Indole Derivatives Useful for Treating Conditions Associated with CGAS - Patent application

Abstract

The present disclosure provides a compound of formula (I): [Formula 1] TIFF2024502258000247.tif31170 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein R1-R8 are as defined herein, and methods of making and using same.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 128,949, filed December 22, 2020, the contents of which are incorporated herein by reference in their entirety.

[0002] The present invention relates to chemical compounds (e.g., compounds that inhibit cyclic GMP-AMP synthase (cGAS) or the cGAS pathway, or pharmaceutically acceptable salts, and / or hydrates, and / or co-crystals, and / or combination pharmaceuticals thereof) that are useful, e.g., for treating conditions, diseases, or disorders in which a decrease or increase in cGAS activity (e.g., an increase in a condition, disease, or disorder associated with cGAS signaling) contributes to the pathology and / or symptoms and / or progression of the condition, disease, or disorder in a subject (e.g., a human). The present invention relates to compositions, and methods of use and preparation thereof. [Background technology]

[0003] Nucleic acids are essential components of cells. They store genetic information and provide guidance to cells on how to execute it. Nevertheless, when nucleic acids are found outside the cell, as occurs as a result of cellular damage (intrinsic cell death, viral infection, mitochondrial damage), or when large amounts of nucleic acids are mislocated in the cytosol, they are recognized as harmful substances (pathogen-associated molecular patterns, or "PAMPs") and trigger a strong immune response. Similar responses have also been observed in many autoinflammatory and autoimmune diseases, suggesting that activation of nucleic acid sensors is a key molecular determinant (Barber, Nat Immunol, 12(10):929-930, 2011).

[0004] Two novel gene products, cGAS and STING, have recently been recognized as key members of a critical pathway for the recognition of excess cytosolic dsDNA (Cai et al. Mol Cell, 54(2):289-296, 2014). Upon binding to dsDNA, cGAS (cyclic GMP / AMP synthase) converts GTP and ATP into cyclic nucleotides called cGAMP (Sun et al. Science 339(6121):786-791, 2013) and STING (Stimulator of Interferon Genes) (Ishikawa et al. Nature 461(7265):788-792, 2009). These cGAMP-recognizing enzymes promote the phosphorylation of the transcription factor IRF3, ultimately resulting in the expression of type I IFN genes (Chen et al. Nat Immunol 17(10):1142-1149, 2016). cGAMP, a cyclic nucleotide composed of one molecule of GMP and one molecule of AMP, couples two phosphates via a highly unusual 2',5' bond and a classical 3',5' bond (Ablasser et al., Nature 498(7454):380-384, 2013) and represents a novel "second" messenger.

[0005] Mutations in the cytosolic DNase Trex1 in patients with Aicardi-Goutières syndrome have been shown to result in an increase in cytosolic dsDNA sufficient to activate the cGAS / STING pathway, resulting in a robust type I IFN response (Crow & Manel, Nat Rev Immunol 15(7):429-440, 2015). This leads to cognitive decline and pathology similar to that commonly observed in lupus patients. A milder form of this defect is seen in patients with familial lupus pernio carrying heterozygous mutations in Trex1 (Fiehn, Curr Rheumatol Rep 19(10):61, 2017). SAVI is another disorder resulting from activation of the cGAS / STING pathway. This disorder has been identified as a common interferonopathy in young people and is the result of mutations that overactivate STING, leading to chronic production of type I IFN cytokines. Symptoms of this condition are evidenced by skin rash, lung inflammation, and chronic inflammation of the limbs, which in extreme cases can lead to amputation (Liu et al., N Engl J Med 371(6):507-518, 2014).

[0006] Beyond these rare genetic disorders, there is growing evidence suggesting that the cGAS / STING pathway may play a role in chronic diseases, where programmed cell death is not efficient enough to remove all generated PAMPs / DAMPs (Motwani et al., Nat Rev Genet 20(11):657-674, 2019). In particular, in lupus patients, where chronic damage to different organs leads to the appearance of anti-DNA antibodies, reducing the contribution of the cGAS / STING pathway to the production of inflammatory cytokines may be beneficial (Harley et al., Nat Rev Genet 10(5):285-290, 2009).

[0007] The underlying cause of diseases caused by overactivation of the cGAS pathway is an increase in inflammatory cytokines (belonging to the so-called type I interferons) in serum and different organs. The type I interferon response is generally paralleled by an increase in the mRNA of ISGs (interferon-stimulated genes). These diseases are classified into a family of pathologies defined as interferonopathies.

[0008] Aicardi-Goutières syndrome (Crow & Manel, Nat Rev Immunol 15(7):429-440, 2015) is a genetically linked disorder characterized by homozygous mutations in the DNA processing enzyme Trex1. Patients in the familial lupus pernio group carry heterozygous mutations in Trex1 (Fiehn, Curr Rheumatol Rep 19(10):61, 2017). A less severe form of Mendelian disorders associated with TREX1 loss-of-function mutations causes RVCL (autosomal dominant retinal vasculopathy with cerebral leukodystrophy), which is characterized by adult-onset pf vasculopathy leading to retinopathy and early-onset ischemic stroke. Because loss of TREX1 function has been shown to increase cytosolic dsDNA, resulting in uncontrolled cGAS activation, this family of Trex1-dependent disorders is expected to respond strongly to cGAS inhibition.

[0009] In patients with infantile-onset STING-associated vasculopathy (SAVI), specific vascular damage has been observed in addition to a strong interferonopathy (Liu et al., N Engl J Med 371(6):507-518, 2014). Therefore, it is predicted that the cGAS / STING pathway also plays an important role in the strong inflammatory pathology observed in non-genetically associated vasculitis, especially in the limbs.

[0010] Based on the similarities in clinical symptoms between AGS and SAVI, diseases including subtypes of systemic lupus erythematosus (SLE), lupus nephritis (LN), and dermatomyositis, which can be caused by DNA viruses such as EBV, cytosolic dsDNA, or mitochondrial dsDNA, are predicted to be caused (at least in part) by aberrant activation of cGAS. Similarly, cGAS activation is predicted to play an important role in the pathogenesis of Sjögren's syndrome (SS), which shares some aspects of pathology with SLE.

[0011] Low-molecular-weight inhibitors of cGAS may also be effective in treating SLE-associated skin rash / redness, a condition commonly observed in SLE patients after exposure to UV light (Skopelja-Gardner et al., Sci Rep 10(1):7908, 2020). The possible involvement of the cGAS / STING pathway in rheumatoid arthritis (RA) has been discussed, particularly because joint inflammation has been observed in rodent models lacking TREX1 or other DNAse function. There is also some evidence that the accumulation of dsDNA in the joints may be responsible for the inflammation observed in RA patients (Wang et al., Int Immunopharmacol 76:105791, 2019).

[0012] Models of age-related macular degeneration (AMD) have been shown to be highly dependent on the cGAS / STING pathway, suggesting that cGAS inhibition may be a therapeutic option for treating this serious eye disease (Kerur et al., Nat Med 24(1):50-61, 2018; Wu et al., Clin Interv Aging 14:1277-1283, 2019).

[0013] Accumulating evidence suggests that cGAS activation is involved in many neuroinflammatory diseases, including Parkinson's disease (or at least its subtypes) (Sliter et al., Nature 561(7722):258-262, 2018), Alzheimer's disease, amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig's disease), and frontotemporal dementia (FTD) (McCauley et al., Nature 585(7823):96-101, 2020).

[0014] Studies have linked cGAS / STING to the development of colitis and therefore suggested cGAS / STING modulation as a potential treatment for ulcerative colitis and inflammatory bowel disease (IBD) (Aden et al., J Exp Med 215(11):2868-2886, 2018; Ahn et al., Cell Rep 21(13):3873-3884, 2017; Canesso et al., Mucosal Immunol 11(3):820-834, 2018; Martin et al., Sci Rep 9(1):14281, 2019). Nevertheless, some data suggest that blockade of the cGAS / STING pathway may worsen outcomes under certain conditions during colitis induction, as in the case of rodent colorectal cancer (Zhu et al., J Immunol 193(10):4779-4782, 2014). In this context, it is worth mentioning that STING activation (likely via cGAS) plays an important role in the development of sepsis-induced inflammation (Hu et al., EBioMedicine 41:497-508, 2019).

[0015] Mounting evidence indicates that cGAS plays a key role in pulmonary inflammation. Damage to the lung epithelium leads to the release of DNA, which can be detected by bronchoalveolar lavage (BAL). Intratracheal application of DNAse leads to amelioration of a silicosis-induced lung inflammation model, suggesting a key role for cGAS. This observation was confirmed using STING-deficient animals, strongly suggesting that cGAS activation is the primary mechanism of inflammation in this and other similar models (Benmerzoug et al., Cell Rep 27(9):2649-2664 e2645, 2019; Benmerzoug et al., Nat Commun 9(1):5226, 2018; Benmerzoug et al., Trends Immunol 40(8):719-734, 2019). While there is strong evidence for the involvement of cGAS in acute lung inflammation, the role of cGAS in idiopathic pulmonary fibrosis is based on recent indirect evidence. The development of liver and kidney fibrosis has been observed to be highly dependent on the activation of the cGAS / STING pathway. Therefore, therapeutic intervention of the cGAS / STING pathway is predicted to be effective in diseases such as liver cirrhosis and endomyocardial fibrosis (Allison, Nat Rev Nephrol 15(11):661, 2019; Bennion et al., J Virol 93(4), 2019; Iracheta-Vellve et al., J Biol Chem 291(52):26794-26805, 2016; Sun et al., Biomed Pharmacother 127:110119, 2020; Wang et al., Lab Invest 100(4):542-552, 2020; Zhang et al., Biomed Pharmacother 125:110022, 2020). Aberrant cGAS / STING activation in conditions such as mitochondrial dysfunction also underlies more common diseases such as nonalcoholic steatohepatitis (NASH) and chronic obstructive pulmonary disease (COPD).

[0016] Partial protection by genetic or pharmacological blockade of the cGAS / STING pathway in a mouse model of acute pancreatitis has recently been reported (Zhao et al., Gastroenterology 154(6):1822-1835 e1822, 2018), suggesting the potential protective effect of cGAS inhibitors in this devastating disease.

[0017] cGAS has been shown to play a role in cellular senescence and regulate chronic inflammation caused by dying cells (Gluck et al., Nat Cell Biol 19(9):1061-1070, 2017; Yang et al., Proc Natl Acad Sci USA 114(23):E4612-E4620, 2017). While it is unclear whether these findings are also useful for aging tissues and whether blocking cGAS can help reduce the chronic inflammation observed in elderly individuals, some evidence in mice has recently emerged supporting this idea. Nevertheless, this observation is relevant for many indications related to elderly patient populations, where chronic activation of the cGAS / STING pathway may be a common comorbidity. This may be particularly true for many neurodegenerative diseases, where mitochondrial damage has been documented, leading to the release of mitochondrial DNA into the cytosol.

[0018] Recent observations in mice have shown that inhibiting cGAS or STING promotes recovery from acute kidney injury induced by cisplatin (Maekawa et al., Cell Rep 29(5):1261-1273 e1266, 2019). Because this drug is used in cancer treatment, blocking cGAS / STING may specifically prevent organ damage leading to kidney failure. Other recent publications have demonstrated highly potent therapeutic effects of blocking the cGAS / STING pathway in a mouse model of APOL1-associated podocytopathy (Davis et al., Sci Rep 9(1):15485, 2019; Wu et al., J Clin Invest 131(20), 2021). These data suggest that cGAS inhibitors may be beneficial for the treatment of kidney injury in general.

[0019] Activation of the cGAS / STING pathway is thought to be one of the first defenses deployed by the immune system to fight viral infection. However, once the acute phase is over, elevated type I interferon levels have been shown to propagate chronic inflammation that damages tissues and hinders tissue recovery (Teijaro et al., Science 340(6129):207-211, 2013; Wilson et al., Science 340(6129):202-207, 2013). Therefore, blocking cGAS during the late stages of the disease is predicted to significantly enhance recovery from chronic viral damage. Summary of the Invention

[0020] The present disclosure relates to compounds and compositions capable of inhibiting the cGAS pathway. The disclosure features methods for treating, preventing, or ameliorating diseases or disorders in which cGAS plays a role by administering a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof to a patient in need thereof. The disclosed methods can be used to treat a variety of cGAS-dependent diseases and disorders by inhibiting the cGAS pathway. Inhibition of the cGAS pathway provides a novel approach to the treatment, prevention, or amelioration of diseases, including, but not limited to, immune, inflammatory, autoimmune, or autoinflammatory diseases, and other cGAS-dependent diseases or disorders.

[0021] In one aspect, the compounds of the present disclosure have utility as therapeutic agents for, among other things, immune disorders, inflammatory disorders, autoimmune disorders, or autoinflammatory disorders. In one aspect, the compounds of the present disclosure have cGAS inhibitory activity, preferably at or below the 30 μM level.

[0022] In a first aspect of the present disclosure, a compound of formula (I): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof and methods of making and using the same, are described, R1 is (C1-C4) alkyl, OH, halogen, -NR a R b and a 5-membered heteroaryl ring containing 1 to 4 heteroatoms selected from O, N, and S, optionally substituted with at least one 5- or 6-membered heterocycloalkyl ring containing oxygen; R2 is (C1-C4) alkyl, (C1-C4) alkylene-OH, -(C1-C4) alkylene-NR9R 10a 5-membered heteroaryl ring containing three nitrogen atoms in positions 1, 2, and 4 relative to one another, optionally substituted with (C1-C4)alkylene-C(O)OH, wherein the 5-membered heteroaryl ring is further substituted with R3 at a carbon atom of the 5-membered heteroaryl ring; R3 is H, halogen, -OH, -NR 11 R 12 , -(C1-C4) alkylene-NR 13 R 14 , (C1-C4) alkyl, halo(C1-C4) alkyl, -(C1-C4) alkylene-OH, -(C1-C4) alkylene-(C1-C4) alkoxy, -C(O)(C1-C4) alkyl, -C(O)(C1-C4) alkylene-O-(C1-C4) alkyl, -C(O)(C1-C4) alkylene-OH, -C(O)NR 15 R 16 , (C1-C4)alkoxy, -(C1-C4)alkylene-S(O) v -(C1-C4)alkyl, -C(O)(C1-C4)alkoxy, -CN, -O(C1-C4)alkylene-OH, -O(C1-C4)alkylene-(C1-C4)alkoxy, -(C1-C4)alkylene-C(O)(C1-C4)alkyl, -(C1-C4)alkylene-C(O)(C1-C4)alkoxy, -(C1-C4)alkylene-C(O)NR 17 R 18 a 6-membered heterocycloalkyl ring Ri containing 1 to 2 heteroatoms selected from O and N; or [ka] and (C1-C4) alkyl is CN, ═N-(C1-C4) alkoxy, ═NO-(C1-C4) alkylene-OR 20 , OH, (C1-C4)alkoxy, —C(O)OH, —C(O)O(C1-C4)alkyl, a 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S, and a 5-6 membered heteroaryl ring containing 1-2 heteroatoms selected from O, N, and S; Each -(C1-C4)alkylene-NR9R 10 and -(C1-C4) alkylene-NR 13 R 14 is optionally substituted on at least one of the (C1-C4)alkylene carbons with OH, (C1-C4)alkoxy, —(C1-C4)alkylene-O(C1-C4)alkyl, (C1-C4)alkyl; each halo(C-C)alkyl and (C-C)alkylene-OH is independently optionally substituted with at least one of OH, (C-C)alkoxy, —O(C-C)alkylene-OH, —(C-C)alkylene-OH, —(C-C)alkylene-(C-C)alkoxy; Ri is optionally substituted with (C1-C4) alkyl; v is 0, 1 or 2; R4 is H, (C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-(C1-C4)alkoxy, -(C1-C4)alkylene-C(O)OH, -C(O)O(C1-C4)alkyl, or a 5-6 membered heteroaryl ring containing 1-2 nitrogen atoms, optionally substituted with one or more (C1-C4)alkoxy; Each R, R, R, and R is independently H, halogen, OH, (C-C) alkyl, (C-C) alkoxy, halo(C-C) alkyl, halo(C-C) alkoxy, (C-C) alkenyl, (C-C) alkynyl, —(C-C) alkylene-OH, —O(C-C) alkylene-OH, CN, —C(O)(C-C) alkoxy, —C(O)NR 21 R 22 or a 5-membered heteroaryl ring containing two nitrogen heteroatoms, wherein each (C2-C6)alkenyl and (C2-C6)alkynyl is independently optionally substituted with one or more (C1-C4)alkoxy; Each R 20 , R 21 and R 22 are independently H or (C1-C4) alkyl; Each R9, R 10 , R11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 and R 18 are independently H, (C-C)alkyl, —(C-C)alkylene-OH, —(C-C)alkylene-O(C-C)alkyl, —C(O)(C-C)alkylene-(C-C)alkoxy, or —C(O)(C-C)alkyl; or R9 and R 10 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. 23 Form R 23 optionally one or more R 24 is replaced by; R 11 and R 12 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. 25 Form R 25 optionally one or more R 26 is replaced by; R 13 and R 14 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. 27 Form R 27 optionally one or more R 28 is replaced by; R 15 and R 16 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. 29 Form R 29 optionally one or more R 30 is replaced by; R 17 and R 18together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. 31 Form R 31 is optionally R 32 is replaced by; Each R 24 , R 26 , R 28 , R 30 and R 32 are independently (C1-C4) alkyl, (C1-C4) alkoxy, NR c R d , OH or ═O; or Each R 24 , R 26 , R 28 , R 30 and R 32 two of which, when attached to the same atom, together form a (C4-C7)spirocycloalkyl or a 4-7 membered spiroheterocycloalkyl ring containing 1-2 heteroatoms selected from O, N and S; R 19 is H, OH or (C1-C4) alkyl; Each R a , R b , R c and R d are independently H, halogen, or (C1-C4) alkyl.

[0023] Another aspect of the present disclosure relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient, the pharmaceutical composition being useful for treating a cGAS-dependent disease or disorder.

[0024] In another aspect, the present invention provides a combination, particularly a pharmaceutical combination, comprising a therapeutically effective amount of a compound according to the definition of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents.

[0025] In another aspect, the present invention provides a combination, particularly a pharmaceutical combination, as disclosed herein for use as a medicament.

[0026] In another aspect, the present disclosure relates to a method of treating a disease or disorder affected by the inhibition of cGAS, comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein the disease or disorder is selected from a cGAS-associated disease or disorder, e.g., an immune disease, an inflammatory disease, an autoimmune disease, and an autoinflammatory disease.

[0027] In another aspect, the cGAS-related disease or disorder is Aicardi-Goutieres syndrome, familial lupus pernio, RVCL (autosomal dominant retinal vasculopathy with cerebral leukodystrophy), vasculitis, systemic lupus erythematosus (SLE), lupus nephritis (LN), dermatomyositis, Sjogren's syndrome (SS), rheumatoid arthritis (RA), age-related macular degeneration (AMD), Parkinson's disease, Alzheimer's, amyotrophic lateral sclerosis (ALS), pre-existing glaucoma, glaucoma, and the like. immune, inflammatory, autoimmune, or autoinflammatory diseases, including frontotemporal dementia (FTD), pulmonary inflammation, acute pulmonary inflammation, idiopathic pulmonary fibrosis, liver and kidney fibrosis, non-alcoholic steatohepatitis (NASH), liver cirrhosis, endocardial fibrosis, acute and chronic kidney injury, APOL1-associated podocytopathy, acute pancreatitis, ulcerative colitis, inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), sepsis, senescence, and aging. DETAILED DESCRIPTION OF THE INVENTION

[0028] The present disclosure relates to compounds and compositions capable of inhibiting cGAS. The disclosure features methods for treating, preventing, or ameliorating diseases or disorders in which cGAS plays a role by administering a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof to a patient in need thereof. The disclosed methods can be used to treat various cGAS-dependent diseases and disorders by inhibiting cGAS or the cGAS pathway. Inhibiting cGAS or the cGAS pathway provides a new approach to the treatment, prevention, or amelioration of diseases, including, but not limited to, systemic lupus erythematosus (SLE), familial lupus pernio, vasculitis, Sjögren's syndrome (SS), and other cGAS-dependent diseases or disorders.

[0029] In one aspect, the compounds of the present disclosure have utility as therapeutic agents, particularly for immune disorders, inflammatory disorders, autoimmune disorders, or autoinflammatory disorders. In one aspect, the compounds of the present disclosure have cGAS inhibitory activity, preferably at or below 30 μM levels. The compounds of the present disclosure have utility in treating immune disorders, inflammatory disorders, autoimmune disorders, autoinflammatory disorders, and other disorders in which such cGAS inhibitory activity may be beneficial to patients. In summary, the present disclosure provides novel cGAS inhibitors useful for treating autoimmune and autoinflammatory disorders.

[0030] In a first aspect of the present disclosure, a compound of formula (I): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof, wherein R1-R8 are as defined above.

[0031] Details of the present disclosure are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, exemplary methods and materials are described herein. Other features, objects, and advantages of the present disclosure will be apparent from the description and claims. In the specification and the appended claims, the singular forms include the plural forms unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All patents and publications cited herein are incorporated by reference in their entirety.

[0032] Definitions of terms and rules used Terms not specifically defined herein should be given the meaning that could be given them by one of ordinary skill in the art in view of the disclosure and context. However, as used in this specification and the appended claims, unless specified to the contrary, the following terms will have the meaning indicated and the following provisions will be observed.

[0033] A. Chemical Nomenclature, Terminology, and Conventions In the groups, radicals, or substructures defined below, the number of carbon atoms is often specified before the group, e.g., (C-C 10 ) Alkyl refers to an alkyl group or radical having 1 to 10 carbon atoms. Generally, for groups containing more than one subgroup, the last listed group is the point of radical attachment. For example, "alkylaryl" refers to a monovalent radical of the formula alkyl-aryl-, and "arylalkyl" refers to a monovalent radical of the formula aryl-alkyl-. Furthermore, the use of a term designating a monovalent radical where a divalent radical is appropriate shall be construed to designate the respective divalent radical, and vice versa. Unless otherwise specified, conventional definitions and conventional stable atom valences of the terminology are presumed and obtained in all formulas and groups. The articles "a" and "an" refer to one or more (e.g., at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

[0034] The term "and / or" means "and" or "or" unless otherwise stated.

[0035] The term "optionally substituted" means that a given chemical substructure (e.g., an alkyl group) can (but does not require) be attached to other substituents (e.g., heteroatoms). For example, an optionally substituted alkyl group can be a fully saturated alkyl chain (e.g., a pure hydrocarbon). Alternatively, the same optionally substituted alkyl group can have a substituent other than hydrogen. For example, it can be attached at any point along the chain to a halogen atom, a hydroxyl group, or other substituent described herein. Thus, the term "optionally substituted" means that a given chemical substructure can potentially include other functional groups, but does not necessarily have any additional functional groups. Suitable substituents used in the optional replacement of the described groups include halogen, oxo, -OH, -CN, -COOH, -CHCN, -O-(C-C)alkyl, (C-C)alkyl, (C-C)alkoxy, (C-C)haloalkyl, (C-C)haloalkoxy, -O-(C-C)alkenyl, -O-(C-C)alkynyl, (C-C)alkenyl, (C-C)alkynyl, -OH, -OP(O)(OH), -OC( Examples of alkyl groups include, but are not limited to, -O)(C-C)alkyl, -C(O)(C-C)alkyl, -OC(O)O(C-C)alkyl, -NH, -NH((C-C)alkyl), -N((C-C)alkyl), -NHC(O)(C-C)alkyl, -C(O)NH(C-C)alkyl, -S(O)(C-C)alkyl, -S(O)NH(C-C)alkyl, and -S(O)N((C-C)alkyl). Substituents may themselves be optionally substituted. As used herein, "optionally substituted" also refers to substituted or unsubstituted, the meaning of which is described below.

[0036] The term "substituted" means that a particular group or moiety has one or more suitable substituents, and that the substituents may be attached to the particular group or moiety at one or more positions. For example, an aryl substituted with a cycloalkyl may indicate that the cycloalkyl is attached to one aryl atom or is fused to the aryl, so that they share two or more common atoms.

[0037] The term "unsubstituted" means that the specified group bears no substituents.

[0038] Unless otherwise defined, "aryl" refers to a cyclic aromatic hydrocarbon group having one to three aromatic rings, including monocyclic or bicyclic groups such as phenyl, biphenyl, or naphthyl. When containing two aromatic rings (such as bicyclic), the aromatic rings of the aryl group are optionally joined at a single point (e.g., biphenyl) or fused (e.g., naphthyl). Aryl groups are optionally substituted at any point of attachment with one or more substituents, e.g., 1 to 5 substituents. Exemplary substituents include -H, -halogen, -CN, -O-(C-C)alkyl, (C-C)alkyl, -O-(C-C)alkenyl, -O-(C-C)alkynyl, (C-C)alkenyl, (C-C)alkynyl, -OH, -OP(O)(OH), -OC(O)(C-C)alkyl, -C(O)(C-C)alkyl, -OC(O)O(C-C)alkyl, NH, NH((C-C)alkyl), N(((C-C)alkyl), -S(O)-(C-C)alkyl, -S(O)NH(C-C)alkyl and —S(O)N((C1-C6)alkyl). The substituents are themselves optionally substituted. Furthermore, when containing two fused rings, the aryl group has an unsaturated or partially saturated ring optionally fused to a fully saturated ring. Exemplary ring systems of these aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, anthracenyl, phenalenyl, phenanthrenyl, indanyl, indenyl, tetrahydronaphthalenyl, tetrahydrobenzoannurenyl, and the like.

[0039] Unless otherwise specified, "heteroaryl" means a monovalent monocyclic or polycyclic aromatic radical of 5 to 24 ring atoms containing one or more ring heteroatoms selected from N, O, or S, with the remaining ring atoms being C. As defined herein, heteroaryl can also be a bicyclic aromatic heterocyclic radical in which the heteroatoms are selected from N, O, or S. The aromatic radical is optionally substituted independently with one or more substituents described herein. Examples include furyl, thienyl, pyrrolyl, pyridyl, pyrazolyl, pyrimidinyl, imidazolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazinyl, indolyl, thiophen-2-yl, quinolyl, benzopyranyl, isothiazolyl, thiazolyl, thiadiazole, indazole, benzimidazolyl, thieno[3,2-b]thiophene, triazolyl, triazinyl, imidazo[1,2-b]thiophene, thiazolyl, thiadiazole, indazole, benzimidazolyl, thieno[3,2-b]thiophene, thiazolyl, triazinyl, imidazo[1,2-b]thiophene, thiazolyl, thiadiazole ... -b]pyrazolyl, furo[2,3-c]pyridinyl, imidazo[1,2-a]pyridinyl, indazolyl, pyrrolo[2,3-c]pyridinyl, pyrrolo[3,2-c]pyridinyl, pyrazolo[3,4-c]pyridinyl, thieno[3,2-c]pyridinyl, thieno[2,3-c]pyridinyl, thieno[2,3-b]pyridinyl, benzothiazolyl, indolyl, indolinyl, indolinonyl, dihydrobenzo Thiophenyl, dihydrobenzofuranyl, benzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, dihydrobenzoxanyl, quinolinyl, isoquinolinyl, 1,6-naphthyridinyl, benzo[de]isoquinolinyl, pyrido[4,3-b][1,6]naphthyridinyl, inolinyl, quinoline[4,3-b][1,6]naphthyridinyl, thieno[2,3-b]pyridinyl Razinyl, quinazolinyl, tetrazolo[1,5-a]pyridinyl, [1,2,4]triazolo[4,3-a]pyridinyl, isoindolyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,4-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, imidazo[5,4-b]pyridinyl, pyrrolo[1,2-a]pyrimidinyl, tetrahydropyrrolo[1,2-a]pyrimidinyl, 3,4-dihydro-2H-1Δ 2-pyrrolo[2,1-b]pyrimidine, dibenzo[b,d]thiophene, pyridin-2-one, furo[3,2-c]pyridinyl, furo[2,3-c]pyridinyl, 1H-pyrido[3,4-b][1,4]thiazinyl, benzoxazolyl, benzisoxazolyl, furo[2,3-b]pyridinyl, benzothiophenyl, 1,5-naphthyridinyl, furo[3,2-b]pyridine, [1,2,4]triazolo[1,5-a]pyridinyl, benzo[1,2,3]triazolyl, imidazo[1,2-a]pyrimidinyl, [1,2,4]triazolo[4,3-

[0023] In addition, when containing two fused rings, aryl groups as defined herein can have an unsaturated or partially saturated ring fused to a fully saturated ring. Exemplary ring systems of these heteroaryl groups include indolinyl, indolinonyl, dihydrobenzothiophenyl, dihydrobenzofuran, chromanyl, thiochromanyl, tetrahydroquinolinyl, dihydrobenzothiazine, 3,4-dihydro-IH-isoquinolinyl, 2,3-dihydrobenzofuran, indolinyl, indolyl, and dihydrobenzoxanyl.

[0040] Halogen or "halo" means fluorine, chlorine, bromine, or iodine.

[0041] "Alkyl" means a straight or branched chain saturated hydrocarbon containing from 1 to 12 carbon atoms. Examples of (C1-C6) alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, and isohexyl.

[0042] "Alkoxy" means a straight or branched chain saturated hydrocarbon containing 1 to 12 carbon atoms including a terminal "O" in the chain, e.g., -O(alkyl). Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, t-butoxy, or pentoxy groups.

[0043] "Alkenyl" refers to a straight- or branched-chain unsaturated hydrocarbon containing 2 to 12 carbon atoms. An "alkenyl" group contains at least one double bond in the chain. The double bond of an alkenyl group can be unconjugated or conjugated to another unsaturated group. Examples of alkenyl groups include ethenyl, propenyl, n-butenyl, isobutenyl, pentenyl, or hexenyl. Alkenyl groups can be unsubstituted or substituted, and can be straight-chain or branched.

[0044] "Alkynyl" refers to a straight or branched chain unsaturated hydrocarbon containing 2 to 12 carbon atoms. An "alkynyl" group contains at least one triple bond in the chain. Examples of alkenyl groups include ethynyl, propargyl, n-butynyl, isobutynyl, pentynyl, or hexynyl. Alkynyl groups can be unsubstituted or substituted.

[0045] "Alkylene" or "alkylenyl" refers to a divalent alkyl radical. Any of the above monovalent alkyl groups may be alkylene by abstraction of a second hydrogen atom from the alkyl. As defined herein, alkylene may also be (C-C) alkylene. Alkylene may further be (C-C) alkylene. Typical alkylene groups include, but are not limited to, -CH-, -CH(CH)-, -C(CH)-, -CHCH-, -CHCH(CH)-, -CHC(CH)-, CHCHCH-, -CHCHCHCH-, and the like.

[0046] "Cycloalkyl" or "carbocyclyl" refers to a monocyclic or polycyclic saturated carbocyclic ring containing 3 to 18 carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, norboranyl, norborenyl, bicyclo[2.2.2]octanyl, or bicyclo[2.2.2]octenyl, and derivatives thereof. (C3-C8)cycloalkyl is a cycloalkyl group containing 3 to 8 carbon atoms. Cycloalkyl groups can be fused (e.g., decalin) or bridged (e.g., norboran).

[0047] "Heterocyclyl" or "heterocycloalkyl" means a saturated, monocyclic, or polycyclic ring containing carbon and at least one heteroatom selected from oxygen, nitrogen, or sulfur (O, N, or S), and which lacks delocalized n-electrons (aromaticity) shared between ring carbons or heteroatoms. The heterocycloalkyl ring structure can be substituted with one or more substituents, which themselves can be optionally substituted. Examples of heterocyclyl rings include, but are not limited to, oxetanyl, azetadinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, thiopyranyl, tetrahydropyranyl, dioxalinyl, piperidinyl, morpholinyl, thiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S-dioxide, piperazinyl, azepinyl, oxepinyl, diazepinyl, tropanyl, oxazolidinonyl, 1,4-dioxanyl, dihydrofuranyl, 1,3-dioxolanyl, imidazolidinyl, imidazolinyl, dithiolanyl, and homotropanyl.

[0048] "Hydroxyalkyl" refers to an alkyl group substituted with one or more -OH groups. Examples of hydroxyalkyl groups include HO-CH2-, HO-CH2CH2-, and CH3-CH(OH)-.

[0049] "Haloalkyl" means an alkyl group substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethyl, difluoromethyl, pentafluoroethyl, trichloromethyl, and the like.

[0050] "Haloalkoxy" means an alkoxy group substituted with one or more halogens. Examples of haloalkyl groups include, but are not limited to, trifluoromethoxy, difluoromethoxy, pentafluoroethoxy, trichloromethoxy, and the like.

[0051] "Cyano" refers to a substituent having a carbon atom attached to a nitrogen atom by a triple bond, e.g., C≡N.

[0052] "Amino" means a substituent containing at least one nitrogen atom (eg, NH2).

[0053] "Alkylamino" refers to an amino or NH group in which one of the hydrogens has been replaced with an alkyl group, e.g., -NH(alkyl). Examples of alkylamino groups include, but are not limited to, methylamino (e.g., -NH(CH)), ethylamino, propylamino, isopropylamino, n-butylamino, sec-butylamino, tert-butylamino, and the like.

[0054] "Dialkylamino" means an amino or NH group in which both hydrogens are replaced with alkyl groups, e.g., -N(alkyl). The alkyl groups of the amino group may be the same or different alkyl groups. Examples of dialkylamino groups include, but are not limited to, dimethylamino (e.g., -N(CH), diethylamino, dipropylamino, diisopropylamino, di-n-butylamino, di-sec-butylamino, di-tert-butylamino, methyl(ethyl)amino, methyl(butylamino), and the like.

[0055] "Spirocycloalkyl" or "spirocyclyl" refers to a carbogen bicyclic ring system in which both rings are bonded through a single atom. The rings can vary in size and nature or can be identical in size and nature. Examples include spiropentane, spriohexane, spiroheptane, spirooctane, spirononane, or spirodecane. One or both rings of the spirocycle can be fused to another carbocyclic, heterocyclic, aromatic, or heteroaromatic ring. (C3-C 12 ) A spirocycloalkyl is a spiro ring containing 3 to 12 carbon atoms.

[0056] "Spiroheterocycloalkyl" or "spiroheterocyclyl" means a spirocycle in which at least one ring is heterocyclic, and one or more carbon atoms may be replaced with a heteroatom (e.g., one or more carbon atoms may be replaced with a heteroatom in at least one ring). One or both rings of the spiroheterocycle may be fused to another carbocyclic, heterocyclic, aromatic, or heteroaromatic ring.

[0057] In the groups, radicals, or substructures defined below, the number of carbon atoms is often specified before the group, e.g., (C-C 10 ) Alkyl refers to an alkyl group or radical having 1 to 10 carbon atoms. Generally, for groups containing more than one subgroup, the last listed group is the point of radical attachment. For example, "alkylaryl" refers to a monovalent radical of the formula alkyl-aryl-, and "arylalkyl" refers to a monovalent radical of the formula aryl-alkyl-. Furthermore, the use of a term designating a monovalent radical where a divalent radical is appropriate shall be construed to designate the respective divalent radical, and vice versa. Unless otherwise specified, conventional definitions and conventional stable atom valences of the terminology are presumed and obtained in all formulas and groups. The articles "a" and "an" refer to one or more (e.g., at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

[0058] The term "and / or" means "and" or "or" unless otherwise stated.

[0059] The term "optionally substituted" means that a given chemical substructure (e.g., an alkyl group) can (but does not require) be attached to other substituents (e.g., heteroatoms). For example, an optionally substituted alkyl group can be a fully saturated alkyl chain (e.g., a pure hydrocarbon). Alternatively, the same optionally substituted alkyl group can have a substituent other than hydrogen. For example, it can be attached at any point along the chain to a halogen atom, a hydroxyl group, or other substituent described herein. Thus, the term "optionally substituted" means that a given chemical substructure can potentially include other functional groups, but does not necessarily have any additional functional groups. Suitable substituents used in the optional replacement of the described groups include halogen, oxo, -OH, -CN, -COOH, -CHCN, -O-(C-C)alkyl, (C-C)alkyl, (C-C)alkoxy, (C-C)haloalkyl, (C-C)haloalkoxy, -O-(C-C)alkenyl, -O-(C-C)alkynyl, (C-C)alkenyl, (C-C)alkynyl, -OH, -OP(O)(OH), -OC( Examples of alkyl groups include, but are not limited to, -O)(C-C)alkyl, -C(O)(C-C)alkyl, -OC(O)O(C-C)alkyl, -NH, -NH((C-C)alkyl), -N((C-C)alkyl), -NHC(O)(C-C)alkyl, -C(O)NH(C-C)alkyl, -S(O)(C-C)alkyl, -S(O)NH(C-C)alkyl, and -S(O)N((C-C)alkyl). Substituents may themselves be optionally substituted. As used herein, "optionally substituted" also refers to substituted or unsubstituted, the meaning of which is described below.

[0060] The term "substituted" means that a particular group or moiety has one or more suitable substituents, and that the substituents may be attached to the particular group or moiety at one or more positions. For example, an aryl substituted with a cycloalkyl may indicate that the cycloalkyl is attached to one aryl atom or is fused to the aryl, so that they share two or more common atoms.

[0061] The term "unsubstituted" means that the specified group bears no substituents.

[0062] B. Terminology and Rules for Salts, Derivatives and Solvates The term "salt" or "salts" refers to acid addition or base addition salts of the compounds of the present invention. "Salt" specifically includes "pharmaceutically acceptable salts." The term "pharmaceutically acceptable salts" refers to salts that retain the biological effectiveness and properties of the compounds of the present invention, and which are typically not biologically or otherwise undesirable. In many cases, the compounds of the present invention are capable of forming acid and / or base salts by virtue of the presence of amino and / or carboxyl groups or groups similar thereto. When both basic and acidic groups are present in the same molecule, the compounds of the present invention may also form internal salts, e.g., zwitterionic molecules.

[0063] Pharmaceutically acceptable base addition acids can be formed with inorganic and organic acids.

[0064] Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like.

[0065] Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, sulfosalicylic acid, and the like.

[0066] Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases.

[0067] Inorganic bases from which salts can be derived include, for example, ammonium salts and metals from columns I to XII of the periodic table. In certain embodiments, salts are derived from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper. Particularly suitable salts include ammonium, potassium, sodium, calcium, and magnesium salts.

[0068] Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, etc. Particular organic amines include isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine, and tromethamine.

[0069] In another embodiment, the present invention provides a compound of the present invention in the form of acetate, ascorbate, adipate, aspartate, benzoate, besylate, bromide / hydrobromide, bicarbonate / carbonate, bisulfate / sulfate, camphorsulfonate, caprate, chloride / hydrochloride, chlortheophyllonate, citrate, ethanedisulfonate, fumarate, gluceptate, gluconate, glucuronate, glutamate, glutarate, glycolate, hippurate, hydroiodide / iodide, isethionate, It may be provided in the lactate, lactobionate, lauryl sulfate, malate, maleate, malonate, mandelate, mesylate, methylsulfate, mucate, naphthoate, napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate / hydrogenphosphate / dihydrogenphosphate, polygalacturonate, propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate, tartrate, tosylate, triphenylacetate, trifluoroacetate or xinafoate salt forms.

[0070] "Solvate" refers to a complex of variable stoichiometry formed by a solute, such as a compound of formula (I), and a solvent, such as water, ethanol, or acetic acid. This physical association may involve varying degrees of ionic and covalent bonding, including hydrogen bonding. In certain instances, the solvate is capable of isolation, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. In general, such solvents selected for the purposes of the disclosure do not interfere with the biological activity of the solute. Solvates include both solution-phase and separable solvates. Representative solvates include hydrates, ethanolates, methanolates, and the like.

[0071] "Hydrate" means a solvate where the solvent molecule is water.

[0072] The compounds of the present disclosure discussed below, including their free bases or acids, their salts, solvates, and may contain oxidized sulfur atoms or quaternized nitrogen atoms in their structure, particularly pharmaceutically acceptable forms thereof, although not otherwise specified or shown, and such forms, particularly pharmaceutically acceptable forms, are intended to be encompassed by the appended claims.

[0073] C. Isomerism Terminology and Rules "Isomers" mean compounds that have the same number and kind of atoms, and hence the same molecular weight, but differ with regard to the arrangement or configuration of the atoms in space. The term includes stereoisomers and geometric isomers.

[0074] "Stereoisomer" or "optical isomer" refers to a stable isomer that has at least one chiral atom or restricted rotation, resulting in a plane of perpendicular asymmetry (e.g., certain biphenyls, allenes, spiro compounds, etc.), capable of rotating plane-polarized light. Because asymmetric centers and other chemical structures may exist in the compounds of the present disclosure, which may result in stereoisomerism, the present disclosure contemplates stereoisomers and mixtures thereof. The compounds of the present disclosure and their salts contain asymmetric carbon atoms and therefore can exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. Typically, such compounds are prepared as racemic mixtures. However, if desired, such compounds can be prepared or isolated as pure stereoisomers, i.e., as individual enantiomers or diastereomers, or as stereoisomer-enriched mixtures. As described in more detail below, individual stereoisomers of the compounds are prepared by synthesis from optically active starting materials containing the desired chiral center, or by conversion to a diastereomeric mixture followed by separation or resolution after preparation of a mixture of enantiomeric products, such as by separation or recrystallization, chromatographic techniques, use of chiral resolving agents, or by direct separation of enantiomers on a chiral chromatographic column. Starting compounds of particular stereochemistry are commercially available or are made by the methods described below and resolved by techniques well known in the art.

[0075] "Enantiomers" mean a pair of stereoisomers that are non-superimposable mirror images of each other.

[0076] "Diastereoisomers" or "diastereomers" mean optical isomers that are not mirror images of each other.

[0077] "Racemic mixture" or "racemate" means a mixture containing equal amounts of individual enantiomers.

[0078] "Non-racemic mixture" means a mixture containing unequal amounts of individual enantiomers.

[0079] "Geometric isomers" are isomers stabilized by restricted freedom of rotation due to double bonds (e.g., cis-2-butene and trans-2-butene) or cyclic structures (e.g., cis-1,3-dichlorocyclobutane and trans-1,3-dichlorocyclobutane). Because carbon-carbon double (olefinic) bonds, C=N double bonds, cyclic structures, and the like may be present in the compounds of the present disclosure, the present disclosure contemplates each of the various stable geometric isomers and mixtures thereof resulting from the substituents around these double bonds and within these cyclic structures. Substituents and isomers are designated using the conventional cis / trans or E or Z notation. The term "E" refers to higher-order substituents on opposite sides of a double bond, and the term "Z" refers to higher-order substituents on the same side of a double bond. A thorough discussion of E and Z isomerism is provided in J. March, Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed., John Wiley & Sons, 1992, which is incorporated herein by reference in its entirety. Some of the examples below represent single E isomers, single Z isomers, and E / Z isomer mixtures. Determination of E and Z isomers can be performed using techniques such as X-ray crystallography, 1 H NMR and 13 This can be done by analytical methods such as C NMR.

[0080] Some of the compounds of the present disclosure can exist in multiple tautomeric forms, and as stated above, the compounds of the present disclosure include all such tautomers.

[0081] It is well known in the art that the biological and pharmacological activity of a compound is highly sensitive to the stereochemistry of the compound. Thus, for example, enantiomers often exhibit significantly different biological activities, including differences in pharmacokinetic properties, including metabolism, protein binding, and the like, and differences in pharmacological properties, including the type of activity exerted, the degree of activity, toxicity, and the like.

[0082] Therefore, while racemic drugs may be used, they are often less effective than the same amount of enantiomerically pure drug. In fact, in some cases, one enantiomer may be pharmacologically inactive and merely serve as a simple diluent. Furthermore, the pharmacological activity of enantiomers may be distinct biological activities. In fact, purified individual isomers have been reported to have faster percutaneous penetration rates compared to the racemic mixture, so some purified enantiomers offer advantages over the racemate.

[0083] Therefore, if one enantiomer is pharmacologically more active, less toxic, or has a more favorable disposition in the body than the other enantiomer, it would be therapeutically beneficial to administer that enantiomer preferentially. In this way, the patient undergoing treatment would receive a lower total dose of the drug and a lower dose of the enantiomer than a potentially toxic or enantiomeric inhibitor.

[0084] The preparation of pure enantiomers, or mixtures of a desired enantiomeric excess (ee) or enantiomeric purity, can be achieved by one or more of the following methods: (a) separation or resolution of enantiomers, or (b) enantioselective synthesis, or a combination thereof, as known to those skilled in the art. These resolution methods generally rely on chiral recognition and include, for example, chromatography using chiral stationary phases, enantioselective host-guest complexation, resolution or synthesis using chiral auxiliaries, enantioselective synthesis, enzymatic and non-enzymatic kinetic resolution, or spontaneous enantioselective crystallization. Such methods are generally elucidated in Chiral Separation Techniques: A Practical Approach (2nd Ed.), G. Subramanian (ed.), Wiley-VCH, 2000; T.E. Beesley and R.P.W. Scott, Chiral Chromatography, John Wiley & Sons, 1999; and Satinder Ahuja, Chiral Separations by Chromatography, Am. Chem. Soc., 2000. Furthermore, there are similarly well-known methods for quantifying enantiomeric excess or purity, e.g., by GC, HPLC, CE, or NMR, and for assigning absolute configuration and conformation, e.g., by CD ORD, X-ray crystallography, or NMR.

[0085] In general, all tautomers, isomers, and mixtures, whether individual geometric or stereoisomers, or racemic or non-racemic mixtures, of a chemical structure or compound are intended, unless the specific stereochemistry or isomer is specifically indicated in the compound name or structure.

[0086] D. Terminology and Rules for Medication Administration and Treatment A "patient" or "subject" is a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or a non-human primate such as a monkey, chimpanzee, baboon, or rhesus monkey. In certain embodiments, the subject is a primate. In yet other embodiments, the subject is a human.

[0087] An "effective amount" or "therapeutically effective amount" when used in reference to a compound means an amount of a compound of the present disclosure that (i) treats or prevents a particular disease, condition, or disorder, (ii) relieves, ameliorates, or eliminates one or more symptoms of a particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of a particular disease, condition, or disorder described herein.

[0088] The term "pharmacologically effective amount" or "therapeutically effective amount" refers to an amount of a compound according to the present disclosure that, when administered to a patient in need thereof, is sufficient to effect treatment of a disease state, condition, or disorder for which the compound has utility. Such an amount will be sufficient to elicit the biological or medical response in a tissue, system, or patient that is desired by a researcher or clinician. The amount of a compound according to the present disclosure that constitutes a therapeutically effective amount will vary depending on the compound and its biological activity, the composition used for administration, the time of administration, the route of administration, the rate of excretion, the duration of treatment, the disease state or disorder being treated and its severity, any drugs used in combination with or concomitantly with the compound of the present disclosure, and factors such as the age, weight, general condition, sex, and diet of the patient. Such a therapeutically effective amount can be routinely determined by one of ordinary skill in the art having regard to their own knowledge, the prior art, and this disclosure.

[0089] The term "pharmaceutical composition" as used herein refers to a compound of the present disclosure or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof together with at least one pharmaceutically acceptable carrier in a form suitable for oral or parenteral administration.

[0090] "Carrier" includes carriers, excipients, and diluents and means a material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material, that contains a pharmaceutical agent and is involved in the transport or transfer of the pharmaceutical agent from one organ or body part to another organ or body part of a subject.

[0091] A subject is "in need of" treatment if such subject would benefit biologically, medically, or in quality of life from such treatment (preferably a human).

[0092] As used herein, the terms "inhibit," "inhibition," or "inhibiting" refer to the reduction or suppression of a given condition, symptom, or disorder or disease, or a significant decrease in a biological activity or fundamental activity of a biological process.

[0093] As used herein, the terms "treat," "treating," or "treatment" of any disease or disorder refer to alleviating or ameliorating the disease or disorder (i.e., slowing or halting the progression of the disease or at least one of its clinical symptoms); or alleviating or ameliorating at least one physical parameter or biomarker associated with the disease or disorder, including those that may not be discernible by the patient.

[0094] As used herein, the terms "prevent," "preventing," or "prevention" of a disease or disorder refer to prophylactic treatment of a disease or disorder or delay in the onset or progression of a disease or disorder.

[0095] "Pharmaceutically acceptable" means that the substance or composition must be chemically and / or toxicologically compatible with the other ingredients that make up the formulation and / or the mammal being treated therewith.

[0096] The term "disorder" means, and is used interchangeably with, the terms disease, condition, or illness, unless otherwise specified.

[0097] "Administer," "administering," or "administration" means administering a disclosed compound or a pharmaceutically acceptable salt of a disclosed compound or composition directly to a subject, or administering to a subject a pharmaceutically acceptable salt of a compound or composition that is capable of forming an equivalent amount of an active compound in the subject's body.

[0098] "Compounds of the disclosure," "compounds of Formula (I)," "disclosed compounds," "compounds of the invention," and equivalent expressions (unless otherwise specified) refer to Formula (I), and (Ia)-(Ih), as described herein, including tautomers, salts, particularly pharmaceutically acceptable salts thereof, and solvates and hydrates thereof, as well as all stereoisomers (including diastereoisomers and enantiomers), rotamers, tautomers, and isotopically labeled compounds (including deuterium substitution), as well as inherently formed substructures (e.g., polymorphs, solvates, and / or hydrates), where the context permits. For purposes of this disclosure, solvates and hydrates are generally considered compositions. Generally, and preferably, compounds of the disclosure and formulas designating compounds of the disclosure are understood to include only stable compounds and to exclude unstable compounds, even if unstable compounds are considered literally encompassed by the compound formula. Similarly, reference to intermediates, whether or not they are claimed as such, is meant to encompass their salts and solvates, where the context so permits. For clarity, specific examples where the context permits may be given in the text, but these examples are merely an aid to understanding and are not intended to exclude other examples where the context so permits.

[0099] By "stable compound" or "stable structure" is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic or diagnostic agent. For example, compounds that have "dangling valencies" or are carbanions are not compounds contemplated by the present disclosure.

[0100] In certain embodiments, the term "about" or "approximately" means within 20%, preferably within 10%, and more preferably within 5% of a given value or range.

[0101] The yield for each reaction described herein is expressed as a percentage of the theoretical yield.

[0102] By "cGAS-dependent disease or disorder" is meant any disease or disorder that is affected directly or indirectly by modulation of cGAS protein levels.

[0103] E. Specific Embodiments and Methods for Testing Compounds of Formula (I) The present disclosure relates to compounds capable of inhibiting cGAS or the cGAS pathway, or pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, or tautomers thereof, that are useful in treating cGAS-related diseases and disorders. The present disclosure further relates to compounds useful for inhibiting cGAS activity, or pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, or tautomers thereof.

[0104] Embodiment 1. Formula (I): [ka] (In the formula, R1 is (C1-C4) alkyl, OH, halogen, -NR a R b and a 5-membered heteroaryl ring containing 1 to 4 heteroatoms selected from O, N, and S, optionally substituted with at least one 5- or 6-membered heterocycloalkyl ring containing oxygen; R2 is (C1-C4) alkyl, (C1-C4) alkylene-OH, -(C1-C4) alkylene-NR9R 10 a 5-membered heteroaryl ring containing three nitrogen atoms in positions 1, 2 and 4 relative to one another, optionally substituted at any available ring nitrogen atom with (C1-C4)alkylene-C(O)OH or benzyl, wherein benzyl is optionally substituted with (C1-C4)alkoxy, and the 5-membered heteroaryl ring is further substituted at a carbon atom of the 5-membered heteroaryl ring with R3; R3 is H, halogen, -OH, -NR 11 R 12 , -(C1-C4) alkylene-NR 13 R 14, (C1-C4) alkyl, halo(C1-C4) alkyl, -(C1-C4) alkylene-OH, -(C1-C4) alkylene-(C1-C4) alkoxy, -C(O)(C1-C4) alkyl, -C(O)(C1-C4) alkylene-O-(C1-C4) alkyl, -C(O)(C1-C4) alkylene-OH, -C(O)NR 15 R 16 , (C1-C4)alkoxy, -(C1-C4)alkylene-S(O) v -(C1-C4)alkyl, -C(O)(C1-C4)alkoxy, -CN, -O(C1-C4)alkylene-OH, -O(C1-C4)alkylene-(C1-C4)alkoxy, -(C1-C4)alkylene-C(O)(C1-C4)alkyl, -(C1-C4)alkylene-C(O)(C1-C4)alkoxy, -(C1-C4)alkylene-C(O)NR 17 R 18 a 6-membered heterocycloalkyl ring Ri containing 1 to 2 heteroatoms selected from O and N, or [ka] and (C1-C4) alkyl is CN, ═N-(C1-C4) alkoxy, ═NO-(C1-C4) alkylene-OR 20 , OH, (C1-C4)alkoxy, —C(O)OH, —C(O)O(C1-C4)alkyl, a 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S, and a 5-6 membered heteroaryl ring containing 1-2 heteroatoms selected from O, N, and S; Each -(C1-C4)alkylene-NR9R 10 and -(C1-C4) alkylene-NR 13 R 14 is optionally substituted on at least one of the (C1-C4)alkylene carbons with OH, (C1-C4)alkoxy, —(C1-C4)alkylene-O(C1-C4)alkyl, (C1-C4)alkyl; each halo(C-C)alkyl and (C-C)alkylene-OH is independently optionally substituted with at least one of OH, (C-C)alkoxy, —O(C-C)alkylene-OH, —(C-C)alkylene-OH, —(C-C)alkylene-(C-C)alkoxy; Ri is optionally substituted with (C1-C4) alkyl; v is 0, 1 or 2; R4 is H, (C1-C4)alkyl, -(C1-C4)alkylene-OH, -(C1-C4)alkylene-(C1-C4)alkoxy, -(C1-C4)alkylene-C(O)OH, -C(O)O(C1-C4)alkyl, or a 5-6 membered heteroaryl ring containing 1-2 nitrogen atoms, optionally substituted with one or more (C1-C4)alkoxy; Each R, R, R, and R is independently H, halogen, OH, (C-C)alkyl, (C-C)cycloalkyl, (C-C)alkoxy, -O(C-C)cycloalkyl, halo(C-C)alkyl, halo(C-C)alkoxy, (C-C)alkenyl, (C-C)alkynyl, -(C-C)alkylene-OH, -O(C-C)alkylene-OH, CN, -C(O)(C-C)alkoxy, -C(O)NR 21 R 22 or a 5-membered heteroaryl ring containing two nitrogen heteroatoms, wherein each (C2-C6)alkenyl and (C2-C6)alkynyl is independently optionally substituted with one or more (C1-C4)alkoxy; Each R 20 , R 21 and R 22 are independently H or (C1-C4) alkyl; Each R9, R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 and R 18are independently H, (C-C)alkyl, —(C-C)alkylene-OH, —(C-C)alkylene-O(C-C)alkyl, —C(O)(C-C)alkylene-(C-C)alkoxy, or —C(O)(C-C)alkyl; or R9 and R 10 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N, and S. 23 Form R 23 optionally one or more R 24 is replaced by; R 11 and R 12 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N, and S. 25 Form R 25 optionally one or more R 26 is replaced by; R 13 and R 14 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N, and S. 27 Form R 27 optionally one or more R 28 is replaced by; R 15 and R 16 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N, and S. 29 Form R 29 optionally one or more R 30 is replaced by; R 17 and R 18 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N, and S. 31 Form R 31 is optionally R 32 is replaced by; Each R 24 , R 26 , R 28 , R 30 and R 32 are independently (C1-C4) alkyl, (C1-C4) alkoxy, NR c R d , OH or ═O; or Each R 24 , R 26 , R 28 , R 30 and R 32 two of which, when attached to the same atom, together form a (C4-C7)spirocycloalkyl or a 4-7 membered spiroheterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S; R 19 is H, OH or (C1-C4) alkyl; Each R a , R b , R c and R d are independently H, halogen, or (C1-C4) alkyl. or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof, and methods of making and using same.

[0105] Embodiment 2. A compound of embodiment 1 wherein the 5-membered heteroaryl ring of R1 is imidazolyl optionally substituted with at least one of (C1-C4) alkyl, OH, and a 5- or 6-membered heterocycloalkyl ring containing oxygen.

[0106] Embodiment 3. A compound of embodiment 1 wherein the 5-membered heteroaryl ring of R1 is pyrazolyl optionally substituted with at least one of (C1-C4)alkyl, OH, and a 5- or 6-membered heterocycloalkyl ring containing oxygen.

[0107] Embodiment 4. Formula (Ia), Formula (Iaa): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 33 or R 33 The compound of embodiment 1, wherein ' is H, (C1-C4) alkyl, or a 5- or 6-membered heterocycloalkyl ring containing an oxygen atom at a carbon or nitrogen position of the ring.

[0108] Embodiment 5. Formula (Ib): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 34 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0109] Embodiment 6. Formula (Ic), Formula (Icc), Formula (Iccc): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 35 , R 35 ' or R 35 The compound of embodiment 1, wherein "" is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0110] Embodiment 7. Formula (Id): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 50 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0111] Embodiment 8. Formula (Ie): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 51 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0112] Embodiment 9. Formula (If): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 52 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0113] Embodiment 10. Formula (Ig): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 53 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0114] Embodiment 11. Formula (Ih): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 54The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0115] Embodiment 12. Formula (Ii): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 55 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0116] Embodiment 13. Formula (Ij): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 56 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0117] Embodiment 14. Formula (Ik): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 57 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0118] Embodiment 15. Formula (II): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 58 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0119] Embodiment 16. Formula (Im): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 59 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0120] Embodiment 17. Formula (In): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 60 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0121] Embodiment 18. Formula (Io): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 61 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0122] Embodiment 19. Formula (Ip): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 62 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0123] Embodiment 20. Formula (Iq): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X is halogen or NH2, and R 63 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0124] Embodiment 21. Formula (Ia1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0125] Embodiment 22. Formula (Iaa1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0126] Embodiment 22. Formula (Ib1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0127] Embodiment 23. Formula (Ib2): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0128] Embodiment 24. Formula (Ib2): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0129] Embodiment 25. Formula (Ic1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0130] Embodiment 26. Formula (Icc1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0131] Embodiment 27. Formula (Icc1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0132] Embodiment 28. Formula (Id1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0133] Embodiment 29. Formula (Ie1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0134] Embodiment 30. Formula (If1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0135] Embodiment 31. Formula (Ig1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0136] Embodiment 32. Formula (Ih1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0137] Embodiment 33. Formula (Ii1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0138] Embodiment 34. Formula (Ij1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0139] Embodiment 35. Formula (Ik1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0140] Embodiment 36. Formula (Il1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0141] Embodiment 37. Formula (Im1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0142] Embodiment 38. Formula (In1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0143] Embodiment 39. Formula (Io1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0144] Embodiment 40. Formula (Ip1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, and tautomer thereof.

[0145] Embodiment 41. Formula (Iq1): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein X is halogen or NH2, and R 63 The compound of embodiment 1, wherein is a 5- or 6-membered heterocycloalkyl ring containing H, (C1-C4) alkyl, or an oxygen atom at a carbon or nitrogen position of the ring.

[0146] Embodiment 42. Formula (IIa): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 36 The compound of any of embodiments 1-41, wherein is H, (C1-C4) alkyl, or -(C1-C4) alkylene-OH.

[0147] Embodiment 43. Formula (IIb): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 37 The compound of any of embodiments 1-42, wherein is H, (C1-C4) alkyl, or -(C1-C4) alkylene-OH.

[0148] Embodiment 44. Formula (IIc): [ka] or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, and R 38 The compound of any of embodiments 1-43, wherein is H, (C1-C4) alkyl, or -(C1-C4) alkylene-OH.

[0149] Embodiment 45. A compound of any of Embodiments 1-44, wherein R4 is H, (C1-C4) alkyl, -(C1-C4) alkylene-(C1-C4) alkoxy, -(C1-C4) alkylene-OH, pyridyl, pyrazolyl, or imidazolyl.

[0150] Embodiment 46. A compound of any of Embodiments 1-44, wherein R4 is H.

[0151] Embodiment 47. A compound of any of Embodiments 1-44, wherein R4 is methyl.

[0152] Embodiment 48. A compound of any of Embodiments 1-47, wherein R5 is H, halogen CN, OH, (C1-C4) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C1-C4) alkoxy, or imidazolyl.

[0153] Embodiment 49. A compound of any of Embodiments 1-47, wherein R5 is methoxy.

[0154] Embodiment 50. A compound of any of Embodiments 1-47 wherein R5 is halogen, preferably F or Cl.

[0155] Embodiment 51. A compound of any of Embodiments 1-47, wherein R5 is OH.

[0156] Embodiment 52. A compound of any of Embodiments 1-47, wherein R5 is CN.

[0157] Embodiment 53. A compound of any of Embodiments 1-52, wherein R6 is H, halogen, CN, OH, (C1-C4) alkyl, —(C1-C4) alkoxy, (C2-C6) alkenyl, or (C2-C6) alkynyl.

[0158] Embodiment 54. A compound of any of Embodiments 1-52, wherein R6 is methoxy.

[0159] Embodiment 55. A compound of any of Embodiments 1-52 wherein R6 is halogen, preferably F or Cl.

[0160] Embodiment 56. R7 is H, halogen, CN, OH, (C1-C4)alkyl, (C1-C4)alkoxy, -O(C1-C4)cycloalkyl, halo(C1-C4)alkoxy, -C(O)NR 21 R 22 and R 21 and R 22 The compound of any of embodiments 1-55, wherein is independently H or (C1-C4) alkyl.

[0161] Embodiment 57. A compound of any of Embodiments 1-55, wherein R7 is H.

[0162] Embodiment 58. A compound of any of Embodiments 1-55 wherein R7 is (C1-C4)alkoxy, preferably methoxy or ethoxy.

[0163] Embodiment 59. A compound of any of Embodiments 1-55, wherein R7 is OH.

[0164] Embodiment 60. A compound of any of Embodiments 1-55, wherein R7 is halogen, preferably F or Cl.

[0165] Embodiment 61. A compound of any of Embodiments 1-55, wherein R7 is CN.

[0166] Embodiment 62. A compound of any of Embodiments 1-55, wherein R7 is -O(C1-C4)cycloalkyl, preferably -O-cyclopropyl.

[0167] Embodiment 63. A compound of any of embodiments 1-62, wherein R8 is H, F, Cl, CN, OH, (C1-C4) alkyl, (C1-C4) alkoxy, preferably H or methyl.

[0168] Embodiment 64. A compound of any of Embodiments 1-62, wherein R8 is H.

[0169] Embodiment 65. A compound of any of Embodiments 1-64, wherein R3 is H.

[0170] Embodiment 66. A compound of any one of Embodiments 1 to 64, wherein R3 is halogen.

[0171] Embodiment 67. A compound of any of Embodiments 1-64, wherein R3 is F, Cl, or Br.

[0172] Embodiment 68. A compound of any of Embodiments 1-64, wherein R3 is -OH.

[0173] Embodiment 69. A compound of any of Embodiments 1-64, wherein R3 is halo(C1-C4)alkyl.

[0174] Embodiment 70. A compound of any of Embodiments 1-64, wherein R3 is halo(C1-C4)alkyl substituted with methoxy.

[0175] Embodiment 71. A compound of any of Embodiments 1-64, wherein R3 is fluoro(C1-C4)alkyl.

[0176] Embodiment 72. A compound of any of Embodiments 1-64, wherein R3 is monofluoromethyl, monofluoroethyl, or monofluoropropyl.

[0177] Embodiment 73. A compound of any of Embodiments 1-64, wherein R3 is difluoromethyl or difluoroethyl.

[0178] Embodiment 74. A compound of any of Embodiments 1-64, wherein R3 is trifluoromethyl or trifluoroethyl.

[0179] Embodiment 75. A compound of any of Embodiments 1-64, wherein R3 is halo(C1-C4)alkyl substituted with at least one of OH, (C1-C4)alkoxy, —O(C1-C4)alkylene-OH, —(C1-C4)alkylene-OH, —(C1-C4)alkylene-(C1-C4)alkoxy.

[0180] Embodiment 76. A compound of any of Embodiments 1-64, wherein R3 is halo(C1-C4)alkyl substituted with at least one of (C1-C4)alkoxy and OH.

[0181] Embodiment 77. A compound of any of Embodiments 1-64 wherein R3 is monofluoroethyl substituted with one methoxy.

[0182] Embodiment 78. A compound of any of Embodiments 1-64 wherein R3 is difluoroethyl substituted with one methoxy.

[0183] Embodiment 79. A compound of any of Embodiments 1-64 wherein R3 is difluoroethyl substituted with OH, or trifluoroethyl substituted with OH.

[0184] Embodiment 80. R3 is -C(O)NR 15 R 16 65. The compound of any of embodiments 1-64, wherein

[0185] Embodiment 81. Each R 15 and R 16 is independently H, (C1-C4) alkyl, —(C1-C4) alkylene-OH, —(C1-C4) alkylene-O(C1-C4) alkyl, —C(O)(C1-C4) alkylene-(C1-C4) alkoxy, or —C(O)(C1-C4) alkyl.

[0186] Embodiment 82. R3 is -C(O)NR 15 R 16 and each R 15 and R 16 65. The compound of any of embodiments 1-64, wherein is independently H, methyl, ethyl, -ethylene-OH, -methylene-OH, -ethylene-O-methyl, or -ethylene-O-ethyl.

[0187] Embodiment 83.R 15 and R 16 together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O and N 29 and preferably R 29 is one R 30 is substituted with R 30 The compound of embodiment 82, wherein is (C1-C4) alkyl or OH.

[0188] Embodiment 84. A compound of any of Embodiments 1-64, wherein R3 is -C(O)(C1-C4)alkylene-O-(C1-C4)alkyl.

[0189] Embodiment 85. A compound of any of Embodiments 1-64, wherein R3 is -C(O)methylene-O-methyl, -C(O)ethylene-O-methyl, -C(O)methylene-O-ethyl, or -C(O)ethylene-O-methyl.

[0190] Embodiment 86. A compound of any of Embodiments 1-64, wherein R3 is -(C1-C4)alkylene-OH.

[0191] Embodiment 87. A compound of any of Embodiments 1-64, wherein R3 is -methylene-OH, -ethylene-OH, -propylene-OH.

[0192] Embodiment 88. A compound of any of Embodiments 1-64, wherein R3 is —(C1-C4)alkylene-OH substituted with (C1-C4)alkoxy.

[0193] Embodiment 89. A compound of any of Embodiments 1-64 wherein R3 is -methylene-OH or -ethylene-OH substituted at the methylene or ethylene carbon with (C1-C4)alkoxy.

[0194] Embodiment 90. A compound of any of Embodiments 1-64 wherein R3 is -methylene-OH or -ethylene-OH substituted at the methylene or ethylene carbon with methoxy or ethoxy.

[0195] Embodiment 91. A compound of any of Embodiments 1-64, wherein R3 is -C(O)(C1-C4)alkoxy.

[0196] Embodiment 92. A compound of any of Embodiments 1-64, wherein R3 is -C(O)methoxy, -C(O)ethoxy, -C(O)propoxy.

[0197] Embodiment 93. A compound of any of Embodiments 1-64, wherein R3 is -(C1-C4)alkylene-C(O)(C1-C4)alkoxy.

[0198] Embodiment 94. A compound of any of Embodiments 1-64, wherein R3 is -methylene-C(O)methoxy, -methylene-C(O)ethoxy, -ethylene-C(O)methoxy, -ethylene-C(O)ethoxy.

[0199] Embodiment 95. A compound of any of Embodiments 1-64, wherein R3 is -CN.

[0200] Embodiment 96. A compound of any of Embodiments 1-64, wherein R3 is -(C1-C4)alkylene-(C1-C4)alkoxy.

[0201] Embodiment 97. A compound of any of Embodiments 1-64 wherein R3 is -methylene-methoxy, methylene-ethoxy, ethylene-methoxy, or ethylene-ethoxy.

[0202] Embodiment 98. R3 is -(C1-C4)alkylene-S(O) v 65. The compound of any of embodiments 1-64, wherein v is -(C1-C4)alkyl and v is 0, 1, or 2.

[0203] Embodiment 99. R3 is -methylene-S(O) v -Methyl, -Methylene-S(O) v -Ethyl, -Ethylene-S(O) v -methyl, or -ethylene-S(O) v -ethyl and v is 0, 1 or 2; preferably, R3 is -methylene-S-methyl, -methylene-S-ethyl, -ethylene-S-methyl, or -ethylene-S-ethyl.

[0204] Embodiment 100. A compound of any of Embodiments 1-64, wherein R3 is -methylene-S(O)-methyl, -methylene-S(O)-ethyl, -ethylene-S(O)-methyl, -ethylene-S(O)-ethyl.

[0205] Embodiment 101. A compound of any of Embodiments 1-64, wherein R3 is -methylene-S(O)2-methyl, -methylene-S(O)2-ethyl, -ethylene-S(O)2-methyl, or -ethylene-S(O)2-ethyl.

[0206] Embodiment 102. R3 is -NR 11 R 12 and R11 and R 12 together with the nitrogen atom to which they are attached form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O, N, and S; 25 65. The compound of any of embodiments 1-64, wherein

[0207] Embodiment 103. R3 is -NR 11 R 12 and R 11 and R 12 together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O and N 25 65. The compound of any of embodiments 1-64, wherein

[0208] Embodiment 104. R3 is -NR 11 R 12 and R 11 and R 12 together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O and N 25 , preferably forming a 5- or 6-membered heterocycloalkyl ring, R 25 but one or more R 26 and R26 is (C1-C4) alkyl, (C1-C4) alkoxy, OH or =O, preferably R 25 is one R 26 is substituted with R 26 65. The compound of any of embodiments 1-64, wherein is OH, methyl, or ═O.

[0209] Embodiment 105. R3 is -NR 11 R 12 and R 11 and R 12 together with the nitrogen atom to which they are attached form a 6-membered heterocycloalkyl ring R containing two heteroatoms selected from O and N 25 65. The compound of any of embodiments 1-64, wherein

[0210] Embodiment 106. R3 is -NR 11 R 12 and each R 11 and R 12 is independently H, (C1-C4)alkyl, —(C1-C4)alkylene-OH, —(C1-C4)alkylene-O(C1-C4)alkyl, —C(O)(C1-C4)alkylene-(C1-C4)alkoxy, or —C(O)(C1-C4)alkyl.

[0211] Embodiment 107. R3 is -NR 11 R 12 and each R 11 and R 12 are independently H, methyl, ethyl, -methylene-OH, -ethylene-OH, -propylene-OH, -methylene-O-methyl, -methylene-O-ethyl, -ethylene-O-methyl, -ethylene-O-ethyl, -C(O)methylene-methoxy, -C(O)methylene-ethoxy, -C(O)ethylene-methoxy, -C(O)ethylene-ethoxy, -C(O)methyl, -C(O)ethyl, -C(O)propyl.

[0212] Embodiment 108. A compound of any of Embodiments 1-64, wherein R3 is -C(O)(C1-C4)alkyl.

[0213] Embodiment 109. A compound of any of Embodiments 1-64, wherein R3 is -C(O)-methyl, or -C(O)-ethyl.

[0214] Embodiment 110. R3 is -(C1-C4)alkylene-NR 13 R 14 and each R 13 and R 14 is independently H, (C1-C4)alkyl, —(C1-C4)alkylene-OH, —(C1-C4)alkylene-O(C1-C4)alkyl, —C(O)(C1-C4)alkylene-(C1-C4)alkoxy, or —C(O)(C1-C4)alkyl.

[0215] Embodiment 111. R3 is -(C1-C4)alkylene-NR 13 R 14 and each R 13 and R 14 The compound of any of embodiments 1-64, wherein is independently H, (C1-C4) alkyl.

[0216] Embodiment 112. R3 is -(C1-C4)alkylene-NR 13 R 14 and R 13 and R 14 together with the nitrogen atom to which they are attached form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O, N, and S; 27 65. The compound of any of embodiments 1-64, wherein

[0217] Embodiment 113. R3 is -(C1-C4)alkylene-NR 13 R 14 and R 13 and R 14 together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O and N 27 65. The compound of any of embodiments 1-64, wherein

[0218] Embodiment 114. R3 is -(C1-C4)alkylene-NR 13 R 14 and R 13 and R 14 together with the nitrogen atom to which they are attached form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O, N, and S; 27 Form R 27 but one or more R 28 is substituted with R 28 The compound of any of embodiments 1-64, wherein is (C1-C4) alkyl, (C1-C4) alkoxy, OH, or =O.

[0219] Embodiment 115. R3 is -(C1-C4)alkylene-NR13 R 14 and R 13 and R 14 together with the nitrogen atom to which they are attached form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O, N, and S; 27 Form R 27 but one or more R 28 and two R 28 when attached to the same atom, form a (C4-C7)spirocycloalkyl or a 4-7 membered spiroheterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0220] Embodiment 116. R3 is -(C1-C4)alkylene-NR 13 R 14 and R 13 and R 14 together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O and N 27 Form R 27 but one or more R 28 and two R 28 when attached to the same atom, form a (C4-C7)spirocycloalkyl or a 4-7 membered spiroheterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S.

[0221] Embodiment 117. R3 is -(C1-C4)alkylene-NR 13 R 14 and R 13 and R 14 together with the nitrogen atom to which they are attached, form a 4-6 membered heterocycloalkyl ring R containing 1-2 heteroatoms selected from O and N 27 Form R 27 but one or more R 28 and two R 28when attached to the same atom, form a (C4-C7)spirocycloalkyl, or a 4- to 7-membered spiroheterocycloalkyl ring containing one oxygen atom.

[0222] Embodiment 118. R3 is -(C1-C4)alkylene-NR substituted on at least one of the (C1-C4)alkylene carbons with OH, (C1-C4)alkoxy, -(C1-C4)alkylene-O(C1-C4)alkyl, (C1-C4)alkyl. 13 R 14 and each R 13 and R 14 is independently H, (C1-C4)alkyl, —(C1-C4)alkylene-OH, —(C1-C4)alkylene-O(C1-C4)alkyl, —C(O)(C1-C4)alkylene-(C1-C4)alkoxy, or —C(O)(C1-C4)alkyl.

[0223] Embodiment 119. R3 is -(C1-C4)alkylene-NR substituted at at least one (e.g., one) of the (C1-C4)alkylene carbons with OH, (C1-C4)alkoxy, -(C1-C4)alkylene-O(C1-C4)alkyl, (C1-C4)alkyl. 13 R 14 and each R 13 and R 14 The compound of any of embodiments 1-64, wherein is independently H or (C1-C4) alkyl.

[0224] Embodiment 120. A compound of any of Embodiments 1-64, wherein R3 is (C1-C4) alkyl.

[0225] Embodiment 121. A compound of any of Embodiments 1-64, wherein R3 is (C1-C4)alkyl substituted with CN.

[0226] Embodiment 122. R3 is CN, =N-(C1-C4)alkoxy, =NO-(C1-C4)alkylene-OR 20, OH, (C1-C4)alkoxy, —C(O)OH, —C(O)O(C1-C4)alkyl, a 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S, and a 5-6 membered heteroaryl ring containing 1-2 heteroatoms selected from O, N, and S.

[0227] Embodiment 123. A compound of any of Embodiments 1-64, wherein R3 is (C1-C4)alkyl substituted with two groups selected from (C1-C4)alkoxy, a 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O and N, and a 5-6 membered heteroaryl ring containing 1-2 heteroatoms selected from O, N, and S.

[0228] Embodiment 124. A compound of any of Embodiments 1-64, wherein R3 is (C1-C4)alkyl substituted with at least one of (C1-C4)alkoxy and a 5-6 membered heteroaryl ring containing 1-2 heteroatoms selected from O and N.

[0229] Embodiment 125. A compound of any of Embodiments 1-64, wherein R3 is (C1-C4)alkyl substituted with at least one of (C1-C4)alkoxy, a 5-membered heteroaryl ring containing 1 to 2 nitrogen atoms, and a 6-membered heteroaryl ring containing 1 nitrogen atom.

[0230] Embodiment 126. A compound of any of Embodiments 1-64, wherein R3 is (C1-C4)alkoxy.

[0231] Embodiment 127. A compound of any of Embodiments 1-64, wherein R3 is methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy.

[0232] Embodiment 128. A compound of any of Embodiments 1-64, wherein R3 is -O(C1-C4)alkylene-OH.

[0233] Embodiment 129. R3 is -C(O)NR 15 R 16 and each R 15 and R 16 is independently H, (C1-C4)alkyl, —(C1-C4)alkylene-OH, —(C1-C4)alkylene-O(C1-C4)alkyl, —C(O)(C1-C4)alkylene-(C1-C4)alkoxy, or —C(O)(C1-C4)alkyl.

[0234] Embodiment 130. R3 is -C(O)NR 15 R 16 and each R 15 and R 16 The compound of any of embodiments 1-64, wherein is independently H or (C1-C4) alkyl.

[0235] Embodiment 131. R3 is -C(O)NR 15 R 16 and each R 15 and R 16 The compound of any of embodiments 1-64, wherein is H.

[0236] Embodiment 132. R3 is -C(O)NR 15 R 16 and each R 15 and R 16 The compound of any of embodiments 1-64, wherein is methyl.

[0237] Embodiment 133. A compound of any of Embodiments 1-64, wherein R3 is -C(O)(C1-C4)alkylene-OH.

[0238] Embodiment 134. A compound of any of Embodiments 1-64, wherein R3 is -O(C1-C4)alkylene-(C1-C4)alkoxy.

[0239] Embodiment 135. A compound of any of Embodiments 1-64, wherein R3 is -(C1-C4)alkylene-C(O)(C1-C4)alkyl.

[0240] Embodiment 136. A compound of any of Embodiments 1-64, wherein R3 is -(C1-C4)alkylene-C(O)(C1-C4)alkoxy.

[0241] Embodiment 137. R3 is -(C1-C4)alkylene-C(O)NR 17 R 18 65. The compound of any of embodiments 1-64, wherein

[0242] Embodiment 138. A compound of any of Embodiments 1-64, wherein R3 is a 6-membered heterocycloalkyl ring Ri containing 1-2 heteroatoms selected from O and N, and Ri is optionally substituted with (C1-C4) alkyl.

[0243] Embodiment 139. A compound of any of Embodiments 1-64, wherein R3 is a 6-membered heterocycloalkyl ring Ri containing 1-2 heteroatoms selected from O and N, Ri being optionally substituted with (C1-C4) alkyl, and further wherein R3 is bonded to R2 at a ring carbon of R3.

[0244] Embodiment 140. A compound of any of Embodiments 1-64, wherein R3 is a 6-membered heterocycloalkyl ring Ri containing two heteroatoms selected from O and N, and Ri is optionally substituted with (C1-C4) alkyl.

[0245] Embodiment 141. A compound of any of Embodiments 1-64, wherein R3 is a 6-membered heterocycloalkyl ring Ri containing two heteroatoms selected from O and N, and Ri is substituted with (C1-C4) alkyl.

[0246] Embodiment 142. A compound of any of Embodiments 1-64, wherein R3 is a 6-membered heterocycloalkyl ring Ri containing one O and one N, and Ri is substituted with (C1-C4) alkyl.

[0247] Embodiment 143. A compound of any of Embodiments 1-64, wherein R3 is a 6-membered heterocycloalkyl ring Ri containing one O and one N, and Ri is substituted at N with (C1-C4) alkyl.

[0248] Embodiment 144.R3 is [ka] 65. The compound of any of embodiments 1-64, wherein

[0249] Embodiment 145.R3 is [ka] 65. The compound of any of embodiments 1-64, wherein

[0250] Embodiment 146.R3 is [ka] 65. The compound of any of embodiments 1-64, wherein

[0251] Embodiment 147. A compound of any of Embodiments 1-64, wherein R3 is (C1-C4)alkyl substituted with (C1-C4)alkoxy, and a 5-6 membered heteroaryl ring containing 1-2 heteroatoms selected from O and N.

[0252] Embodiment 148. A compound of any of Embodiments 1-64 wherein R3 is (C1-C4)alkyl substituted with (C1-C4)alkoxy and a 5-membered heteroaryl ring containing two nitrogen heteroatoms.

[0253] Embodiment 149. A compound of any of Embodiments 1-64 wherein R3 is (C1-C4)alkyl substituted with (C1-C4)alkoxy and a 6-membered heteroaryl ring containing two nitrogen heteroatoms.

[0254] Embodiment 150. A compound of any of Embodiments 1-64 wherein R3 is (C1-C4)alkyl substituted with (C1-C4)alkoxy and a 6-membered heterocycloalkyl ring containing two heteroatoms selected from O and N.

[0255] Embodiment 151. A compound of any of Embodiments 1-64 wherein R3 is (C1-C4)alkyl substituted with (C1-C4)alkoxy and an N-containing 4-membered heterocycloalkyl ring.

[0256] Embodiment 152. 6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 6-chloro-7-fluoro-2-(5-fluoro-4H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-fluoro-1H-1,2,4-triazol-5-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-1H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 2-(5-bromo-4H-1,2,4-triazol-3-yl)-6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indole; 2-(3-bromo-1H-1,2,4-triazol-5-yl)-6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indole; 2-(5-bromo-1H-1,2,4-triazol-3-yl)-6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-5-carbonitrile; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-5-carbonitrile; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-5-carbonitrile; 1-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one; 6-chloro-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-5-carbonitrile; 6-chloro-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-5-carbonitrile; 6-chloro-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-5-carbonitrile; 6,7-dichloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6,7-dichloro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6,7-dichloro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-Dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(5-(2,2,2-trifluoroethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(5-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Difluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Difluoro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-Difluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 2-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-ol; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-methoxy-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 5,6-Dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 5,6-Dichloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 5,6-Dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; Ethyl 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate; Ethyl 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carboxylate; Ethyl 3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carboxylate; 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxamide; 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carboxamide; 3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carboxamide; 5,6-Dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 5,6-Dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 5,6-Dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 2-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-1-yl)ethan-1-ol; 2-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-1-yl)ethan-1-ol; 2-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-1-yl)ethan-1-ol; 6-chloro-5-methoxy-1-(2-methoxyethyl)-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-methoxy-1-(2-methoxyethyl)-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-methoxy-1-(2-methoxyethyl)-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-7-carbonitrile; 6-chloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; Ethyl 5-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate; Ethyl 5-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carboxylate; Ethyl 3-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carboxylate; 2-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)acetate methyl; 2-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)acetic acid methyl ester; 2-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)methyl acetate; 7-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-5-carboxamide; 7-chloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-5-carboxamide; 7-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-5-carboxamide; 5-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carboxamide; 4,5-Dichloro-1-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 4,5-Dichloro-1-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 4,5-Dichloro-1-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-5-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-5-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-5-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-7-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-7-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-7-ol; 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carbonitrile; 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carbonitrile; 3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carbonitrile; (5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)methanol; (5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)methanol; (3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)methanol; 2-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-1-yl)ethan-1-ol; 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(1H-1,2,4-triazol-3-yl)-1H-indole; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-methoxyethyl)-N-methyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-methoxyethyl)-N-methyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-methoxyethyl)-N-methyl-1H-1,2,4-triazole-5-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-hydroxyethyl)-N-methyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-hydroxyethyl)-N-methyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-hydroxyethyl)-N-methyl-1H-1,2,4-triazole-5-carboxamide; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(morpholino)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(morpholino)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(morpholino)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypyrrolidin-1-yl)methanone; (S)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (S)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (S)-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypyrrolidin-1-yl)methanone; (R)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (R)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (R)-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypyrrolidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(4-hydroxypiperidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(4-hydroxypiperidin-1-yl)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(4-hydroxypiperidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypiperidin-1-yl)methanone; (S)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (S)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (S)-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypiperidin-1-yl)methanone; (R)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (R)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (R)-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypiperidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(4-methylpiperazin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(4-methylpiperazin-1-yl)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(4-methylpiperazin-1-yl)methanone; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(methoxymethyl)-4H-1,2,4-triazol-3-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(methoxymethyl)-1H-1,2,4-triazol-5-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(methoxymethyl)-1H-1,2,4-triazol-3-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylthio)methyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(3-((methylthio)methyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylthio)methyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-ol; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-1-methyl-1H-indole; 6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(3-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (S)-6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (S)-6-chloro-2-(3-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (S)-6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (R)-6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (R)-6-chloro-2-(3-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (R)-6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(methoxymethyl)-4H-1,2,4-triazol-3-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(methoxymethyl)-1H-1,2,4-triazol-5-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(methoxymethyl)-1H-1,2,4-triazol-3-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylsulfonyl)methyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(3-((methylsulfonyl)methyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylsulfonyl)methyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one; 6-chloro-7-fluoro-2-(5-fluoro-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-fluoro-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 4-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)morpholine; 4-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)morpholine; 4-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)morpholine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-one; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-one; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-one; N-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-methylacetamide; N-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-methylacetamide; N-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-methylacetamide; N-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylacetamide; N-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylacetamide; N-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylacetamide; 2-((5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(methyl)amino)ethan-1-ol; 2-((5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(methyl)amino)ethan-1-ol; 2-((3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(methyl)amino)ethan-1-ol; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoroethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(3-(1,1-difluoroethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoroethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoroethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(3-(1,1-difluoroethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoroethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; 6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole-7-carbonitrile; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole-7-carbonitrile; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole-7-carbonitrile; 1-(5-(6-chloro-5-ethoxy-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-one; 1-(5-(6-chloro-5-ethoxy-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-one; 1-(3-(6-chloro-5-ethoxy-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-one; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; 3-(6,7-dichloro-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-3-yl)-1H-pyrazol-5-ol; 3-(6,7-dichloro-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-3-yl)-1H-pyrazol-5-ol; 3-(6,7-dichloro-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-3-yl)-1H-pyrazol-5-ol; 3-(6,7-dichloro-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-3-yl)isoxazol-5-ol; 3-(6,7-dichloro-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-3-yl)isoxazol-5-ol; 3-(6,7-dichloro-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-3-yl)isoxazol-5-ol; 6,7-Dichloro-3-(1H-pyrazol-3-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-3-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-Dichloro-3-(1H-pyrazol-3-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)propanenitrile; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)propanenitrile; 2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)propanenitrile; (R)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)propanenitrile; (R)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)propanenitrile; (R)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)propanenitrile; (S)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)propanenitrile; (S)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)propanenitrile; (S)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)propanenitrile; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-2-(5-isopropoxy-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-2-(3-isopropoxy-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-2-(5-isopropoxy-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-2-(3-fluoro-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1H-indole; 6-chloro-7-fluoro-2-(3-fluoro-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1H-indole; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-((5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(methyl)amino)ethan-1-ol; 2-((5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(methyl)amino)ethan-1-ol; 2-((3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(methyl)amino)ethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)pyrrolidin-3-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)pyrrolidin-3-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)pyrrolidin-3-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (S)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (R)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; 2-((5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)oxy)ethan-1-ol; 2-((5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)oxy)ethan-1-ol; 2-((3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)oxy)ethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2,2-trifluoroethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2,2-trifluoroethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2,2-trifluoroethan-1-ol; 6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-2-(3-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-6-chloro-2-(3-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-6-chloro-2-(3-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(3-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(3-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(3-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 1-(5-(6-chloro-5-ethoxy-7-fluoro-3-(1H-imidazol-1-yl)-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-one; 1-(5-(6-chloro-5-ethoxy-7-fluoro-3-(1H-imidazol-1-yl)-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-one; 1-(3-(6-chloro-5-ethoxy-7-fluoro-3-(1H-imidazol-1-yl)-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-one; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-one; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-one; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-one; 5-(6-chloro-7-cyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-cyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-cyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 5-(6,7-difluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6,7-difluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6,7-difluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 5,6-Dichloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 5,6-Dichloro-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 5,6-Dichloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-Dichloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 5,6-Dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 5,6-Dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 5,6-Dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-Dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-Dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-5-(difluoromethoxy)-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-(difluoromethoxy)-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-(difluoromethoxy)-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-cyclopropoxy-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-cyclopropoxy-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-cyclopropoxy-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-5-ol; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-5-ol; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-5-ol; 5-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 6-chloro-5-hydroxy-2-(5-(2-hydroxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-5-hydroxy-2-(3-(2-hydroxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-5-hydroxy-2-(5-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(2-hydroxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(3-(2-hydroxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 2-(5-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(5-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(3-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-ol; 5-(6,7-dicyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6,7-dicyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6,7-dicyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)morpholine; 4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)morpholine; 4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)morpholine; (S)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)morpholine; (S)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)morpholine; (S)-4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)morpholine; (R)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)morpholine; (R)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)morpholine; (R)-4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)morpholine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylethan-1-amine; 4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; 4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; 4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethyl)morpholine; (R)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; (R)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; (R)-4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethyl)morpholine; (S)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; (S)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; (S)-4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethyl)morpholine; 2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(3-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(3-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(3-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)ethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)ethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)ethan-1-amine; 6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; 6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; 6-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (S)-6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (S)-6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (S)-6-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (R)-6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (R)-6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (R)-6-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; 152. The compound of any of embodiments 1-151, selected from: or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

[0257] Embodiment 153. 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; and (S)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol, or a pharmaceutically acceptable salt thereof.

[0258] Embodiment 154. 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; and (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol, or a pharmaceutically acceptable salt thereof.

[0259] Embodiment 155. 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-one; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-one; and 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-one, or a pharmaceutically acceptable salt thereof.

[0260] Embodiment 156. 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; and (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine, or a pharmaceutically acceptable salt thereof.

[0261] Embodiment 157. 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; and (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylethan-1-amine, or a pharmaceutically acceptable salt thereof.

[0262] Non-limiting exemplary compounds of the present disclosure include those in Table 1 below. As discussed below, each of the exemplary compounds is represented by one tautomeric form for structural features that allow tautomerism. For convenience, tautomers A, B, and C refer to tautomers with respect to the triazole motif in the compounds of the present invention. Unless otherwise specified, IC 50 is reported for potential mixtures in solution of coexisting tautomers and / or racemates, regardless of the specific tautomer.

[0263] [Table 1]

[0264] Table 2

[0265] Table 3

[0266] Table 4

[0267] Table 5

[0268] Table 6

[0269] Table 7

[0270] Table 8

[0271] Table 9

[0272] Table 10

[0273] Table 11

[0274] Table 12

[0275] Table 13

[0276] Table 14

[0277] Table 15

[0278] Table 16

[0279] Table 17

[0280] Table 18

[0281] Table 19

[0282] Table 20

[0283] Table 21

[0284] Table 22

[0285] Table 23

[0286] Table 24

[0287] Table 25

[0288] Table 26

[0289] Table 27

[0290] Table 28

[0291] Table 29

[0292] Table 30

[0293] Table 31

[0294] Table 32

[0295] Table 33

[0296] Table 34

[0297] Table 35

[0298] Table 36

[0299] Table 37

[0300] Table 38

[0301] Table 39

[0302] Table 40

[0303] Table 41

[0304] Table 42

[0305] Table 43

[0306] Table 44

[0307] Table 45

[0308] Table 46

[0309] Table 47

[0310] Table 48

[0311] Table 49

[0312] Table 50

[0313] Table 51

[0314] Table 52

[0315] Table 53

[0316] Table 54

[0317] Table 55

[0318] Table 56

[0319] Table 57

[0320] Table 58

[0321] Table 59

[0322] Table 60

[0323] Table 61

[0324] Table 62

[0325] Table 63

[0326] Table 64

[0327] Table 65

[0328] Table 66

[0329] Table 67

[0330] Table 68

[0331] Table 69

[0332] Table 70

[0333] Table 71

[0334] Table 72

[0335] Table 73

[0336] Table 74

[0337] [Table 75]

[0338] [Table 76]

[0339] [Table 77]

[0340] [Table 78]

[0341] [Table 79]

[0342] In another embodiment of the present disclosure, the compounds of the present disclosure are enantiomers. In some embodiments, the compounds are (S)-enantiomers. In other embodiments, the compounds are (R)-enantiomers. In still other embodiments, the compounds of the present disclosure can be (+) or (-) enantiomers.

[0343] It is understood that all isomers, including mixtures thereof, are included within the present disclosure. When a compound contains a double bond, the substituent may be in the E or Z configuration. When a compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis or trans configuration. All tautomers are also intended to be included.

[0344] The compounds of the present disclosure, as well as their pharmaceutically acceptable salts, hydrates, solvates, and stereoisomers, may exist in their tautomeric form (e.g., as an amide or imino ether), and all such tautomeric forms are contemplated herein as part of the disclosure.

[0345] The compounds of the present disclosure may contain asymmetric chiral centers and therefore may exist in different stereoisomeric forms. All stereoisomers of the compounds of the present disclosure, as well as mixtures thereof, including racemic mixtures, are intended to form part of the present disclosure. Furthermore, the present disclosure encompasses all geometric and positional isomers. For example, if a compound of the present disclosure incorporates a double bond or a fused ring, both the cis- and trans-forms, as well as mixtures, are included within the scope of the present disclosure. Each compound disclosed herein includes all enantiomers consistent with the general structure of the compound. The compounds may be in racemic or enantiomerically pure form, or other forms in terms of stereochemistry. Analytical results may reflect data collected for a racemic, enantiomerically pure, or other forms in terms of stereochemistry.

[0346] Diastereomeric mixtures can be separated into their individual diastereomers based on their physical chemical differences by methods well known to those skilled in the art, such as, for example, chromatography and / or fractional crystallization. Enantiomers can be separated by converting the enantiomeric mixture to a diastereomeric mixture by reacting it with an appropriate optically active compound (e.g., a chiral auxiliary such as a chiral alcohol or Moschel's acid chloride), separating the diastereomers, and converting the individual diastereomers to their corresponding pure enantiomers (e.g., by hydrolysis). Additionally, some compounds of the present disclosure may be atropisomers (e.g., substituted biaryls) and are considered part of the present disclosure. Enantiomers can also be separated using chiral HPLC columns.

[0347] Compounds of the present disclosure may also exist in different tautomeric forms, and all such forms are encompassed within the scope of the present disclosure and chemical structures and names. Also, for example, all keto-enol and imine-enamine forms of the compounds are included in the present disclosure.

[0348] All stereoisomers of the compounds (including salts, solvates, and esters of the compounds), such as those that may exist due to asymmetric carbons on various substituents, including enantiomeric forms (which may exist even in the absence of an asymmetric carbon), rotamers, atropisomers, and diastereomeric forms (e.g., geometric isomers, optical isomers, and the like), as well as positional isomers (e.g., 4-pyridyl and 3-pyridyl), are intended to be within the scope of the present disclosure. Individual stereoisomers of the compounds of the present disclosure may, for example, be substantially free of other isomers, or may be present, for example, as a racemate or mixed with all or selected other stereoisomers.

[0349] The chiral centers of the compounds of the present disclosure can have the S or R configuration, as defined by the IUPAC 1974 Recommendations. In certain embodiments, each asymmetric atom has the (R)- or (S)-configuration in at least 50% enantiomeric excess, at least 60% enantiomeric excess, at least 70% enantiomeric excess, at least 80% enantiomeric excess, at least 90% enantiomeric excess, at least 95% enantiomeric excess, or at least 99% enantiomeric excess. Substituents of atoms bearing unsaturated double bonds are present in cis-(Z)- or trans-(E)-form, where possible.

[0350] The use of the terms "salts," "solvates," "esters," and the like is intended to apply equally to salts, solvates, and esters of enantiomers, stereoisomers, rotamers, tautomers, positional isomers, or racemates of the compounds of the present invention.

[0351] The compounds of the present disclosure can form salts that are also within the scope of the present disclosure, and a reference to a compound of any formula disclosed herein will generally be understood to include a reference to the salts thereof, unless otherwise specified.

[0352] Compounds and intermediates can be isolated and used as compounds themselves.The formulas given herein are intended to represent both isotopically labeled and unlabeled forms of compounds.Isotopically labeled compounds have the structure shown by the formulas provided herein, except that one or more atoms are replaced by atoms with selected atomic mass or mass number.Examples of isotopes that can be incorporated into compounds of the present disclosure include hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and each of the following: 2 H, 3 H, 11 C. 13 C. 14 C. 15 N, 18 F, 31 P, 32 The present disclosure includes various isotopically labeled compounds as defined herein, e.g., 3 H, 13 C, and 14 Such isotopically labeled compounds may be useful in metabolic studies, including drug or substrate tissue distribution assays, or in radiation treatment of patients. 14 C), reaction kinetic studies ( 2 H or 3 H), positron emission tomography (PET) or single photon emission computed tomography (SPECT). 18 F, 11 C, or labeled compounds, may be particularly desirable for PET or SPECT studies.

[0353] Additionally, heavier isotopes, especially deuterium (i.e. 2Substitution with a deuterium atom (H or D) may result in increased metabolic stability and therefore certain therapeutic advantages, such as increased in vivo half-life, reduced dosage, reduced CYP450 inhibition (competitive or time-dependent), or improved therapeutic index. For example, substitution with deuterium may modulate undesirable side effects of non-deuterated compounds, such as competitive CYP450 inhibition or time-dependent CYP450 inactivation. It is understood that deuterium in this context is considered a substituent in the compounds of the present disclosure. The concentration of such heavier isotopes, particularly deuterium, can be defined by an isotopic enrichment factor. As used herein, the term "isotopic enrichment factor" refers to the ratio between the isotopic abundance and the natural abundance of a particular isotope. When a substituent in a compound of the present disclosure is designated as deuterium, such compounds have an isotopic enrichment factor for each designated deuterium atom of at least 3500 (52.5% deuterium incorporation at each designated deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation), or at least 6633.3 (99.5% deuterium incorporation).

[0354] Isotopically labeled compounds of the present disclosure can generally be prepared by carrying out the disclosed procedures of the schemes or examples and preparations by conventional techniques well known to those skilled in the art, or by substituting the appropriate isotopically labeled reagent for the non-isotopically labeled reagent described below.

[0355] Pharmaceutically acceptable solvates in accordance with the present disclosure include those wherein the solvent of crystallization may be isotopically substituted, eg, D2O, d6-acetone, d6-DMSO.

[0356] The present disclosure relates to compounds that are modulators of cGAS activity. In one embodiment, the compounds of the present disclosure decrease cGAS activity. In yet another embodiment, the compounds of the present disclosure reduce cGAS activity. In another embodiment, the compounds of the present disclosure are inhibitors of cGAS activity.

[0357] In some embodiments, compounds of the present disclosure are selective relative to other proteins. As used herein, a "selective modulator," "selective inhibitor," or "selective compound" refers to a compound of the present disclosure that, for example, modulates, decreases, or reduces the level of a particular protein activity more effectively than other proteins. A "selective modulator," "selective inhibitor," or "selective compound" can be identified, for example, by comparing the ability of a compound to modulate, decrease, or reduce the level of a particular protein or inhibit a particular protein with its ability to modulate, decrease, or reduce the level of its activity. In some embodiments, selectivity is measured by the EC 50 or IC 50 It can be determined by measuring

[0358] In some embodiments, the compounds of the present application are selective cGAS modulators. As used herein, "selective cGAS modulators," "selective cGAS inhibitors," or "selective cGAS compounds" refer to compounds of the present application that modulate, decrease, or reduce cGAS activity levels more effectively than, for example, other proteins.

[0359] In some embodiments, the inhibition of cGAS is at least 50% by IC 50 It is measured by

[0360] Efficacy is IC 50 A lower IC when determined under substantially similar conditions can be determined by the IC value. 50 Compounds with higher IC 50In some embodiments, the substantially similar conditions include determining inhibition of protein levels in cells expressing the particular protein or any fragment thereof.

[0361] The present disclosure is directed to compounds described herein and pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, or tautomers thereof, and pharmaceutical compositions comprising one or more compounds described herein or pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, or tautomers thereof.

[0362] F. Methods for synthesizing compounds of formula (I) The compounds of the present disclosure may be made by a variety of methods, including standard chemistry. Suitable synthetic routes are illustrated in the schemes provided below.

[0363] The compounds of the present disclosure can be prepared by methods known in the art of organic synthesis, as illustrated in part by the following synthetic schemes. In the following schemes, it is well understood that protecting groups for sensitive or reactive groups are employed where necessary in accordance with general principles or chemistry. Protecting groups are manipulated according to standard methods of organic synthesis. (T.W. Green and P.G. Mughuts, "Protective Groups in Organic Synthesis", Third Edition, Wiley, New York 1999). These groups are removed at a convenient stage of the compound synthesis using methods readily apparent to those skilled in the art. The selected processes, as well as the reaction conditions and the order of their execution, shall be consistent with the preparation of compounds of formula (I).

[0364] Those skilled in the art will recognize if a stereocenter exists in the compounds of the present disclosure. Accordingly, the present disclosure includes both possible stereoisomers (unless specified in the synthesis), including not only racemates but also individual enantiomers and / or diastereomers. When a compound is desired as a single enantiomer or diastereomer, it may be obtained by stereospecific synthesis or by resolution of the final product or any convenient intermediate. Separation of the final product, intermediate, or starting material can be affected by any suitable method known in the art. See, for example, "Stereochemistry of Organic Compounds" by E.L. Eliel, S.H. Wilen, and L.N. Mander (Wiley-Interscience, 1994).

[0365] The compounds described herein can be made from commercially available starting materials or can be synthesized using known organic, inorganic, and / or enzymatic processes.

[0366] Preparation of compounds The compounds of the present disclosure can be prepared by many methods well known to those skilled in the art of organic synthesis. For example, the compounds of the present disclosure can be synthesized using the methods described below, along with synthetic methods known in the art of organic synthetic chemistry, or variations thereof as would be understood by those skilled in the art. Preferred methods include, but are not limited to, the methods described below.

[0367] General procedures for the synthesis of intermediates and compounds of general formula M1-34 are described in the following reaction schemes and illustrated in the preparations and examples.

[0368] The following reaction schemes describe general routes to the corresponding indole intermediates, which were further transformed to give the corresponding compounds of the invention.

[0369] [ka] Compounds of the general structure (M2) were obtained by reacting anilines (M1) with a halogenating agent such as bromine in a suitable solvent such as acetic acid, following published procedures (e.g., WO 2016 / 103037). Subsequent conversion of (M2) in a Pd-catalyzed cross-coupling reaction with the corresponding alkyne afforded (M3) (e.g., Org. Process Res. Dev. 2015, 19, 1282-1285). Treatment of (M3) with a base such as sodium hydride or KOtBu results in cycloisomerization to the corresponding indole (M4). Alkylation of the indole NH to afford (M5) can be achieved using, for example, a base such as sodium hydride, KOtBu, and a suitable alkylating agent such as iodomethane, dimethyl sulfate, or other alkyl halides.

[0370] [ka] Intermediate (M2) can be converted to the corresponding indole, and initial enamine formation with pyruvate followed by intramolecular Heck coupling affords indole 2-carboxylate (M6). Subsequent conversion to the corresponding alcohol, e.g., MeOH and sulfuric acid, or TMS-diazomethane in MeOH affords ester (M7). Alternatively, utilizing an appropriate ortho-directing group such as Boc or phenylsulfonamide, selective deprotonation of (M8) at the indole 2-position with a base such as LDA can be achieved, followed by treatment with the corresponding chloroformate to afford (M9). Removal of the protecting group using appropriate conditions (Greene's Protective Groups in Organic Synthesis, 5th Edition) affords (M7).

[0371] [ka] The synthesis of triazole intermediates generally begins with the protection of 1,3-dibromotriazole (M10) with an appropriate protecting group, preferably, but not limited to, PMB or SEM protected. The dibromide (M11) can undergo halogen-metal exchange using n-butyllithium, iPrMgCl, or TurboGrignard at temperatures between -78°C and 0°C to give (M12). Utilizing appropriate electrophiles provides access to the corresponding ketones (M13), esters (M14), and amides (M15). Alternatively, the latter can be obtained by direct deamidation of esters (M14) with amines in solvents such as THF, EtOH, or iPrOH at elevated temperatures. Fluorination of ketones (M13) with fluorinating agents such as DAST provides access to difluorinated compounds (M16). Reduction of the ketone (M13) (e.g., with NaBH4) provides the desired alcohol (M17), which can be alkylated and further functionalized to (M19) or converted to the monofluoro analog (M18) using a reagent such as DAST. Intermediate (M18) can be further utilized to displace the fluorine with an appropriate amine, optionally requiring first removal of a protecting group, to provide intermediate (M20).

[0372] Scheme 3 depicts only one tautomer or positional isomer about the triazole ring for each of intermediates M11-M20. Each intermediate may be a mixture of up to all three tautomers or positional isomers about the triazole ring, as shown below using M13 as an example. Such mixtures are used directly in the next step without separation. [ka] [ka] An appropriately substituted indole (M4) can be halogenated using a suitable agent, such as NBS, in a suitable solvent, such as DCM, ACN, or THF, to give (M21). This can then be treated with a suitable boronic acid / ester to introduce a suitable five-membered heterocycle, such as a pyrazole, to give (M22). In the next step, halogenation is carried out in a manner similar to that at the beginning of the reaction sequence, e.g., bromination with NBS. Intermediate (M23) and bromotriazole (M13-20) can be cross-coupled in a Pd-cross-coupling reaction, typically using PdCl(dppf) and bis(pinacolato)diboron, a base such as KOAc or KCO, a solvent such as water, THF, dioxane, or a surfactant such as TPGS-750M, at a suitable temperature ranging from ambient to 130 °C, to give (M24). Intermediate (M24) can be directly deprotected to give the corresponding NH analog (M26, R' = H), for example, by treatment with triflic acid, or optionally includes N-alkylation with iodomethane or dimethyl sulfate before deprotection to (M26, R' = alkyl).

[0373] [ka] Following a similar procedure described by Hartwig et al. (Org. Lett. 2012, 14(16), 4266-4269), indoles (M4 / M5), optionally substituted or unsubstituted at the indole NH, are converted to the corresponding organoboronates (M27) by iridium-catalyzed CH-borylation, which are then further transformed, usually without isolation / purification, in Suzuki coupling with the corresponding protected bromotriazoles (M13-20). Deprotection of M28 is then typically carried out using triflic acid or TFA or a mixture of both to give M29, which can be halogenated to M30 by using an appropriate reagent such as NBS in a suitable solvent such as DCM, ACN, or THF. Introduction of a 5-membered heterocycle, such as imidazole, can be achieved by Ullmann coupling with a suitable copper salt, such as CuI, and a base, such as K2CO3 or Cs2CO3, in a polar solvent (e.g., DMSO, DMF, or NMP), in the presence of a suitable ligand, such as proline, at a temperature ranging from 60 to 150°C, to give (M31). Alternatively, intermediate (M30), after a deprotection step, usually carried out using a strong acid, such as hydrochloric acid in dioxane, can be subjected to a Suzuki reaction with a suitable 5-membered heterocycle, such as pyrazole, to give (M26).

[0374] Alternatively, access to intermediate (M29) can be achieved starting from the corresponding ester (M7) by treatment with an aqueous solution of hydrazine hydrate in a protic solvent such as EtOH at temperatures up to 100° C. The resulting hydrazide (M33) can be treated with a readily available iminoester in a solvent such as EtOH at temperatures up to 100° C. to give intermediate (M34), which is typically subjected to further condensation without isolation / purification by treatment with a base, e.g., sodium ethylate or DBU, at temperatures up to 160° C. to give the desired triazole intermediate (M29).

[0375] The mixtures of enantiomers, diastereomers, and cis / trans isomers obtained by the above processes can be separated into single components by chiral salt techniques, chromatography using normal-phase, reverse-phase, or chiral columns, depending on the nature of the separation.

[0376] Racemates obtained from compounds or intermediates of the present disclosure can be resolved into their optical antipodes by known methods, for example, by separation of diastereomeric salts obtained with optically active acids or bases and liberating the optically active acid or base compounds. Thus, basic moieties can be used to resolve compounds of the present disclosure into their optical antipodes, particularly by fractional crystallization of salts formed with optically active acids, such as tartaric acid, dibenzoyltartaric acid, diacetyltartaric acid, di-O,O'-p-toluoyltartaric acid, mandelic acid, malic acid, or camphor-10-sulfonic acid. Racemates or racemic intermediates of the present disclosure can also be resolved by chiral chromatography, for example, high-pressure liquid chromatography (HPLC) using a chiral adsorbent.

[0377] Any resulting mixture of stereoisomers can be separated on the basis of the physical chemical differences of the components into pure or substantially pure geometric or optical isomers, diastereomers, racemates, for example, by chromatography and / or fractional crystallization.

[0378] In the descriptions and formulae set forth above, it should be understood that the various groups R, R, R, R, R, R, R, R, R, R, and R are selected consistent with the definitions defined above at each position in the compounds of formula (I), unless otherwise specified. Additionally, for synthetic purposes, the compounds of General Schemes 1-5 are merely representative, with radicals selected to illustrate the general synthetic methodology for the compounds of formula (I) defined herein.

[0379] G. Methods of Using Compounds of Formula (I) The compounds of the invention, in free form or in pharmaceutically acceptable salt form, exhibit valuable pharmacological properties, e.g., cGAS modulating properties (as demonstrated, for example, in the in vitro and in vivo tests provided in the next section), and are therefore indicated for use as therapeutic or research chemicals, e.g., as tool compounds.

[0380] The compounds of the present invention are useful for the treatment of Aicardi-Goutières syndrome, familial lupus pernio, RVCL (autosomal dominant retinal vasculopathy with cerebral leukodystrophy), vasculitis, systemic lupus erythematosus (SLE), lupus nephritis (LN), dermatomyositis, Sjögren's syndrome (SS), rheumatoid arthritis (RA), age-related macular degeneration (AMD), Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), pulmonary inflammation, acute pulmonary inflammation, idiopathic pulmonary fibrosis, and liver fibrosis. and renal fibrosis, non-alcoholic steatohepatitis (NASH), liver cirrhosis, endocardial fibrosis, acute and chronic kidney injury, APOL1-associated podocytopathy, acute pancreatitis, ulcerative colitis, inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), sepsis, senescence, and aging; preferably, the present invention may be useful for the treatment of an indication selected from Aicardi-Goutières syndrome (AGS), vasculitis, systemic lupus erythematosus (SLE), familial lupus pernio, and Sjogren's syndrome.

[0381] The compounds of the present invention are also useful in the treatment of Aicardi-Goutières syndrome, familial lupus pernio, RVCL (autosomal dominant retinal vasculopathy with cerebral leukodystrophy), vasculitis, systemic lupus erythematosus (SLE), lupus nephritis (LN), dermatomyositis, Sjögren's syndrome (SS), rheumatoid arthritis (RA), age-related macular degeneration (AMD), Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), pulmonary inflammation, acute pulmonary inflammation, idiopathic pulmonary edema, and pulmonary fibrosis. It may be useful for the treatment of indications selected from fibrosis, liver and kidney fibrosis, non-alcoholic steatohepatitis (NASH), liver cirrhosis, endocardial fibrosis, acute kidney injury, ulcerative colitis, inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), sepsis, senescence, and aging; preferably, Aicardi-Goutières syndrome (AGS), vasculitis, systemic lupus erythematosus (SLE), familial lupus pernio, and Sjogren's syndrome.

[0382] Thus, in a further aspect, the present invention provides the use of a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, or a composition comprising a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, in therapy. In a further embodiment, the therapy is selected from diseases that can be treated by modulation of cGAS. In another embodiment, the disease is selected from the foregoing list; preferably, Aicardi-Goutières syndrome (AGS), vasculitis, systemic lupus erythematosus (SLE), familial lupus pernio, and Sjögren's syndrome.

[0383] Thus, in a further aspect, the present invention provides a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, or a composition comprising a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, for use in therapy. In a further embodiment, the therapy is selected from diseases that can be treated by modulation of cGAS. In another embodiment, the disease is selected from the foregoing list; preferably, Aicardi-Goutières syndrome (AGS), vasculitis, systemic lupus erythematosus (SLE), familial lupus pernio, and Sjögren's syndrome.

[0384] In another aspect, the present disclosure provides a method for treating a disease or disorder treated by modulation of cGAS, comprising administering a therapeutically acceptable amount of a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, or a composition comprising a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof. In a further embodiment, the disease is selected from the list above; preferably, Aicardi-Goutières syndrome (AGS), vasculitis, systemic lupus erythematosus (SLE), familial lupus pernio, and Sjögren's syndrome.

[0385] In another aspect, the present invention provides a method for treating a disease treated by modulation of cGAS, comprising administering a therapeutically acceptable amount of a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, or a composition comprising a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof. In a further embodiment, the disease is selected from the list above; preferably, Aicardi-Goutières syndrome (AGS), vasculitis, systemic lupus erythematosus (SLE), familial lupus pernio, and Sjögren's syndrome.

[0386] Thus, in a further aspect, the present invention provides the use of a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, or a composition comprising a compound of the present invention, or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, for the manufacture of a medicament. In a further embodiment, the medicament is for the treatment of a disease that can be treated by modulation of cGAS. In another embodiment, the disease is selected from the foregoing list; preferably, Aicardi-Goutières syndrome (AGS), vasculitis, systemic lupus erythematosus (SLE), familial lupus pernio, and Sjögren's syndrome.

[0387] H. Administration and Pharmaceutical Compositions of Compounds of Formula (I) In another aspect, the present invention provides a pharmaceutical composition comprising a compound of the present invention, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In a further embodiment, the composition comprises at least two pharmaceutically acceptable carriers, such as those described herein. The pharmaceutical composition can be formulated for a specific route of administration, such as oral administration, parenteral administration (e.g., by injection, infusion, transdermal or topical administration), and rectal administration. Topical administration may also involve inhalation or intranasal application. The pharmaceutical composition of the present invention can be in solid form (including, but not limited to, capsules, tablets, pills, granules, powders, or suppositories) or liquid form (including, but not limited to, solutions, suspensions, or emulsions). Tablets can be either film-coated or enteric-coated by methods known in the art. Typically, the pharmaceutical composition comprises: a) diluents, such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine; b) lubricants, for example silica, talcum, stearic acid, its magnesium or calcium salts and / or polyethylene glycol; also for tablets, c) binders, such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone; optionally, d) disintegrants, such as starch, agar, alginic acid or its sodium salt, or effervescent mixtures; and e) Absorbents, colorants, flavors and sweeteners It is a tablet or gelatin capsule containing the active ingredient together with one or more of the following.

[0388] The compounds of the present invention can be administered simultaneously with, before, or after one or more other therapeutic agents. The compounds of the present invention can be administered separately, by the same or different administration route, or together in the same pharmaceutical composition as other agents. Therapeutic agents are, for example, compounds, peptides, antibodies, antibody fragments, or nucleic acids that are therapeutically active or enhance therapeutic activity when administered to a patient in combination with a compound of the present invention.

[0389] In one embodiment, the present invention provides a product comprising a compound of the present invention and at least one other therapeutic agent as a combined preparation for simultaneous, separate, or sequential use in therapy. In one embodiment, the treatment is treatment of a disease or condition mediated by cGAS. Products provided as combined preparations include compositions comprising a compound of the present invention and the other therapeutic agent together in the same pharmaceutical composition, or a compound of the present invention and the other therapeutic agent in separate forms, e.g., in the form of a kit.

[0390] In one embodiment, the present invention provides a pharmaceutical composition comprising a compound of the present invention and another therapeutic agent. Optionally, the pharmaceutical composition may include a pharmaceutically acceptable carrier, as described above.

[0391] In one embodiment, the present invention provides a kit comprising two or more separate pharmaceutical compositions, at least one of which comprises a compound of the present invention. In one embodiment, the kit comprises a means for keeping the compositions separate, such as a container, a divided bottle, or a divided foil packet. An example of such a kit is a blister pack commonly used for packaging tablets, capsules, and the like.

[0392] The kits of the invention can be used to administer different dosage forms (e.g., oral and parenteral), to administer the separate compositions at different dosage intervals, or to titrate the separate compositions relative to one another. To aid compliance, the kits of the invention typically include directions for administration.

[0393] In the combination therapy of the present invention, the compound of the present invention and the other therapeutic agent may be manufactured and / or formulated by the same or different manufacturers. Furthermore, the compound of the present invention and the other therapeutic agent may be combined into a combination therapy (i) prior to release of the combination product to the physician (e.g., in the case of a kit containing the compound of the present invention and the other therapeutic agent); (ii) by the physician (or under the physician's guidance) immediately prior to administration; or (iii) by the patient themselves, e.g., during sequential administration of the compound of the present invention and the other therapeutic agent. [Example]

[0394] The present disclosure is further illustrated by the following examples and synthetic schemes, which should not be construed as limiting the scope or spirit of the disclosure to the specific procedures described herein. It should be understood that the examples are provided to illustrate particular embodiments, and that no limitation on the scope of the disclosure is thereby intended. Furthermore, it should be understood that resort can be made to various other embodiments, modifications, and equivalents thereof, which may suggest themselves to those skilled in the art, without departing from the spirit of the present disclosure and / or the scope of the appended claims.

[0395] The compounds of the present disclosure can be prepared by methods known in the art of organic synthesis. In all methods, it is understood that protecting groups for sensitive or reactive groups may be used where necessary, in accordance with general principles of chemistry. Protecting groups are manipulated according to standard methods of organic synthesis (T.W. Green and P.G. Mughuts (1999) Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons). These groups are removed at a convenient stage of the compound synthesis using methods readily apparent to those skilled in the art.

[0396] Abbreviations used in the examples below and elsewhere in this specification are as follows: AIBN Azobisisobutyronitrile Bn Benzyl br Broad Bu4NI Tetrabutylammonium iodide d doublet dd Doublet of Doublets ddd doublet doublet doublet ddq Quartet Doublet Doublet ddt triplet doublet doublet dq Quartet Doublet dt Triplet doublet dtd doublet triplet doublet CCl4 Carbon tetrachloride Cs2CO3 Cesium Carbonate Cu(OAc)2Copper(II) acetate DAST Diethylaminosulfur trifluoride DBU 1,8-diazabicyclo[5.4.0]undec-7-ene DCM dichloromethane di-tBu-bipy 4,4'-di-tert-butyl-2,2'-dipyridyl DIBAL-H Diisobutylaluminum hydride DMA N,N-dimethylacetamide DMAP 4-dimethylaminopyridine DME 1,2-dimethoxyethane DMF N,N-dimethylformamide DMP Dess-Martin Periodinane or 1,1,1-Tris(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3-(1H)-one DMSO dimethyl sulfoxide EC 50 50% effective concentration ee enantiomeric excess Et2O diethyl ether EtOAc ethyl acetate 4-Et-Py 4-Ethylpyridine HATU 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate HCl Hydrogen chloride hept HPLC High-Performance Liquid Chromatography h or hr Time HRMS high resolution mass spectrometry g grams I C 50 50% inhibitory concentration K2CO3 Potassium Carbonate KI potassium iodide K3PO4 Tripotassium Phosphate KOAc Potassium Acetate LiAlH4 Lithium Aluminum Hydride LCMS Liquid Chromatography Mass Spectrometry LiHMDS Lithium bis(trimethylsilyl)amide m multiplet MeCN acetonitrile MeOH Methanol mg milligram MgCl2 Magnesium chloride MHz Megahertz min mL milliliter mmol millimole M molar concentration MS mass spectrometry NaBH(OAc)3 Sodium triacetoxyborohydride NaHCO3 Sodium Bicarbonate Na2S2O3 Sodium thiosulfate Na2SO4 Sodium Sulfate NBS N-Bromosuccinimide NEt3 Triethylamine NH4OAc Ammonium Acetate NH4OH Ammonium hydroxide NiBr2(DME) Nickel(II) bromide ethylene glycol dimethyl ether complex NiBr2(glyme) Nickel(II) bromide ethylene glycol dimethyl ether complex NiI2 Nickel(II) iodide NMR nuclear magnetic resonance PCC Pyridinium Chlorochromate PdCl2(dppf)2[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride PdCl2(dppf)·DCM [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane \Pd(Ph3P)4 tetrakis(triphenylphosphine)palladium(0) PtO2 platinum(IV) oxide q quartet qd Quartet of Doublets quint quintet quintd doublet quintet rt room temperature Rt retention time s singlet SFC Supercritical Fluid Chromatography t triplet TEA Triethylamine td triplet of doublets tdd doublet doublet triplet THF tetrahydrofuran Ti(Oi-Pr)4 Titanium Isopropoxide TfOH triflic acid Ts Tosil TsCl 4-toluenesulfonyl chloride tt Triplet of Triplets ttd doublet triplet triplet TLC thin layer chromatography UPLC Ultra High Performance Liquid Chromatography Xphos Pd G2 Chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) μW microwave

[0397] Analysis details NMR: Measurements were performed on a Bruker Ultrashield™ 400 (400 MHz), Bruker Ascend™ (400 MHz), or Bruker Cryosystem (600 MHz) spectrometer with or without tetramethylsilane (TMS) as an internal standard. Chemical shifts (δ) are reported in ppm downfield from TMS, and spectral splitting patterns are referred to as singlet (s), doublet (d), triplet (t), quartet (q), quintet (quint), septet (sept), multiplet, unresolved or overlapping signals (m), or broad signal (br). Deuterated solvents are given in parentheses and have chemical shifts for dimethyl sulfoxide (δ 2.50 ppm), methanol (δ 3.31 ppm), chloroform (δ 7.26 ppm), or other solvents as indicated by the NMR spectral data. · LC-MS method: Mass spectrometry results are reported as the ratio of mass to charge. Method A: Waters UPLC Acquity; Column: Acquity CORTECS C18+, 2.7 μm, 2.1 × 50 mm, 80 °C; Eluent A: HO + 0.05% HCOOH + 4.76% iPrOH + 3.75 mM ammonium acetate; Eluent B: iPrOH + 0.05% HCOOH; Gradient: Initial 1% B; 1.4 min 1% to 50% B, 0.3 min 50% to 98% B; 0.1 min 98% B; Flow rate: 1.0 mL / min. Method B: Waters UPLC Acquity; Column: Acquity UPLC BEH C18, 1.7 μm, 2.1 × 50 mm, 80 °C, Eluent A: HO + 0.05% HCOOH + 4.76% iPrOH + 3.75 mM ammonium acetate, Eluent B: iPrOH + 0.05% HCOOH, Gradient: 1 to 98% B in 1.7 min, Flow rate: 0.6 mL / min. Method C: Waters UPLC Acquity; Column: Ascentis® Express C18 2.7 μm, 2.1 × 50 mm, 80 °C, Eluent A: water + 4.76% iPrOH + 0.05% FA + 3.75 mM ammonium acetate, Eluent B: iPrOH + 0.05% HCOOH, Gradient: initial 1 to 50% B in 1.4 min; 50 to 98% B in 0.3 min, Flow rate: 1.0 mL / min.

[0398] Preparation method Flash column chromatography system Method A: Typically, the sample was adsorbed onto Isolute. System: Teledyne ISCO, CombiFlash RF Column: Pre-packed RediSep RF cartridge Method B: Typically, the sample is loaded as a solution in DCM. System: Biotage ISOLERA or SELEKT Column: Pre-packed KPSil cartridge or SFAR cartridge

[0399] Achiral reversed-phase (RP) chromatography: System: Waters System XBridge-C18 or Sunfire-C18 (5 um, 30 x 100 mm or 50 x 250 mm column, as described in the Examples) Detection: Waters DAD 2998 detector; Waters Acquity Qda mass spectrometer Column temperature: RT Eluent A: Water + 0.2% HCOOH or water 0.1% TFA (as described in the Examples) Eluent B: Acetonitrile Flow rate: 49 mL / min or 100 mL / min Gradient: as described in the Examples

[0400] All starting materials, building blocks, reagents, acids, bases, dehydrating agents, solvents, and catalysts utilized to synthesize the compounds of the present invention are either commercially available or can be produced by organic synthesis methods known to those skilled in the art.

[0401] Synthesis of indole intermediates Example A: 6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indole [ka] Step 1: 2-Chloro-3-fluoro-1-methoxy-4-nitrobenzene A solution of sodium (3.71 g, 161 mmol) in MeOH (125 mL) was added dropwise via a dropping funnel to an ice-cold solution of 3-chloro-2,4-difluoronitrobenzene (26 g, 134 mmol) in MeOH (500 mL). The ice cooling was removed, and the reaction mixture was stirred at room temperature for 16 h. The solvent was removed in vacuo. Water was added, and the aqueous phase was extracted with DCM. The combined organic extracts were dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc (0-40% EtOAc) to give the title compound (9.5 g). UPLC-MS (Method B): Rt = 1.02 min; mass not detected; 1 H NMR(400 MHz,DMSO-d6)δ 8.23(dd, J=9.5,8.7 Hz,1H),7.23(dd,J=9.6,1.8 Hz,1H),4.04(s,3H).

[0402] Step 2: 3-chloro-2-fluoro-4-methoxyaniline A solution of 2-chloro-3-fluoro-1-methoxy-4-nitrobenzene (9.1 g, 44.1 mmol) in EtOH (250 mL) was warmed to 80 °C and treated with a solution of NH4Cl (11.79 g, 220 mmol) in water (125 mL). Iron powder (12.31 g, 220 mmol) was added to the mixture, and the reaction was stirred at 80 °C for 1 h. The reaction mixture was filtered through Celite and washed with EtOAc. The filtrate was concentrated, and the residue was diluted with water and extracted twice with EtOAc. The combined organic phases were dried over Na2SO4, filtered, and the solvent removed in vacuo to give the title compound (8.17 g), which was used without further purification. UPLC-MS (Method A): Rt = 0.63 min; 255.1 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 6.78-6.66(m,2H),4.91(s,2H),3.74(s,3H).

[0403] Step 3: 6-Bromo-3-chloro-2-fluoro-4-methoxyaniline To an ice-cold solution of 3-chloro-2-fluoro-4-methoxyaniline (2.01 g, 8.59 mmol) in THF (80 mL) was added NBS (1.60 g, 9.01 mmol). The reaction mixture was stirred at room temperature for 1 h, warmed to room temperature at 0 °C, and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Biotage) using heptane / EtOAc (0-20% EtOAc) to give the title compound (1.61 g). UPLC-MS (Method A): Rt = 0.93 min; mass not detected; 1 H NMR(400 MHz,DMSO-d6)δ 7.08(d,J=2.2 Hz,1H),5.05(s,2H),3.78(s,3H).

[0404] Step 4: 3-chloro-2-fluoro-4-methoxy-6-((trimethylsilyl)ethynyl)aniline To a solution of 6-bromo-3-chloro-2-fluoro-4-methoxyaniline (17 g, 66.8 mmol) in THF (400 mL) under argon was added TEA (46.3 mL, 334 mmol), ethynyltrimethylsilane (11.11 mL, 80 mmol), CuI (1.02 g, 5.34 mmol), and PdCl(dppf)DCM adduct (6.55 g, 8.02 mmol). The reaction mixture was stirred at 70 °C for 2 h. The reaction mixture was cooled to room temperature, filtered through hyflo, and washed with TBME. The filtrate was diluted with water and extracted with TBME. The combined organic phase was washed with brine, dried over NaSO, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc (0-100% EtOAc) to give the title compound (12.5 g). UPLC-MS (Method B): Rt = 1.46 min; 272.1 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 6.80(d,J=1.9 Hz,1H),5.07(s,2H),3.77(s,3H),0.25(s,9H).

[0405] Step 5: 6-Chloro-7-fluoro-5-methoxy-1H-indole To a solution of 3-chloro-2-fluoro-4-methoxy-6-((trimethylsilyl)ethynyl)aniline (27.2 g, 83 mmol) in DMF (400 mL) was added 60% NaH in mineral oil (8.0 g, 200 mmol) portionwise at room temperature, and the reaction mixture was stirred at 60 °C for 1 h. The reaction mixture was cooled to room temperature, poured slowly into ice-cold aqueous citric acid solution (500 mL), and extracted with EtOAc (4 × 700 mL). The combined organic phases were dried over NaSO, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Biotage) using heptane and EtOAc (0-20% EtOAc) to give the title compound (12.5 g). UPLC-MS (Method B): Rt = 0.92 min; 199.9 [M+H] + ; 1H NMR(400 MHz,DMSO-d6)δ 11.58(s,1H),7.40(d,J=3.0 Hz,1H),7.08(d,J=1.1 Hz,1H),6.47(t,J=3.2 Hz,1H),3.85(s,3H).

[0406] Step 6: 6-Chloro-7-fluoro-5-methoxy-1-methyl-1H-indole A suspension of 6-chloro-7-fluoro-5-methoxy-1H-indole (5 g, 25.1 mmol) in acetone (100 mL) was cooled to 0 °C. Potassium tert-butoxide (3.37 g, 30.1 mmol) was slowly added, followed by dimethyl sulfate (4.74 mL, 50.1 mmol). The ice bath was removed, and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was quenched with saturated NH4Cl under ice bath cooling and extracted twice with EtOAc. The combined organic phases were dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Biotage) on silica using heptane and EtOAc (0-30% EtOAc) to give the title compound (3.77 g). UPLC-MS (Method A): Rt = 1.19 min; 214.1 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 7.34(d,J=3.0 Hz,1H),7.06(d,J=1.2 Hz,1H),6.41(t,J=2.8 Hz,1H),3.91(d,J=2.1 Hz,3H),3.85(s,3H).

[0407] Example B: 2-bromo-6-chloro-7-fluoro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole, 6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole [ka] Step 1: 3-Bromo-6-chloro-7-fluoro-5-methoxy-1H-indole To a solution of 6-chloro-7-fluoro-5-methoxy-1H-indole (1 g, 5.01 mmol) from Example A in THF (50 mL) was added NBS (0.89 g, 5.01 mmol). The mixture was stirred at room temperature for 30 minutes. The solvent was removed to dryness in vacuo to give the title compound (1.9 g), which was used in the next step without further purification. UPLC-MS (Method A): Rt = 1.16 min; 278.0 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 12.07(s,1H),7.65(d,1H),6.84(s,1H),3.91(s,3H).

[0408] Step 2: 6-chloro-7-fluoro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole To a mixture of TPGS-750M (76 ml, 2% in water) and THF (70 ml) under argon, 3-bromo-6-chloro-7-fluoro-5-methoxy-1H-indole (1.94 g, 6.97 mmol), 1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.91 g, 10.5 mmol), KPO (4.44 g, 20.9 mmol), and PdCl(dtbpf) (1.36 g, 2.09 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours and diluted with EtOAc. The organic phase was washed with water and brine and diluted with NaSO. で After drying, filtration, and removal of the solvent in vacuo, the crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc (0-60% EtOAc) to give the title compound (1.91 g) as a pale yellow solid. UPLC-MS (Method A): Rt = 1.02 min; 350.1; 1H NMR(400 MHz,DMSO-d6)δ 11.69(s,1H),8.27(d,1H),7.99-7.89(m,1H),7.67(d,1H),7.17(s,1H),5.44(m,1H),3.98(s, 1H),3.95(s,3H),3.74-3.55(m,1H),2.31-2.10(m,1H),2.02-1.92(m,2H),1.76-1.47(m,3H).

[0409] Step 3: 2-bromo-6-chloro-7-fluoro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole, 6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole To a solution of 6-chloro-7-fluoro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole (200 mg, 0.57 mmol) in THF (15 mL) was added NBS (102 mg, 0.57 mmol). The mixture was stirred at room temperature for 30 min and the solvent was removed in vacuo to give the title compound (378 mg), which was used without further purification. UPLC-MS (Method A): Rt = 1.16 min; 430.1 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 12.50(s,1H),8.24(d,1H),7.94(d,1H),7.03(d,1H),5.50(m,1H),4.02-3.87 (m,4H),3.67(m,1H),2.27-2.11(m,1H),2.02-1.90(m,2H),1.80-1.51(m,3H).

[0410] Example C: Ethyl 6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indole-2-carboxylate [ka] Step 1: (3-chloro-2-fluoro-4-methoxyphenyl)hydrazine 3-Chloro-2-fluoro-4-methoxyaniline (13.13 g, 74.8 mmol) was suspended in a mixture of concentrated hydrochloric acid (350 mL) and water (175 mL) under argon. The suspension was cooled to 2 °C, and a solution of sodium nitrite (6.45 g, 93 mmol) in water (25.8 mL) was added within 20 min, while maintaining the temperature of the mixture below 5 °C. The resulting solution was stirred for an additional 30 min. A solution of tin(II) chloride (56.7 g, 299 mmol) in a mixture of concentrated hydrochloric acid (63.5 mL) and water (15.9 mL) was added within 30 min at a temperature below 5 °C. The resulting suspension was stirred for 90 min. Water was added, and the resulting solution was adjusted to pH 7-8 by adding sodium hydroxide (222 g, 5.55 mol) while maintaining the temperature below 20 °C by cooling with an ice bath. Ethyl acetate (600 mL) was added and the mixture was stirred vigorously for 15 minutes. The mixture was filtered through hyflo and rinsed thoroughly with ethyl acetate. The filtrate phases were separated and the aqueous phase was extracted with ethyl acetate (500 mL). The combined organic extracts were washed once with brine (300 mL), dried over Na2SO4, filtered, and the solvent removed in vacuo to give the title compound (12 g) as a brown solid. UPLC-MS (Method A): Rt = 0.36 min; no ionization. 1 H NMR(400 MHz,DMSO-d6)δ 7.07(dd,1H),6.86(dd,1H),6.44(br s,1H),3.97(br s,2H),3.77(s,3H).

[0411] Step 2: Ethyl (E)-2-(2-(3-chloro-2-fluoro-4-methoxyphenyl)hydraziylidene)propanoate and Ethyl (Z)-2-(2-(3-chloro-2-fluoro-4-methoxyphenyl)hydraziylidene)propanoate To a suspension of 3-chloro-2-fluoro-4-methoxyphenyl)hydrazine (1.5 g, 7.85 mmol) in EtOH (42 mL) was added AcOH (0.46 mL, 8 mmol) and ethyl 2-oxopropanoate (1.76 mL, 15.7 mmol), giving a clear solution. The mixture immediately turned into a thick suspension, which was stirred at room temperature for 1 h. The reaction mixture was concentrated, and the crude product was purified by flash chromatography on silica gel (Biotage) using cyclohexane and EtOAc (0-25% EtOAc) to give the title compound (1.93 g) as a mixture of E / Z isomers. The crude product was purified by column chromatography on silica gel (Teledyne) using cyclohexane and EtOAc (3%-25%) to give the title compound. (E)-isomer: yellow solid (1.64 g). UPLC-MS (Method A): Rt = 1.06 min; 289.10 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 9.24(br s,1H),7.38(dd,1H),7.02(dd,1H),4.19(q,2H),3.85(s,3H),2.09(s,3H),1.26(t,3H).(Z)-isomer: Yellow solid (0.29 g) UPLC-MS (Method A): Rt=1.47 min;289.10 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 11.93(br s,1H),7.43(dd,1H),7.01(dd,1H),4.26(q,2H),3.84(s,3H),2.12(s,3H),1.29(t,3H).

[0412] Step 3: Ethyl 6-chloro-7-fluoro-5-methoxy-1H-indole-2-carboxylate To a solution of ethyl (E)-2-(2-(3-chloro-2-fluoro-4-methoxyphenyl)hydraziylidene)propanoate and ethyl (Z)-2-(2-(3-chloro-2-fluoro-4-methoxyphenyl)hydraziylidene)propanoate (6.83 g, 23.66 mmol) in toluene (130 mL) was added 4-methylbenzenesulfonic anhydride (6.11 g, 35.49 mmol). The dark solution was stirred at room temperature for 30 minutes and at 50 °C for 3 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (300 mL), and subsequently washed with water (3 × 100 mL) and 20% aqueous KHCO solution (100 mL). The aqueous phase was re-extracted with ethyl acetate (2 × 100 mL). The combined organic phases were dried over NaSO, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc (0-25% EtOAc) to give the title compound (3.14 g) as a yellow solid. UPLC-MS (Method A): Rt = 1.11 min; no ionization; 1 H NMR(400 MHz,DMSO-d6)δ 12.43(s,1H),7.17(dd,2H),4.34(q,2H),3.88(s,3H),1.34(t,3H).

[0413] Step 4: Ethyl 6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indole-2-carboxylate To a suspension of ethyl 6-chloro-7-fluoro-5-methoxy-1H-indole-2-carboxylate (1.28 g, 4.71 mmol) in acetone (70 mL) cooled to 0 °C, potassium tert-butoxide (0.79 g, 7.1 mmol) was added, followed by dimethyl sulfate (0.90 mL, 9.42 mmol). The ice bath was removed, and the mixture was stirred at room temperature for 20 min. Saturated aqueous NaHCO3 was added, and the mixture was extracted with CHCl2. The combined organic phases were dried on an IST cartridge phase separator, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc (0-100% EtOAc) to give the title compound (1.15 g) as a yellow solid. UPLC-MS (Method A): Rt = 1.43 min; 286.0 [M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 7.22(d,J=2.1 Hz,1H),7.18(d,J=1.3 Hz,1H),4.33(q,J=7.1 Hz,2H),4.16(d,J=1.5 Hz,3H),3.88(s,3H),1.33(t,J=7.1 Hz,3H).

[0414] Example D: Ethyl 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate [ka] Step 1: 6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indole-2-carbohydrazide To a suspension of ethyl 6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indole-2-carboxylate (9.23 g, 32.3 mmol) in EtOH (350 mL) was added hydrazine monohydrate (39.2 mL, 808 mmol), and the mixture was refluxed for 10 hours. The reaction mixture was cooled to room temperature. Water (350 mL) was added, and the suspension was cooled in an ice bath and stirred for 15 minutes. The solid was collected by filtration, washed with water / EtOH (1:1), and dried under high vacuum at 40° C. to give the title compound (8.4 g) as a colorless solid. UPLC-MS (Method A): Rt=0.79 min; 271.1 [M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 9.84(s,1H),7.13(d,J=1.2 Hz,1H),6.95(d,J=2.2 Hz,1H),4.52(s,2H),4.10(d,J=1.9 Hz,3H),3.87(s,3H).

[0415] Step 2: Ethyl 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate To a suspension of 6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indole-2-carbohydrazide (500 mg, 1.84 mmol) in EtOH (18 mL) was added ethyl 2-ethoxy-2-iminoacetate (0.41 mL, 2.76 mmol). The mixture was heated in a sealed tube at 70° C. for 19 hours to form ethyl 2-(2-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indole-2-carbonyl)hydrazinyl)-2-iminoacetate. DBU (0.83 mL, 5.5.2 mmol) was added, and the mixture was heated in a sealed tube at 115° C. for 3 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc, and 10% aqueous citric acid was added. The aqueous phase was extracted with EtOAc, and the combined organic phases were washed with brine, dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc / EtOH (95:5) (0 to 100% EtOAc / EtOH (95:5)) to give the title compound (0.42 g) as a yellow solid. UPLC-MS (Method A): Rt = 1.05 min; 352.1 [M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 15.43(d,J=153.0 Hz,1H),7.36-6.93(m,2H),4.38(d,J=8.7 Hz,2H),4.26(d,J=1.8 Hz,3H),3.90(s,3H),1.45-1.26(m,3H).

[0416] Synthesis of 1,2,4-triazole intermediates As discussed above in connection with Scheme 3, each triazole intermediate may represent a mixture of up to three regioisomers. The regioisomers were not separated but used directly. In each of the following examples, only one regioisomer is represented.

[0417] Example E: 3,5-Dibromo-1-(4-methoxybenzyl)-1H-1,2,4-triazole [ka] 3,5-Dibromo-4H-1,2,4-triazole (119.5 g, 500 mmol) was dissolved in ACN (600 mL). 1-(Chloromethyl)-4-methoxybenzene (81 mL, 601 mmol) and K2CO3 (83 g, 601 mmol) were added, and the reaction mixture was stirred at 60 °C for 3 h. The reaction mixture was concentrated, diluted with water (700 mL), and extracted with EtOAc (2 × 1000 mL). The combined organic phases were dried over Na2SO4, filtered, and the solvent was removed in vacuo. The brown oil was dissolved in DCM (150 mL), and heptane (1400 mL) was added slowly. The colorless precipitate was collected by filtration, washed with heptane, and dried under vacuum to give the title compound (109.1 g). UPLC / MS (Method A): Rt = 0.94 min, 348.1 [M+H] + obtained.

[0418] Example F: 1-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one and others [ka] 3,5-Dibromo-1-(4-methoxybenzyl)-1H-1,2,4-triazole (11.0 g, 31.7 mmol) from Example E was dissolved in THF (400 mL). Under an inert anhydrous atmosphere, n-butyllithium (22.78 mL, 36.5 mmol) was added dropwise over 5 minutes at −78° C., and the mixture was stirred at −78° C. for 45 minutes. A solution of N,2-dimethoxy-N-methylacetamide (5.0 g, 35.7 mmol) in THF (10 mL) was added to the mixture. The reaction mixture was stirred at −78° C. for 45 minutes, quenched with saturated aqueous NH4Cl (400 mL), and extracted with EtOAc (2×300 mL). The combined organic phase was dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Biotage) on silica using heptane and EtOAc (0-20% EtOAc) to give the title compound (4.60 g). UPLC / MS (Method A): Rt = 0.90 min, 340.1 and 342.1 [M+H] + .

[0419] The following intermediates were prepared by halogen metal exchange with n-butyllithium or iPrMgCl and subsequent reaction with the corresponding electrophiles (Weinreb amides, esters, carbamoyl chlorides) similar to the procedure described above for 1-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one:

[0420] [Table 80]

[0421] Example G: 3-Bromo-5-(1,1-difluoro-2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1-(4-methoxybenzyl)-1H-1,2,4-triazole and others [ka] To a solution of 1-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-((tetrahydro-2H-pyran-2-yl)oxy)ethan-1-one (6 g, 14.62 mmol) in DCM (120 mL) at room temperature was added DAST (19.32 mL, 146 mmol), and the reaction was heated at 40 °C for 5.5 h. The reaction mixture was cooled to ambient temperature and carefully added to ice-cold saturated NaHCO solution. The aqueous phase was extracted twice with EtOAc. The combined organic phases were dried over NaSO, filtered, and the solvent was evaporated. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane / EtOAc (0-10% EtOAc) to give the title compound (3.82 g). UPLC / MS (Method A): Rt = 1.24 min, 432.2 [M+H] + .

[0422] The following intermediates were prepared similarly to the above procedures using the corresponding ketone or alcohol.

[0423] [Table 81]

[0424] Example H: 1-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol [ka] 1-(3-Bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one (2.76 g, 8.11 mmol) from Example F was dissolved in MeOH (50 mL) and THF (150 mL). NaBH (0.376 g, 9.74 mmol) was added, and the mixture was stirred at 23 °C for 20 min. The reaction was quenched with saturated aqueous NH Cl, and the aqueous phase was extracted twice with EtOAc. The combined organic phases were dried over Na SO , filtered, and the solvent was evaporated. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane / EtOAc (0-40% EtOAc) to give the title compound (2.76 g). UPLC / MS (Method A): Rt = 0.68 min, 342.1 [M+H] + .

[0425] The following intermediates were prepared similarly to the above procedure using the corresponding ketones.

[0426] [Table 82]

[0427] Example I: 3-Bromo-5-(1-(2-((tert-butyldimethylsilyl)oxy)ethoxy)-2,2,2-trifluoroethyl)-1-(4-methoxybenzyl)-1H-1,2,4-triazole [ka] To a solution of 1-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2,2,2-trifluoroethan-1-ol (1.0 g, 2.73 mmol) and 2-(tert-butyldimethylsiloxy)ethanol (0.482 g, 2.73 mmol) in toluene (15 mL) was added 2-(tributylphosphoranylidene)acetonitrile (1.43 mL, 5.46 mmol). The reaction was stirred at room temperature under argon for 4 hours. Additional 2-(tert-butyldimethylsiloxy)ethanol (0.250 g, 1.35 mmol) and 2-(tributylphosphoranylidene)acetonitrile (0.7 mL, 5.22 mmol) were added, and the reaction was stirred at room temperature overnight. The mixture was concentrated, saturated aqueous NaHCO3 was added, and the aqueous phase was extracted twice with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered, and the solvent was evaporated. The crude product was purified by flash chromatography on silica (Teledyne) using cyclohexane / EtOAc (0-10% EtOAc) to give the title compound (773 mg). UPLC-MS (Method A): Rt = 1.62 min, 524.3 [M+H] + .

[0428] Example J: 3-Bromo-1-(4-methoxybenzyl)-5-(2,2,2-trifluoro-1-methoxyethyl)-1H-1,2,4-triazole [ka] To a solution of 1-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2,2,2-trifluoroethan-1-ol (1 g, 2.73 ml) in THF (20 mL) was added NaH (60% in mineral oil) (0.262 g, 6.55 mmol), and the reaction was stirred at room temperature for 20 minutes. Iodomethane (0.342 mL, 5.46 mmol) was added, and the reaction was stirred at room temperature for 2 hours. The mixture was quenched with saturated aqueous NaHCO3, and the aqueous phase was extracted twice with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane / EtOAc (0-35% EtOAc) to give the title compound (587 mg). UPLC-MS (Method A): Rt=1.05 min, 380.1[M+H] + .

[0429] The following intermediates were prepared similarly to the above procedure using the corresponding alcohols.

[0430] [Table 83]

[0431] Example K: 3-Bromo-1-(4-methoxybenzyl)-5-(((4-methoxybenzyl)oxy)methyl)-1H-1,2,4-triazole [ka] To a solution of (5-bromo-4H-1,2,4-triazol-3-yl)methanol (0.95 g, 5.34 mmol) in DMF (30 mL), NaH (60% in mineral oil) (0.534 g, 13.34 mmol) was added portionwise, and the mixture was stirred at room temperature for 30 minutes. 1-(Chloromethyl)-4-methoxybenzene (1.67 mL, 12.28 mmol) was added, and the reaction was stirred at room temperature for 2 days. The mixture was concentrated, diluted with water (150 mL), and the aqueous phase was extracted with EtOAc (2 x 200 mL). The combined organic phases were dried over Na2SO4, filtered, and the solvent was evaporated. The crude product was purified by flash chromatography (Biotage) on silica using heptane / EtOAc (0-80% EtOAc) to give the title compound (1.02 g). UPLC / MS (Method A): Rt = 1.11 min, 418.3 [M+H] + .

[0432] The following intermediates were prepared similarly to the above procedure using the corresponding commercially available triazole building blocks.

[0433] [Table 84]

[0434] Example L: 3-Bromo-5-fluoro-1-(4-methoxybenzyl)-1H-1,2,4-triazole [ka] To a solution of 3,5-dibromo-1-(4-methoxybenzyl)-1H-1,2,4-triazole (16.5 g, 47.5 mmol) from Example E in DMSO (40 mL) was added CsF (14.45 g, 95.0 mmol), and the reaction was heated at 100 °C for 90 min. The reaction mixture was cooled to room temperature and poured into ice water. The aqueous phase was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried over NaSO, filtered, and the solvent was evaporated. The crude product was purified by flash chromatography on silica (Biotage) using heptane / EtOAc (0-20% EtOAc) to give the title compound (12.2 g) as a mixture of isomers. UPLC-MS (Method A): Rt = 0.91 min, no ionization. δ 7.35~7.21(m,2H), 7.00~6.86(m,2H), 5.20(s,2H), 3.75(s,3H).

[0435] Example M: ​​(R)-1-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)pyrrolidin-3-ol [ka] 3,5-Dibromo-1-(4-methoxybenzyl)-1H-1,2,4-triazole (3 g, 8.65 mmol) from Example E, (R)-pyrrolidin-3-ol (0.753 g, 8.65 mmol), and K2CO3 (1.43 g, 10.4 mmol) were suspended in DMSO (20 mL) and heated at 50 °C for 6 days. The reaction mixture was diluted with water and extracted twice with EtOAc. The combined organic phases were dried over Na2SO4, filtered, and the solvent was evaporated. The crude product was purified by flash chromatography on silica (Biotage) using EtOAc / MeOH (0-30% MeOH) to give the title compound (2.51 g). UPLC-MS (Method A): Rt = 0.63 min, 353.1 [M+H] + .

[0436] The following intermediates were prepared similarly to the above procedure using the corresponding amines.

[0437] [Table 85]

[0438] Example N: N-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-N-methylacetamide [ka] To a solution of 3-bromo-1-(4-methoxybenzyl)-N-methyl-1H-1,2,4-triazol-5-amine (1.8 g, 6.06 mmol) from Example M in dioxane (20 mL) was added EtN (1.26 mL, 9.09 mmol) and acetyl chloride (0.517 mL, 7.27 mmol). The reaction mixture was stirred at room temperature for 1 h and then at 80 °C for 1 h. Additional acetyl chloride (0.517 mL, 7.27 mmol) was added and heating was continued for 2 h. The mixture was cooled to room temperature, diluted with water, and extracted twice with EtOAc. The combined organic phases were dried over NaSO, filtered, and the solvent was evaporated. The crude product was purified by flash chromatography on silica (Biotage) using heptane / EtOAc (0-100% EtOAc) to give the title compound (1.41 g). UPLC-MS (Method A): Rt=0.72 min, 339.1[M+H] + .

[0439] The following intermediate was prepared similarly to the above procedure using 2-methoxyacetyl chloride.

[0440] [Table 86]

[0441] Example O: 1-(5-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-3-yl)pyrrolidin-2-one [ka] 3,5-Dibromo-1-(4-methoxybenzyl)-1H-1,2,4-triazole from Example E (3 g, 8.65 mmol), pyrrolidin-2-one (0.736 g, 8.65 mmol), N,N-dimethylethane-1,2-diamine (0.152 g, 1.729 mmol), CuI (0.165 g, 0.865 mmol) and KCO (2.63 g, 19.02 mmol) were suspended in toluene (100 mL) and stirred at 110 °C for 5 days. Additional pyrrolidin-2-one (0.736 g, 8.65 mmol), N1,N1-dimethylethane-1,2-diamine (0.152 g, 1.729 mmol), CuI (0.165 g, 0.865 mmol), and K2CO3 (2.63 g, 19.02 mmol) were added, and heating was continued for 5 days. The reaction mixture was quenched with saturated aqueous NH4Cl, and the aqueous phase was extracted twice with EtOAc. The combined organic phases were washed with water and brine, dried over Na2SO4, filtered, and the solvent was evaporated. The crude product was purified by flash chromatography on silica (Biotage) using heptane / EtOAc (0-50% EtOAc) to give the title compound (884 mg). UPLC-MS (Method A): Rt = 0.74 min, 351.2 [M+H] + .

[0442] Example P: 3-Bromo-1-(4-methoxybenzyl)-5-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)-1H-1,2,4-triazole [ka] 2-(Tetrahydro-2H-pyran-2-yloxy)ethanol (2.99 mL, 21.61 mmol) was dissolved in THF (100 mL), NaH (0.864 g, 21.61 mmol) was added portionwise, and the mixture was stirred at 23 °C for 45 min. 3,5-Dibromo-1-(4-methoxybenzyl)-1H-1,2,4-triazole (5 g, 14.41 mmol) from Example E was added, and stirring was continued at room temperature for 2.5 h. The mixture was quenched with 10% citric acid and extracted with EtOAc. The organic layer was dried on an IST cartridge phase separator, and the filtrate was concentrated. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane / EtOAc (0-100% EtOAc) to give the title compound (4.35 g). UPLC-MS (Method A): Rt = 1.06 min, 412.4 [M+H] + .

[0443] The following intermediates were prepared similarly to the above procedure using sodium methylate in MeOH.

[0444] [Table 87]

[0445] Example Q: Methyl 5-bromo-2-(4-methoxybenzyl)-2H-1,2,3-triazole-4-carboxylate and methyl 4-bromo-1-(4-methoxybenzyl)-1H-1,2,3-triazole-5-carboxylate (1:1 mixture) [ka] To a solution of methyl 4-bromo-1H-1,2,3-triazole-5-carboxylate (7.08 g, 32.7 mmol) in acetonitrile (300 mL) was added 1-(chloromethyl)-4-methoxybenzene (5.62 g, 35.9 mmol), followed by KCO (5.41 g, 39.2 mmol), and the reaction was heated at 60 °C for 6 h. The reaction mixture was concentrated, diluted with water (250 mL), and the aqueous phase was extracted with EtOAc (2 × 400 mL). The crude product was purified by flash chromatography on silica (Biotage) using heptane / EtOAc (0–50% EtOAc) to afford the title compound (8.55 g) as a 1:1 mixture of regioisomers, which was used without further separation. UPLC-MS (Method A): Rt = 0.92 and 0.95 min, 326.1 [M+H] + .

[0446] Synthesis of Compounds of the Invention In the following examples, tautomerization or positional isomerization is possible for each compound, but only one form is shown for illustrative purposes. Mixtures of positional isomers or tautomers were not separated. Each compound of the present invention is represented below in only one tautomeric form. To avoid confusion, a list of compounds including tautomers is provided in Table 1.

[0447] Example 1: 6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole The title compound was synthesized by the method shown in Scheme 10 below. [ka]

[0448] Step 1: 6-chloro-7-fluoro-5-methoxy-2-(1-(4-methoxybenzyl)-5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole [ka] To a suspension of 2-bromo-6-chloro-7-fluoro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole (378 mg, 0.864 mmol) in dioxane (40 mL) was added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (1.8 g, 6.91 mmol), KOAc (848 mg, 8.64 mmol), and PdCl(dppf)DCM adduct (106 mg, 0.130 mmol), and the mixture was heated at 110 °C for 2 h. 3-Bromo-1-(4-methoxybenzyl)-5-(trifluoromethyl)-1H-1,2,4-triazole (349 mg, 1.04 mmol), K2CO3 (358 mg, 2.59 mmol), PdCl2(dppf)DCM adduct (106 mg, 0.13 mmol), and water (3.6 mL) were added to the mixture, and heating was continued at 11 °C for 60 min. The reaction mixture was cooled to room temperature, diluted with EtOAc, and the organic phase was washed with water and brine. The organic phase was dried on an IST cartridge phase separator, and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Teledyne) using cyclohexane and EtOAc (0-50% EtOAc) to give the title compound (798 mg, 0.92 mmol) as a brown oil. UPLC-MS (Method A): Rt = 1.47 min, 605.3 [M+H] + .

[0449] Step 2: 6-chloro-7-fluoro-5-methoxy-2-(1-(4-methoxybenzyl)-5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1-methyl-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole [ka] To a solution of 6-chloro-7-fluoro-5-methoxy-2-(1-(4-methoxybenzyl)-5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole (798 mg, 0.92 mmol) in DMF (9.2 mL) was added sodium hydride (60% in mineral oil) (44.3 mg, 1.11 mmol) at 0° C. After 60 min at 0° C., iodomethane (69 μl, 1.11 mmol) was added and the mixture was stirred at room temperature for 6 h. The reaction mixture was quenched by the addition of water and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried on an IST cartridge phase separator and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc (0-50% EtOAc) to give the title compound (214 mg, 0.31 mmol) as a pale yellow oil. UPLC-MS (Method A): Rt = 1.57 min, 619.2 [M+H] + .

[0450] Step 3: 6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole [ka] To a solution of 6-chloro-7-fluoro-5-methoxy-2-(1-(4-methoxybenzyl)-5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1-methyl-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole (214 mg, 0.31 mmol) in 1,2-DCE (7.7 mL) was added triflic acid (276 μL, 3.11 mmol). The reaction mixture was stirred at room temperature for 30 min, carefully quenched by the addition of saturated aqueous NaHCO3, and extracted twice with EtOAc. The organic layer was dried on an IST cartridge phase separator, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc (0–100% EtOAc) to give the title compound (35 mg, 0.08 mmol) as a colorless solid. UPLC-MS (Method A): Rt=1.18 min, 415.3[M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 15.29(s,1H),13.01(s,1H),7.92(s,1H),7.45(s,1H),7.12(d,1H),3.97-3.81(m,6H).

[0451] The following examples were synthesized similarly to the procedures described above, using the corresponding protected triazole building blocks, optionally including N-methylation.

[0452] [Table 88]

[0453] [Table 89]

[0454] [Table 90]

[0455] Example 11: 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole The title compound was synthesized by the method shown in Scheme 11 below. [ka]

[0456] Step 1: Ethyl 6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carboxylate [ka] To a solution of ethyl 6,7-dichloro-1H-indole-2-carboxylate (10 g, 38.7 mmol) in DME (160 mL) was added NBS (7.59 g, 42.6 mmol), and the reaction was stirred at room temperature for 60 minutes. To the reaction mixture were added 1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (12.71 g, 45.7 mmol), K2CO3 (26.8 g, 194 mmol), water (35 mL), and PdCl2(dppf) DCM adduct (3.16 g, 3.87 mmol), and the reaction was heated at 100 °C for 2.5 hours. The reaction mixture was cooled to room temperature, diluted with water and aqueous sodium chloride, and the aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Biotage) using heptane and EtOAc (0-50% EtOAc) to give the title compound (10.7 g). UPLC-MS (Method C): Rt = 1.28 min, 408.2 [M+H] + . 1H NMR(600 MHz,DMSO-d6)δ 12.07(s,1H),8.25(s,1H),7.86(s,1H),7.68(d,J=8.6 Hz,1H),7.33(d,J=8.6 Hz,1H),5.48(dd,J=10.3,2.1 Hz,1H),4.32(q,J=7.1 Hz,2H),4.02-3.92(m,1H),3.73-3.61(m,1H),2.23-2.11(m,1H),1.98(d,J=11.4 Hz,2H),1.75-1.67(m,1H),1.56(dq,J=9.1,4.5 Hz,2H),1.31(t,J=7.1 Hz,3H).

[0457] Step 2: 6,7-Dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carbohydrazide [ka] To a solution of ethyl 6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carboxylate (2.01 g, 4.92 mmol) in EtOH (10 mL) was added hydrazine hydrate (6.0 g, 120 mmol), and the reaction mixture was stirred at 100° C. for 20 h. The reaction mixture was concentrated to dryness, and the crude product was purified by flash chromatography on silica (Biotage) using heptane, EtOAc, and MeOH (0-100% EtOAc and 0-20% EtOAc / MeOH) to give the title compound (1.54 g). UPLC-MS (Method C): Rt=0.93 min, 394.1 [M+H] + .

[0458] Step 3: 6,7-Dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole [ka] 6,7-Dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carbohydrazide (800 mg, 2.03 mmol) and ethyl 2,2,2-trifluoroacetimidate (500 mg, 3.54 mmol) were suspended in EtOH (16 mL), and the reaction mixture was stirred at 50° C. for 3 days to form 6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-N'-(2,2,2-trifluoro-1-iminoethyl)-1H-indole-2-carbohydrazide. Sodium methoxide in EtOH (3.18 mL, 8.12 mmol) was added, and the reaction mixture was heated in a microwave at 160° C. for 10 minutes. The reaction mixture was concentrated, 10% aqueous citric acid and EtOAc were added, and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Biotage) using heptane and EtOAc (0-100% EtOAc) to give the title compound (840 mg) as a pale yellow solid. UPLC-MS (Method C): Rt = 1.21 min, 471.1 [M+H] + .

[0459] Step 4: 6,7-Dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole [ka] A suspension of 6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole (833 mg, 1.59 mmol) in 4 N HCl in dioxane (40 mL, 160 mmol) was stirred at room temperature for 30 h. The reaction mixture was carefully poured into saturated aqueous NaHCO (300 mL) and the aqueous phase was extracted with EtOAc (2 × 400 mL). The combined organic phases were dried over NaSO, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Biotage) on silica using heptane and EtOAc (0 to 100% EtOAc) to give the title compound (840 mg) as a pale yellow solid. UPLC-MS (Method C): Rt=1.06 min, 387.1[M+H] + . 1 H NMR(600 MHz,DMSO-d6)δ 15.20(s,1H),13.06(s,1H),12.22(s,1H),7.90(s,2H),7.78(d,J=8.5 Hz,1H),7.36(d,J=8.5,2.3 Hz,1H).

[0460] The following examples optionally include N-alkylation of the indole and were synthesized similarly to the procedures described above using the corresponding indole building blocks and commercially available iminoesters, respectively.

[0461] [Table 91]

[0462] [Table 92]

[0463] [Table 93]

[0464] [Table 94]

[0465] [Table 95]

[0466] Example 32: 4,5-Dichloro-1-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole [ka] Step 1: 4,5-Dichloro-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carboxylic acid [ka] A mixture of ethyl 4,5-dichloro-1H-indole-2-carboxylate (1 g, 3.87 mmol), 4-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (1.62 g, 5.81 mmol), CsCO (1.26 g, 3.87 mmol), and CuBr (0.06 g, 0.39 mmol) in DMF (15 mL) was heated at 180 °C for 16 h. The reaction mixture was cooled to room temperature and quenched with saturated aqueous NaHCO, and the aqueous phase was extracted with EtOAc. The aqueous phase was acidified to pH 1 with 1 N HCl and extracted three times with EtOAc. The combined organic phases were dried over NaSO, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Biotage) using heptane, EtOAc, and MeOH (0-100% EtOAc and 0-30% EtOAc / MeOH) to give the title compound (707 mg). UPLC-MS (Method B): Rt = 1.09 min, 382.0 [M+H] + .

[0467] Step 2: 4,5-Dichloro-1-(1H-pyrazol-4-yl)-1H-indole-2-carboxylate methyl ester [ka] 4,5-Dichloro-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carboxylic acid (700 mg, 1.841 mmol) was dissolved in a solution of HCl in MeOH (15 ml, 18.75 mmol), and the reaction mixture was stirred at 50° C. for 16 hours. The reaction mixture was cooled to room temperature and concentrated. 1 M NaOH (20 mL) was added, and the mixture was stirred for 5 minutes. The resulting precipitate was collected by filtration, washed with water, and dried under high vacuum to give the title compound (256 mg) as a colorless solid. UPLC-MS (Method B): Rt=1.07 min, 312.1 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 13.17(s,1H),8.03-7.80(m,2H),7.49(d,J=8.9 Hz,1H),7.38(d,J=0.9 Hz,1H),7.15(dd,J=8.9,0.9 Hz,1H),3.77(s,3H).

[0468] Step 3: 4,5-Dichloro-1-(1H-pyrazol-4-yl)-1H-indole-2-carbohydrazide [ka] To a solution of methyl 4,5-dichloro-1-(1H-pyrazol-4-yl)-1H-indole-2-carboxylate (250 mg, 0.81 mmol) in EtOH (5 mL) was added hydrazine hydrate (500 mg, 9.99 mmol), and the reaction mixture was stirred at 100° C. for 16 hours. The reaction mixture was cooled to room temperature and concentrated to dryness. The residue was triturated with DCM (5 mL) to give the title compound (223 mg) as a yellow solid, which was used without further purification. UPLC-MS (Method B): Rt=0.85 min, 312.1 [M+H] + ; 1H NMR(400 MHz,DMSO-d6)δ 13.14(s,1H),9.94 - 9.80(m,1H),7.85(s,2H),7.40(d,J=8.8 Hz,1H),7.14(d,J=8.8 Hz,1H),7.10(s,1H),4.45(s,2H).UPLC-MS(Method B): Rt=1.07min,312.1[M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 13.17(s,1H),8.03-7.80(m,2H),7.49(d,J=8.9 Hz,1H),7.38(d,J=0.9 Hz,1H),7.15(dd,J=8.9,0.9 Hz,1H),3.77(s,3H).

[0469] Step 4: 4,5-Dichloro-1-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole [ka] A mixture of 4,5-dichloro-1-(1H-pyrazol-4-yl)-1H-indole-2-carbohydrazide (220 mg, 0.709 mmol) and ethyl 2,2,2-trifluoroacetimidate (100 mg, 0.709 mmol) in EtOH (16 mL) was heated at 50° C. for 3 days to form 4,5-dichloro-1-(1H-pyrazol-4-yl)-N′-(2,2,2-trifluoro-1-iminoethyl)-1H-indole-2-carbohydrazide. A solution of sodium ethoxide in EtOH (1.11 mL, 2.84 mmol) was added, and the reaction mixture was heated in a microwave at 160° C. for 10 minutes. The reaction mixture was cooled to room temperature and concentrated to dryness. 10% aqueous citric acid (150 mL) was added, and the mixture was extracted with EtOAc (2×350 mL). The combined organic phases were dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Biotage) using heptane, EtOAc, and MeOH (0-100% EtOAc and 0-40% EtOAc / MeOH) to give the title compound (127 mg). UPLC-MS (Method B): Rt = 1.13 min, 387.1 [M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 15.42(s,1H),13.21(s,1H),8.15-7.62(m,2H),7.47(d,J=8.8 Hz,1H),7.41(s,1H),7.22(d,J=8.8 Hz,1H).

[0470] Example 33: 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-5-ol [ka] A suspension of 6-chloro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole (283 mg, 0.61 mmol) in DCM (15 mL) was cooled to 0 °C. A 1 M solution of BBr in DCM (6.06 mL, 6.06 mmol) was slowly added, and the mixture was stirred at 0 °C for 5 h. The mixture was carefully added to MeOH (120 mL) and concentrated to dryness. The residue was diluted with EtOAc and neutralized (pH 7) with saturated aqueous NaHCO3. The aqueous phase was extracted with EtOAc, and the combined organic phases were washed with brine, dried on an IST cartridge phase separator, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc (0-100% EtOAc) to give the title compound (106 mg). UPLC-MS (Method B): Rt = 0.92 min, 369.0 [M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 14.77(s,1H),12.97(s,1H),11.61(s,1H),9.57(s,1H),7.82(d,J=110.1 Hz,2H),7.44(s,1H),7.19(s,1H).

[0471] The following examples were synthesized in a manner similar to the procedure described above.

[0472] [Table 96]

[0473] Example 35: 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carbonitrile [ka] Step 1: 5-(6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxamide [ka] Ethyl 5-(6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate (339 mg, 0.52 mmol) was suspended in a solution of 7 M ammonia in MeOH (10 mL, 70.0 mmol) and the reaction mixture was stirred in a sealed tube at 60° C. for 16 h. The reaction mixture was concentrated to dryness to give the title compound (353 mg), which was used without further purification. UPLC-MS (Method B): Rt=1.08 min, 468.3 [M+H] + .

[0474] Step 2: 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carbonitrile [ka] 5-(6,7-Dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxamide (253 mg, 0.380 mmol) was suspended in 1,2-DCE (10 mL) and POCl (1 mL, 10.73 mmol) was added. The reaction mixture was stirred at 100 °C for 1 h, cooled to room temperature and concentrated to dryness. Saturated aqueous bicarbonate solution (100 mL) was added and the aqueous phase was extracted with EtOAc (2 x 200 mL). The combined organic phases were dried over NaSO, filtered and the solvent was removed in vacuo. The compound was purified by preparative reverse-phase chromatography (XBridge-C18 (5 um, 50 x 250 mm), eluent A: HO + 0.2% HCOOH, B: ACN, gradient: initial 0.8% B; 0.8% to 28% B in 21 min, flow rate: 100 mL / min) to give the title compound (9 mg). UPLC-MS (Method B): Rt = 1.04 min; 344.0 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 15.46 (s, 1H), 12.18 (s, 1H), 7.93 (s, 2H), 7.76 (d, J = 8.6 Hz, 1H), 7.35 (d, J = 8.6 Hz, 1H). One hidden proton.

[0475] Example 36: (5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)methanol [ka] To a solution of ethyl 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate (72 mg, 0.144 mmol) in THF (20 mL) was added a 2 M solution of LiAlH in THF (0.3 mL, 0.60 mmol) dropwise over 2 min at 0 °C, and the mixture was stirred at 0 °C for 2 h. Sodium sulfate decahydrate (925 mg, 2.87 mmol) was added portionwise, and the mixture was stirred for 20 min. The solids were removed by filtration, washed with THF, and the filtrate was concentrated. The compound was purified by preparative reverse-phase chromatography (XBridge-C18 (5 μm, 50 × 250 mm), eluent A: HO + 0.2% HCOOH, B: ACN, gradient: initial 0.8% B; 0.8% to 28% B in 21 min, flow rate: 100 mL / min) to give the title compound (10 mg). UPLC-MS (Method B): Rt = 0.93 min; 349.1 [M+H] + . 1 H NMR (400 MHz, DMSO-d6) δ 11.75 (s, 1H), 8.03 (s, 2H), 7.68 (d, J = 8.5 Hz, 1H), 7.26 (d, J = 8.5 Hz, 1H), 4.67 (s, 2H). Two hidden protons.

[0476] Example 37: 2-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-1-yl)ethan-1-ol [ka] Step 1: 6,7-Dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carboxamide [ka] A suspension of ethyl 6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carboxylate (2.11 g, 4.66 mmol) in ammonia (20 ml, 140 mmol, 7 M solution in MeOH) was heated at 50° C. for 6 days. The reaction mixture was concentrated, water (100 mL) was added, and the aqueous phase was extracted with EtOAc. The combined organic phases were dried over sodium sulfate, filtered, and the solvent removed in vacuo to give the title compound (1.84 g), which was used without further purification. UPLC-MS (Method C): Rt=1.01 min, 381.1 [M+H] + .

[0477] Step 2: (E)-6,7-Dichloro-N-((dimethylamino)methylene)-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carboxamide [ka] A suspension of 6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carboxamide (1.84 g, 4.37 mmol) in 1,1-dimethoxy-N,N-dimethylmethanamine (17 ml, 127 mmol) was heated at 120° C. for 30 minutes. The reaction mixture was cooled to room temperature and concentrated to dryness to give the title compound (1.97 g), which was used without further purification. UPLC-MS (Method C): Rt=1.19 min; 436.3 [M+H] + .

[0478] Step 3: 6,7-Dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-2-(4H-1,2,4-triazol-3-yl)-1H-indole [ka] A mixture of (E)-6,7-dichloro-N-((dimethylamino)methylene)-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole-2-carboxamide (1.92 g, 3.98 mmol) and hydrazine monohydrate (0.215 mL, 4.38 mmol) in AcOH (19 mL) was heated at 90 °C for 15 min. The reaction was cooled to room temperature, saturated aqueous NaHCO (100 mL) was added, and the aqueous phase was extracted with EtOAc (400 mL). The combined organic phases were dried over sodium sulfate, filtered, and the solvent removed in vacuo. The crude product was purified by flash chromatography (Biotage) on silica using heptane, EtOAc, and MeOH (0-100% EtOAc and 0-20% EtOAc / MeOH) to give the title compound (1.10 mg). UPLC-MS (Method C): Rt=1.03 min, 405.2[M+H] + . 1 H NMR(600 MHz,DMSO-d6)δ 14.39(s,1H),11.85(s,1H),8.77(s,1H),8.30(s,1H),7.86(s,1H),7.67(d,J=8.5 Hz,1H),7.28(d,J=8.5 Hz,1H),5.44(dd,J=10.0,2.1 Hz,1H),3.70-3.56(m,1H),3.31(s,1H),2.16(q,J=10.3 Hz,1H),2.03-1.87(m,3H),1.68(q,J=10.8,9.0 Hz,1H),1.59-1.47(m,3H).

[0479] Step 4: 6,7-Dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-2-(1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-1,2,4-triazol-3-yl)-1H-indole [ka] To a solution of 6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-2-(1H-1,2,4-triazol-3-yl)-1H-indole (400 mg, 0.99 mmol) in DMF (5 mL) was added K2CO3 (548 mg, 3.97 mmol) and 2-(2-bromoethoxy)tetrahydro-2H-pyran (249 mg, 1.19 mmol), and the reaction was stirred at 50 °C for 1 h. The reaction mixture was diluted with water (50 mL), and the aqueous phase was extracted with EtOAc (2 × 150 mL). The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Biotage) on silica using heptane and EtOAc (0 to 100% EtOAc) to give the title compound (560 mg). UPLC-MS (Method C): Rt=1.28 min, 533.3[M+H] + .

[0480] Step 5: 2-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-1-yl)ethan-1-ol [ka] A solution of 6,7-dichloro-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-2-(1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-1,2,4-triazol-3-yl)-1H-indole (560 mg, 0.89 mmol) in 4 N HCl in dioxane (5 mL, 20.00 mmol) was stirred at room temperature for 30 min. The reaction mixture was carefully poured into saturated aqueous NaHCO3 solution and the aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered and the solvent was removed in vacuo. The resulting solid was triturated in MeOH, filtered, washed with MeOH and dried under high vacuum to give the title compound as a colorless solid. UPLC-MS (Method C): Rt = 0.81 min, 363.2 [M+H] + . 1H NMR(600 MHz,DMSO-d6)δ 12.88(s,1H),11.75(s,1H),8.63(s,1H),8.31-7.78(m,2H),7.69(d,J=8.5 Hz,1H),7.26(d,J=8.5 Hz,1H),5.04(d,J=5.6 Hz,1H),4.30(t,J=5.4 Hz,2H),3.81(q,J=4.8 Hz,2H).

[0481] The following examples were synthesized in a manner similar to the procedure described above.

[0482] [Table 97]

[0483] Example 39: 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide The title compound was synthesized by the method shown in Scheme 12 below. [ka]

[0484] Step 1: 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide [ka] A suspension of ethyl 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate (0.41 g, 1.17 mmol) and dimethylamine (33% solution in EtOH, 10.4 mL, 58.4 mmol) was heated in a sealed tube at 90 °C for 46 h. The reaction was cooled in an ice bath, and the solid was collected by filtration and washed with cold EtOH. The solid was suspended in 5% aqueous citric acid, filtered, washed thoroughly with 5% aqueous citric acid and water, and dried under high vacuum at 60 °C to give the title compound (0.32 g) as a colorless solid. UPLC-MS (Method A): Rt = 1.01 min, 352.0 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 13.16(d,J=925.1 Hz,1H),7.14(d,J=1.2 Hz,1H),7.03(d,J=2.2 Hz,1H),4.26(d,J=1.7 Hz,3H),3.88(s,3H),3.37(s,3H),3.05(s,3H).

[0485] Step 2: 5-(3-bromo-6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide [ka] To a suspension of 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide (0.29 g, 0.83 mmol) in THF (14 mL) was added NBS (0.16 g, 0.87 mmol), and the resulting suspension was stirred at room temperature for 45 min. The reaction mixture was diluted with water, cooled in an ice bath, and adjusted to pH 4-5 by the addition of citric acid (0.16 g, 0.83 mmol). The resulting precipitate was collected by filtration, washed with ice-cold THF / water (1:2), and dried under high vacuum to give the title compound (0.32 g) as a colorless solid. UPLC-MS (Method A): Rt = 1.13 min, 429.9 [M+H] + ;1 H NMR(400 MHz,DMSO-d6) δ 15.33(s,1H),6.92(d,J=1.2 Hz,1H),4.06(d,J=1.7 Hz,3H),3.95(s,3H),3.47(s,3H),3.08(s,3H).

[0486] Step 3: 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide [ka] A mixture of 5-(3-bromo-6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide (0.151 g, 0.35 mmol), 1H-imidazole (0.120 g, 1.76 mmol), copper(I) iodide (6.7 mg, 0.035 mmol), potassium carbonate (0.146 g, 1.05 mmol), and L-proline (8.1 mg, 0.07 mmol) in DMSO (3 mL) was heated in a sealed tube under argon at 110° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (40 mL) and water (20 mL). AcOH (0.21 mL) was added to adjust the pH to 4-5, the phases were separated, and the aqueous phase was combined with ethyl acetate (2 x 25 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by SFC chromatography (column: 100 x 50 Reprospher PEI 100 A 3 μm, gradient: 35-43% in MeOH / DCM over 4 min) to give the title compound (42 mg). UPLC-MS (Method A): Rt = 0.78 min, 418.1 [M+H] + ; 1H NMR(400 MHz,DMSO-d6)δ 15.26(s,1H),7.79(d,J=1.1 Hz,1H),7.32(t,J=1.3 Hz,1H),7.07(d,J=1.1 Hz,1H),6.71(d,J=1.2 Hz,1H),4.15(d,J=1.7 Hz,3H),3.85(s,3H),3.27(s,3H),3.02(s,3H).

[0487] The following examples were synthesized in a manner similar to the above procedure using ethyl 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate and the corresponding amine, respectively.

[0488] [Table 98]

[0489] [Table 99]

[0490] [Table 100]

[0491] The following examples were synthesized in a similar manner to the above procedure, starting from ethyl 6-chloro-7-fluoro-5-methoxy-1H-indole-2-carboxylate or ethyl 6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indole-2-carboxylate and using the corresponding iminoesters, respectively.

[0492] [Table 101]

[0493] [Table 102]

[0494] [Table 103]

[0495] Example 56: 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylsulfonyl)methyl)-4H-1,2,4-triazol-3-yl)-1H-indole [ka] To a suspension of 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylthio)methyl)-4H-1,2,4-triazol-3-yl)-1H-indole (52 mg, 0.13 mmol) in DCM (2 mL) was added m-CPBA (75 mg, 0.28 mmol) and the mixture was stirred at room temperature for 90 minutes. The reaction mixture was diluted with DCM (3 mL) and stirred for 10 minutes. The solid was collected by filtration, washed with a small amount of DCM, and dried under high vacuum to give the title compound (41 mg) as a beige solid. UPLC-MS: Rt=0.68 min; 439.3 [M+H] + ; 1 H NMR(400 MHz,DMSO-d6)δ 14.71(s,1H),7.79(s,1H),7.31(s,1H),7.06(s,1H),6.72(s,1H),4.76(s,2H),4.09(d,J=1.8 Hz,3H),3.86(s,3H),3.06(s,3H).

[0496] Example 57: 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one The title compound was synthesized by the method shown in steps 1 and 2 of Scheme 13 below. [ka]

[0497] Step 1: 1-(3-(6-chloro-7-fluoro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indol-2-yl)-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one 6-chloro-7-fluoro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole (1.5 g, 4.29 mmol), 4,4'-di-tert-butyl-2,2'-bipyridine (0.023 g, 0.09 mmol), (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (0.028 g, 0.043 mmol), A mixture of 6-chloro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole was heated at 80° C. for 15 minutes under argon to form 6-chloro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indole. This mixture was slowly added to a solution of 1-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one (1.46 g, 4.29 mmol), KPO (2.73 g, 12.9 mmol), and PdCl(dtbpf) (0.838 g, 1.29 mmol) in THF (20 mL) and TPGS-750M (2% in water) (20 mL) at room temperature, and the mixture was stirred at room temperature for 15 min. The reaction mixture was diluted with brine (300 mL) and extracted with EtOAc (2 × 350 mL). The combined organic phases were dried over NaSO, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Biotage) on silica using heptane and EtOAc (0 to 100% EtOAc) to give the title compound (697 mg). UPLC-MS (Method A): Rt=1.28 min, 609.2[M+H] + .

[0498] Step 2: 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one To a solution of 1-(3-(6-chloro-7-fluoro-5-methoxy-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-1H-indol-2-yl)-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one (146 mg, 0.24 mmol) in 1,2-DCE (20 mL) was added triflic acid (0.021 mL, 0.24 mmol) and the reaction was stirred at room temperature for 30 min. UPL- / MS (desired product formed). The reaction mixture was quenched with saturated aqueous NaHCO3 (150 mL) and the aqueous phase was extracted with EtOAc (2 x 300 mL). The combined organic phases were dried over Na2SO4, filtered and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Biotage) using heptane, EtOAc, MeOH (0-100% EtOAc and EtOAc to 0-20% EtOAc / MeOH). The resulting solid was triturated with aqueous bicarbonate (10 mL), filtered, washed with water, and dried under high vacuum to give the title compound (35 mg). UPLC-MS (Method A): Rt = 0.78 min, 407.0 [M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 12.94(s,1H),12.14(s,1H),8.22(s,1H),7.90(s,1H),7.11(s,1H),4.86(s,2H),3.93(s,3H),3.41(s,3H).

[0499] The following examples were synthesized by methods similar to those described above, using the corresponding triazole building blocks, optionally including indole NH-methylation (step 3).

[0500] [Table 104]

[0501] [Table 105]

[0502] [Table 106]

[0503] [Table 107]

[0504] [Table 108]

[0505] [Table 109]

[0506] Example 79: 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine [ka] To a solution of 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole (50 mg, 0.13 mmol) in MeOH (1 mL) was added dimethylamine (2 M in MeOH, 0.990 mL, 1.980 mmol), and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated, and the crude product was purified by flash chromatography on silica (Teledyne) using cyclohexane, EtOAc, and MeOH (0-100% EtOAc and EtOAc to 0-20% EtOAc / MeOH) to give the title compound (20 mg). UPLC-MS (Method B): Rt = 0.56 min, 404.1 [M+H] + . 1H NMR(400 MHz,DMSO-d6)δ 8.08(s,2H),7.09(s,1H),3.89(d,J=16.8 Hz,4H),2.19(s,6H),1.41(d,J=6.9 Hz,3H).

[0507] The following examples were synthesized in a manner similar to the above procedure using the corresponding monofluorinated precursors.

[0508] [Table 110]

[0509] Example 82: 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)propanenitrile [ka] To a solution of 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole (200 mg, 0.51 mmol) in DMSO (4 mL) was added KCN (99 mg, 1.53 mmol) and K2CO3 (141 mg, 1.02 mmol), and the reaction was heated at 80 °C for 6 h. Additional KCN (99 mg, 1.53 mmol) and K2CO3 (141 mg, 1.02 mmol) were added, and heating was continued for 2 h. The reaction mixture was cooled to room temperature, diluted with water and aqueous sodium chloride, and the aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Teledyne) on silica using cyclohexane and EtOAc (0-100% EtOAc) to give the title compound (61 mg) as a colorless solid. UPLC-MS (Method B): Rt = 0.89 min, 400.2 [M+H] + . 1 H NMR(400 MHz,DMSO-d6) δ 14.51(s,1H),12.95(s,1H),7.95(s,1H),7.51(s,1H),7.11(d,J=1.2 Hz,1H),4.63(d,J=7.4 Hz,1H),3.93(s,3H),3.84(d,J=1.7 Hz,3H),1.68(d,J=7.2 Hz,3H).

[0510] Examples 83a, 83, and 84: 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol (Example 83a), (S)- ... (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol (Example 83) and (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol (Example 84) Examples 83a, 83, and 84 were prepared according to Scheme 14 below. [ka]

[0511] Step 1: 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol [ka] A mixture of 6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indole (1.20 g, 5.62 mmol), 4,4′-di-tert-butyl-2,2′-bipyridine (0.03 g, 0.11 mmol), (1,5-cyclooctadiene)(methoxy)iridium(I) dimer (0.04 g, 0.056 mmol), and bis(pinacolato)diboron (1.71 g, 6.74 mmol) in THF (7.5 mL) was stirred at 80° C. for 60 minutes to form 6-chloro-7-fluoro-5-methoxy-1-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole. The reaction mixture was cooled to room temperature and slowly added to a solution of 1-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol (2.02 g, 5.90 mmol), CsCO (5.49 g, 16.9 mmol), and PdCl(dtbpf) (0.37 g, 0.56 mmol) in THF (7.5 mL) and water (16 mL) at 70 °C. The reaction mixture was stirred at 70 °C for 60 min, cooled to room temperature, and diluted with water (100 mL). The aqueous phase was extracted with EtOAc (2 × 250 mL), and the combined organic phases were washed with brine, dried over NaSO, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Biotage) using heptane and EtOAc (0-100% EtOAc) to give the title compound (2.20 g). UPLC-MS (Method A): Rt = 1.22 min, 475.4 [M+H] + .

[0512] Step 2: 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol [ka] To a mixture of 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol (2.20 g, 4.45 mmol) in DCM (200 mL) was added triflic acid (1.98 mL, 22.2 mmol) and the reaction was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated aqueous NaHCO (300 mL) and the aqueous phase was extracted with EtOAc (2 × 300 mL). The combined organic phases were dried over NaSO, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Biotage) on silica using heptane, EtOAc, and MeOH (0-100% EtOAc and 0-20% EtOAc to MeOH) to give the title compound (0.92 g). UPLC-MS (Method A): Rt=0.90 min, 355.2[M+H] + .

[0513] Step 3: 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol [ka] To a solution of 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol (0.89 g, 2.43 mmol) in THF (15 mL) was added NBS (0.48 g, 2.68 mmol) and the reaction was stirred at room temperature for 30 minutes. The reaction mixture was concentrated to give the title compound (1.39 g), which was used without further purification. UPLC-MS (Method A): Rt=0.99 min, 435.2 [M+H] + .

[0514] Step 4: 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol (Example 83a) [ka] A mixture of 1-(5-(3-bromo-6-chloro-7-fluoro-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol (1.38 g, 2.39 mmol), imidazole (0.65 g, 9.55 mmol), KCO (0.99 g, 7.16 mmol), CuI (0.045 g, 0.24 mmol), and L-proline (0.055 g, 0.48 mmol) in DMSO (8.0 mL) was stirred at 100° C. for 18 h. The reaction mixture was cooled to room temperature and carefully quenched with 10% citric acid (30 mL). Water (300 mL) was added, saturated with solid NaCl, and the aqueous phase was extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered, and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (Biotage) using DCM and MeOH (0-10% MeOH) to give the title compound (0.62 g). UPLC-MS (Method A): Rt = 0.62 min, 421.4 [M+H] + .

[0515] Step 5: Examples 83 and 84 Separation of a small sample of the enantiomers was carried out by preparative chiral SFC chromatography on a Sepiatec 100 Preparative SFC instrument (column: ChiralPak AD 250 × 30 mm, 5 μm; mobile phase: 25% aqueous NH OH in 22% MeOH + 0.1% CO , flow rate: 90 mL / min; column temperature: 40 °C, back pressure 120 bar) to give the enantiomerically pure title compound.

[0516] Example 84: (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol UPLC / MS (Method A): Rt=0.67 min, 421.4 [M+H]+. Analytical chiral SFC: R t = 2.1 min; ee99.6 (Waters UPC 2 Analytical SFC system; Column: ChiralPak AD, 100 x 4.6 mm, 5 μm; 25% aqueous NH 4 OH in 22% methanol + 0.1% CO 2 ; Flow rate: 3 mL / min; Column temperature: 40 °C, back pressure: 1800 psi). 1 H NMR (400 MHz, DMSO-d) δ 7.78 (s, 1H), 7.32 (s, 1H), 7.05 (s, 1H), 6.70 (s, 1H), 6.05 (d, J = 5.0 Hz, 1H), 4.89 (m, 1H), 4.08 (s, 3H), 3.85 (s, 3H), 3.74-3.50 (m, 2H), 3.26 (s, 3H). The absolute stereochemistry (R) was assigned by X-ray crystallography.

[0517] Example 83: (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol UPLC / MS (Method A): Rt=0.67 min, 421.4 [M+H]+. Analytical chiral SFC: t = 2.9 min; ee98.1 (Waters UPC 2Analytical SFC system; Column: ChiralPak AD, 100 × 4.6 mm, 5 μm; 25% aqueous NH OH in 22% methanol + 0.1% CO ; Flow rate: 3 mL / min; Column temperature: 40 °C, back pressure: 1800 psi. H NMR (400 MHz, DMSO-d ) δ 7.78 (s, 1H), 7.32 (d, J = 1.4 Hz, 1H), 7.05 (s, 1H), 6.70 (s, 1H), 6.05 (s, 1H), 4.89 (m, 1H), 4.08 (s, 3H), 3.85 (s, 3H), 3.67 (m, 2H), 3.26 (s, 3H). The following examples were synthesized by methods similar to those described above using the corresponding indole intermediates and triazole building blocks.

[0518] [Table 111]

[0519] [Table 112]

[0520] [Table 113]

[0521] [Table 114]

[0522] [Table 115]

[0523] [Table 116]

[0524] [Table 117]

[0525] [Table 118]

[0526] [Table 119]

[0527] Example 120: 5-(6,7-dicyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide [ka] A mixture of 5-(6,7-difluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide (65 mg, 0.154 mmol), KCO (85 mg, 0.62 mmol), and KCN (100 mg, 1.54 mmol) in DMSO (1 mL) was heated at 130° C. for 4 h. The reaction mixture was cooled to room temperature, filtered through a pad of Celite, and the filtrate was concentrated. The compound was purified by preparative reverse-phase chromatography (XBridge-C18 (5 um, 50 x 250 mm), eluent A: HO + 0.2% HCOOH, B: ACN, gradient: initial 0.8% B; 0.8% to 28% B in 21 min, flow rate: 100 mL / min) to give the title compound (25 mg) as a white solid. UPLC-MS (Method A): Rt = 0.47 min; 402.3 [M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 7.78(s,1H),7.32(s,1H),7.08(d,J=14.5 Hz,2H),4.31(s,3H),3.23(s,3H),3.01(s,3H).

[0528] Example 121: 4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)morpholine [ka] To a solution of 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-ol (121 mg, 0.28 mmol) in DCM (40 mL) was added morpholine (0.36 mL, 4.13 mmol) followed by DAST (0.26 mL, 1.93 mmol) and the reaction was stirred at room temperature for 10 min. The reaction mixture was concentrated to dryness and the crude product was purified by flash chromatography on silica (Biotage) using EtOAc and MeOH (0-30% MeOH) to give the title compound (94 mg). UPLC-MS (Method A): Rt = 0.64 min, 460.4 [M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 7.78(s,1H),7.31(s,1H),7.04(s,1H),6.71(s,1H),4.10(s,3H),3.94-3.81(m,4H),3.58-3.53(m,4H),2.40-2.32(m,4H),1.37(d,J=7.0 Hz,3H).

[0529] The following examples were synthesized by methods similar to those described above using the corresponding alcohol intermediates and commercially available amines.

[0530] [Table 120]

[0531] Examples 124, 124a, and 124b: 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine (Example 124), (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine (Example 124), (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine (Example 124a), and (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine (Example 124b); [ka] To a suspension of 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol (see, e.g., Example 83a) (504 mg, 1.174 mmol) in CHCl (30 mL) was added 2 M dimethylamine in THF (5.87 mL, 11.74 mmol). DAST (0.93 mL, 7.04 mmol) was added dropwise over 2 min at 0 °C, and the reaction mixture was stirred at 0 °C for 10 min. The solvent was removed in vacuo, and the crude product was purified by flash chromatography on silica (Biotage) using EtOAc and MeOH (0 to 50% MeOH) to give the title compound (0.53 mg). UPLC-MS (Method A): Rt=0.57 min, 448.4[M+H] + . 1H NMR(400 MHz,DMSO-d6)δ 14.30(s,1H),7.77(s,1H),7.31(s,1H),7.05(s,1H),6.71(s,1H),4.10(s,3H) ,3.99-3.89(m,1H),3.85(s,3H),3.81-3.67(m,2H),3.22(s,3H),2.14(s,6H).

[0532] Separation of 3.89 g of racemic 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine was carried out by preparative chiral SFC chromatography on a Sepiatec 100 Preparative SFC apparatus (column: ChiralPak IB-N 250 × 30 mm, 5 μm; mobile phase: 25% aqueous NH OH in 20% MeOH + 0.1% CO , flow rate: 80 mL / min; column temperature: 40 °C, back pressure 130 bar) to give the enantiomerically pure title compound.

[0533] Example 124a: (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine, Peak 1 (1.80 g), UPLC / MS (Method A): Rt=0.54 min, 448.2 [M+H]+. Analytical chiral SFC: R t = 1.17 min; ee 99.5% (Waters UPC 2 Analytical SFC system; Column: ChiralPak IB-N, 100 × 4.6 mm, 3 μm; A is CO2, B is MeOH (+0.05% NH4OH), gradient B 20%, flow rate: 3.0 mL / min, column temperature: 40 °C, back pressure: 1800 psi). 1H NMR (400 MHz, DMSO-d6) δ 14.30 (s, 1H), 7.77 (s, 1H), 7.31 (s, 1H), 7.05 (s, 1H), 6.71 (s, 1H), 4.10 (s, 3H), 3.99-3.89 (m, 1H), 3.85 (s, 3H), 3.81-3.67 (m, 2H), 3.22 (s, 3H), 2.14 (s, 6H). Absolute stereochemistry (R configuration) was assigned by X-ray crystallography.

[0534] Example 124b: (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine, Peak 2 (1.81 g), UPLC / MS (Method A): Rt=0.54 min, 448.2 [M+H]+. Analytical chiral SFC: t = 1.1.84 min; ee 99.5% (Waters UPC 2 Analytical SFC device, column: ChiralPak IB-N, 100 × 4.6 mm, 3 μm; A is CO2, B is MeOH (+0.05% NH4OH), gradient B 20%, flow rate: 3.0 mL / min, column temperature: 40 °C, back pressure: 1800 psi). 1H NMR(400 MHz,DMSO-d6)δ 14.30(s,1H),7.77(s,1H),7.31(s,1H),7.05(s,1H),6.71(s,1H),4.10(s,3H),3.92(t,J=7.5,6.0 Hz,1H),3.85(s,3H),3.82-3.67(m,2H),3.22(s,3H),2.14(s,6H).

[0535] Examples 125, 125a, and 125b: 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine (Example 125), (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine (Example 125a) and (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine (Example 125b) Examples 125, 125a, and 125b were prepared according to Scheme 15 below. [ka]

[0536] Step 1: N-benzyl-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine [ka] 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol (see, e.g., Example 83a) (3 g, 7.13 mmol) was suspended in CHCl (285 mL) and N-benzylmethylamine was added. The suspension was cooled to 0° C. and DAST (2.83 mL, 21.4 mmol) was added. The ice bath was removed and the yellow solution was stirred at room temperature for 5 minutes. The reaction mixture was washed with saturated aqueous bicarbonate solution, the organic phase was dried over NaSO, filtered and the solvent was removed in vacuo. The crude product was purified by flash chromatography (Biotage) on silica using DCM and DCM / MeOH (4:1) (0-70% DCM / MeOH 4:1) to give the title compound (3.71 g). UPLC-MS (Method A): Rt = 0.99 min, 524.4 [M+H] + .

[0537] Step 2: 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine (Example 125) [ka] To a cooled solution of N-benzyl-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine (3.6 g, 6.87 mmol) in AcOH (69 mL) at 0 °C was added Pd / C 10% (0.37 g, 0.34 mmol). The flask was evacuated, fitted with a hydrogen balloon, and purged with hydrogen gas. The mixture was stirred at room temperature for 2 h, diluted with EtOAc, filtered through a pad of hyflo, and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography (Biotage) on silica using DCM and DCM / MeOH (7:3) (0 to 100% DCM / MeOH 7:3) to give the title compound (2.63 g). UPLC-MS (Method A): Rt=0.51 min, 434.1[M+H] + . 1 H NMR(400 MHz,DMSO-d6)δ 7.78(t,J=1.1 Hz,1H),7.32(t,J=1.3 Hz,1H),7.05(t,J=1.1 Hz,1H),6.71(d,J=1.1 Hz,1H),4.09(d,J=1.9 Hz,3H),3.94(t,J=6.0 Hz,1H),3.85(s,3H),3.59(dd,J=6.0,2.1 Hz,2H),3.23(s,3H),2.23(s,3H).

[0538] Step 3: Examples 125a and 125b Separation of 13.75 g of racemic 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine was achieved by preparative chiral SFC chromatography on an MG II Preparative SFC apparatus (column: ChiralCel OD 250 × 30 mm, 10 μm, mobile phase A was CO , mobile phase B was EtOH (+0.1% NH OH in water), gradient B 30%, flow rate: 70 mL / min, column temperature: 38 °C, back pressure: 100 bar, wavelength: 260 nm) to give the enantiomerically pure title compound.

[0539] Example 125a: (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine, Peak 1 (6.62 g), UPLC / MS (Method A): Rt=0.49 min, 434.3 [M+H]+. Analytical chiral SFC: R t = 2.1 min; ee 100% (Waters UPC 2 Analytical SFC system; Column: ChiralCel OD, 150 × 4.6 mm, 3 μm, A is CO, B is MeOH (+0.05% diethylamine), gradient B 30%, flow rate: 2.5 mL / min, column temperature: 35 °C, back pressure: 100 bar, wavelength: 220 nm). 1 H NMR (400 MHz, DMSO-d6) δ 7.78 (t, J = 1.1 Hz, 1H), 7.32 (t, J = 1.3 Hz, 1H), 7.05 (t, J = 1.1 Hz, 1H), 6.71 (d, J = 1.1 Hz, 1H), 4.09 (d, J = 1.9 Hz, 3H), 3.94 (t, J = 6.0 Hz, 1H), 3.85 (s, 3H), 3.59 (dd, J = 6.0, 2.1 Hz, 2H), 3.23 (s, 3H), 2.23 (s, 3H). The absolute stereochemistry (R configuration) was assigned by X-ray crystallography.

[0540] Example 125b: (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine, Peak 2 (5.94 g), UPLC / MS (Method A): Rt=0.46 min, 434.4 [M+H]+. Analytical chiral SFC: t = 2.9 min; ee 99.2% (Waters UPC 2 Analytical SFC system; Column: ChiralCel OD, 150 × 4.6 mm, 3 μm, A is CO, B is MeOH (+0.05% diethylamine), gradient B 30%, flow rate: 2.5 mL / min, column temperature: 35 °C, back pressure: 100 bar, wavelength: 220 nm). 1H NMR(400 MHz,DMSO-d6)δ 7.78(t,J=1.1 Hz,1H),7.32(t,J=1.3 Hz,1H),7.05(t,J=1.1 Hz,1H),6.71(d,J=1.1 Hz,1H),4.08(d,J=1.9 Hz,3H),3.94(t,J=6.0 Hz,1H),3.85(s,3H),3.60(dd,2H),3.23(s,3H),2.23(s,3H).

[0541] [Table 121]

[0542] [Table 122]

[0543] Biochemical Assays and Data The activity of the compounds according to the present disclosure can be assessed by the following method.

[0544] Example 131: Quantitation of cGAS protein inhibition Reagent buffers were prepared in filtered, autoclaved water as follows: ·50mM Tris buffer pH7.5 (1M Tris buffer pH7.5, Invitrogen, catalog number 15567-027); · 50 mM NaCl (5 M NaCl, sodium chloride solution, Sigma, 59222C-); ·5mM MgCl2 (1M MgCl2, Sigma, M1028); 0.1 mM ZnCl2 (zinc chloride [7646-85-7], powder, cell culture tested, Sigma, Z-0152); and ·0.001% Tween 20 (TWEEN 20, Sigma Aldrich, P1379-).

[0545] A buffer for the cGAS enzyme was prepared with filtered and autoclaved water as follows. ·50mM Tris buffer pH7.5; 5mM MgCl2; and 0.001% Tween 20.

[0546] Compounds were dispensed into a 386-well plate. Human truncated cGAS enzyme (4.2 mg / mL 147-522 human cGAS, molecular weight 43,909 g / mol) was stored in 50 mM Tris, pH 8, 500 mM NaCl, and 5% (v / v) glycerol and diluted with cGAS buffer enzyme immediately before use. The enzyme solution was transferred to reagent buffer to a final concentration of 30 nM. The reaction was initiated by mixing the enzyme with ISD (45 bp double-stranded DNA, molecular weight 27,670 g / mol, 5 mM), GTP, and ATP to final concentrations of 5 μM, 0.5 mM, and 0.5 mM, respectively, in a final volume of 10 μM. The reaction plate was then centrifuged at 1000 rpm for 1 minute and incubated at room temperature for 1 hour. After the 1-hour incubation, a final concentration of 200 nM [ 15N5]-2'3'-cGAMP and 30 μL of 100% acetonitrile / 0.175% TFA were added to the reaction mixture. The plate was centrifuged at 1000 rpm for 1 minute and then sealed at 170°C for 3 seconds using a ThermoScientific sealer (ALPS™ 50V) and an aluminum sealing cover (Pierce Seal, 4titude, product code: 4TI-0531).

[0547] cGAMP concentrations were measured using an LC-MS / MS system consisting of a THERMO Dionex Ultimate LC system (Reinach, Switzerland) equipped with a high-pressure pump, autosampler, and column heating compartment, and a SCIEX Triple Quad 5500 (Framingham, MA, USA) mass spectrometer for detection. Sample plates were centrifuged at 2000 rpm for 10 minutes. Up to three plates were placed in the autosampler for injection. A 10 μL aliquot of each sample was injected onto an XBridge BEH Amide 3.5 μm, 2.1 × 50 mm column (P / N 186004859) with an XBridge BEH Amide 5 μm, 2.1 × 5 mm VanGuard Cartridge (P / N 186007760) precolumn (both WATERS, MA, USA) maintained at 40 °C. An isocratic flow of solvent (60% ACN, 8 mM ammonium acetate, 5 mM ammonium hydroxide, 0.04% acetic acid) was applied at 1.0 mL / min and sprayed into the mass spectrometer ion source. MS parameters were optimized based on the properties of the compounds being detected and run in positive multiple reaction mode (MRM) based on mass transitions. LC and MS parameters were also optimized to allow for a run time of approximately 8 hours per 384-well plate with a sample-to-sample measurement time of approximately 75 seconds. All data were analyzed in Excel. Dose-response curves were generated using the automated fitting function in XLfit. IC 50 is the cGAMP concentration ratio (cGAMP as an internal standard [ 15 N5]-2'3'-cGAMP) versus compound concentration.

[0548] The activities of representative compounds of the present disclosure are reported in Table 1 above. Unless otherwise stated, IC 50 Regardless of the specific tautomer, the potential mixture of coexisting tautomers and / or racemates is reported. The compounds of the present invention exhibit IC activity against cGAS in the nanomolar to submillimolar range. 50 to provide.

Claims

1. Formula (I): 【Chemistry 1】 (In the formula, R １ (C １ -C ４ ) alkyl, OH, halogen, -NR ａ R ｂ and a 5-membered heteroaryl ring containing 1 to 4 heteroatoms selected from O, N, and S, optionally substituted with at least one 5- or 6-membered heterocycloalkyl ring containing oxygen; R ２ (C １ -C ４ ) alkyl, (C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-NR ９ R １０ , (C １ -C ４ ) a 5-membered heteroaryl ring containing three nitrogen atoms at positions 1, 2 and 4 relative to one another, optionally substituted with alkylene-C(O)OH, said 5-membered heteroaryl ring being bonded to a carbon atom of the 5-membered heteroaryl ring by R ３ is further substituted with; R ３ is H, halogen, -OH, -NR １１ R １２ , -(C １ -C ４ ) alkylene-NR １３ R １４ , (C １ -C ４ ) alkyl, halo (C １ -C ４ ) alkyl, -(C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-(C １ -C ４ ) alkoxy, —C(O)(C １ -C ４ ) alkyl, —C(O)(C １ -C ４ ) alkylene-O-(C １ -C ４ ) alkyl, —C(O)(C １ -C ４ ) alkylene-OH, -C(O)NR １５ R １６ , (C １ -C ４ ) alkoxy, -(C １ -C ４ ) alkylene-S(O) ｖ - (C １ -C ４ ) alkyl, —C(O)(C １ -C ４ ) alkoxy, -CN, -O(C １ -C ４ ) alkylene-OH, -O(C １ -C ４ ) alkylene-(C １ -C ４ ) alkoxy, -(C １ -C ４ ) alkylene-C(O)(C １ -C ４ ) alkyl, -(C １ -C ４ ) alkylene-C(O)(C １ -C ４ ) alkoxy, -(C １ -C ４ ) alkylene-C(O)NR １７ R １８ , a 6-membered heterocycloalkyl ring Ri containing 1 to 2 heteroatoms selected from O and N; or 【Chemistry 2】 and (C １ -C ４ ) alkyl is CN, ═N—(C １ -C ４ ) alkoxy, =N-O-(C １ -C ４ ) alkylene-OR ２０ , OH, (C １ -C ４ )alkoxy, —C(O)OH, —C(O)O(C １ -C ４ ) optionally substituted with at least one of an alkyl, a 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S, and a 5-6 membered heteroaryl ring containing 1-2 heteroatoms selected from O, N, and S; Each - (C １ -C ４ ) alkylene-NR ９ R １０ and -(C １ -C ４ ) alkylene-NR １３ R １４ is as described above (C １ -C ４ ) At least one of the alkylene carbons is OH, (C １ -C ４ ) alkoxy, -(C １ -C ４ ) alkylene-O(C １ -C ４ ) alkyl, (C １ -C ４ ) optionally substituted with alkyl; Each halo (C １ -C ４ ) alkyl and (C １ -C ４ ) alkylene-OH is independently OH, (C １ -C ４ ) alkoxy, —O(C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-(C １ -C ４ ) optionally substituted with at least one alkoxy; Ri is (C １ -C ４ ) optionally substituted with alkyl; v is 0, 1 or 2; R ４ is one or more (C １ -C ４ ) optionally substituted with alkoxy; H, (C １ -C ４ ) alkyl, -(C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-(C １ -C ４ ) alkoxy, -(C １ -C ４ ) alkylene -C(O)OH, -C(O)O(C １ -C ４ ) an alkyl or 5-6 membered heteroaryl ring containing 1-2 nitrogen atoms; Each R ５ , R ６ , R ７ , and R ８ are independently H, halogen, OH, (C １ -C ４ ) alkyl, (C １ -C ４ ) alkoxy, halo (C １ -C ４ ) alkyl, halo (C １ -C ４ ) alkoxy, (C ２ -C ６ ) alkenyl, (C ２ -C ６ ) alkynyl, -(C １ -C ４ ) alkylene-OH, -O(C １ -C ４ ) alkylene -OH, CN, -C(O)(C １ -C ４ ) alkoxy, —C(O)NR ２１ R ２２ or a 5-membered heteroaryl ring containing two nitrogen heteroatoms, each (C ２ -C ６ ) alkenyl and (C ２ -C ６ )alkynyl is independently one or more (C １ -C ４ ) optionally substituted with alkoxy; Each R ２０ , R ２１ and R ２２ are independently H or (C １ -C ４ ) alkyl; Each R ９ , R １０ , R １１ , R １２ , R １３ , R １４ , R １５ , R １６ , R １７ and R １８ are independently H, (C １ -C ４ ) alkyl, -(C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-O(C １ -C ４ ) alkyl, —C(O)(C １ -C ４ ) alkylene-(C １ -C ４ ) alkoxy, or —C(O)(C １ -C ４ ) alkyl; or R ９ and R １０ together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. ２３ Forming R ２３ optionally one or more R ２４ is substituted with; R １１ and R １２ together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. ２５ Forming R ２５ optionally one or more R ２６ is substituted with; R １３ and R １４ together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. ２７ Forming R ２７ optionally one or more R ２８ is substituted with; R １５ and R １６ together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. ２９ Forming R ２９ optionally one or more R ３０ is substituted with; R １７ and R １８ together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R containing 1 to 2 heteroatoms selected from O, N and S. ３１ Forming R ３１ is optionally R ３２ is substituted with; Each R ２４ , R ２６ , R ２８ , R ３０ and R ３２ are independently １ -C ４ ) alkyl, (C １ -C ４ ) Alkoxy, NR ｃ R ｄ , OH or ═O; or Each R ２４ , R ２６ , R ２８ , R ３０ and R ３２ When two of them are bonded together to the same atom, (C ４ -C ７ ) forms a spirocycloalkyl or 4-7 membered spiroheterocycloalkyl ring containing 1-2 heteroatoms selected from O, N and S; R １９ is H, OH or (C １ -C ４ ) alkyl; Each R ａ , R ｂ , R ｃ and R ｄ are independently H, halogen, or (C １ -C ４ ) alkyl or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof.

2. R １ The 5-membered heteroaryl ring of １ -C ４ 2. The compound of claim 1, which is an imidazolyl or pyrazolyl, optionally substituted with at least one of an alkyl, OH, and a 5- or 6-membered heterocycloalkyl ring containing oxygen.

3. Formula (Ia), (Ib) or (Ic): 【Chemistry 3】 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, R ３３ , R ３４ and R ３５ independently at a carbon or nitrogen position of the ring, H, (C １ -C ４ 3. The compound according to claim 1 or 2, wherein the aryl group is a 5- or 6-membered heterocycloalkyl ring containing an oxygen atom.

4. Formula (Ia1), (Ib1) or (Ic1): 【Chemistry 4】 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, R ３３ and R ３５ independently at a carbon or nitrogen position of the ring, H, (C １ -C ４ 4. The compound according to claim 1, wherein the aryl group is a 5- or 6-membered heterocycloalkyl ring containing an oxygen atom.

5. Formula (IIa), (Ib) or (Ic): 【Chemistry 5】 or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, R ３６ , R ３７ and R ３８ are independently H, (C １ -C ４ ) alkyl, or -(C １ -C ４ 5. The compound according to claim 1, wherein the alkylene group is aryl, aryl, or aryl.

6. R ４ But, H, (C １ -C ４ ) alkyl, -(C １ -C ４ ) alkylene-(C １ -C ４ ) alkoxy, -(C １ -C ４ 6. The compound according to any one of claims 1 to 5, wherein said alkylene-OH is pyridyl, pyrazolyl or imidazolyl.

7. R ５ H, F, Cl, CN, OH, (C １ -C ４ ) alkyl, (C ２ -C ６ ) alkenyl, (C ２ -C ６ ) alkynyl, (C １ -C ４ 7. The compound according to claim 1, wherein said aryl group is alkoxy or imidazolyl.

8. R ６ H, F, Cl, CN, OH, (C １ -C ４ ) alkyl, -(C １ -C ４ ) alkoxy, (C ２ -C ６ ) alkenyl, or (C ２ -C ６ 8. The compound according to claim 1, wherein R is 1 or 2. 9.) alkynyl.

9. R ７ H, F, Cl, CN, OH, (C １ -C ４ ) alkyl, (C １ -C ４ ) alkoxy, halo (C １ -C ４ ) alkoxy, —C(O)NR ２１ R ２２ and R ２１ and R ２２ are independently H or (C １ -C ４ 9. The compound according to claim 1, wherein:

10. R ８ H, F, Cl, CN, OH, (C １ -C ４ ) alkyl, (C １ -C ４ 10. The compound according to claim 1, wherein:

11. R ３ is H, halogen, -NR １１ R １２ , -(C １ -C ４ ) alkylene-NR １３ R １４ , (C １ -C ４ ) alkyl, halo (C １ -C ４ ) alkyl, -(C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-(C １ -C ４ ) alkoxy, —C(O)(C １ -C ４ ) alkyl, —C(O)(C １ -C ４ ) alkylene-O-(C １ -C ４ ) alkyl, —C(O)(C １ -C ４ ) alkylene-OH, -C(O)NR １５ R １６ , (C １ -C ４ ) alkoxy, -(C １ -C ４ ) alkylene-S(O) ｖ - (C １ -C ４ ) alkyl, —C(O)(C １ -C ４ ) alkoxy, -CN, -O(C １ -C ４ ) alkylene-OH, -O(C １ -C ４ ) alkylene-(C １ -C ４ ) alkoxy, -(C １ -C ４ ) alkylene-C(O)(C １ -C ４ ) alkyl, -(C １ -C ４ ) alkylene-C(O)(C １ -C ４ ) alkoxy; Said (C １ -C ４ ) alkyl is CN, ═N—(C １ -C ４ ) alkoxy, =N-O-(C １ -C ４ ) alkylene-OR ２０ , OH, (C １ -C ４ )alkoxy, —C(O)OH, —C(O)O(C １ -C ４ ) optionally substituted with at least one of an alkyl, a 4-6 membered heterocycloalkyl ring containing 1-2 heteroatoms selected from O, N, and S, and a 5-6 membered heteroaryl ring containing 2 nitrogen atoms; Said -(C １ -C ４ ) alkylene-NR １３ R １４ However, １ -C ４ ) At least one of the alkylene carbons is OH, (C １ -C ４ ) alkoxy, -(C １ -C ４ ) alkylene-O(C １ -C ４ ) alkyl, (C １ -C ４ ) optionally substituted with alkyl; Each halo (C １ -C ４ ) alkyl and (C １ -C ４ ) alkylene-OH is independently OH, (C １ -C ４ ) alkoxy, —O(C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-(C １ -C ４ ) optionally substituted with at least one alkoxy; Ri is (C １ -C ４ ) optionally substituted with alkyl; v is 0, 1 or 2; R ２０ is H or (C １ -C ４ ) alkyl; Each R １１ , R １２ , R １３ , R １４ , R １５ and R １６ are independently H, (C １ -C ４ ) alkyl, -(C １ -C ４ ) alkylene-OH, -(C １ -C ４ ) alkylene-O(C １ -C ４ ) alkyl, —C(O)(C １ -C ４ ) alkylene-(C １ -C ４ ) alkoxy, or —C(O)(C １ -C ４ ) alkyl; or R １１ and R １２ together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R ２５ Forming R ２５ But, R ２６ optionally substituted with; R １３ and R １４ together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R ２７ Forming R ２７ But, R ２８ optionally substituted with; R １５ and R １６ together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring R ２９ Forming R ２９ But, R ３０ optionally substituted with; Each R ２６ , R ２８ and R ３０ But independently, (C １ -C ４ ) alkyl, (C １ -C ４ ) Alkoxy, NR ｃ R ｄ , OH or ═O; or Each R ２６ , R ２８ , R ３０ and R ３２ When two of the bonds are bonded together to the same atom, (C ４ -C ７ ) forms a spirocycloalkyl or 4-7 membered spiroheterocycloalkyl ring containing 1-2 heteroatoms selected from O, N and S; Each R ｃ and R ｄ are independently H, halogen, or (C １ -C ４ ) alkyl; A compound according to any one of claims 1 to 10.

12. R ３ is H, F, Cl, Br, fluoroethyl, fluoromethyl, difluoromethyl, difluoroethyl, trifluoromethyl, trifluoroethyl, cyanoethyl, -C(O)NH ２ , N,N-dimethylcarboxamide, methoxyacetyl, methoxypropanoyl, acetyl, propanoyl, methylcarboxyl, ethylcarboxyl, dimethylaminomethyl, dimethylaminoethyl, methoxydifluoroethyl, ethoxydifluoroethyl, methoxyfluoroethyl, hydroxydifluoroethyl, methoxydifluoroethyl, hydroxymethyl, hydroxyethyl, hydroxymethoxyethyl, dimethylamino, dimethylamido, CN, cyanoethyl, methyl-(hydroxy)ethylamino, methylsulfonylmethyl, methylthioethyl, methylthiomethyl, -N((C １ -C ４ ) alkyl) C(O) methylene-(C １ -C ４ ) alkoxy, —C(O)N(CH ３ ) Ethylene-OH, hydroxymethoxyethyl, dimethoxyethyl, (C １ -C ４ ) alkoxy-substituted fluoro (C １ -C ４ ) alkyl, (C １ -C ４ ) alkoxy-substituted difluoro (C １ -C ４ ) alkyl, (C １ -C ４ ) alkoxy-substituted trifluoro(C １ -C ４ ) alkyl, hydroxy (C １ -C ４ ) alkoxy-substituted trifluoro(C １ -C ４ ) alkyl, -NR １１ R １２ , -(C １ -C ４ ) alkylene-NR １３ R １４ , hydroxy (C １ -C ４ ) Alkoxy (C １ -C ４ ) alkyl, hydroxy (C １ -C ４ ) alkoxy, (C １ -C ４ ) alkoxyacetyl, (C １ -C ４ ) alkoxypropionoyl, methoxymethyl, methoxyethyl, morpholinyl, pyrrolidinyl, hydroxypyrrolidinyl, -C(O)(C １ -C ３ ) alkylene (C １ -C ４ ) alkoxy, —C(O)N(CH ３ ) methoxyethyl, N,N-dimethylmethoxyethyl, two (C １ -C ４ ) alkoxy group-substituted (C １ -C ４ ) alkyl, methoxycarbonylmethyl, 【Chemistry 6】 and the -(C １ -C ４ ) alkylene-NR １３ R １４ However, (C １ -C ４ ) At the alkylene carbon, OH or (C １ -C ４ ) substituted with alkoxy; Each R １１ , R １２ , R １３ , R １４ are independently H, (C １ -C ４ ) alkyl, or -(C １ -C ４ ) alkylene-OH; A compound according to any one of claims 1 to 11.

13. R ３ The compound according to any one of claims 1 to 12, wherein is fluoroethyl, difluoroethyl, trifluoromethyl, hydroxymethoxyethyl, methoxy N,N-dimethylaminoethyl, N,N-dimethylcarboxamido.

14. 6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 6-chloro-7-fluoro-2-(5-fluoro-4H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-fluoro-1H-1,2,4-triazol-5-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-1H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 2-(5-bromo-4H-1,2,4-triazol-3-yl)-6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indole; 2-(3-bromo-1H-1,2,4-triazol-5-yl)-6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indole; 2-(5-bromo-1H-1,2,4-triazol-3-yl)-6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-5-carbonitrile; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-5-carbonitrile; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-5-carbonitrile; 1-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one; 6-chloro-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-5-carbonitrile; 6-chloro-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-5-carbonitrile; 6-chloro-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-5-carbonitrile; 6,7-dichloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6,7-dichloro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6,7-dichloro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6,7-dichloro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-pyrazol-4-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-4-yl)-2-(5-(2,2,2-trifluoroethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-4-yl)-2-(3-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-4-yl)-2-(5-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-difluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-difluoro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-difluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 2-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-ol; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-methoxy-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 5,6-dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 5,6-dichloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 5,6-dichloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; Ethyl 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate; Ethyl 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carboxylate; Ethyl 3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carboxylate; 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxamide; 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carboxamide; 3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carboxamide; 5,6-dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 5,6-dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 5,6-dichloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 2-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-1-yl)ethan-1-ol; 2-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-1-yl)ethan-1-ol; 2-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-1-yl)ethan-1-ol; 6-chloro-5-methoxy-1-(2-methoxyethyl)-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-methoxy-1-(2-methoxyethyl)-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-methoxy-1-(2-methoxyethyl)-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-7-carbonitrile; 6-chloro-1-methyl-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; Ethyl 5-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxylate; Ethyl 5-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carboxylate; Ethyl 3-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carboxylate; 2-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)methyl acetate; 2-(5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)methyl acetate; 2-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)methyl acetate; 7-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-5-carboxamide; 7-chloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-5-carboxamide; 7-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-5-carboxamide; 5-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carboxamide; 4,5-dichloro-1-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 4,5-dichloro-1-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 4,5-dichloro-1-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-5-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-5-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-5-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-7-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-7-ol; 6-chloro-3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-7-ol; 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazole-3-carbonitrile; 5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-3-carbonitrile; 3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazole-5-carbonitrile; (5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)methanol; (5-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)methanol; (3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)methanol; 2-(3-(6,7-dichloro-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-1-yl)ethan-1-ol; 6,7-dichloro-3-(1H-pyrazol-4-yl)-2-(4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-4-yl)-2-(1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-4-yl)-2-(1H-1,2,4-triazol-3-yl)-1H-indole; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-methoxyethyl)-N-methyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-methoxyethyl)-N-methyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-methoxyethyl)-N-methyl-1H-1,2,4-triazole-5-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-hydroxyethyl)-N-methyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-hydroxyethyl)-N-methyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N-(2-hydroxyethyl)-N-methyl-1H-1,2,4-triazole-5-carboxamide; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(morpholino)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(morpholino)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(morpholino)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypyrrolidin-1-yl)methanone; (S)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (S)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (S)-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypyrrolidin-1-yl)methanone; (R)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (R)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypyrrolidin-1-yl)methanone; (R)-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypyrrolidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(4-hydroxypiperidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(4-hydroxypiperidin-1-yl)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(4-hydroxypiperidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypiperidin-1-yl)methanone; (S)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (S)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (S)-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypiperidin-1-yl)methanone; (R)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (R)-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(3-hydroxypiperidin-1-yl)methanone; (R)-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(3-hydroxypiperidin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(4-methylpiperazin-1-yl)methanone; (5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(4-methylpiperazin-1-yl)methanone; (3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(4-methylpiperazin-1-yl)methanone; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(methoxymethyl)-4H-1,2,4-triazol-3-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(methoxymethyl)-1H-1,2,4-triazol-5-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(methoxymethyl)-1H-1,2,4-triazol-3-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylthio)methyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(3-((methylthio)methyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylthio)methyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-ol; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-1-methyl-1H-indole; 6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(3-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (S)-6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (S)-6-chloro-2-(3-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (S)-6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (R)-6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (R)-6-chloro-2-(3-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; (R)-6-chloro-2-(5-(1-hydroxy-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(methoxymethyl)-4H-1,2,4-triazol-3-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(methoxymethyl)-1H-1,2,4-triazol-5-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(methoxymethyl)-1H-1,2,4-triazol-3-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylsulfonyl)methyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(3-((methylsulfonyl)methyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-((methylsulfonyl)methyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one; 6-chloro-7-fluoro-2-(5-fluoro-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-fluoro-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 4-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)morpholine; 4-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)morpholine; 4-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)morpholine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-one; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-one; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-one; N-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-methylacetamide; N-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-methylacetamide; N-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-methylacetamide; N-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylacetamide; N-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylacetamide; N-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylacetamide; 2-((5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(methyl)amino)ethan-1-ol; 2-((5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(methyl)amino)ethan-1-ol; 2-((3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(methyl)amino)ethan-1-ol; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoroethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(3-(1,1-difluoroethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoroethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoroethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(3-(1,1-difluoroethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoroethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; 6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(3-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (R)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(3-(1-fluoroethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; (S)-6-chloro-7-fluoro-2-(5-(1-fluoroethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole-7-carbonitrile; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole-7-carbonitrile; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indole-7-carbonitrile; 1-(5-(6-chloro-5-ethoxy-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-one; 1-(5-(6-chloro-5-ethoxy-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-one; 1-(3-(6-chloro-5-ethoxy-7-fluoro-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-one; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; 3-(6,7-dichloro-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-3-yl)-1H-pyrazol-5-ol; 3-(6,7-dichloro-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-3-yl)-1H-pyrazol-5-ol; 3-(6,7-dichloro-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-3-yl)-1H-pyrazol-5-ol; 3-(6,7-dichloro-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-3-yl)isoxazol-5-ol; 3-(6,7-dichloro-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-3-yl)isoxazol-5-ol; 3-(6,7-dichloro-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-3-yl)isoxazol-5-ol; 6,7-dichloro-3-(1H-pyrazol-3-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-3-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-dichloro-3-(1H-pyrazol-3-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-5-methoxy-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)propanenitrile; 2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)propanenitrile; 2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)propanenitrile; (R)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)propanenitrile; (R)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)propanenitrile; (R)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)propanenitrile; (S)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)propanenitrile; (S)-2-(5-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)propanenitrile; (S)-2-(3-(6-chloro-7-fluoro-5-methoxy-1-methyl-3-(1H-pyrazol-4-yl)-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)propanenitrile; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-2-(5-isopropoxy-4H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-2-(3-isopropoxy-1H-1,2,4-triazol-5-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-2-(5-isopropoxy-1H-1,2,4-triazol-3-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-2-(3-fluoro-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1H-indole; 6-chloro-7-fluoro-2-(3-fluoro-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1H-indole; 6-chloro-7-fluoro-2-(5-fluoro-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1H-indole; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-one; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-one; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-2-(3-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-2-(5-(1,1-difluoro-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-((5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)(methyl)amino)ethan-1-ol; 2-((5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)(methyl)amino)ethan-1-ol; 2-((3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)(methyl)amino)ethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)pyrrolidin-3-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)pyrrolidin-3-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)pyrrolidin-3-ol; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)pyrrolidin-3-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; 2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (S)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (S)-2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; (R)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethan-1-ol; (R)-2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethan-1-ol; 2-((5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)oxy)ethan-1-ol; 2-((5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)oxy)ethan-1-ol; 2-((3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)oxy)ethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2-difluoroethan-1-ol; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2-difluoroethan-1-ol; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-2-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2,2-trifluoroethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2,2-trifluoroethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2,2,2-trifluoroethan-1-ol; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2,2,2-trifluoroethan-1-ol; 6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-2-(3-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-6-chloro-2-(3-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-4H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-6-chloro-2-(3-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-5-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-6-chloro-2-(5-(2,2-difluoro-1-methoxyethyl)-1H-1,2,4-triazol-3-yl)-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(3-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(3-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(3-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(5-(1-(1H-imidazol-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 1-(5-(6-chloro-5-ethoxy-7-fluoro-3-(1H-imidazol-1-yl)-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-one; 1-(5-(6-chloro-5-ethoxy-7-fluoro-3-(1H-imidazol-1-yl)-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-one; 1-(3-(6-chloro-5-ethoxy-7-fluoro-3-(1H-imidazol-1-yl)-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-one; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-one; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-one; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-one; 5-(6-chloro-7-cyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-7-cyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-7-cyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 5-(6,7-difluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6,7-difluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6,7-difluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 5,6-dichloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 5,6-dichloro-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 5,6-dichloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-dichloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 5,6-dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 5,6-dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 5,6-dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6,7-dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6,7-dichloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole-7-carbonitrile; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole-7-carbonitrile; 6-chloro-5-(difluoromethoxy)-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-(difluoromethoxy)-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-(difluoromethoxy)-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-cyclopropoxy-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-5-cyclopropoxy-3-(1H-imidazol-1-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-5-cyclopropoxy-3-(1H-imidazol-1-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indole; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-4H-1,2,4-triazol-3-yl)-1H-indol-5-ol; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-indol-5-ol; 6-chloro-3-(1H-imidazol-1-yl)-1-methyl-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-1H-indol-5-ol; 5-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 6-chloro-5-hydroxy-2-(5-(2-hydroxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-5-hydroxy-2-(3-(2-hydroxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-5-hydroxy-2-(5-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(2-hydroxyethyl)-4H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(3-(2-hydroxyethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 6-chloro-2-(5-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole-7-carbonitrile; 2-(5-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(5-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethan-1-ol; 2-(3-(6-chloro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-ol; 5-(6,7-dicyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-4H-1,2,4-triazole-3-carboxamide; 5-(6,7-dicyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-3-carboxamide; 3-(6,7-dicyano-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-N,N-dimethyl-1H-1,2,4-triazole-5-carboxamide; 4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)morpholine; 4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)morpholine; 4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)morpholine; (S)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)morpholine; (S)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)morpholine; (S)-4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)morpholine; (R)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)morpholine; (R)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)morpholine; (R)-4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)morpholine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-methylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N,N-dimethylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N,N-dimethylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxy-N-methylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxy-N-methylethan-1-amine; 4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; 4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; 4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethyl)morpholine; (R)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; (R)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; (R)-4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethyl)morpholine; (S)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; (S)-4-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-2-methoxyethyl)morpholine; (S)-4-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-2-methoxyethyl)morpholine; 2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(3-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(3-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (R)-2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-4H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(3-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-5-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; (S)-2-(5-(1-(azetidin-1-yl)-2-methoxyethyl)-1H-1,2,4-triazol-3-yl)-6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indole; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)-N-methylethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; 1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; 1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)ethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; (S)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; (S)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)ethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; (R)-1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)-N-(2-methoxyethyl)ethan-1-amine; (R)-1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)-N-(2-methoxyethyl)ethan-1-amine; 6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; 6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; 6-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (S)-6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (S)-6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (S)-6-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (R)-6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-4H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (R)-6-(1-(5-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-3-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; (R)-6-(1-(3-(6-chloro-7-fluoro-3-(1H-imidazol-1-yl)-5-methoxy-1-methyl-1H-indol-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-2-oxa-6-azaspiro[3.3]heptane; 2. The compound of claim 1, or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, selected from:

15. A pharmaceutical composition comprising a compound according to any one of claims 1 to 14, or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof, and a pharma- ceutically acceptable carrier or excipient.

16. A combination comprising a compound according to any one of claims 1 to 14, or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof, and one or more therapeutically active agents.

17. 15. A pharmaceutical composition for modulating cGAS activity in a subject, comprising a therapeutically effective amount of a compound of any one of claims 1 to 14, or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof.

18. A pharmaceutical composition for treating a disease or condition, comprising a compound according to any one of claims 1 to 14 or a pharma- ceutical acceptable salt, hydrate, solvate, stereoisomer or tautomer thereof, wherein the disease or condition is selected from the group consisting of Aicardi-Goutières syndrome, familial lupus pernio, RVCL (autosomal dominant retinal vasculopathy with cerebral leukodystrophy), vasculitis, systemic lupus erythematosus (SLE), lupus nephritis (LN), dermatomyositis, Sjogren's syndrome (SS), rheumatoid arthritis (RA), and rheumatoid arthritis (RA). , age-related macular degeneration (AMD), Parkinson's disease, Alzheimer's, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), pulmonary inflammation, acute pulmonary inflammation, idiopathic pulmonary fibrosis, hepatic and renal fibrosis, non-alcoholic steatohepatitis (NASH), liver cirrhosis, endocardial fibrosis, acute and chronic kidney injury, APOL1-associated podocytopathy, acute pancreatitis, ulcerative colitis, inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), sepsis, aging, and aging.

19. 19. The pharmaceutical composition of claim 18, wherein the disease or condition is selected from the group consisting of Aicardi-Goutieres syndrome (AGS), vasculitis, systemic lupus erythematosus (SLE), familial lupus pernio, and Sjogren's syndrome.

20. A compound according to any one of claims 1 to 14, or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, for use as a medicament.

21. Aicardi-Goutières syndrome, familial lupus pernio, RVCL (autosomal dominant retinal vasculopathy with cerebral leukodystrophy), vasculitis, systemic lupus erythematosus (SLE), lupus nephritis (LN), dermatomyositis, Sjögren's syndrome (SS), rheumatoid arthritis (RA), age-related macular degeneration (AMD), Parkinson's disease, Alzheimer's, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), pulmonary inflammation, acute pulmonary inflammation, idiopathic pulmonary fibrosis, liver fibrosis and renal fibrosis 15. The compound of any one of claims 1 to 14, or a pharmacologic acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, for use in the treatment of a disorder or disease selected from the group consisting of chronic obstructive pulmonary disease (COPD), chronic myocardial infarction, ...

22. Aicardi-Goutières syndrome, familial lupus pernio, RVCL (autosomal dominant retinal vasculopathy with cerebral leukodystrophy), vasculitis, systemic lupus erythematosus (SLE), lupus nephritis (LN), dermatomyositis, Sjögren's syndrome (SS), rheumatoid arthritis (RA), age-related macular degeneration (AMD), Parkinson's disease, Alzheimer's, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), pulmonary inflammation, acute pulmonary inflammation, idiopathic pulmonary fibrosis, hepatic and renal fibrosis, non-alcoholic fatty liver disease, and chronic kidney disease.

15. Use of a compound according to any one of claims 1 to 14, or a pharma- ceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, in the manufacture of a medicament for use in the treatment of a disorder or disease selected from the group consisting of chronic obstructive steatohepatitis (NASH), liver cirrhosis, endocardial fibrosis, acute and chronic renal injury, APOL1-associated podocytopathy, acute pancreatitis, ulcerative colitis, inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), sepsis, senescence, and aging.

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