining variables are as described elsewhere herein for each of formulas (I) and (VI). In certain embodiments, compounds of formula (I) or (VI), 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen, C 1~3 Alkyl or haloC 1~3 R is alkyl; 9 is HaroC 1~3 Alkyl-R u -C 3~5 Cycloalkyl or C 3~5 cycloalkyl, -R u -C 3~5 Cycloalkyl or C3~5 Cycloalkyl can have one, two or three R 11 each R 11 are independently halo or haloC 1~3 alkyl; and the remainder of the variables are as described elsewhere herein for each of formulas (I) and (VI), as provided herein.

[0102] In certain embodiments, a compound of formula (I) or (VI), 1 is 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 8 is hydrogen, C 1~3 Alkyl or haloC 1~3 R is alkyl; 9 is HaroC 1~3 Alkyl-R u -C 3~5 Cycloalkyl or C 3~5 cycloalkyl, -R u -C 3~5 Cycloalkyl or C 3~5 Cycloalkyl can have one, two or three R 11 each R 11 are independently halo or haloC 1~3 m and n are both 1 and k is 0. In certain embodiments, provided herein are compounds of formula (I) or (VI), where R 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen, C 1~3 Alkyl or haloC 1~3 R is alkyl; 9 is HaroC 1~3 Alkyl-R u -C 3~5Cycloalkyl or C 3~5 cycloalkyl, -R u -C 3~5 Cycloalkyl or C 3~5 Cycloalkyl can have one, two or three R 11 each R 11 are independently halo or haloC 1~3 m and n are both 1 and k is 0. In certain embodiments, provided herein is a compound of formula (I) or (VI), or a pharma- ceutically acceptable salt thereof, wherein R 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; the remaining variables are as described elsewhere herein for each of formulas (I) and (VI), as provided herein.

[0103] In certain embodiments, a compound of formula (I) or (VI), 1 is 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 8 is hydrogen; R 9 is -CH 2 CHF 2 , cyclopropylmethyl, cyclobutyl or bicyclo[1.1.1]pentan-1-yl, or cyclopropylmethyl, cyclobutyl or bicyclo[1.1.1]pentan-1-yl is selected from the group consisting of one, two or three R 11 each R 11 is independently fluoro or trifluoromethyl; m and n are both 1 and k is 0. In certain embodiments, provided herein is a compound of formula (I) or (VI), where R 1 is hydrogen or fluoro; X ​​is CH; R 4is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 8 is hydrogen; R 9 , -, -CH 2 CHF 2 , cyclopropylmethyl, cyclobutyl or bicyclo[1.1.1]pentan-1-yl, or cyclopropylmethyl, cyclobutyl or bicyclo[1.1.1]pentan-1-yl is selected from the group consisting of one, two or three R 11 each R 11 is independently fluoro or trifluoromethyl; m and n are both 1 and k is 0), as provided herein.

[0104] In certain embodiments, a compound of formula (I) or (VI), 8 is hydrogen, alkyl or haloalkyl; R 9 -R u -cycloalkyl or cycloalkyl, -R u -cycloalkyl or cycloalkyl is one, two or three R 11 each R 11 are independently halo or haloC 1~3 Provided herein are compounds of formula (I) or (VI), where R is alkyl and the other variables are as described elsewhere herein for each of formulas (I) and (VI). In certain embodiments, compounds of formula (I) or (VI), where R is 8 is hydrogen, alkyl or haloalkyl; R 9 -R u -cycloalkyl or cycloalkyl, -R u -cycloalkyl or cycloalkyl is one, two or three R 11 each R 11 are independently halo or haloC 1~3Provided herein are compounds of formula (I) or (VI), where R is alkyl and the other variables are as described elsewhere herein for each of formulas (I) and (VI). In certain embodiments, compounds of formula (I) or (VI), where R is 8 is hydrogen, alkyl or haloalkyl; R 9 is cyclopropylmethyl or cyclobutyl, where cyclopropylmethyl or cyclobutyl is optionally substituted with 1, 2 or 3 fluoro or trifluoromethyl, and the other variables are as described elsewhere herein for each of formulas (I) and (VI). In certain embodiments, provided herein are compounds of formula (I) or (VI) where k is 0; m is 1; n is 1, and the other variables are as described elsewhere herein for each of formulas (I) and (VI). In certain embodiments, provided herein are compounds of formula (I) or (VI) where R 11 is fluoro, and the other variables are as described elsewhere herein for each of formulas (I) and (VI). In certain embodiments, formula (VIa): [ka] Provided herein is a compound of formula (I), (II), (IV), (IVa) or (VI), or a pharma- ceutically acceptable salt thereof, wherein j is 1 or 2. In certain embodiments, a compound of formula (VIa), or a pharma- ceutically acceptable salt thereof, wherein R 11 are each independently halo, cyano, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 j is 1 or 2, and the remaining variables are as described elsewhere herein for formula (VIa). In certain embodiments, provided herein is a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof, wherein R 11 are each independently halo, cyano, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 j is 1; and the remaining variables are as described elsewhere herein for formula (VIa). In certain embodiments, provided herein is a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof, wherein R 11 is HaroC 1~3j is alkyl; j is 1; and the remainder of the variables are as described elsewhere herein for formula (VIa). In certain embodiments, a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof is provided herein, 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 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 HaroC 1~3 Provided herein is a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof, wherein: j is alkyl; k is 0; m is 1; and n is 1. In certain embodiments, a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof is provided herein, 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 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 trifluoromethyl; j is 1; k is 0; m is 1; and n is 1) are provided herein.

[0105] In certain embodiments, a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof, 1 is 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 HaroC 1~3 Provided herein is a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof, 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 6 is methyl; R 11 is trifluoromethyl; j is 1; k is 0; m is 1; and n is 1) are provided herein.

[0106] In certain embodiments, a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen, fluoro or chloro; X ​​is CH; R4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 are each independently halo, cyano, haloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 alkylsulfonyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 j is 1 or 2; k is 0; m is 1; and n is 1), as provided herein.

[0107] In certain embodiments, a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof, 11 are each independently fluoro, cyano, or -CF 3 , -CHF 2 , -OCF 3 Or -S(O) 2 CH 3 or two R 11 The groups, together with the carbon atom to which they are attached, form a cyclopropyl; j is 1 or 2; and the remainder of the variables are as described elsewhere herein for Formula (VIa) provided herein.

[0108] In certain embodiments, a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof, 1 is 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 are each independently fluoro, cyano, or -CF 3 , -CHF 2 , -OCF 3 Or -S(O) 2 CH 3 or two R's 11The groups, together with the carbon atom to which they are attached, form a cyclopropyl; j is 1 or 2, k is 0; m is 1 and n is 1) as provided herein.

[0109] In certain embodiments, a compound of formula (VIa) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 are each independently fluoro, cyano, or -CF 3 , -CHF 2 , -OCF 3 Or -S(O) 2 CH 3 or two R's 11 The groups, together with the carbon atom to which they are attached, form a cyclopropyl; j is 1 or 2, k is 0; m is 1 and n is 1) as provided herein.

[0110] In certain embodiments, the compound of formula (VIb): [ka] Provided herein are compounds of Formula (I), (II), (IV), (IVa) or (VI) having the formula:

[0111] In certain embodiments, the compound of formula (VIc): [ka] Provided herein are compounds of Formula (I), (II), (IV), (IVa) or (VI) having the formula:

[0112] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharma- ceutically acceptable salt thereof,11 are each independently halo, cyano, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 and the remainder of the variables are as described elsewhere herein for each of formulas (VIb) and (VIc) provided herein.

[0113] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharma- ceutically acceptable salt thereof, 1 is 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 are each independently halo, cyano, haloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 alkylsulfonyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 and the remainder of the variables are as described elsewhere herein for each of Formulas (VIb) and (VIc) provided herein.

[0114] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharma- ceutically acceptable salt thereof, 1 is 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 are each independently halo, cyano, haloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 alkylsulfonyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 cycloalkyl) are provided herein.

[0115] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 are each independently halo, cyano, haloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 alkylsulfonyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 and the remainder of the variables are as described elsewhere herein for formula (VIb) or (VIc) as provided herein.

[0116] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R5 is methoxy or cyclopropyl; R 6 is methyl; R 11 are each independently halo, cyano, haloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 alkylsulfonyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 m is 1; n is 1; j is 1 or 2, and k is 0), as provided herein.

[0117] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharma- ceutically acceptable salt thereof, 11 are each independently fluoro, cyano, or -CF 3 , -CHF 2 , -OCF 3 Or -S(O) 2 CH 3 or two R 11 the groups, together with the carbon atom to which they are attached, form a cyclopropyl; j is 1 or 2; and the remainder of the variables are as described elsewhere herein for each of Formulas (VIb) and (VIc) provided herein.

[0118] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharma- ceutically acceptable salt thereof, 1 is 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 are each independently fluoro, cyano, or -CF 3 , -CHF 2 , -OCF 3 Or -S(O) 2 CH 3 or two R's 11The groups, together with the carbon atom to which they are attached, form a cyclopropyl; m is 1; n is 1; j is 1 or 2, and k is 0) as provided herein.

[0119] In certain embodiments, a compound of formula (VIb) or (VIc) or a pharma- ceutically acceptable salt thereof, 1 is hydrogen or fluoro; X ​​is CH; R 4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl; R 11 are each independently fluoro, cyano, or -CF 3 , -CHF 2 , -OCF 3 Or -S(O) 2 CH 3 or two R's 11 The groups, together with the carbon atom to which they are attached, form a cyclopropyl; m is 1; n is 1; j is 1 or 2, and k is 0) as provided herein.

[0120] In certain embodiments, a compound of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb) or (VIc), wherein each R 11 are independently halo, cyano, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 and forming a cycloalkyl or oxo; the other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb) and (VIc).

[0121] In certain embodiments, a compound of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb) or (VIc), wherein each R 11 are independently halo, cyano C 1~3 Alkyl, haloC 1~3 Alkyl, Hydroxyl, HaloC 1~3 Alkoxy, C 1~3 Alkylsulfonyl or haloC 1~3 alkylsulfonyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 and forming a cycloalkyl or oxo; the other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb) and (VIc).

[0122] In certain embodiments, a compound of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb) or (VIc), wherein each R 11 are independently halo, cyano C 1~3 Alkyl, haloC 1~3 Alkyl, Hydroxyl, HaloC 1~3 Alkoxy or C 1~3 alkylsulfonyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5and forming a cycloalkyl or oxo; the other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb) and (VIc).

[0123] In certain embodiments, a compound of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb) or (VIc), wherein each R 11 are independently halo, cyano, C 1~3 Alkyl, haloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 and the other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc). In certain embodiments, a compound of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc), wherein each R 11 are independently fluoro, cyano, -CHF 2 , -CF 3 , -OCF 3 , -OCHF 2 Or -S(O) 2 CH 3 or two R's 11 and the other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb), and (VIc). In certain embodiments, compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc), where each R 11 are independently fluoro, cyano, -CHF 2 , -CF 3 , -OCF 3 Or -S(O) 2 CH 3 or two R's 11Provided herein are compounds of formula (I), (II), (IV), (IVa), (VI), (VIa), (VIb), or (VIc), where each R 11 are independently fluoro, cyano, -CHF 2 , -CF 3 , -OCF 3 Or -S(O) 2 CH 3 and the other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (IVa), (VI), (VIa), (VIb) and (VIc) as provided herein.

[0124] In certain embodiments, the compound of formula (VII): [ka] Provided herein are compounds of formula (I), (II), (IV), (VI) or (X) or a pharma- ceutically acceptable salt thereof, wherein q is 0, 1, 2 or 3. In certain embodiments, compounds of formula (VIIa): [ka] Provided herein is a compound of formula (I), (II), (IV), (VI) or (X) or a pharma- ceutically acceptable salt thereof, having the formula: 11 are independently halo, cyano, haloC 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy or haloC1~3 alkoxy; k is 0; X is CH; R 1 is hydrogen; the other variables are as described for formula (I), (II), (IV), (VI) and (X), respectively. In certain embodiments, compounds of formula (VII) or (VIIa) are provided herein, 11 are independently halo, cyano, haloalkyl, or hydroxyl; k is 0; X is CH; R 1 is hydrogen; the other variables are as described for formula (I), (II), (IV), (VI) and (X), respectively. In more particular embodiments, compounds of formula (VII) or (VIIa), 11 are independently halo, cyano or haloC 1~3 alkyl; k is 0; X is CH; R 1 is hydrogen; the other variables are as described for formula (I), (II), (IV), (VI) and (X), respectively. In more particular embodiments, compounds of formula (VII) or (VIIa), 4 is hydrogen; R 5 is methoxy; R 6 is methyl, and X, R 1 , R 11 and k is as defined above) are provided herein.

[0125] In certain embodiments, the compound of formula (VIII): [ka] Provided herein are compounds of formula (I), (II) or (IV) having the formula: wherein ring A is cycloalkyl, heterocyclyl, aryl or heteroaryl; q is 0, 1, 2 or 3; the other variables are as described for formula (I), (II) and (IV), respectively. In certain embodiments, provided herein are compounds of formula (VIII) wherein ring A is heterocyclyl or heteroaryl. In certain embodiments, provided herein are compounds of formula (VIII) wherein ring A is heterocyclyl. In certain embodiments, provided herein are compounds of formula (VIII) wherein ring A is heteroaryl. In certain embodiments, provided herein are compounds of formula (VIII) wherein ring A is pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazolyl, imidazolyl, thiazolyl or pyrazolyl. In certain embodiments, provided herein are compounds of formula (VIII) where ring A is pyridinyl or pyrazolyl. In certain embodiments, provided herein are compounds of formula (VIII) where ring A is pyridinyl. In certain embodiments, provided herein are compounds of formula (VIII) where ring A is pyrazolyl. In certain embodiments, provided herein are compounds of formula (VIII) where ring A is azolyl. In certain embodiments, provided herein are compounds of formula (VIII) where X is CH and R 1 is hydrogen; R 4 is hydrogen; R 5 is methoxy; R 6 is methyl; 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 k is 0; q is 0, 1, 2 or 3, and ring A is as described above.

[0126] In certain embodiments, the compound of formula (X): [ka] Provided herein is a compound of formula (I) or a pharma- ceutically acceptable salt thereof, having the formula: 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl; 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 Optionally substituted with R u and R 11 Provided herein are compounds of formula (I) and (X), respectively, where R 2 is C 1~6 Alkyl, haloC 1~6 Alkyl, deutero-C 1~6 Alkyl, Hydroxy C 1~6 Alkyl, C 1~6 Alkoxy C 1~6 Alkyl, Cyano C 1~6 Alkyl, -R u -C3~6 Cycloalkyl, -R u -3- to 7-membered heterocyclyl, C 3~6 cycloalkyl, 3- to 7-membered heterocyclyl, or 5- to 10-membered heteroaryl; C 1~6 Alkyl, haloC 1~6 Alkyl, deutero-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- to 7-membered heterocyclyl, C 3~6 Cycloalkyl, 3- to 7-membered heterocyclyl, or 5- to 10-membered heteroaryl is selected from one, two, or three independently selected R 11 Optionally substituted with R u and R 11 Provided herein are compounds of formula (I) and (X), respectively, where R 2 is C 1~3 Alkyl, haloC 1~3 Alkyl, deutero-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- to 6-membered heterocyclyl, C 3~6 cycloalkyl, 3- to 6-membered heterocyclyl, or 5- to 6-membered heteroaryl; C 1~3 Alkyl, haloC 1~3 Alkyl, deutero-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, -Ru -3- to 6-membered heterocyclyl, C 3~6 Cycloalkyl, 3- to 6-membered heterocyclyl, or 5- to 6-membered heteroaryl is selected from one, two, or three independently selected R 11 optionally substituted with R u and R 11 Provided herein are compounds of formula (I) and (X), respectively, where R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, cyanoalkyl, -R u -cycloalkyl or -R u -heterocyclyl, alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, cyanoalkyl-R u -cycloalkyl or -R u Heterocyclyl is R 11 Optionally substituted with R 11 and other variables are as described elsewhere herein for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X), 2 is C 1~3 Alkyl, haloC 1~3 Alkyl, deutero-C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, Cyano C 1~3 Alkyl, -R u -C 3~5 Cycloalkyl, -R u -3- to 5-membered heterocyclyl, C 1~3 Alkyl, haloC 1~3 Alkyl, deutero-C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, Cyano C 1~3 Alkyl, -R u -C 3~5 Cycloalkyl, -R u - 3- to 5-membered heterocyclyl is an independently selected R 11 is optionally substituted with a group, R 11and other variables are as described elsewhere herein for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X), 2 is haloalkyl, deuteroalkyl, -R u -cycloalkyl or -R u -heterocyclyl, haloalkyl, deuteroalkyl, -R u -cycloalkyl or -R u -heterocyclyl is an independently selected R 11 is optionally substituted with a group, R 11 and other variables are as described elsewhere herein for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X), 2 is HaroC 1~3 Alkyl, deutero-C 1~3 Alkyl, -R u -C 3~5 Cycloalkyl or -R u -3- to 5-membered heterocyclyl, haloC 1~3 Alkyl, deutero-C 1~3 Alkyl, -R u -C 3~5 Cycloalkyl or -R u - 3- to 5-membered heterocyclyl is an independently selected R 11 is optionally substituted with a group, R 11 and other variables are as described elsewhere herein for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X), 2 is haloalkyl or -R u -heterocyclyl, -R u -heterocyclyl is optionally substituted with an independently selected halo; and other variables are as described elsewhere herein for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X), 2 is HaroC 1~3 Alkyl or -R u-3- to 5-membered heterocyclyl, -R u -3- to 5-membered heterocyclyl is optionally substituted with an independently selected halo; and other variables are as described elsewhere herein for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X), 2 is fluoroethyl or 3-fluorooxetan-3-yl)methyl; the other variables are as described elsewhere herein for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X), 2 is fluoroethyl; and the other variables are as described elsewhere herein for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X), 2 is 3-fluorooxetan-3-yl)methyl; the other variables are as described elsewhere herein for each of formulas (I) and (X). In certain embodiments, compounds of formula (I) or (X), 2 is alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, or cyanoalkyl, and each alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, or cyanoalkyl is selected from one R 11 Optionally substituted with R 11 Provided herein are compounds of formula (X), where X is CH and R 1 is hydrogen and R 4 is hydrogen; R 5 is methoxy; R 6 is methyl; 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; k is 0; R 2 is as described above) are provided herein.

[0127] In certain embodiments, the compound of formula (III), (IIIa) or (V), 2a and R 2b may each independently represent one, two, or three independently selected R 11 each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 Provided herein are compounds of formula (III), (IIIa) or (V), where R is an alkylsulfinyl group, and the other variables are as described elsewhere herein for each of formulas (III), (IIIa) and (V). In certain embodiments, compounds of formula (III), (IIIa) or (V), where R is an alkylsulfinyl group, 2a and R 2b may each independently represent one, two, or three independently selected R 11 C optionally substituted with 3~6 Form a cycloalkyl, R11 is as described for formula (I)) provided herein.

[0128] In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI) or (X), where m is 0 or 1; n is 0, 1 or 2, and other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (IVa), (VI) and (X). In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI) or (X), where m is 0 or 1; n is 0 or 1, and other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (IVa), (VI) and (X). In certain embodiments, provided herein are compounds of Formula (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa) or (X), where 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). In certain embodiments, provided herein are compounds of Formula (I), (II), (IIa), (IIb), (IIc), (IV), (IVa), (IVb), (IVc), (IVd), (IVe), (IVf), (VI), (VIa) or (X), where 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 2aand R 2b may each independently represent one, two, or three independently selected R 11 or one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0130] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a and R 2b may each independently represent one, two, or three independently selected R 11 forming a cycloalkyl substituted with 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0131] In certain embodiments, the compound of formula (I), (III), (IIIa) or (V), 2a and R 2b may each independently represent one, two, or three independently selected R 11 C optionally substituted with 3~6 form a cycloalkyl; each R 11 is as described elsewhere herein for each of formulas (III), (IIIa) and (V), provided herein.

[0132] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR7 , -SR 7 or -NR 8 R 9 and -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 or one, two or three independently selected R 11 R u , R 7 , R 8 , R 9 and R 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), provided herein.

[0133] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R2b may each independently represent one, two, or three independently selected R 11 or one, two or three independently selected R 11 R 7 , R 8 , R 9 and R 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0134] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 C replaced by 3~6 cycloalkyl or one, two or three independently selected R 11 R u , R 7 , R 8 , R 9 and R 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0135] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is cycloalkyl, heterocyclyl, -OR 7 , -SR 7 or -NR 8 R 9 and the cycloalkyl or heterocyclyl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 C replaced by 3~6 cycloalkyl or one, two or three independently selected R 11 R 7 , R 8 , R 9 and R 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0136] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 C replaced by 3~5 cycloalkyl or one, two or three independently selected R 11 R u , R 7 , R 8 , R 9 and R 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0137] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -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 one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 R u , R 7, R 8 , R 9 and R 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0138] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 R u , R 7 , R 8 , R 9 and R 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0139] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -R u -cycloalkyl or cycloalkyl, -R u -cycloalkyl or cycloalkyl is one, two or three independently selected R 11 Optionally substituted with R2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0140] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl or heterocyclyl; -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl or heterocyclyl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0141] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is cycloalkyl, heterocyclyl, aryl, or heteroaryl, and the cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from one, two, or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2aand R 2b may each independently represent one, two, or three independently selected R 11 R 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0142] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is cycloalkyl, heterocyclyl, aryl, or heteroaryl, and the cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from one, two, or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0143] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two, or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0144] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is heteroaryl, the heteroaryl being selected from one, two, or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0145] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 R 7 , R 8 , R 9 and R 11 is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), provided herein.

[0146] In certain embodiments, a compound of formula (I), (II), (IV) or (IVa), wherein R 2a and R 2b may each independently represent one, two, or three independently selected R 11 or forming an oxetanyl; R 11 Provided herein are compounds of formula (I), (II), (IV) or (IVa), where R 2a and R 2b may be one or two R 11 or form oxetanyl; each R 11 are independently fluoro, cyano, -CHF 2 , -CF 3 , -OCF 3 Or -S(O) 2 CH 3 or two R's 11 the groups, together with the carbon atom to which they are attached, form a cyclopropyl; m is 1; n is 1; and the other variables are as described elsewhere herein for each of Formulas (I), (II), (IV), and (IVa) provided herein.

[0147] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -OR 7 , -SR 7 or -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 7 , R 8 , R 9 and R 11is as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), provided herein.

[0148] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -R u -cycloalkyl, -OR 7 , -SR 7 or -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 7 is haloalkyl or cycloalkyl; R 8 is hydrogen; R 9 -R u -cycloalkyl or cycloalkyl, -R u -cycloalkyl or cycloalkyl is one, two or three independently selected R 11 and the remaining variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V). In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -R u -cycloalkyl, -OR 7 , -SR 7 or -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 7 is haloalkyl or cycloalkyl; R 8 is hydrogen; R 9 -Ru -cycloalkyl or cycloalkyl, -R u -cycloalkyl or cycloalkyl is one, two or three independently selected R 11 Optionally substituted with R 11 are each independently halo or haloC 1~3 and the remaining variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V). In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a is cyclopropylmethyl, -OR 7 , -SR 7 or -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 7 is -CH 2 CF 3 or cyclobutyl; R 8 is prime;R 9 is cyclopropylmethyl or cyclobutyl, and cyclopropylmethyl or cyclobutyl is a cycloalkyl group having one, two or three R 11 each R 11 is independently fluoro or trifluoromethyl, and the remaining variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V). 2b is hydrogen.

[0149] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -OR 7 , -SR 7 or -NR 8 R9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 7 is -CH 2 CF 3 or cyclobutyl; R 9 is cyclopropylmethyl or cyclobutyl, and cyclopropylmethyl or cyclobutyl is a cycloalkyl group having one, two or three R 11 each R 11 is independently fluoro or trifluoromethyl, and the remaining variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), and (V), as provided herein.

[0150] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 7 -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 Optionally substituted with R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 -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 or R 8 and R 9together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo), provided herein.

[0151] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 7 is cycloalkyl, heterocyclyl, or heteroaryl, and the cycloalkyl, heterocyclyl, or heteroaryl is selected from one, two, or three independently selected R 11 Optionally substituted with R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is cycloalkyl, heterocyclyl, or heteroaryl, and the cycloalkyl, heterocyclyl, or heteroaryl is selected from one, two, or three independently selected R 11 or R 8 and R9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 and heterocyclyl is further optionally substituted with oxo, and each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo), provided herein.

[0152] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 7 is one, two, or three independently selected R 11 cycloalkyl or heterocyclyl optionally substituted with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is cycloalkyl or heterocyclyl, and the cycloalkyl or heterocyclyl is selected from one, two, or three independently selected R 11 or R 8 and R 9together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 Optionally substituted with R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl) are provided herein.

[0153] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 7 -R u -heterocyclyl or heterocyclyl, -R u -heterocyclyl or heterocyclyl is one, two or three independently selected R 11 each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl) are provided herein.

[0154] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 7 is haloalkyl; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 8 , R 9 and R 11 are as described for formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), respectively, provided herein.

[0156] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 9 1, 2 or 3 R 11 -R optionally substituted with u -cycloalkyl, R 11Provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), respectively, as described elsewhere herein. In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 9 is one, two, or three independently selected R 11 is cycloalkyl optionally substituted with R 11 Provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), respectively, as described elsewhere herein. In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 9 is cyclopropyl optionally substituted with 1, 2 or 3 fluoro, and the remainder of the variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V) provided herein.

[0157] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 and each R 11 independently, for each of formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), represents halo, cyano, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl) are provided herein.

[0158] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is haloalkyl, -R u -heterocyclyl or heterocyclyl, haloalkyl, -R u -heterocyclyl or heterocyclyl is one, two or three independently selected R 11 Optionally substituted with R 11 are as described for formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), respectively, provided herein.

[0159] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa) or (V), wherein R 2a -OR 7 ;R 7 is 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 Optionally substituted with R 11 are as described for formulas (I), (II), (III), (IIIa), (IV), (IVa) and (V), respectively, provided herein.

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

[0161] In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI) or (X), where m is 0 and the other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (IVa), (VI) and (X). In certain embodiments, provided herein are compounds of formula (I), (II), (IV), (IVa), (VI) or (X), where m is 0 and n is 0 or 1 and the other variables are as described elsewhere herein for each of formulas (I), (II), (IV), (VI) and (X).

[0162] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 Provided herein are compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively, where each R is an alkylsulfinyl, and the other variables are as described herein for each of formulas (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X). In certain embodiments, compounds of formula (I), (Il), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), where each R is an alkylsulfinyl, 11 are independently halo, cyano, C 1~3 Alkyl or haloC 1~3Provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively. In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein each R 11 are independently halo, cyano or haloC 1~3 Provided herein are compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) and (X), respectively. In certain embodiments, compounds of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein each R 11 are independently halo, cyano, haloC 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy or haloC 1~3 and alkoxy, and the other variables are as described herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). 11 are independently halo, cyano, haloC 1~3 It is alkyl or hydroxyl.

[0163] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein each R11 are independently halo, cyano or haloC 1~3 and alkyl, and the other variables are as described herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). 11 is independently halo or cyano.

[0164] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein each R 11 are independently fluoro, chloro, bromo, cyano, -CHF 2 or -CF 3 and the other variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). In certain embodiments, each R 11 is independently Cl or cyano.

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

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

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

[0168] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R 4 is hydrogen, halo, C 1~3 Alkyl or haloC 1~3 and the other variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). 4 is hydrogen, fluoro, chloro, methyl or -CF 3 In a more particular embodiment, R 4 is hydrogen, fluoro, chloro or methyl. In a more particular embodiment, R 4 is hydrogen.

[0169] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl or C 1~3 and the other variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). 5 is chloro, bromo, methyl, cyclopropyl or methoxy.

[0170] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R 6 is halo, cyano, C 1~3 Alkyl, C 3~5 Cycloalkyl or C 1~3 and the other variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). 6 is chloro, bromo, cyano, methyl, cyclopropyl or methoxy.

[0171] In certain embodiments, a compound of formula (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX) or (X), wherein R 4 is hydrogen or methyl; R 5 is methoxy; R 6 is methyl, and the other variables are as described elsewhere herein for each of formulas (I), (II), (III), (IIIa), (IV), (IVa), (V), (VI), (VII), (VIIa), (VIII), (IX), and (X). 4 is hydrogen; R 5 is methoxy and R 6 In certain embodiments, a compound of formula (I), (II), (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 R4 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6 is methyl and the other variables are as described elsewhere herein for each of formulas (I), (II), (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) as provided herein. In certain embodiments, a compound of formula (I), (II), (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 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6is methyl and the other variables are as described elsewhere herein for each of formulas (I), (II), (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) as provided herein. In certain embodiments, a compound of formula (I), (II), (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 is hydrogen, fluoro, chloro or methyl; R 5 is methoxy or cyclopropyl; R 6is methyl and the other variables are as described elsewhere herein for each of formulas (I), (II), (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) as provided herein. In certain embodiments, a compound of formula (I), (II), (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 is hydrogen, fluoro or chloro; R 5 is methoxy; R 6 is methyl and the other variables are as described elsewhere herein for each of formulas (I), (II), (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) as provided herein.

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

[0173] In certain embodiments, a compound of formula (I), (II), (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; X is CH, and the other variables are as described elsewhere herein for each of formulas (I), (II), (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) are provided herein.

[0174] In certain embodiments, provided herein is a pharmaceutical composition comprising any of the compounds described herein (e.g., a compound of Formula (I), (I), (II), (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 pharma- ceutically acceptable salt thereof; and a pharma- ceutically acceptable carrier.

[0175] In certain embodiments, a compound of formula (I) comprising: 4-((2S,4S)-4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 1) 4-((2R,4R)-4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 2) 4-((2S,4S)-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; (Example 3) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (Example 4) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; (Example 5) 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; (±)-trans-4-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 6) 4-((2S,4S)-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 7) 4-((2S,4S)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 8) 4-((2R,4R)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (Example 9) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid (Example 10) 4-((2R,4R)-4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (Example 11) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; (Example 12) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; (Example 13) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; (Example 14) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; (Example 15) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; (Example 16) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; 4-(-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; (Example 17) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; (Example 18) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 19) 4-((2R,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 20) 4-((2R,4R)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 21) 4-((2R,4R)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 22) 4-((2R,4R)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 23) 4-((2R,4R)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 24) 4-((2R,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; (Example 25) 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; 4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 26) 4-((2R,4R)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; (Example 27) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 28) 4-((2R,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 29) 4-((2S,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((3R,5S)-1,1-difluoro-6-((5-methoxy-7-methyl-1H-indol-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-indol-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-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-((3R,5R)-1,1-difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-(1,1-difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; (±)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 31) (S)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 32) (R)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((5S,7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; (Example 33) 4-((5R,7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; (or Example 33) 4-((5R,7R)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-((5S,7R)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-((5S,7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; (Example 34) 4-((5R,7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; (or Example 34) 4-((5R,7R)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-((5S,7R)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(5R,7S)-2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; (Example 35 or 36) 4-(5S,7S)-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; (or Example 36 or 35) 4-(5S,7R)-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(5R,7R)-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; (Example 37) 4-((2S,4S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-(4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; (Example 38) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; 4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid; (Example 39) (S)-4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid; (R)-4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid; (R)-4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; (Example 40) (S)-4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; 4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; 4-((2S,4S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 41) 4-((2R,4R)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; (Example 42) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-Cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 43) 4-((2S,4S)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 44) 4-((2R,4R)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (S)-4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 46 or 47) 4-((2S,4r,6S)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 47 or 46) 4-((2S,4s,6R)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 48 or 49) 4-((2S,4r,6S)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 49 or 48) 4-((2S,4s,6R)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (S)-4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)-2-fluorobenzoic acid; 4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)-2-fluorobenzoic acid; (S)-4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azadispiro[2.1.5 5 .1 3]undecane-7-yl)benzoic acid; (Example 51) (R)-4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azadispiro[2.1.5 5 .1 3 ]Undecane-7-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azadispiro[2.1.5 5 .1 3 ]Undecane-7-yl)benzoic acid; (S)-4-(7-((3-chloro-5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-2,2-difluoro-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((3-chloro-5-methoxy-7-methyl-1H-indol-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-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2,2-difluoro-7-((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 52 or 55) 4-((2S,4r,6S)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 55 or 52) 4-((2S,4s,6R)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 56 or 57) 4-((2S,4r,6S)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 57 or 56) 4-((2S,4s,6R)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (S)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 58) (R)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 59 or 60) 4-((2S,4r,6S)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 60 or 59) 4-((2S,4s,6R)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2S)-2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 62 or 63) 4-((2S,4r,6S)-2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 62 or 63) 4-((2S,4s,6R)-2-fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-4-(2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-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-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazin-2-yl)benzoic acid; (Example 65) (S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazin-2-yl)benzoic acid; (R)-4-(4-(2,2-difluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 66) (S)-4-(4-(2,2-difluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; 4-(4-(2,2-difluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (R)-4-(4-((3,3-difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 67) (S)-4-(4-((3,3-difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; 4-(4-((3,3-difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazin-2-yl)benzoic acid; (Example 68) (S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazin-2-yl)benzoic acid; (R)-4-(4-((3-fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 69) (S)-4-(4-((3-fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; 4-(4-((3-fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (R)-4-(4-(2-fluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 70) (S)-4-(4-(2-fluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; 4-(4-(2-fluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (±)-trans-4-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 71) 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 81) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 72) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 73) 4-((2R,4R)-4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 74) 4-((2R,4R)-4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 75) 4-((2R,4R)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 76) 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 77) 4-((2R,4R)-4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(3-cyanoazetidin-1-yl)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid; (Example 78) 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(5-azaspiro[2.3]hexan-5-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 79) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(methylsulfonyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(3-fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 80) 4-((2R,4R)-4-(3-fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(3-fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(3-fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(3-fluoroazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid; (Example 82) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-yloxy)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 83) 4-((2R,4R)-4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(2,2-difluoroethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-Cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 84) 4-((2R,4R)-4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-Cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid; (Example 85) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid; and 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethoxy)piperidin-2-yl)benzoic acid Provided herein is a compound selected from:

[0176] In certain embodiments, provided herein is a compound of formula (I) selected from the group consisting of the compounds in Table A below, and pharma- ceutically acceptable salts thereof.

[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, provided herein is a compound of formula (I) selected from the group consisting of the compounds in Table B below, and pharma- ceutically acceptable salts thereof.

[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, provided herein is a compound of formula (I) selected from the group consisting of the compounds in Table C below, and pharma- ceutically acceptable salts thereof.

[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, provided herein is a compound of formula (I) selected from the group consisting of the compounds in Table D below, and pharma- ceutically acceptable salts thereof.

[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 certain embodiments, the compound of formula (I) may be selected from the following list of compounds: 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(9-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-9-azaspiro[5.5]undecan-8-yl)benzoic acid; 4-(1,1-difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-(1-Methoxy-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-(1,1-difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(1-Methoxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-Methoxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-ethoxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(trifluoromethyl)piperidin-2-yl)benzoic acid; 4-(4-(difluoromethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-fluoro-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-methylpiperidin-2-yl)benzoic acid; 4-(4-ethyl-4-fluoro-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-fluoro-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-propylpiperidin-2-yl)benzoic acid; 4-((1R,3S,5S)-3-ethoxy-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azabicyclo[3.2.1]octan-1-yl)benzoic acid; 4-((2R,8R)-8-ethoxy-3-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-2-azabicyclo[2.2.2]octan-1-yl)benzoic acid; 4-((3R,5R)-5-ethoxy-2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azabicyclo[2.2.2]octan-3-yl)benzoic acid; 4-((2R,4R)-4-cyclopropoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-cyclobutoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopentyloxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclobutylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopentylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclohexylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylmethoxy)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydrofuran-3-yl)methoxy)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-2-ylmethoxy)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydrofuran-2-yl)methoxy)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydro-2H-pyran-2-yl)methoxy)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydro-2H-pyran-3-yl)methoxy)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((tetrahydro-2H-pyran-4-yl)methoxy)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(trifluoromethoxy)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(3-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-2-yl)benzoic acid; 4-(3-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-4-yl)benzoic acid; 4-(6-ethoxy-3-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-2-yl)benzoic acid; 4-(6-ethoxy-3-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(2-fluoro-2-methylcyclopropoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(2,2-dimethylcyclopropoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(3,3-difluorocyclobutoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-acetamido-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-((2,2-difluorocyclopropyl)methoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-((2-fluoro-2-methylcyclopropyl)methoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2-methylcyclopropyl)methoxy)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-((2,2-dimethylcyclopropyl)methoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1-methylcyclopropoxy)piperidin-2-yl)benzoic acid; 4-(5-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)octahydrofuro[3,2-c]pyridin-4-yl)benzoic acid; 4-((6S)-5-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)octahydrofuro[3,2-c]pyridin-6-yl)benzoic acid; 4-(6-(((5S)-5-Methoxy-7-methyloctahydro-1H-indol-4-yl)methyl)-2H-6l4-pyrano[3,2-c]pyridin-5-yl)benzoic acid; 4-(6-(((7S)-5-methoxy-7-methyloctahydro-1H-indol-4-yl)methyl)-2H-6l4-pyrano[3,2-c]pyridin-7-yl)benzoic acid; 4-((1R)-2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1,2,3,4-tetrahydro-2l4-isoquinolin-1-yl)benzoic acid; (S)-4-(5-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((6-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-((5-methoxy-6,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((7-cyclopropyl-5-methoxy-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((7-cyano-5-methoxy-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-((5-methoxy-7-(trifluoromethyl)-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-1-((7-(difluoromethyl)-5-methoxy-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid; rac-4-((2R,4S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-3,7,8,9-tetrahydropyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-6,7,8,9-tetrahydro-3H-benzo[e]indol-9-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(5-methyl-1,6-dihydro-2H-furo[3,2-e]indol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-3,6,7,8-tetrahydrocyclopenta[e]indol-8-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-3,7,8,9-tetrahydrothiopyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(4-methyl-6,6-dioxido-3,7,8,9-tetrahydrothiopyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(6-methoxy-8-methyl-1,3,4,5-tetrahydrobenzo[cd]indol-5-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-(6-methoxy-8-methyl-4,5-dihydro-1H-pyrano[2,3,4-cd]indol-5-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-3,7,8,9-tetrahydropyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-6,7,8,9-tetrahydro-3H-benzo[e]indol-9-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(5-methyl-1,6-dihydro-2H-furo[3,2-e]indol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-3,6,7,8-tetrahydrocyclopenta[e]indol-8-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-3,7,8,9-tetrahydrothiopyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(4-methyl-6,6-dioxido-3,7,8,9-tetrahydrothiopyrano[3,2-e]indol-9-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(6-methoxy-8-methyl-1,3,4,5-tetrahydrobenzo[cd]indol-5-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-(6-methoxy-8-methyl-4,5-dihydro-1H-pyrano[2,3,4-cd]indol-5-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-1-naphthoic acid; 5-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)quinoline-8-carboxylic acid; 8-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)quinoline-5-carboxylic acid; 8-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)imidazo[1,2-a]pyridine-5-carboxylic acid; 5-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid; 6-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid; 4-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid; rac-7-((2R,4S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2,3-dihydro-1H-indene-4-carboxylic acid; 7-((2R,4R)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2,3-dihydrobenzofuran-4-carboxylic acid; (S)-3-(4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1,2,3,4-tetrahydroquinolin-7-yl)propanoic acid; (S)-2-((4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1,2,3,4-tetrahydroquinolin-7-yl)oxy)acetic acid; 4-(9-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)-1-oxa-9-azaspiro[5.5]undecan-8-yl)benzoic acid; 4-(7-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)-1-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(8-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; (4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)phosphonic acid; rac-4-((2R,4S)-4-ethoxy-1-((5-methoxy-7-(methyl-d3)-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-ethoxy-1-((5-ethyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; N-hydroxy-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzamide; (4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)boronic acid; Imino(4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)(methyl)-16-sulfanone; (S)-4-(4,4-difluoro-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(5-ethoxy-2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azabicyclo[4.1.0]heptan-1-yl)benzoic acid; 4-(5-ethoxy-2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azabicyclo[4.1.0]heptan-3-yl)benzoic acid; 4-(1-ethoxy-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-(1-ethoxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; Methyl 4-(4-(ethylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoate; 7-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2,3-dihydrobenzofuran-4-carboxylic acid; 8-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)imidazo[1,2-a]pyridine-5-carboxylic acid; 4-((2S)-3-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-3-azabicyclo[4.1.0]heptan-2-yl)benzoic acid; 4-(((2R,4R)-2-(4-(2H-tetrazol-5-yl)phenyl)-4-(cyclopropylmethoxy)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole; 5-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-6-oxo-1,6-dihydropyridine-2-carboxylic acid; 4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2,2-dimethyl-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-((2S)-4-(cyclopropylmethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2-fluorobenzoic acid; and 4-[4-(ethylamino)-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]-2-piperidinyl]-2-fluoro-benzoic acid; or Stereoisomers and pharma- ceutically acceptable salts thereof The compound is not selected from the group consisting of

[0236] In some embodiments, the compound of formula (I) is not a compound disclosed in PCT Publication No. WO 2022 / 028527, which is incorporated by reference herein to the exclusion of the compounds disclosed herein.

[0237] Any combination of the groups described above for the various variables is contemplated herein. Accordingly, throughout the specification, groups and substituents thereof will be chosen by one of ordinary skill in the art to provide stable moieties and compounds.

[0238] The compounds of the present disclosure include the compounds themselves as well as their salts. Salts in the sense of the present disclosure are preferably pharma- ceutically acceptable salts of the compounds of the present disclosure. Also included are salts that are not suitable per se for pharmaceutical use, but may be used, for example, for the isolation or purification of the compounds of the present disclosure. Salts may be formed, for example, between anions and positively charged substituents (e.g., amino) in the compounds described herein. Suitable anions include chloride, bromide, iodide, sulfate, nitrate, phosphate, citrate, methanesulfonate, trifluoroacetate, and acetate. Similarly, salts may be formed between cations and negatively charged substituents (e.g., carboxylate) in the compounds described herein. Suitable cations include sodium, potassium, magnesium, calcium, and ammonium cations, such as tetramethylammonium.

[0239] As used herein, "pharmaceutically acceptable salt" refers to 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 with a pharmaceutically acceptable cation, such as sodium, potassium, magnesium, calcium, aluminum, lithium and ammonium. Lists of suitable salts can be found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418; S. M. Berge 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]; each of which is incorporated herein by reference in its entirety.

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

[0241] Examples of isotopes that may be incorporated into compounds according to the present disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, chlorine, bromine, and iodine, e.g. 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 according to the present disclosure, particularly those incorporating one or more radioisotopes, may be useful, for example, for investigating the mechanism of action or distribution of the active compound in the body. 3 H, 14 C and / or 18 Compounds labeled with F isotopes are suitable for this purpose. Furthermore, for example, the incorporation of deuterium isotopes may result in higher metabolic stability of the compounds, resulting in certain therapeutic effects, such as an increased half-life in the body or a reduced effective dose required.

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

[0243] In certain embodiments, hydrogen atoms of the compounds described herein may be replaced with deuterium atoms. In certain embodiments, "deuterated," as applied to a chemical group, unless otherwise indicated, refers to a chemical group that is isotopically enriched with an amount of deuterium substantially greater than its natural abundance, e.g., at least 90% deuterium at a particular position.

[0244] Isotopic variants of the compounds of the present disclosure can be prepared by using corresponding isotopic modifications of particular reagents and / or starting compounds therein by a variety of methods, including those described below and in the Examples.

[0245] C. Preparation The term "pharmaceutical composition" as used herein is intended to include a product containing an active ingredient and an inactive ingredient that constitutes a carrier, as well as any product that results directly or indirectly from the combination, complexation or assembly of any two or more of the ingredients, or from the dissociation of one or more of the ingredients, or from any other type of reaction or interaction of one or more of the ingredients. Thus, the pharmaceutical composition of the present disclosure includes any composition made by mixing a compound of the present disclosure or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

[0246] The term "pharmaceutically acceptable carrier" refers to a carrier or adjuvant that may be administered to a patient, together with a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, which does not impair its pharmacological activity and which is non-toxic when administered in a dosage sufficient to deliver a therapeutic amount of the compound.

[0247] The amount to be administered depends on the compound formulation, administration route, etc., and is generally determined empirically, and will necessarily vary depending on the target, host, administration route, etc. In general, the amount of active compound in a unit dose of a formulation can be varied or adjusted from about 1 milligram (mg) to about 100 mg or from about 1 mg to about 1000 mg depending on the specific application. For convenience, the total daily dose can be divided and administered in portions throughout the day.

[0248] Solid dosage forms of the 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 pharma- ceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and / or a) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders, such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia, c) humectants, such as glycerol, d) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarders, such as paraffin, f) absorption accelerators, such as quaternary ammonium compounds, g) wetting agents, such as cetyl alcohol and glycerol monostearate, h) absorbents, such as kaolin and bentonite clay, and i) lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents.

[0249] Solid pharmaceutical compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar, as well as high molecular weight polyethylene glycols and the like.

[0250] The solid dosage forms of the pharmaceutical composition of tablets, dragees, capsules, pills and granules can be prepared with coatings and shells, such as enteric coatings and other pharmaceutical coatings. They can optionally contain opacifying agents, and they can also be formulated to release the active ingredient only, or preferentially, in a certain part of the intestinal tract, optionally with a delay. Examples of embedded pharmaceutical compositions that can be used include polymeric substances and waxes.

[0251] The active compounds can also be in microencapsulated form, if appropriate, with one or more of the above-mentioned excipients.

[0252] The liquid dosage form of the pharmaceutical composition for oral administration includes pharma- ceutical acceptable emulsion, solution, suspension, syrup and elixir.In addition to active compound, liquid dosage form can 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, oil (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol and fatty acid ester of sorbitan and mixtures thereof.

[0253] The compound suspensions may contain, in addition to the active compound, suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar, and tragacanth, and mixtures thereof.

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

[0255] In addition to the inert diluent, these pharmaceutical compositions may also contain adjuvants such as preservatives, wetting agents, emulsifiers, dispersing agents, sweeteners, flavorings and aromatics. Prevention of microbial action may be ensured by including various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol sorbic acid, and the like. It may be desirable to include isotonic agents such as sugars, sodium chloride, and the like. Prolonged absorption of injectable pharmaceutical dosage forms may be brought about by including agents that delay absorption, such as aluminum monostearate and gelatin. The compound may be incorporated into sustained release or targeted delivery systems, such as polymer matrices, liposomes and microspheres. Such formulations may provide more effective distribution of the compound.

[0256] Pharmaceutical compositions that are injectable formulations can be sterilized, for example, by filtration through a bacteria-retaining filter or by incorporating sterilizing agents in the form of sterile solid pharmaceutical compositions that can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.

[0257] Dosage forms for topical administration of the compounds or pharmaceutical compositions of the present disclosure include powders, patches, sprays, ointments and inhalants. The active compound is mixed under sterile conditions with a pharma- ceutically acceptable carrier and any preservatives, buffers or propellants that may be required.

[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 buccally, at dosages ranging from about 0.01 milligrams per kilogram (mg / kg) to about 1000 mg / kg, (e.g., about 0.01 to about 100 mg / kg, about 0.1 to about 100 mg / kg) every 4 to 120 hours or depending on the requirements of the particular drug, dosage form, and / or route of administration. Other routes of administration include enteral, intraarterial, intraperitoneal, and intrathecal administration. The interrelationship of dosages (based on milligrams per square meter of body surface) for animals and humans is described by Freireich et al., Cancer Chemother. Rep. 50, 219-244 (1966). Body surface area may be approximately determined from the height and weight of the patient. See, e.g., Scientific Tables, Geigy Pharmaceuticals, Ardsley, NY, 537 (1970). In certain embodiments, the compositions are administered orally or by injection. The methods herein contemplate administration of a therapeutically effective amount of a compound or compound composition to achieve a desired or described effect. Typically, the pharmaceutical compositions of the present disclosure will be administered about 1 to about 6 times per day, or alternatively as a continuous infusion. Such administration can be used as a chronic or acute treatment.

[0259] Lower or higher doses than those recited 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 particular compound used, age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, severity and course of the disease, condition or symptom, predisposition of the patient to the disease, and the judgment of the treating physician.

[0260] The dosage form contains from about 0.001 mg to about 2,000 mg (including from about 0.001 mg to about 1,000 mg, from about 0.001 mg to about 500 mg, from about 0.01 mg to about 250 mg) of a compound of formula (I) or a salt thereof (e.g., a pharma- ceutically acceptable salt) as defined anywhere herein. The dosage form may further comprise a pharma- ceutically acceptable carrier and / or an additional therapeutic agent.

[0261] The appropriate dosage level may be determined by any suitable method. Preferably, the active substance is administered 1 to 4 times per day when administered topically, or less frequently when a drug delivery system is used. Nevertheless, the actual dosage level and time course of administration of the active ingredient in the pharmaceutical composition of the present disclosure may be varied to obtain an amount of the active ingredient effective to achieve the desired therapeutic response for a particular patient, composition and method of administration without being intolerably toxic to the patient. In some cases, the dosage may deviate from the amount specified, depending in particular on the patient's age, sex, weight, diet and general health, route of administration, individual response to the active ingredient, nature of the formulation and the time or interval at which administration is performed. Thus, in some cases, it may be sufficient to administer less than the minimum amount mentioned above, while in other cases the upper limit described may be exceeded. In the case of administration of larger amounts, it may be desirable to divide these into multiple individual doses over the course of a day.

[0262] D.How to use Provided herein are methods of using the compounds disclosed herein or pharma- ceutically acceptable salts thereof or pharmaceutical compositions thereof for the treatment, prevention, or amelioration of diseases or disorders mediated or otherwise affected by the complement alternative pathway. In more particular embodiments, provided herein are methods of using the compounds disclosed herein or pharma- ceutically acceptable salts thereof or pharmaceutical compositions thereof for the treatment, prevention, or amelioration of diseases or disorders mediated or otherwise affected by complement factor B (CFB). In more particular embodiments, provided herein are methods of using the compounds disclosed herein or pharma- ceutically acceptable salts thereof or pharmaceutical compositions thereof for the treatment, prevention, or amelioration of diseases or disorders mediated or otherwise affected by inhibition of the complement alternative pathway. In more particular embodiments, provided herein are methods of using the compounds disclosed herein or pharma- ceutically acceptable salts thereof or pharmaceutical compositions thereof for the treatment, prevention, or amelioration of diseases or disorders mediated or otherwise affected by inhibition of complement factor B.

[0263] Examples of known complement-related diseases or disorders include neurological disorders, multiple sclerosis, stroke, Guillain-Barre syndrome, traumatic brain injury, Parkinson's disease, disorders of inappropriate or undesirable complement activation, hemodialysis complications, hyperacute allograft rejection, xenograft rejection, interleukin-2 induced toxicity during IL-2 therapy, inflammatory diseases, inflammation in autoimmune diseases, Crohn's disease, adult respiratory distress syndrome, thermal injury including burns or frostbite, myocarditis, post-ischemic reperfusion states, 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 nephritis, hepatic fibrosis, hemolytic anemia, myasthenia gravis, tissue regeneration, and nerve regeneration. In addition, other known complement-related diseases include pulmonary diseases and disorders such as dyspnea, hemoptysis, ARDS, asthma, chronic obstructive pulmonary disease (COPD), emphysema, pulmonary embolism and infarction, pneumonia, fibrosing dust diseases, inert dusts and minerals (e.g., silicon, coal dust, beryllium and asbestos), pulmonary fibrosis, organic dust diseases, chemical injuries (due to irritating gases and chemicals such as chlorine, phosgene, sulfur dioxide, hydrogen sulfide, nitrogen dioxide, ammonia and hydrochloric acid), smoke damage, thermal injuries (e.g., burns, frostbite), asthma, allergies, bronchoconstriction, hypersensitivity. pneumonia, parasitosis, Goodpasture's syndrome, pulmonary vasculitis, microimmune vasculitis, immune complex associated inflammation; eye diseases including age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, macular oedema, Behçet's uveitis, multifocal choroiditis, Vogt-Koyanagi-Harada syndrome, intermediate uveitis, scattershot chorioretinitis, sympathetic ophthalmia, ocular cicatricial pemphigoid, ocular pemphigus, non-arteritic ischemic optic neuropathy, postoperative inflammation and retinal vein occlusion uveitis (including Behçet's disease and other subtypes of uveitis), antiphospholipid syndrome.

[0264] In certain embodiments, provided herein are methods of treating renal disease, chronic kidney disease, 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 nephropathy (MCD), paroxysmal nocturnal hemoglobinuria (PNH), ANCA-associated vasculitis, lupus nephritis, or polycystic kidney disease (PKD).

[0265] E. Embodiment Embodiment 1: Formula (I): [ka] (In the formula, R 1 is hydrogen, fluoro, chloro or methyl; X is N or CH; Z is NR 2 or CR 2a R 2b and; R 2 is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -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 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 optionally replaced with; R 2a is 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 one, two or three independently selected R 11 Optionally substituted with; and R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 is alkyl; or R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl or heterocyclyl, the cycloalkyl or heterocyclyl being selected from one, two or three independently selected R 11 optionally replaced with; R 3 is halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 4 is hydrogen, halo, cyano, C 1~3 Alkyl or haloC 1~3 is alkyl; R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, HaloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 is 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 is alkoxy; R 7 is 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 optionally replaced with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 optionally substituted with; or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 optionally replaced with; Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; or The Two R's 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 cycloalkyl, 3- to 6-membered heterocyclyl or oxo, 3~5 cycloalkyl or 3- to 6-membered heterocyclyl is optionally substituted with 1 or 2 independently selected halo; R 12 is alkyl, deuteroalkyl or haloalkyl; R 13 and R 14 are each independently hydrogen, alkyl, deuteroalkyl, or haloalkyl, or R 13 and R 14 together with the nitrogen atom to which they are attached, one, two or three independently selected R 11 forming a heterocyclyl optionally substituted with; R u is a methylene, ethylene or propylene linker optionally substituted with 1 to 6 independently selected halo; k is 0, 1, 2 or 3; t is 1 or 2; m is 0, 1 or 2; and n is 0, 1 or 2, provided that Z is NR 2 when m is 1 and n is 1 or 2; and Z is CR 2a R 2b and R 2a and R 2b together with the carbon atom to which they are attached form a cycloalkyl, and when m is 1, the cycloalkyl is 11 (Replaced by or a pharma- ceutically acceptable salt thereof.

[0266] Embodiment 2: m is 0 or 1; n is 0, 1 or 2 with the proviso that Z is NR 2 wherein, m is 1 and n is 1 or 2.

[0267] Embodiment 3: m is 0 or 1; and n is 0 or 1, with the proviso that Z is NR 2 wherein 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 for embodiment 1. or a pharma- ceutically acceptable salt thereof, wherein:

[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 for embodiment 1. or a pharma- ceutically acceptable salt thereof, wherein:

[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 for embodiment 1. or a pharma- ceutically acceptable salt thereof, wherein:

[0271] Embodiment 7: Formula (IVa): [ka] or a pharma- ceutically acceptable salt thereof, wherein:

[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 for embodiment 1. or a pharma- ceutically acceptable salt thereof, wherein:

[0273] Embodiment 9: R 2a and R 2b may each independently represent one, two, or three independently selected R 11 or one, two or three independently selected R 11The compound according to any one of embodiments 1 to 8, wherein the compound forms a heterocyclyl optionally substituted with

[0274] Embodiment 10: R 2a and R 2b may each independently represent one, two, or three independently selected R 11 The compound of any one of embodiments 1-8, wherein the compound forms a cycloalkyl substituted with

[0275] Embodiment 11: R 2a and R 2b may each independently represent one, two, or three independently selected R 11 C optionally substituted with 3~6 The compound of embodiment 5 or 8, which forms a cycloalkyl.

[0276] Embodiment 12: R 2a -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 one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 or one, two or three independently selected R 11The compound according to any one of embodiments 1 to 8, wherein the compound forms a heterocyclyl optionally substituted with

[0277] Embodiment 13: R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 or one, two or three independently selected R 11 The compound according to any one of embodiments 1 to 8, wherein the compound forms a heterocyclyl optionally substituted with

[0278] Embodiment 14: R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 C replaced by 3~6cycloalkyl or one, two or three independently selected R 11 The compound according to any one of embodiments 1 to 8, which forms a 4-6 membered heterocyclyl optionally substituted with

[0279] Embodiment 15: R 2a is cycloalkyl, heterocyclyl, -OR 7 , -SR 7 or -NR 8 R 9 and the cycloalkyl or heterocyclyl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 C replaced by 3~6 cycloalkyl or one, two or three independently selected R 11 The compound according to any one of embodiments 1 to 8, which forms a 4-6 membered heterocyclyl optionally substituted with

[0280] Embodiment 16: R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2bmay each independently represent one, two, or three independently selected R 11 C replaced by 3~5 cycloalkyl or one, two or three independently selected R 11 The compound according to any one of embodiments 1 to 8, which forms a 4-5 membered heterocyclyl optionally substituted with

[0281] Embodiment 17: R 2a -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 one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 The compound according to any one of embodiments 1 to 8, wherein the compound forms a heterocyclyl optionally substituted with

[0282] Embodiment 18: R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 The compound according to any one of embodiments 1 to 8, wherein the compound forms a heterocyclyl optionally substituted with

[0283] Embodiment 19: R 2a -R u -cycloalkyl or cycloalkyl, -R u -cycloalkyl or cycloalkyl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 The compound of any one of embodiments 1-8, wherein is alkyl.

[0284] Embodiment 20: R 2a -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl or heterocyclyl; -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl or heterocyclyl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 The compound of any one of embodiments 1-8, wherein is alkyl.

[0285] Embodiment 21: R 2a is cycloalkyl, heterocyclyl, aryl, or heteroaryl, and the cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from one, two, or three independently selected R 11Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 The compound according to any one of embodiments 1 to 8, wherein the compound forms a heterocyclyl optionally substituted with

[0286] Embodiment 22:R 2a is cycloalkyl, heterocyclyl, aryl, or heteroaryl, and the cycloalkyl, heterocyclyl, aryl, or heteroaryl is selected from one, two, or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 The compound of any one of embodiments 1-8, wherein is alkyl.

[0287] Embodiment 23: R 2a is heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two, or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 The compound of any one of embodiments 1-8, wherein is alkyl.

[0288] Embodiment 24: R 2a is heteroaryl, the heteroaryl being selected from one, two, or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3The compound of any one of embodiments 1-8, wherein is alkyl.

[0289] Embodiment 25:R 2a is cycloalkyl, heterocyclyl, aryl, heteroaryl, -OR 7 , -SR 7 or -NR 8 R 9 wherein cycloalkyl, heterocyclyl, aryl or heteroaryl is one, two or three independently selected R 11 Optionally substituted with R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 alkyl; or R 2a and R 2b may each independently represent one, two, or three independently selected R 11 R 7 , R 8 , R 9 and R 11 The compound of any one of embodiments 1 to 8, wherein:

[0290] Embodiment 26:R 2a -OR 7 , -SR 7 or -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 7 , R 8 , R 9 and R 11 The compound of any one of embodiments 1 to 8, wherein:

[0291] Embodiment 27: R 2a -R u -cycloalkyl, -OR7 , -SR 7 or -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 R is alkyl; 7 is haloalkyl or cycloalkyl; R 8 is hydrogen; R 9 -R u -cycloalkyl or cycloalkyl, -R u -cycloalkyl or cycloalkyl is one, two or three independently selected R 11 Optionally substituted with R 11 are each independently halo or haloC 1~3 The compound of any one of embodiments 1-8, wherein is alkyl.

[0292] Embodiment 28: R 7 -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 substituted with), one, two or three independently selected R 11 cycloalkyl or heterocyclyl optionally substituted with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 -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 11or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; R u The compound of any one of embodiments 1-8, 12-18, 25, and 26, wherein is a methylene, ethylene, or propylene linker optionally substituted with 1-6 independently selected halo.

[0293] Embodiment 29:R 7 is cycloalkyl, heterocyclyl, or heteroaryl, and the cycloalkyl, heterocyclyl, or heteroaryl is selected from one, two, or three independently selected R 11 Optionally substituted with R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is cycloalkyl, heterocyclyl, or heteroaryl, and the cycloalkyl, heterocyclyl, or heteroaryl is selected from one, two, or three independently selected R 11 or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R11 and heterocyclyl is further optionally substituted with oxo, and each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 alkylsulfinyl; R u The compound of any one of embodiments 1-8, 12-18, 25, and 26, wherein is a methylene, ethylene, or propylene linker optionally substituted with 1-6 independently selected halo.

[0294] Embodiment 30: R 7 is one, two, or three independently selected R 11 cycloalkyl or heterocyclyl optionally substituted with; R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is cycloalkyl or heterocyclyl, and the cycloalkyl or heterocyclyl is selected from one, two, or three independently selected R 11 or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 The compound according to any one of embodiments 1-8, 12-18, 25, and 26, which is alkylsulfinyl.

[0295] Embodiment 31: R 7 -R u -heterocyclyl or heterocyclyl, -R u -heterocyclyl or heterocyclyl is one, two or three independently selected R 11 each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 The compound according to any one of embodiments 1-8, 12-18, 25, and 26, which is alkylsulfinyl.

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

[0297] Embodiment 33: R2a -NR 8 R 9 ;R 2b are hydrogen, deuterium, halogens, C 1~3 Alkyl, deutero-C 1~3 Alkyl or haloC 1~3 The compound of any one of embodiments 1-8, 12-18, 25, and 26, wherein is alkyl.

[0298] Embodiment 34: R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is 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 and each R 11 are independently halo, cyano, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 The compound of embodiment 33, which is alkylsulfinyl.

[0299] Embodiment 35: R 8 is hydrogen, deuterium, alkyl, deuteroalkyl or haloalkyl; R 9 is haloalkyl, -R u -heterocyclyl or heterocyclyl, haloalkyl, -R u-heterocyclyl or heterocyclyl is one, two or three independently selected R 11 The compound of embodiment 33, optionally substituted with

[0300] Embodiment 36: R 2a -OR 7 ;R 7 is 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 Optionally substituted with R 11 The compound according to any one of embodiments 1 to 8, 12 to 18, 25 and 26, wherein:

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

[0302] Embodiment 38: R 2b The compound of any one of embodiments 1-8, 12-37, wherein is hydrogen.

[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. or a pharma- ceutically acceptable salt thereof.

[0304] Embodiment 40:R 3 is halo, cyano, alkyl or haloalkyl; R 4 is hydrogen, halo, C 1~3 Alkyl or haloC 1~3 R is alkyl; 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl, 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 8 is hydrogen, deuterium, alkyl or haloalkyl; R 9 is cycloalkyl or heterocyclyl, and the cycloalkyl or heterocyclyl is selected from one, two, or three independently selected R 11 or R 8 and R 9 together with the nitrogen atom to which they are attached form a heterocyclyl or heteroaryl, the heterocyclyl or heteroaryl being selected from one, two or three independently selected R 11 each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, HaloC 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 40. The compound of embodiment 39, wherein: is 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. or a pharma- ceutically acceptable salt thereof.

[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. or a pharma- ceutically acceptable salt thereof.

[0307] Embodiment 43: Formula (VIIa): [ka] or a pharma- ceutically acceptable salt thereof.

[0308] Embodiment 44: Formula (VIII): [ka] wherein ring A is cycloalkyl, heterocyclyl, aryl, or heteroaryl; q is 0, 1, 2, or 3; and X, R1 , R 3 , R 4 , R 5 , R 6 , R 11 and k are as described for embodiments 1, 4 and 6, respectively. or a pharma- ceutically acceptable salt thereof.

[0309] Embodiment 45: A compound of embodiment 44, wherein Ring A is heterocyclyl or heteroaryl.

[0310] Embodiment 46: A compound of embodiment 44, wherein Ring A is heteroaryl.

[0311] Embodiment 47: A compound according to embodiment 44, wherein Ring A is pyridinyl, pyrimidinyl, pyridazinyl, 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 of embodiment 44, wherein and k are as described for 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 of embodiment 44, wherein and k are as described for 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 of embodiment 44, wherein and k are as described for 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 of embodiment 44, wherein and k are as described for embodiment 44.

[0316] Embodiment 52: Formula (IX): [ka] (wherein 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. or a pharma- ceutically acceptable salt thereof.

[0317] Embodiment 53: Formula (X): [ka] (wherein 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 for embodiment 1. or a pharma- ceutically acceptable salt thereof.

[0318] Embodiment 54: R 2is an alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, alkoxyalkyl, cyanoalkyl, -R u -cycloalkyl, -R u -heterocyclyl, cycloalkyl, heterocyclyl or heteroaryl; 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 Optionally substituted with R u and R 11 The compound of embodiment 53, wherein:

[0319] Embodiment 55: R 2 is alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, or cyanoalkyl, and alkyl, haloalkyl, deuteroalkyl, hydroxyalkyl, or cyanoalkyl is R 11 Optionally substituted with R 1 , R 3 , R 4 , R 5 , R 6 , R 11 , R 11 The compound of embodiment 53, wherein k, m, and n are as described for embodiment 1.

[0320] Embodiment 56: R 2 is C 1~6 Alkyl, haloC 1~6 Alkyl, deutero-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- to 7-membered heterocyclyl, C 3~6cycloalkyl, 3- to 7-membered heterocyclyl, or 5- to 10-membered heteroaryl; C 1~6 Alkyl, haloC 1~6 Alkyl, deutero-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- to 7-membered heterocyclyl, C 3~6 Cycloalkyl, 3- to 7-membered heterocyclyl, or 5- to 10-membered heteroaryl is selected from one, two, or three independently selected R 11 Optionally substituted with R 1 , R 3 , R 4 , R 5 , R 6 , R 11 The compound of embodiment 53, wherein k, m, and n are as described for embodiment 1.

[0321] Embodiment 57: R 2 is HaroC 1~3 Alkyl or -R u -3- to 5-membered heterocyclyl, -R u - 3- to 5-membered heterocyclyl is optionally substituted with independently selected halo; R 1 , R 3 , R 4 , R 5 , R 6 The compound of embodiment 53, wherein k, m, and n are as described for embodiment 1.

[0322] Embodiment 58: R 2 is fluoroethyl or 3-fluorooxetan-3-yl)methyl; R 1 , R 3 , R 4 , R 5 , R 6 The compound of embodiment 53, wherein k, m, and n are as described for 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. or a pharma- ceutically acceptable salt thereof.

[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. or a pharma- ceutically acceptable salt thereof.

[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. or a pharma- ceutically acceptable salt thereof.

[0326] Embodiment 62: Formula (IIe): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 are as described for embodiments 1, 4, 6 and 59, respectively. or a pharma- ceutically acceptable salt thereof.

[0327] Embodiment 63: Formula (IIf): [ka] (Wherein, p is 1 or 2; X, R 1 , R 4 , R 5 , R 6 and R 11 are as described for embodiments 1, 4 and 6, respectively. or a pharma- ceutically acceptable salt thereof.

[0328] Embodiment 64: Formula (IVk): [ka] (Wherein, p is 1 or 2; X, R 1 , R 4 , R 5 , R 6 and R 11 are as described for embodiments 1, 4 and 6, respectively. or a pharma- ceutically acceptable salt thereof.

[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. 61. The compound according to embodiment 1, 4, 6, 59 or 60, or a pharma- ceutically acceptable salt thereof, having the following structure:

[0330] Embodiment 66: Formula (IVj): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 are as described for embodiments 1, 4, 6, 59 and 60, respectively. 61. The compound according to embodiment 1, 4, 6, 59 or 60, or a pharma- ceutically acceptable salt thereof, having the following structure:

[0331] Embodiment 67: Formula (IIb): [ka] or a pharma- ceutically acceptable salt thereof.

[0332] Embodiment 68: m is 1; n is 1; X, R 1 , R 4 , R 5 , R 6 and R 11 The compound according to embodiment 67, wherein:

[0333] Embodiment 69: Formula (IId): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 are as described for embodiments 1, 4, 6 and 59, respectively. or a pharma- ceutically acceptable salt thereof.

[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. or a pharma- ceutically acceptable salt thereof.

[0335] Embodiment 71: Formula (IVg): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 are as described for embodiments 1, 4, 6 and 59, respectively. or a pharma- ceutically acceptable salt thereof.

[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. or a pharma- ceutically acceptable salt thereof.

[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. or a pharma- ceutically acceptable salt thereof.

[0338] Embodiment 74: Formula (IVh) [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11 are as described for embodiments 1, 4, 6 and 59, respectively. or a pharma- ceutically acceptable salt thereof.

[0339] Embodiment 75: Formula (IVi): [ka] (In the formula, X, R 1 , R 4 , R 5 , R 6 and R 11are as described for embodiments 1, 4, 6 and 59, respectively. or a pharma- ceutically acceptable salt thereof.

[0340] Embodiment 76: Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, deutero-C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 The compound according to any one of the preceding embodiments, which forms a cycloalkyl or oxo.

[0341] Embodiment 77: Each R 11 are independently fluoro, cyano, oxo, hydroxyl, methyl, -CHF 2 , -CF 3 or -OCHF 2 or two R 11 Compounds according to any one of embodiments 1-75, wherein the groups, together with the carbon atom to which they are attached, form a cyclobutyl or oxo.

[0342] Embodiment 78: Each R 11 are independently halo, cyano, haloC 1~3 Alkyl, haloC 1~3 Alkoxy or C 1~3 alkylsulfonyl; or two R 11 The groups, together with the carbon atom to which they are attached, are represented by C 3~5 The compound according to any one of embodiments 1 to 75, which forms a cycloalkyl.

[0343] Embodiment 79: Each R 11 are independently fluoro, cyano, -CF 3 , -CHF2 , -OCF 3 Or -S(O) 2 CH 3 or two R 11 The groups, together with the carbon atom to which they are attached, form a cyclopropyl; compounds according to any one of embodiments 1-75.

[0344] Embodiment 80: Each R 11 are independently halo, cyano, oxo, C 1~3 Alkyl, haloC 1~3 Alkyl, Cyano C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy, HaloC 1~3 Alkoxy, C 1~3 Alkylthio, HaloC 1~3 Alkylthio, C 1~3 Alkylsulfonyl, C 1~3 Alkylsulfinyl or haloC 1~3 The compound according to any one of embodiments 1-75, which is alkylsulfinyl.

[0345] Embodiment 81: Each R 11 are independently halo, cyano, haloC 1~3 Alkyl, Hydroxy C 1~3 Alkyl, C 1~3 Alkoxy C 1~3 Alkyl, haloC 1~3 Alkoxy C 1~3 Alkyl, Hydroxyl, C 1~3 Alkoxy or haloC 1~3 The compound of any one of embodiments 1-75, which is alkoxy.

[0346] Embodiment 82: Each R 11 are independently halo, cyano or haloC 1~3 The compound according to any one of embodiments 1-75, wherein is alkyl or hydroxyl.

[0347] Embodiment 83: Each R 11 are independently halo, cyano or haloC 1~3The compound according to any one of embodiments 1-75, wherein is alkyl.

[0348] Embodiment 84: Each R 11 are independently F, Cl, Br, cyano, -CHF 2 or -CF 3 The compound of any one of embodiments 1-75, wherein

[0349] Embodiment 85: Each R 11 The compound of any one of embodiments 1-75, wherein is independently halo or cyano.

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

[0351] Embodiment 87:R 11 The compound of any one of embodiments 1-76, 78, 80-83, or 85, wherein is halo.

[0352] Embodiment 88:R 11 The compound of any one of embodiments 1-76, 78, 80-83, or 85, wherein is fluoro.

[0353] Embodiment 89:R 11 Cyano or haloC 1~3 The compound of any one of embodiments 1-76, 78, or 80-83, wherein is alkyl.

[0354] Embodiment 90:R 11 is HaroC 1~3 The compound of any one of embodiments 1-76, 78, 80, or 89, wherein is alkyl.

[0355] Embodiment 91:R 11 Fluoro C 1~3 The compound of any one of embodiments 1-76, 78, 80, or 89, wherein is alkyl.

[0356] Embodiment 92:R11 is cyano, -CHF 2 or -CF 3 The compound of any one of embodiments 1-76, 78, or 80-83, wherein

[0357] Embodiment 93:R 11 -CF 3 90. The compound of any one of embodiments 1-76, 78, 80, or 89, wherein

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

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

[0360] Embodiment 96: A 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 is halo, methyl or -CF 3 The compound of embodiment 96, wherein

[0362] Embodiment 98:R 3 is methyl.

[0363] Embodiment 99:R 4 is hydrogen, halo, C 1~3 Alkyl or haloC 1~3 The compound according to any one of embodiments 1-98, wherein is alkyl.

[0364] Embodiment 100:R 4 is hydrogen, fluoro, chloro, methyl or -CF 3 The compound of any one of embodiments 1-99, wherein

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

[0366] Embodiment 102:R 4 The compound of any one of embodiments 1-101, wherein is hydrogen.

[0367] Embodiment 103:R 5 Halo, C 1~3 Alkyl, C 3~5 Cycloalkyl or C 1~3 The compound of any one of embodiments 1-102, which is alkoxy.

[0368] Embodiment 104:R 5 The compound according to any one of embodiments 1-103, 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 The compound of any one of embodiments 1-104, which is alkoxy.

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

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

[0372] Embodiment 108:R 4 is hydrogen; R 5 is methoxy and R 6The compound of any one of embodiments 1-107, wherein is methyl.

[0373] Embodiment 109:R 1 The compound of any one of embodiments 1-108, wherein X is hydrogen and X is CH.

[0374] EMBODIMENT 110: 4-((2S,4S)-4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 1) 4-((2R,4R)-4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(4-fluoro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 2) 4-((2S,4S)-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(4-bromo-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; (Example 3) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (Example 4) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; (Example 5) 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)piperidin-2-yl)benzoic acid; (±)-trans-4-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 6) 4-((2S,4S)-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(2H-indazol-2-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 7) 4-((2S,4S)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(4-(difluoromethyl)-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 8) 4-((2R,4R)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-chloro-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (Example 9) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid (Example 10) 4-((2R,4R)-4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(4-cyano-1H-pyrazol-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (Example 11) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(4-(methylsulfonyl)-1H-pyrazol-1-yl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; (Example 12) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; (Example 13) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2-oxopyrrolidin-1-yl)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; (Example 14) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; (Example 15) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-((2,2,2-trifluoroethyl)amino)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; (Example 16) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; 4-(-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(sulfamoylamino)piperidin-2-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; (Example 17) 4-((2S,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; (Example 18) 4-((2R,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(oxetan-3-ylamino)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 19) 4-((2R,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 20) 4-((2R,4R)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(cyclobutylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 21) 4-((2R,4R)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(bicyclo[1.1.1]pentan-1-ylamino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 22) 4-((2R,4R)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-((2,2-difluoroethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 23) 4-((2R,4R)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(((1-fluorocyclopropyl)methyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 24) 4-((2R,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-((3,3-difluorocyclobutyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; (Example 25) 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; 4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-((3,3-difluorocyclobutyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 26) 4-((2R,4R)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-((cyclopropylmethyl)amino)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; (Example 27) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 28) 4-((2R,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 29) 4-((2S,4R)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(difluoromethoxy)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((3R,5S)-1,1-difluoro-6-((5-methoxy-7-methyl-1H-indol-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-indol-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-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-((3R,5R)-1,1-difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; 4-(1,1-difluoro-6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid; (±)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 31) (S)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 32) (R)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((5S,7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; (Example 33) 4-((5R,7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; (or Example 33) 4-((5R,7R)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-((5S,7R)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-1-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-((5S,7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; (Example 34) 4-((5R,7S)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; (or Example 34) 4-((5R,7R)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-((5S,7R)-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxa-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(5R,7S)-2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; (Example 35 or 36) 4-(5S,7S)-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; (or Example 36 or 35) 4-(5S,7R)-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(5R,7R)-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; 4-(2,2-difluoro-8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azaspiro[4.5]decan-7-yl)benzoic acid; (±)-trans-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; (Example 37) 4-((2S,4S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-((2R,4R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-(4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-phenylpiperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; (Example 38) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(pyridin-2-yl)piperidin-2-yl)benzoic acid; 4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid; (Example 39) (S)-4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid; (R)-4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.4]octan-1-yl)benzoic acid; (R)-4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; (Example 40) (S)-4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; 4-(2-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-azaspiro[3.3]heptan-1-yl)benzoic acid; 4-((2S,4S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 41) 4-((2R,4R)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-cyclopropyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; (Example 42) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4R)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-cyclobutyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (mixture of example 43) 4-((2S,4S)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 44) 4-((2R,4R)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(cyclopropylmethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (S)-4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 46 or 47) 4-((2S,4r,6S)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 47 or 46) 4-((2S,4s,6R)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-(difluoromethyl)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 48 or 49) 4-((2S,4r,6S)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 49 or 48) 4-((2S,4s,6R)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-(trifluoromethyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (S)-4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)-2-fluorobenzoic acid; 4-(2,2-difluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)-2-fluorobenzoic acid; (S)-4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azadispiro[2.1.5 5 .1 3 ]undecane-7-yl)benzoic acid; (Example 51) (R)-4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azadispiro[2.1.5 5 .1 3 ]Undecane-7-yl)benzoic acid; 4-(8-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-8-azadispiro[2.1.5 5 .1 3 ]Undecane-7-yl)benzoic acid; (S)-4-(7-((3-chloro-5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-2,2-difluoro-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((3-chloro-5-methoxy-7-methyl-1H-indol-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-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2,2-difluoro-7-((3-fluoro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 52 or 55) 4-((2S,4r,6S)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 55 or 52) 4-((2S,4s,6R)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-cyano-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 56 or 57) 4-((2S,4r,6S)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 57 or 56) 4-((2S,4s,6R)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-(difluoromethoxy)-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (S)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 58) (R)-4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-oxo-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 59 or 60) 4-((2S,4r,6S)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 60 or 59) 4-((2S,4s,6R)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-2-methyl-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2S)-2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 62 or 63) 4-((2S,4r,6S)-2-Fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (Example 63 or 62) 4-((2S,4s,6R)-2-fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-fluoro-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4s,6S)-4-(2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-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-indol-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-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-((2R,4r,6R)-2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; 4-(2-hydroxy-7-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-7-azaspiro[3.5]nonan-6-yl)benzoic acid; (R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazin-2-yl)benzoic acid; (Example 65) (S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(2,2,2-trifluoroethyl)piperazin-2-yl)benzoic acid; (R)-4-(4-(2,2-difluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 66) (S)-4-(4-(2,2-difluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; 4-(4-(2,2-difluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (R)-4-(4-((3,3-difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 67) (S)-4-(4-((3,3-difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; 4-(4-((3,3-difluorocyclobutyl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (R)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazin-2-yl)benzoic acid; (Example 68) (S)-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3,3,3-trifluoropropyl)piperazin-2-yl)benzoic acid; (R)-4-(4-((3-fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 69) (S)-4-(4-((3-fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; 4-(4-((3-fluorooxetan-3-yl)methyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (R)-4-(4-(2-fluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (Example 70) (S)-4-(4-(2-fluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; 4-(4-(2-fluoroethyl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperazin-2-yl)benzoic acid; (±)-trans-4-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 71) 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 81) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 72) 4-((2R,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethoxy)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 73) 4-((2R,4R)-4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(3-cyanoazetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; (Example 74) 4-((2R,4R)-4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-(4-(3-(difluoromethyl)azetidin-1-yl)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 75) 4-((2R,4R)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2R,4S)-1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-(1-((3-chloro-5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4S)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; (Example 76) 4-((2R,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-(3-(trifluoromethyl)azetidin-1-yl)piperidin-2-yl)benzoic acid; 4-((2S,4R)-1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)meth...

Claims

1. Formula (IIc): 【Chemical Formula 2-1】 (wherein R1 is hydrogen, fluoro, chloro or methyl; X is N or CH; R3 is halo, cyano, C1-3 alkyl or halo C1-3 alkyl; R4 is hydrogen, halo, cyano, C1-3 alkyl or halo C1-3 alkyl; R5 is halo, C1-3 alkyl, C3-5 cycloalkyl, halo C1-3 alkyl, halo C1-3 alkoxy or C1-3 alkoxy; R6 is halo, cyano, C1-3 alkyl, C3-5 cycloalkyl, halo C1-3 alkyl, C1-3 alkoxy or halo C1-3 alkoxy; each R11 is independently halo, k is 0, 1, 2 or 3; m is 0, 1 or 2; and n is 0, 1 or 2) a compound of or a pharmaceutically acceptable salt thereof.

2. In the formula, R1 is hydrogen, fluoro, chloro or methyl; X is N or CH; R3 is halo, cyano, C1-3 alkyl or halo C1-3 alkyl; R4 is hydrogen, halo, cyano, C1-3 alkyl or halo C1-3 alkyl; R5 is halo, C1-3 alkyl, C3-5 cycloalkyl, halo C1-3 alkyl, halo C1-3 alkoxy or C1-3 alkoxy; R6 is halo, cyano, C1-3 alkyl, C3-5 cycloalkyl, halo C1-3 alkyl, C1-3 alkoxy or halo C1-3 alkoxy; R11 is fluoro; k is 0, 1, 2 or 3; m is 0, 1 or 2; and n is 0, 1 or 2, the compound according to Claim 1 or a pharmaceutically acceptable salt thereof.

3. In the formula, k is 0; m is 1; n is 1, the compound according to Claim 1 or a pharmaceutically acceptable salt thereof.

4. In the formula, R1 is hydrogen, fluoro or chloro; X is CH; R4 is hydrogen, fluoro, chloro or methyl; R5 is methoxy or cyclopropyl; R6 is methyl; R11 is fluoro, the compound according to Claim 1 or a pharmaceutically acceptable salt thereof.

5. The compound of formula (IIc) is of formula (IVf): [Chemical Formula 4-1] The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is a compound of

6. The compound of formula (IIc) is a compound of formula (IVl): [[Chemical Formula 4-2]] The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is a compound of

7. The compound is the following: 【Chemical 11】 【Chem.】 The compound according to claim 1, which is selected from the group consisting of the compound of

8. A pharmaceutical composition comprising the compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

9. The compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof for use in medicine.

10. The compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof for use in the treatment or prevention of a disease or disorder associated with complement factor B (CFB).

11. The compound or a pharmaceutically acceptable salt thereof according to claim 10, wherein the disease or disorder is selected from 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.

12. The disease or disorder is selected from multiple sclerosis, Guillain - Barré syndrome, traumatic brain injury, Parkinson's disease, age - related macular degeneration, geographic atrophy, diabetic retinopathy, uveitis, retinitis pigmentosa, macular edema, Behçet's uveitis, multifocal choroiditis, Vogt - Koyanagi - Harada syndrome, intermediate uveitis, punctate choroiditis, sympathetic ophthalmia, ocular cicatricial pemphigoid, ocular pemphigoid, non - arteritic ischemic optic neuropathy, postoperative inflammation, retinal vein occlusion, 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, myocarditis, post - ischemic reperfusion state, myocardial infarction, stroke, balloon angioplasty, post - pump syndrome during cardiopulmonary bypass or renal bypass, atherosclerosis, hemodialysis, renal ischemia, mesenteric artery reperfusion after aortic reconstruction, infectious diseases or sepsis, immune complex disorders and autoimmune diseases, rheumatoid arthritis, systemic lupus erythematosus (SLE), SLE nephritis, proliferative nephritis, liver fibrosis, hemolytic anemia, myasthenia gravis, tissue regeneration, nerve regeneration, dyspnea, hemoptysis, ARDS, asthma, chronic obstructive pulmonary disease (COPD), emphysema, pulmonary embolism and infarction, pneumonia, fibrotic dust diseases, pulmonary fibrosis, asthma, allergy, bronchoconstriction, hypersensitivity pneumonia, parasitic diseases, Goodpasture's syndrome, pulmonary vasculitis, microscopic polyangiitis, immune complex - related inflammation, antiphospholipid antibody syndrome, glomerulonephritis, obesity and metabolic syndrome, the compound according to claim 10 or a pharmaceutically acceptable salt thereof.

13. The disease or disorder is selected from kidney diseases, chronic kidney diseases, diabetic nephropathy, glomerular kidney diseases, 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 and polycystic kidney disease (PKD), the compound according to claim 10 or a pharmaceutically acceptable salt thereof.