Heterocyclic PAD4 inhibitor

Abstract

The present disclosure relates generally to substituted heterocyclic compounds of formula (Ia) that are inhibitors of PAD4, to methods for making these compounds, to pharmaceutical compositions containing these compounds, and to the use of these compounds in the treatment of diseases or disorders associated with the enzymatic activity of PAD4. TIFF2023515780000994.tif26150

Description

Technical Field

[0001] Cross - reference to related applications This application claims the priority of Indian Provisional Patent Application No. 202041006146 filed on February 12, 2020, the content of which is specifically incorporated herein by reference.

[0002] Field of the Invention The present invention generally relates to substituted heterocyclic compounds, methods for producing these compounds, pharmaceutical compositions containing these compounds, and the use of these compounds in the treatment of diseases or disorders associated with PAD4 enzyme activity.

Background Art

[0003] PAD4 is a member of the peptidylarginine deiminase (PAD) family of enzymes that has the ability to catalyze the citrullination of arginine to citrulline within the range of peptide sequences. PAD4 is involved in the deimination or citrullination of various proteins in vitro and in vivo, resulting in multifunctional responses in various diseases (Jones J.E. et al., Curr. Opin. Drug Discov. Devel., 12(5)(2009), 616 - 627). Examples of typical diseases or disorders include, in addition to oncology indications, rheumatoid arthritis, diseases with a neutrophil contribution to the etiology (e.g., vasculitis, systemic lupus erythematosus, ulcerative colitis). PAD4 inhibitors also have broad applicability as tools and therapeutic agents for human diseases or disorders through epigenetic mechanisms.

[0004] Inhibitors of PAD4 are useful against rheumatoid arthritis (RA). RA is an autoimmune disease that affects approximately 1% of the population (Wegner N. et al., Immunol. Rev., 233(1)(2010), 34-54). RA is characterized by joint inflammation that leads to the erosive destruction of bone and cartilage. Although not consistent, a weak genetic association between PAD4 polymorphisms and susceptibility to RA has been suggested in many population studies (Kochi Y. et al., Ann. Rheum. Dis., 70(2011),512-515). PAD4 (along with family member PAD2) was detected in synovial tissue where it is involved in the deimination of various joint proteins. This process is presumed to lead to the disruption of resistance to citrullinated substrates such as fibrinogen, vimentin, and collagen, and the initiation of an immune response against these substrates in RA joints. These anti-citrullinated protein antibodies (ACPA) contribute to the etiology of the disease and may be used as a diagnostic test for RA (e.g., the commercially available CCP2 or cyclic citrullinated peptide 2 test). In addition, increased citrullination may also contribute directly to the etiology of the disease through its ability to directly affect the function of several joint and inflammatory mediators (e.g., fibrinogen, antithrombin, and multiple chemokines). Anti-PAD4 antibodies can be measured in a subset of RA patients and may correlate with a more erosive form of the disease.

[0005] PAD4 inhibitors are also useful for reducing the activity of pathological neutrophils in various diseases. According to research, the process of neutrophil extracellular trap (NET) formation, an innate defense mechanism by which neutrophils can immobilize and kill pathogenic bacteria, is associated with histone citrullination and is defective in PAD4 knockout mice (Neeli I. et al., J. Immunol., 180(2008), 1895 - 1902, and Li P. et al., J. Exp. Med., 207(9)(2010), 1853 - 1862). Therefore, PAD4 inhibitors may be applicable to diseases in which NET formation in tissues contributes to local damage and disease pathology. Such diseases include, but are not limited to, small vessel vasculitis (Kessenbrock K. et al., Nat. Med., 15(6)(2009), 623 - 625), systemic lupus erythematosus (Hakkim A. et al., Proc. Natl. Acad. Sci. USA, 107(21)(2010), 9813 - 9818, and Villanueva E. et al., J. Immunol., 187(1)(2011), 538 - 52), ulcerative colitis (Savchenko A. et al., Pathol. Int., 61(5)(2011), 290 - 7), cystic fibrosis, asthma (Dworski R. et al., J. Allergy Clin. Immunol., 127(5)(2011), 1260 - 6), deep vein thrombosis (Fuchs T. et al., Proc. Natl. Acad. Sci. USA, 107(36)(2010), 15880 - 5), periodontitis (Vitkov L. et al., Ultrastructural Pathol., 34(1)(2010), 25 - 30), sepsis (Clark S.R. et al., Nat. Med., 13(4)(2007), 463 - 9), appendicitis (Brinkmann V. et al., Science, 303(2004), 1532 - 5), and stroke.In addition, there is evidence indicating the potential contribution of NETs to lesions in skin diseases affecting the skin, such as cutaneous lupus erythematosus (Villanueva E. et al., J. Immunol., 187(1)(2011), 538 - 52) and psoriasis (Lin A.M. et al., J. Immunol., 187(1)(2011), 490 - 500). Therefore, PAD4 inhibitors may be beneficial in addressing NET skin diseases when administered via the systemic or skin routes. PAD4 inhibitors may further affect additional functions within neutrophils and may have broader applicability to neutrophil diseases.

[0006] According to research, the efficacy of PAD inhibitors (e.g., chloroamidine) as tools has been demonstrated in numerous animal model diseases, including collagen-induced arthritis (Willis V.C. et al., J. Immunol., 186(7)(2011), 4396 - 4404), dextran sulfate sodium (DSS)-induced experimental colitis (Chumanevich A.A. et al., Am. J. Physiol. Gastrointest. Liver Physiol., 300(6)(2011), G929 - G938), spinal cord repair (Lange S. et al., Dev. Biol., 355(2)(2011), 205 - 14), and experimental autoimmune encephalomyelitis (EAE). Reports on DSS colitis have also demonstrated that chloroamidine promotes apoptosis of inflammatory cells both in vitro and in vivo, suggesting that PAD4 inhibitors may be more generally effective in a broad range of inflammatory diseases.

[0007] PAD4 inhibitors are also useful in the treatment of cancer (Slack J.L. et al., Cell. Mol. Life Sci., 68(4)(2011), 709-720). Overexpression of PAD4 has been demonstrated in many cancers (Chang X. et al., BMC Cancer, 9(2009), 40). An antiproliferative role for PAD4 inhibitors is suggested from the observation that PAD4 citrullinates arginine residues in histones at the promoters of p53 target genes such as p21, which are involved in cell cycle arrest and induction of apoptosis (Li P. et al., Mol. Cell Biol., 28(15)(2008), 4745-4758).

[0008] The above-described role of PAD4 in deiminating arginine residues in histones may indicate the role of PAD4 in the epigenetic regulation of gene expression. PAD4 is the major PAD family member observed to be endogenous in the nucleus as well as in the cytoplasm. Initial evidence that PAD4 may act as a histone demethyliminase has been inconsistent and unproven. However, it is possible that indirectly, via depletion of available arginine residues by conversion to citrulline, PAD4 may reduce histone arginine methylation (and thus the epigenetic regulation associated with this mark). PAD4 inhibitors are useful as epigenetic tools or therapeutic agents that affect the expression of various target genes in additional disease settings. Through such mechanisms, PAD4 inhibitors may also be effective in controlling citrullination levels in stem cells and thus may therapeutically affect the pluripotent state and differentiation potential of a wide variety of stem cells including, but not limited to, embryonic stem cells, neural stem cells, hematopoietic stem cells and cancer stem cells. Accordingly, there remains an unmet need to identify and develop PAD4 inhibitors for the treatment of PAD4-mediated diseases or disorders. SUMMARY OF THE INVENTION

[0009] Accordingly, formula (Ia):

Chemical formula

[0010] In another general aspect, there is provided a pharmaceutical composition comprising at least one compound of formula (I), or a stereoisomer, enantiomer, diastereomer, tautomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

[0011] In another general aspect, there is provided a method of treating a disease or disorder associated with PAD4 enzyme activity, the method comprising administering to a subject in need thereof a therapeutically effective amount of at least one compound of formula (I), or a stereoisomer, enantiomer, diastereomer, tautomer thereof, or a pharmaceutically acceptable salt thereof.

[0012] Details of one or more embodiments of the present invention are set forth in the following description. Other features, objects, and advantages of the present invention will be apparent from the following description, including the claims.

Mode for Carrying Out the Invention

[0013] 1. Definitions The following are the definitions of the terms used in this specification. In this specification, the first definition provided for a group or term applies to that group or term throughout the specification, individually or as part of another group, unless otherwise specified. The present invention is described in connection with exemplary embodiments, but it should be understood that this is not intended to limit the scope of the present invention. Numerous modifications and further refinements of the inventive features of the present invention may be envisioned by those skilled in the art upon viewing this disclosure in the relevant field. All such modifications and refinements are considered to be within the scope of the present invention. As used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural forms unless the context clearly dictates otherwise. All references, including patents, patent applications, and documents cited herein, are hereby expressly incorporated by reference in their entirety.

[0014] As used herein, the term "C" 1-6 "alkyl" refers to cyclic, straight-chain, and branched hydrocarbon groups containing 1 to 6 carbon atoms, and includes the same. C 1-6 Typical non-limiting examples of C alkyl include methyl, ethyl, propyl, isopropyl, butyl, t-butyl, isobutyl, pentyl, hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

[0015] As used herein, the term "alkenyl" refers to straight-chain and branched hydrocarbon groups having 2 to 20 carbon atoms and containing 1 to 6 double bonds, and includes the same. Typical non-limiting examples of alkenyl include vinyl, 2-propenyl, 3-butenyl, 2-butenyl, 4-pentenyl, 3-pentenyl, 2-hexenyl, 3-hexenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 3-octenyl, 3-nonenyl, 4-decenyl, 3-undecenyl, 4-dodecenyl, and the like.

[0016] As used herein, the term "alkynyl" refers to and includes straight-chain or branched-chain hydrocarbon groups containing 2 to 12 carbon atoms and at least one carbon-carbon triple bond. Typical non-limiting examples of alkynyl include ethynyl, 2-propynyl, 3-butynyl, 2-butynyl, 4-pentynyl, 3-pentynyl, 2-hexynyl, 3-hexynyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 3-octynyl, 3-nonynyl, 4-decynyl, and the like.

[0017] As used herein, the term "cycloalkyl" refers to and includes saturated or partially unsaturated (containing 1 or 2 double bonds) cyclic hydrocarbon groups containing a total of 3 to 20 carbon atoms forming 1 to 3 rings (e.g., monocyclic, bicyclic, or tricyclic). The cycloalkyl may optionally be substituted. The rings of polycyclic cycloalkyls may be fused to, bridged to, and / or joined together via 1 or more spiro bonds with 1 or 2 aromatic cycloalkyl or heterocyclic rings. Typical non-limiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclododecyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclohexadienyl, cycloheptadienyl, and the like.

[0018] As used herein, the terms "heterocycle", "heterocyclyl" or "heterocyclo" refer to a saturated, unsaturated or partially unsaturated 3- to 20-membered ring group (e.g., a 3- to 13-membered monocyclic, 7- to 17-membered bicyclic, or 10- to 20-membered tricyclic ring system), optionally substituted, having at least one heteroatom in a ring containing at least one carbon atom, and include such. The heteroatom is selected from nitrogen, oxygen and / or sulfur atoms. Each ring of the heterocyclic group may have 1, 2, 3, 4 or 5 heteroatoms, provided that at least one ring contains at least one heteroatom. The heteroatoms of nitrogen and sulfur may optionally be oxidized, and the heteroatoms of nitrogen may optionally be quaternized. The rings of a polycyclic heterocycle may be fused, bridged, and / or joined together via one or more spiro bonds. Typical non-limiting examples of heterocyclic groups include azetidinyl, pyrrolidinyl, oxetanyl, imidazolinyl, oxazolidinyl, isoxazolinyl, thiazolidinyl, isothiazolidinyl, tetrahydrofuranyl, piperidinyl piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothienyl, and the like.

[0019] As used herein, the term "aryl" refers to a monocyclic, bicyclic or tricyclic aromatic group of an aromatic homocycle (i.e., hydrocarbon) containing 6 to 14 carbons in the ring portion, and includes such, and optionally, 1 to 3 additional rings (any of cycloalkyl, heterocycle or heteroaryl) may be fused to the ring and included. Typical non-limiting examples of aryl groups include phenyl, biphenyl, naphthyl (including 1-naphthyl and 2-naphthyl), anthracenyl, and the like.

[0020] The groups defined above may, if desired, be attached to a carbon atom substituted with any group known to those skilled in the art and have one or more hydrogen atoms. Throughout the specification, the groups and their substituents may be selected to provide stable moieties and compounds.

[0021] As used herein, the term "subject" refers to and includes any human or non-human organism that may benefit from treatment with a PAD4 inhibitor. Exemplary subjects include humans and animals.

[0022] As used herein, the terms "treat" or "treatment" refer to and include the treatment of a condition in a subject, e.g., in a human or animal, including (a) inhibiting the condition, i.e., preventing its onset; (b) alleviating the condition, i.e., causing regression of the condition; and / or (c) preventing the condition from occurring in the subject.

[0023] As used herein, the terms "prevent" or "prevention" refer to and include prophylactic treatment (i.e., prevention and / or risk reduction) of a subclinical condition in a subject, e.g., in a human or animal, aimed at reducing the probability of developing a clinical condition. A subject may be selected for prophylactic therapy based on factors known to increase the risk of developing a clinical condition compared to the general population. "Prophylactic" therapy can be divided into (a) primary prevention, and (b) secondary prevention. Primary prevention is defined as treatment in a subject who has not yet presented with a clinical condition, whereas secondary prevention is defined as preventing a second occurrence of the same or a similar clinical condition.

[0024] The term "therapeutically effective amount" refers to the amount of a compound or composition according to the present invention that is effective when administered alone or in combination to prevent or treat a disease or disorder associated with the activity of the PAD4 enzyme, and includes this. When applied to a combination, the term refers to the combined amount of active ingredients that provides a prophylactic or therapeutic effect, regardless of whether they are administered in combination, sequentially, or simultaneously.

[0025] "Pharmaceutically acceptable carrier" refers to a medium generally acceptable in the art for delivering a biologically active agent to humans and / or animals. A pharmaceutically acceptable carrier is formulated according to numerous factors well known within the purview of those skilled in the art. These factors include, but are not limited to, the type and nature of the active agent being formulated, the subject to whom the composition of the active agent formulation is to be administered, the intended route of administration of the compound or composition, and the indication of the targeted treatment. Pharmaceutically acceptable carriers include both aqueous and non-aqueous liquid media. Such carriers can contain, in addition to the active agent, many different components and additives, and such additional components are formulated into the preparation for various reasons, for example, for the stabilization of the active agent, binders, etc., as well known to those skilled in the art. Typical non-limiting examples of such carriers include diluents, preservatives, fillers, flow regulators, disintegrants, wetting agents, emulsifiers, anti-precipitants, sweeteners, flavoring and odor-masking agents, fragrances, antibacterial agents, antifungal agents, lubricants, dispensing agents, coating agents, and the like. Descriptions of suitable pharmaceutically acceptable carriers and the factors involved in their selection are provided in various readily available sources of information such as, for example, Allen, L.V., Jr. et al., Remington: The Science and Practice of Pharmacy (2 Volumes), 22nd Edition, Pharmaceutical Press (2012).

[0026] Prodrugs and solvates of the compounds of the present invention are also contemplated herein. As used herein, the term "prodrug" refers to a compound that, when administered to a subject, undergoes a chemical transformation by a metabolic or chemical process to yield a compound of formula (I), or a salt and / or solvate thereof. Solvates of the compounds of formula (Ia) include hydrates.

[0027] Any tautomeric forms that may exist are also considered to form part of the present invention herein. All isomers of the compounds of formula (Ia), including enantiomeric forms (which may exist even in the absence of asymmetric carbon, for example, atropisomers) and diastereomeric forms, such as stereoisomers, that may result from the presence of asymmetric carbon are considered to be within the scope of the present invention. Individual stereoisomers of the compounds of formula (Ia) may be substantially free of other isomers, or may be mixed, for example, as a racemate or with all or other selected stereoisomers. The chiral centers of these compounds may have the S or R configuration as defined by the IUPAC 1974 recommendations. In general, the compounds according to the present invention may be described herein, for convenience, without specific stereochemistry, and all stereoisomeric forms are included within the scope of the present invention.

[0028] The present invention is intended to encompass all isotopes of atoms present in the compounds. Isotopes include those atoms having the same atomic number but different mass numbers. General examples, but not limited to, isotopes of hydrogen are deuterium (symbol D or 2 H) and tritium (symbol T or 3 H). For example, a methyl group can be represented as CH3 or CD3. Isotopes of carbon include 13 C and 14 C. Isotopically labeled compounds of the present invention can generally be prepared by conventional techniques known to those skilled in the art or, alternatively, by using appropriately isotopically labeled reagents in place of the unlabeled reagents used, by methods similar to those described herein.

[0029] The compounds of formula (I) form salts which are also within the scope of the present invention. References to the compounds of formula (I) herein are understood to include references to their salts, unless otherwise specified. As used herein, the term "salt" refers to acidic and / or basic salts formed with inorganic and / or organic acids and bases. Additionally, when the compounds of formula (I) contain both basic and acidic moieties, zwitterions ("inner salts") may be formed, which are included within the scope of the term "salt" as used herein. Pharmaceutically acceptable salts include those generally acceptable in the art of pharmaceutical science for administration to subjects, including humans and animals. Generally, pharmaceutically acceptable salts are non-toxic and are physiologically acceptable salts. The salts of the compounds according to the present invention can be formed, for example, by reacting the compound in a medium such that the salt precipitates, or in an aqueous medium, with an equivalent amount of an acid or a base, followed by lyophilization.

[0030] Compounds of formula (Ia) containing a basic moiety can form salts with various organic and inorganic acids. Exemplary acid addition salts include acetates (salts formed with acetic acid or trihaloacetic acids such as trifluoroacetic acid), adipates, alginates, ascorbates, aspartates, benzoates, benzenesulfonates, bisulfates, borates, butyrates, citrates, camphorates, camphorsulfonates, cyclopentanepropionates, digluconates, dodecylsulfates, ethanesulfonates, fumarates, glucoheptanoates, glycerophosphates, hemisulfates, heptanoates, hexanoates, hydrochlorides (formed with hydrochloric acid), hydrobromides (formed with hydrobromic acid), hydroiodides, 2-hydroxyethanesulfonates, lactates, maleates (formed with maleic acid), methanesulfonates (formed with methanesulfonic acid), 2-naphthalenesulfonates, nicotinates, nitrates, oxalates, pectinates, persulfates, 3-phenylpropionates, phosphates, picrates, pivalates, propionates, salicylates, succinates, sulfates (salts formed with sulfuric acid etc.), sulfonates (such as the salts described herein), tartrates, thiocyanates, toluenesulfonates such as tosylates, undecanoates, etc.

[0031] The compounds of formula (Ia) containing an acidic moiety may form salts with various organic and inorganic bases. Exemplary basic salts include ammonium salts, alkali metal salts (such as sodium, lithium, and potassium salts), alkaline earth metal salts (such as calcium and magnesium salts), organic bases (e.g., organic amines), for example, salts formed with benzathine, dicyclohexylamine, hydrabamine (formed with N,N-bis(dehydroabietyl)-ethylenediamine), N-methyl-D-glucamine, N-methyl-D-glucamide, salts with t-butylamine, and salts with amino acids (such as arginine, lysine, etc.). The basic nitrogen-containing group may be quaternized with reagents such as lower alkyl halides (e.g., methyl, ethyl, propyl, and butyl chloride, bromide, and iodide), dialkyl sulfates (e.g., dimethyl, diethyl, dibutyl, and diamyl sulfate), long-chain halides (e.g., decyl, lauryl, myristyl, and stearyl chloride, bromide, and iodide), aralkyl halides (e.g., benzyl and phenethyl bromide), etc.

[0032] The present invention encompasses compounds of formula (I), including their stereoisomers, enantiomers, diastereomers, tautomers, and pharmaceutically acceptable salts, methods for producing these compounds, pharmaceutical compositions containing these compounds, and the use of these compounds in the treatment of diseases or disorders associated with the activity of the PAD4 enzyme.

[0033] 2. Description of Specific Embodiments of the Invention In a first aspect, the present invention provides a compound of formula (I):

Chemical formula

Chemical formula

Chemical formula

[0034] In a second aspect, the present invention, within the scope of the first aspect, provides a compound of formula (II):

Chemical formula

Chemical formula

[0035] In a third aspect, the present invention is a compound within the scope of the second aspect, or a pharmaceutically acceptable salt thereof, wherein herein, R1 is independently

Chemical formula

[0036] In a fourth aspect, the present invention is a compound, or a pharmaceutically acceptable salt thereof, within the scope of the third aspect, wherein herein, R1 is independently

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0037] In a fifth aspect, the present invention is a compound within the scope of the fourth aspect, or a pharmaceutically acceptable salt thereof, wherein here, R4 is C 1-2 alkyl,

Chemical formula

[0038] In a sixth aspect, the present invention is a compound within the scope of the fifth aspect, or a pharmaceutically acceptable salt thereof, wherein here, R4 is independently CH3,

Chemical formula

[0039] In a seventh aspect, the present invention, within the scope of the first aspect, is of formula (III):

Chemical formula

Chemical formula

Chem.

[0040] In an eighth aspect, the present invention, within the scope of the first aspect, provides a compound of formula (IV):

Chem.

Chem.

[0041] In a ninth aspect, the present invention, within the scope of the first aspect, provides a compound of formula (V):

Chemical formula

Chemical formula

Chemical formula

[0042] In a tenth aspect, the invention, within the scope of the first aspect, provides a compound of formula (VI):

Chemical formula

Chemical formula

Chemical formula

[0043] In a 11th aspect, the invention is a compound within the scope of the 10th aspect, or a pharmaceutically acceptable salt thereof, wherein here R1 is independently

Chemical formula

Chemical formula

[0044] In one aspect, the invention is of formula (Ia):

Chemical formula

Chemical formula

Chemical formula

[0045] In another aspect, the present invention provides compounds of formula (IIa)-(XIII):

Chemical formula

[0046] In another aspect, the present invention provides compounds of formula (IIa): [Chemical formula] [wherein: R1 is independently [Chemical formula] selected from; R2 is independently H, F, Cl, C 1-3 alkyl (optionally substituted with one or more substituents selected from F, Cl, and OH), and OC 1-3 alkyl; R3 is independently selected from H, F, Cl, CH3, and CH2OH; R4 is independently H, F, Cl, -C(=O)R b C 1-6 alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C 3-6 cycloalkyl), -NH-C 1-6 alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C 3-6 cycloalkyl), -(CH2) r -aryl (substituted with one or more R5), -O-C 1-6 alkyl (substituted with one or more R5), -(CH2) r -C 3-12 cycloalkyl (substituted with one or more R5), and -(CH2) r -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR6, O, and S, and substituted with one or more R5); R5 is independently H, F, Cl, =O, C 1-4 alkyl (optionally substituted with one or more R e ), -(CH2) r OR b ), -(CH2) r S(O) p R c ), -(CH2) r S(O) p NRa R a 、 -(CH2) r NR a S(O) p R c 、 -(CH2) r NR a R a 、 -(CH2) r NR a C(=O)R b 、 -(CH2) r NR a C(=O)OR b 、 -(CH2) r NR a C(=O)NR a R a 、 -(CH2) r C(=O)R b 、 -(CH2) r C(=O)OR b 、 -(CH2) r C(=O)NR a R a 、 -(CH2) r OC(=O)R b 、 -(CH2) r OC(=O)OR b 、 -(CH2) r O(CH2) r C(=O)NR a R a 、 C 3-6 cycloalkyl (optionally substituted with one or more R e ), aryl (optionally substituted with one or more R e ), and heterocyclyl (optionally substituted with one or more R e ); R6 is, independently, H, C 1-6 alkyl (optionally substituted with one or more R e ), C(=O)R b 、 -C(=O)NR a R a 、 C 3-6 cycloalkyl (optionally substituted with one or more R e ), aryl (optionally substituted with one or more R ewhich may be optionally replaced as desired), and heterocyclyl (one or more R e which may be optionally replaced as desired) is selected from; R7 is independently selected from H, F, and Cl; R8 is independently H, and C 1-6 alkyl (optionally substituted with one or more substituents selected from F, Cl, and C 3-6 cycloalkyl)); R a is independently H, and C 1-6 alkyl (optionally substituted with one or more R e which may be optionally replaced as desired); or R a and R a together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more R e which may be optionally replaced as desired); R b is independently H, C 1-6 alkyl (optionally substituted with one or more R e which may be optionally replaced as desired), -(CH2) r -C 3-10 carbocyclyl (optionally substituted with one or more R e which may be optionally replaced as desired), and -(CH2) r -heterocyclyl (optionally substituted with one or more R e which may be optionally replaced as desired); R c is independently C 1-6 alkyl (optionally substituted with one or more R e which may be optionally replaced as desired), -(CH2) r -C 3-10 carbocyclyl (optionally substituted with one or more R e which may be optionally replaced as desired), and -(CH2) r -heterocyclyl (optionally substituted with one or more R e which may be optionally replaced as desired); R e is independently F, Cl, Br, NH2, -NH-C 1-4 alkyl, -N(C1-4 (alkyl)2, =O, OH, -OC 1-6 alkyl, C 1-6 alkyl (one or more Rs f optionally substituted as desired), -(CH2) r -C 3-6 cycloalkyl (one or more Rs f optionally substituted as desired), -(CH2) r -aryl (one or more Rs f optionally substituted as desired), and -(CH2) r -heterocyclyl (one or more Rs f optionally substituted as desired); R f is independently F, Cl, OH, OC 1-5 alkyl, C 1-5 alkyl (optionally substituted with OH as desired), C 3-6 cycloalkyl, and phenyl; p is independently selected from 0, 1, and 2 at each occurrence; and r is independently selected from 0, 1, 2, 3, and 4 at each occurrence] To provide a compound represented by, or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof.

[0047] In another aspect, the present invention provides a compound of formula (IIIa):

Chemical formula

Chemical formula

[0048] In another aspect, the present invention is a compound of formula (IIa)-(IIIa), or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof, wherein: R1 is, independently,

Chemical formula

[0049] In another aspect, the present invention is a compound represented by formula (IIa)-(IIIa), or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof, wherein: R4 is, independently, H, F, Cl, C 1-5 alkyl (optionally substituted with one or more substituents selected from F, Cl, and OH), C 3-6 cycloalkyl,

Chemical formula

Chemical formula

Chemical formula

[0050] In another aspect, the present invention relates to a compound represented by formulas (IIa)-(IIIa), or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof, wherein: R4 is independently

Chem.

Chem.

Chem.

[0051] In yet another aspect, the present invention relates to formula (IVa):

Chem.

Chem.

[0052] In another aspect, the present invention is a compound represented by formula (IVa), or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof, wherein: R1 is independently

Chemical formula

Chemical formula

[0053] In another aspect, the present invention is a compound represented by formula (IIa)-(IIIa), or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof, wherein: R4 is independently

Chemical formula

[0054] In another aspect, the present invention relates to formula (Va): [Chemical formula] [wherein: R1 is independently [Chemical formula] selected from; R2 is independently selected from H, F, Cl, CH3, and OCH3; R3 is independently selected from H, F, Cl, CN, CH3, and CH2OH; R4 is independently H, F, Cl, -C(=O)R b C 1-6 alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C 3-6 cycloalkyl), -NH-C 1-6 alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C 3-6 cycloalkyl), -(CH2) r -aryl (substituted with one or more R5), -O-C 1-6 alkyl (substituted with one or more R5), -(CH2) r -C 3-12 cycloalkyl (substituted with one or more R5), and -(CH2) r -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR6, O, and S, and substituted with one or more R5) selected from; R5 is independently H, F, Cl, =O, C 1-4Alkyl (one or more Rs e optionally substituted as desired), -(CH2) r OR b 、-(CH2) r S(O) p R c 、-(CH2) r S(O) p NR a R a 、-(CH2) r NR a S(O) p R c 、-(CH2) r NR a R a 、-(CH2) r NR a C(=O)R b 、-(CH2) r NR a C(=O)OR b 、-(CH2) r NR a C(=O)NR a R a 、-(CH2) r C(=O)R b 、-(CH2) r C(=O)OR b 、-(CH2) r C(=O)NR a R a 、-(CH2) r OC(=O)R b 、-(CH2) r OC(=O)OR b 、-(CH2) r O(CH2) r C(=O)NR a R a 、C 3-6 Cycloalkyl (one or more Rs e optionally substituted as desired), aryl (one or more Rs e optionally substituted as desired), and heterocyclyl (one or more Rs e optionally substituted as desired); R6 is, independently, H, C 1-6 Alkyl (one or more Rs ewhich may be optionally replaced, -C(=O)R b , -C(=O)OR b , -C(=O)NR a R a , C 3-6 cycloalkyl (which may be optionally replaced by one or more R e ), aryl (which may be optionally replaced by one or more R e ), and heterocyclyl (which may be optionally replaced by one or more R e ); R7 is independently selected from H, F, and Cl; R8 is independently H and C 1-6 alkyl (which may be optionally replaced by one or more substituents selected from F, Cl, and C 3-6 cycloalkyl); R a is independently H, C 1-6 alkyl (which may be optionally replaced by one or more R e ), -(CH2) r -C 3-10 carbocyclyl (which may be optionally replaced by one or more R e ), and -(CH2) r -heterocyclyl (which may be optionally replaced by one or more R e ); or R a and R a together with the nitrogen atom to which both are attached form a heterocyclic ring (which may be optionally replaced by one or more R e ); R b is independently H, C 1-6 alkyl (which may be optionally replaced by one or more R e ), -(CH2) r -C 3-10 carbocyclyl (which may be optionally replaced by one or more R e ), and -(CH2) r -heterocyclyl (which may be optionally replaced by one or more R e ); R c is, independently, C 1-6 alkyl (one or more Rs e optionally substituted by), -(CH2) r -C 3-10 carbocyclic (one or more Rs e optionally substituted by), and -(CH2) r -heterocyclic (one or more Rs e optionally substituted by); R e is, independently, F, Cl, Br, NH2, -NH-C 1-4 alkyl, -N(C 1-4 alkyl)2, =O, OH, -OC 1-6 alkyl, -CO2H, C 1-6 alkyl (one or more Rs f optionally substituted by), -(CH2) r -C 3-6 cycloalkyl (one or more Rs f optionally substituted by), -(CH2) r -aryl (one or more Rs f optionally substituted by), and -(CH2) r -heterocyclic (one or more Rs f optionally substituted by); R f is, independently, F, Cl, Br, CN, OH, C 1-5 alkyl (optionally substituted by OH), C 2-5 alkenyl, C 2-5 alkynyl, C 3-6 cycloalkyl, and phenyl; p is, in each occurrence, independently selected from 0, 1, and 2; and r is, in each occurrence, independently selected from 0, 1, 2, 3, and 4] To provide a compound represented by, or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof.

[0055] In another aspect, the present invention is a compound represented by formula (Va), or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof, wherein: R1 is independently

Chemical formula

Chemical formula

Chemical formula

[0056] In another aspect, the present invention is formula (VIa):

Chemical formula

Chemical formula

[0057] In another aspect, the present invention is a compound represented by formula (VIa), or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof, wherein: R1 is independently

Chemical formula

[0058] In another aspect, the present invention relates to formula (VII): [Chemical formula] [wherein: R1 is, independently, [Chemical formula] selected from; R2 is, independently, selected from H, F, Cl, CH3, and OCH3; R3 is, independently, selected from H, F, and CH3; R4 is, independently, H, F, Cl, Br, -C(=O)R b , C 1-6 alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C 3-6 cycloalkyl), -NH-C 1-6 alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C 3-6 cycloalkyl), -(CH2) r -aryl (substituted with one or more R5), -O-C 1-6 alkyl (substituted with one or more R5), -(CH2)r -C 3-12 Cycloalkyl (substituted with one or more R5), and -(CH2) r -Selected from 4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR6, O, and S, and substituted with one or more R5); R5 is independently H, F, Cl, Br, CN, =O, C 1-4 Alkyl (optionally substituted with one or more R e ), C 2-4 Alkenyl (optionally substituted with one or more R e ), C 2-4 Alkynyl (optionally substituted with one or more R e ), -(CH2) r OR b 、-(CH2) r S(O) p R c 、-(CH2) r S(O) p NR a R a 、-(CH2) r NR a S(O) p R c 、-(CH2) r NR a R a 、-(CH2) r NR a C(=O)R b 、-(CH2) r NR a C(=O)OR b 、-(CH2) r NR a C(=O)NR a R a 、-(CH2) r C(=O)R b 、-(CH2) r C(=O)OR b 、-(CH2) r C(=O)NR a R a 、-(CH2) r OC(=O)R b 、-(CH2) rOC(=O)OR b 、-(CH2) r O(CH2) r C(=O)NR a R a 、C 3-6 cycloalkyl (optionally substituted with one or more R e ), aryl (optionally substituted with one or more R e ), and heterocyclyl (optionally substituted with one or more R e ); R6 is independently H, C 1-6 alkyl (optionally substituted with one or more R e ), -S(O) p R c ), -S(O) p NR a R a ), -C(=O)R b ), -C(=O)OR b ), -C(=O)NR a R a ), C 3-6 cycloalkyl (optionally substituted with one or more R e ), aryl (optionally substituted with one or more R e ), and heterocyclyl (optionally substituted with one or more R e ); R7 is independently selected from H, F, and Cl; R8 is independently H and C 1-6 alkyl (optionally substituted with one or more substituents selected from F, Cl, and C 3-6 cycloalkyl); R a is independently H, C 1-6 alkyl (optionally substituted with one or more R e ), C 2-6 alkenyl (optionally substituted with one or more R e ), C 2-6 alkynyl (optionally substituted with one or more R ewhich may be optionally replaced, -(CH2) r -C 3-10 carbocyclyl (optionally substituted with one or more Rs e and may be optionally replaced), and -(CH2) r -heterocyclyl (optionally substituted with one or more Rs e or is selected from; or R a and R a together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more Rs e and may be optionally replaced); R b is independently H, C 1-6 alkyl (optionally substituted with one or more Rs e ), C 2-6 alkenyl (optionally substituted with one or more Rs e ), C 2-6 alkynyl (optionally substituted with one or more Rs e ), -(CH2) r -C 3-10 carbocyclyl (optionally substituted with one or more Rs e and may be optionally replaced), and -(CH2) r -heterocyclyl (optionally substituted with one or more Rs e and may be optionally replaced) is selected; R c is independently C 1-6 alkyl (optionally substituted with one or more Rs e ), C 2-6 alkenyl (optionally substituted with one or more Rs e ), C 2-6 alkynyl (optionally substituted with one or more Rs e ), -(CH2) r -C 3-10 carbocyclyl (optionally substituted with one or more Rs e and may be optionally replaced), and -(CH2) r -heterocyclyl (optionally substituted with one or more Rs e and may be optionally replaced) is selected; R e is independently selected from F, Cl, Br, CN, NH2, -NH-C 1-4 alkyl, -N(C 1-4 alkyl)2, =O, OH, -OC 1-6 alkyl, -CO2H, C 1-6 alkyl (optionally substituted by one or more Rs f ), C 2-6 alkenyl, C 2-6 alkynyl, -(CH2) r -C 3-6 cycloalkyl (optionally substituted by one or more Rs f ), -(CH2) r -aryl (optionally substituted by one or more Rs f ), and -(CH2) r -heterocyclyl (optionally substituted by one or more Rs f ); R f is independently selected from F, Cl, Br, CN, OH, C 1-5 alkyl (optionally substituted by OH), C 2-5 alkenyl, C 2-5 alkynyl, C 3-6 cycloalkyl, and phenyl; p is independently selected from 0, 1, and 2 at each occurrence; and r is independently selected from 0, 1, 2, 3, and 4 at each occurrence] To provide a compound represented by, or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof.

[0059] In another aspect, the present invention provides a compound of formula (VIII):

Chemical formula

Chemical formula

[0060] In another aspect, the present invention provides a compound of formula (IX):

Chemical formula

Chemical formula

[0061] In another aspect, the present invention relates to a compound of formula (X):

Chemical formula

Chemical formula

[0062] In another aspect, the present invention relates to formula (XI):

Chemical formula

Chemical formula

[0063] In another aspect, the present invention provides a compound of formula (XII):

Chemical formula

Chemical formula

[0064] In another aspect, the present invention is a compound represented by formula (IX)-(XII), or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof, wherein: R4 is independently H, F, Cl, Br,

Chemical formula

Chemical formula

Chemical formula

[0065] In another aspect, the present invention is formula (XIII):

Chemical formula

Chemical formula

[0066] In another aspect, the present invention relates to a compound of formula (XIV): [Chemical formula] [wherein: X2 is independently selected from CR4 and N; X3 is independently selected from O and S; R1 is independently [Chemical formula] selected from; R2 is independently selected from CH2OH, CH2CH2OH and OCH3; R3 is independently selected from CH2OH, CH2CH2OH, CH2NH2, CH2CH2NH2, and CH2CH2N3; R4 is independently selected from H and -O-C 1-4 alkyl (substituted with one or more R5); provided that R4 is not both -O-C 1-4 alkyl (substituted with one or more R5); R5 is independently selected from OH and heterocyclyl (optionally substituted with one or more R e as desired); R8 is independently selected from H, and C 1-6 alkyl (optionally substituted with C 3-6 cycloalkyl); and R e is independently selected from NH2 and C 1-3 alkyl) To provide a compound represented by the formula, or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof.

[0067] In another aspect, the present invention relates to a compound of formula (XV): [Chemical formula] [wherein: R4 is independently H, OCH3, OCH2CH2OH, [Chemical formula] selected from; R8 is C 1-3 alkyl (C 3-6 substituted with cycloalkyl); and R e is independently selected from NH2 and C 1-3 alkyl; other variable groups are as defined in formula (XIV)] To provide a compound represented by, or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof.

[0068] As typical examples according to the present invention, but not limited to, ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (1); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (2); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (3); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (4); 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (5); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (6); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(1-isopropyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (7); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (8); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (9); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (10); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-(difluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (11); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-(difluoromethoxy)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (12); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methoxyazetidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (13); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (14); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (15); 6-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (16); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)-methanone (17); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(1-isopropyl-1H-pyrazol-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (18); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (19); 5-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (20);

[0069] ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (21); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (22); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (23); 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (24); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (25); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-(difluoromethoxy)phenyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (26); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (27); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (28); 6-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (29); 5-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (30); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (31); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (32); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(3-(methoxymethyl)-azetidin-1-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (33); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(6-((3R,5R)-3-amino-5-fluoropiperidin-1-yl)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (34); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone(35); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(((R)-2-fluoro-3-hydroxy-3-methylbutyl)amino)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone(36); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-3-(hydroxymethyl)azetidin-1-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone(37); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoropyrazolo[1,5-a]pyridin-6-yl)methanone(38); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoropyrazolo[1,5-a]pyridin-6-yl)methanone(39); 3((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoropyrazolo[1,5-a]pyridin-6-yl)methanone(40);

[0070] ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (41); 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (42); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (43); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-(difluoromethoxy)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (44); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(5-fluoro-2-methoxypyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (45); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (46); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-(difluoromethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (47); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (48); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (49); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methoxyazetidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (50); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-((R)-3-hydroxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (51); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (52); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (53); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (54); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (55); 4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorobenzamide (56); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (57); N-(7-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-4-chloro-1-methyl-1H-indazol-3-yl)methanesulfonamide (58); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (59); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (60);

[0071] ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-fluoro-3-hydroxyphenyl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (61); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (62); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (63); 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (64); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (65); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (66); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (67); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (68); 4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorobenzamide (69); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (70); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (71); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(5-fluoro-2-methoxypyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (72); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-(difluoromethoxy)-3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (73); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (74); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (75); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (76); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-hydroxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone(77); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-((R)-3-hydroxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone(78); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methoxyazetidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone(79); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone(80);

[0072] 5-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one(81); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone(82); 6-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one(83); 4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorobenzamide (84); 4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-chlorobenzamide (85); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (86); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (87); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(4-hydroxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (88); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (89); 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (90); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-3-(hydroxymethyl)azetidin-1-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (91); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (92); 4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-fluorobenzamide (93); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (94); 5-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (95); 6-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (96); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (97); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (98); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (99); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (100);

[0073] ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (101); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (102); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (103); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(1-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (104); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (105); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (106, 107 as diastereomers); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyrimidin-6-yl)methanone (108); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyrimidin-6-yl)methanone (109); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyrimidin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (110); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyrimidin-6-yl)methanone (111); 4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyrimidin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorobenzamide (112); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyrazin-6-yl)methanone (113); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyrazin-6-yl)methanone (114); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyrazin-6-yl)methanone (115); (2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyrazin-6-yl)(2,6-diazaspiro[3.3]heptan-2-yl)methanone (116); (R)-N-(3-Amino-2-fluoropropyl)-2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyrazine-6-carboxamide (117); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (118); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (119); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindoline-1-one (120);

[0074] ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (121); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (122); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (123); 4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-fluorobenzamide (124); 4-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-chlorobenzamide (125); 5-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindoline-1-one (126); ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (127); ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-2-methylphenyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (128); ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-methoxypyridin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (129); ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-(4-aminopiperidin-1-yl)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (130); ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (131); 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (132); 4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorobenzamide (133); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (134); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (135); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (136); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (137); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (138); 5-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (139); 6-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (140);

[0075] 4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorobenzamide (141); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone (142); 6-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (143); 5-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylbenzo[b]thiophen-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (144); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (145); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (146); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (147); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (148); 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (149); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]-heptane-2-carbonyl)-4-methoxy-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (150); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (151); 4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-fluorobenzamide (152); 4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-chlorobenzamide (153); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (154); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (155); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (156); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (157); 3-((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-ethoxypiperidin-1-yl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (158); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (159); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-(4-aminopiperidin-1-yl)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (160);

[0076] ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (161); 4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-chlorobenzamide (162); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (163); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylbenzofuran-6-yl)methanone (164); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylbenzofuran-6-yl)methanone (165); 6-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (166); ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylbenzofuran-6-yl)methanone cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (167); 5-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (168); ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylbenzofuran-6-yl)methanone (169); 4-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorobenzamide (170); ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylbenzofuran-6-yl)methanone (171); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-methoxypyridin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylbenzofuran-6-yl)methanone (172); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methoxyazetidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylbenzofuran-6-yl)methanone (173); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylbenzofuran-6-yl)methanone (174); 6-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one (175); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (176); 6-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (177); 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (178); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone(179); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(1-isopropyl-1H-pyrazol-4-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone(180);

[0077] ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone(181); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone(182); 4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-chlorobenzamide(183); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone(184); 4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-fluorobenzamide(185); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-methoxypyridin-4-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (186); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (187); 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-3-methylpicolinamide (188); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (189); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methoxyazetidin-1-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (190); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-(4-aminopiperidin-1-yl)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (191); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(piperazin-1-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (192); 1-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)piperazin-2-one (193); ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (194); 5-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one (195); 4-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-fluorobenzamide (196); ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (197); ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (198); 4-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-chlorobenzamide (199); ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (200);

[0078] ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(piperazin-1-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (201); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(6-(4-aminopiperidin-1-yl)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (202); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone (203); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone (204); 1-[2-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]imidazolidin-2-one (205); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylbenzamide (206); 4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluoro-5-methylbenzamide (207); 4-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluoro-5-methylbenzamide (208); [2-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanol (209); [3-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanol (210); N-{[3-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}methanesulfonamide (211); (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(3-methoxyphenyl)-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidine-3-amine (212); N-[3-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanesulfonamide (213); N-[4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]acetamide (214); N-{[3-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}acetamide (215); N-[4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanesulfonamide (216); 4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-N,N-dimethylbenzamide (217); (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(1H-indazol-5-yl)-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}-5-fluoropiperidin-3-amine (218); (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(1-methyl-1H-indazol-5-yl)-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}-5-fluoropiperidin-3-amine (219); (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-[3-(2H-1,2,3,4-tetrazol-5-yl)phenyl]-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}-5-fluoropiperidin-3-amine (220);

[0079] N-{[4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}acetamide (221); (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(1H-indazol-4-yl)-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}-5-fluoropiperidin-3-amine (222); 2-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)benzamide (223); N-{[4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}methanesulfonamide (224); 6-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-8-fluoro-5-methyl-1,2-dihydroquinolin-2-one (225); N-[5-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)pyridin-2-yl]acetamide (226); [3-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanol(227); N-{[4-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}acetamide(228); 4-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)benzamide(229); 4-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-N,N-dimethylbenzamide(230); N-[4-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanesulfonamide(231); N-{[3-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}acetamide(232); [2-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanol(233); N-{[4-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}methanesulfonamide (234); N-{[3-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl} methanesulfonamide (235); [3-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanol (236); 2-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)benzamide (237); (3R)-1-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-4-yl)-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}piperidine-3-amine (238); 6-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-8-fluoro-5-methyl-1,2-dihydroquinolin-2-one (239); N-[5-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)pyridin-2-yl]acetamide (240);

[0080] (3R,5R)-1-{2-[1-(Cyclopropylmethyl)-6-(4-methanesulfonylpiperidin-1-yl)-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (241); 1-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-N,N-dimethylpiperidine-4-carboxamide (242); N-[1-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylacetamide (243); N-[1-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylacetamide (244); Methyl N-[1-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylcarbamate (245); N-[1-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylmethanesulfonamide (246); N-[1-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)azetidin-3-yl]-N-methylmethanesulfonamide (247); (3R)-1-{2-[1-(Cyclopropylmethyl)-6-(4-methanesulfonylpiperidin-1-yl)-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (248); (3R)-1-{2-[1-(Cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (249); 2-[1-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N,N-dimethylacetamide (250); (3R)-1-{2-[1-(Cyclopropylmethyl)-6-[4-(3-methoxyazetidine-1-carbonyl)piperidin-1-yl]-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (251); N-[1-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylacetamide (252); N-[1-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylacetamide (253); N-[1-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylmethanesulfonamide (254); Methyl N-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylcarbamate (255); N-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)azetidin-3-yl]-N-methylmethanesulfonamide (256); 1-[2-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]imidazolidin-2-one (257); 1-[4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]pyrrolidin-2-one (258); 3-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylphenol (259); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluoro-5-methylbenzamide (260);

[0081] 1-[4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]imidazolidin-2-one (261); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylbenzamide (262); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)benzamide (263); 5-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-N-methylpyridine-2-carboxamide (264); ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-((R)-3-hydroxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (265); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (266); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)morpholin-3-one (267); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(4-methanesulfonylpiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (268); 8-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-3-methyl-1-oxa-3,8-diazaspiro[4.5]decan-2-one (269); (3R)-1-{2-[1-(Cyclopropylmethyl)-6-(4-methanesulfonylpiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (270); N-[1-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)piperidin-4-yl]-N-methylacetamide (271); Methyl N-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)piperidin-4-yl]-N-methylcarbamate (272); 1-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)piperidin-4-yl]pyrrolidin-2-one (273); (5S)-5-{[(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)oxy]methyl}pyrrolidin-2-one (274); 4-{[(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)oxy]methyl}pyrrolidin-2-one (275); (3R)-1-{4-chloro-2-[1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (276); 4-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluoro-5-methylbenzamide (277); 3-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-chlorophenol (278); 4-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorobenzamide (279); 1-[4-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]imidazolidin-2-one (280);

[0082] 1-[2-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]imidazolidin-2-one (281); 3-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylphenol (282); 3-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorophenol (283); 5-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2,3-dihydro-1H-isoindol-1-one (284); 6-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2,3-dihydro-1H-isoindol-1-one (285); 4-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylbenzamide (286); 5-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-N-methylpyridine-2-carboxamide (287); (3R)-1-{2-[1-(cyclopropylmethyl)-6-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl}-1H-pyrrolo[2,3-b]pyridin-2-yl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (288); (3R,5R)-1-{4-chloro-2-[6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (289); (3R,5R)-1-{4-chloro-2-[1-(cyclopropylmethyl)-6-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (290); (3R)-1-{4-chloro-2-[6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (291); (3R)-1-{4-chloro-2-[1-(cyclopropylmethyl)-6-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (292); 5-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-2,3-dihydro-1H-isoindol-1-one (293); 4-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-3-chlorobenzamide (294); (7R)-2-{2-[1-(cyclopropylmethyl)-6-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl}-1H-indol-2-yl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptane-7-amine (295); (7R)-2-{2-[1-(cyclopropylmethyl)-6-(3-methoxyazetidin-1-yl)-1H-indol-2-yl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptane-7-amine (296); (7R)-2-{2-[1-(cyclopropylmethyl)-6-(3-fluoro-1H-indazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptane-7-amine (297); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-6-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (298); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (299); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (300);

[0083] 3-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylphenol (301); 1-[2-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]imidazolidin-2-one (302); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methoxybenzamide (303); 1-[4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)phenyl]pyrrolidin-2-one (304); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluoro-5-methylbenzamide (305); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(7-fluoro-1H-indazol-6-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}-2-azabicyclo[2.2.1]heptane-7-amine (306); 5-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-N-methylpyridine-2-carboxamide (307); Methyl N-[5-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)pyridin-2-yl]carbamate (308); (3R)-1-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}piperidin-3-amine (309); (3R)-1-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-6-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (310); (3R)-1-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (311); 6-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-8-fluoro-5-methyl-1,2-dihydroquinolin-2-one (312); 3-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-chlorophenol (313); 3-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorophenol (314); 6-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2,3-dihydro-1H-isoindol-1-one (315); 4-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylbenzamide (316); 5-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2,3-dihydro-1H-isoindol-1-one (317); (7R)-2-{2-[1-(cyclopropylmethyl)-6-(morpholin-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (318); 4-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)morpholin-3-one (319); (7R)-2-{2-[1-(cyclopropylmethyl)-6-(4-methanesulfonylpiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (320);

[0084] (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(1H-indazol-6-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (321); (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(1H-indazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (322); (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(1H-indazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (323); 6-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-8-fluoro-5-methyl-1,2-dihydroquinolin-2-one (324); Methyl N-[1-(2-{6-[(3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)piperidin-4-yl]-N-methylcarbamate (325); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(7-fluoro-1H-indazol-4-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (326); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(3-fluoro-1H-indazol-4-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (327); 1-[4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]imidazolidin-2-one (328); 1-[4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]pyrrolidin-2-one (329); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(7-fluoro-1H-indazol-6-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (330); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-5-fluoro-2-methylbenzamide (331); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-6-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (332); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-5-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (333); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-methylbenzamide (334); 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-3-(trifluoromethyl)benzamide (335); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(7-fluoro-1H-indazol-6-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (336); N-[7-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-4-chloro-1-methyl-1H-indazol-3-yl]methanesulfonamide (337); 1-[2-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]imidazolidin-2-one (338); 4-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-chlorobenzamide (339); 5-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-N-methylpyridine-2-carboxamide (340);

[0085] (7R)-2-{2-[1-(cyclopropylmethyl)-6-(1H-pyrazol-4-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptane-7-amine (341); N-{[4-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}methanesulfonamide (342); N-{[3-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}acetamide (343); [3-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanol (344); (3R)-1-{2-[1’-(cyclopropylmethyl)-1H,1’H-[5,6’-biindol]-2’-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (345); 6-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-8-fluoro-5-methyl-1,2-dihydroquinolin-2-one (346); N-[4-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanesulfonamide (347); N-[5-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)pyridin-2-yl]acetamide (348); (R)-(3-aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (349); (7R)-2-{2-[1-(cyclopropylmethyl)-6-(morpholin-4-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (350); (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(4-methanesulfonylpiperidin-1-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine (351); Methyl N-[1-(2-{6-[(3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylcarbamate (352); N-[1-(2-{6-[(3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylacetamide (353); N-[1-(2-{6-[(3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylmethanesulfonamide (354); (3R,5R)-1-{2-[1-(Cyclopropylmethyl)-6-[4-(pyrrolidine-1-carbonyl)piperidin-1-yl]-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (355); 1-[1-(2-{6-[(3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]pyrrolidin-2-one (356); 3-[1-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-1,3-oxazolidin-2-one (357); Methyl N-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylcarbamate (358); N-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylacetamide (359); N-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylmethanesulfonamide (360);

[0086] (3R)-1-{2-[1-(cyclopropylmethyl)-6-[4-(pyrrolidine-1-carbonyl)piperidin-1-yl]-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (361); N-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-N-methylmethanesulfonamide (362); 1-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]pyrrolidin-2-one (363); 3-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-1,3-oxazolidin-2-one (364); (3R)-1-{2-[1-(cyclopropylmethyl)-6-[4-(1H-pyrazol-1-yl)piperidin-1-yl]-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}piperidin-3-amine (365); N-[1-(2-{6-[(3R)-3-aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)azetidin-3-yl]-N-methylmethanesulfonamide (366); N-{[3-(2-{6-[(3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}methanesulfonamide (367); (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-[3-(2H-1,2,3,4-tetrazol-5-yl)phenyl]-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (368); N-[4-(2-{6-[(3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanesulfonamide (369); N-{[4-(2-{6-[(3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methyl}methanesulfonamide (370); [3-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]methanol (371); 2-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)benzamide (372); 4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)benzamide (373); (3R,5R)-1-{2-[1’-(Cyclopropylmethyl)-1H,1’H-[5,6’-biindole]-2’-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (374); [4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-chloro-5-fluorophenyl]methanol (375); 6-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-8-fluoro-5-methyl-1,2-dihydroquinolin-2-one (376); 4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-3-chlorobenzamide (377); 4-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-methylbenzamide (378); (3R,5R)-1-{2-[1-(Cyclopropylmethyl)-6-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl}-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine (379); 2-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)propan-2-ol (homochiral) (380);

[0087] 2-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-1,1-difluoropropan-2-ol (diastereomer mixture) (381); 2-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-1,1,1-trifluoropropan-2-ol (diastereomer mixture) (382); 2-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-1,1,1-trifluoropropan-2-ol (383); 1-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-1-cyclopropylethan-1-ol (384); 1-(2-{6-[(3R)-3-Aminopiperidine-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)ethan-1-ol (diastereomer mixture) (385); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (386); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (387); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (388); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (389); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (390); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (391); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (392); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (393); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (394); (R)-1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (395); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (396); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (397); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (398); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (399); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (400);

[0088] (R)-1-(4-(2-(6-(3-Aminopiperidin-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (401); (R)-1-(4-(2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (402); (S)-1-(4-(2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (403); (S)-1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (404); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (405); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (406); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (407); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (408); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (409); (R)-1-(4-(2-(6-(3-aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (410); 1-(4-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (411); 1-(4-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (412); (R)-1-(4-(2-(6-(3-aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (413); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (414); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (415); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (416); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxy-2-methylpropan-1-one (417); (R)-1-(4-(2-(6-(3-Aminopiperidin-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxy-2-methylpropan-1-one (418); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (419); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (420);

[0089] ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (421); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (422); (S)-1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (423); (S)-1-(4-(2-(6-((R)-3-Aminopiperidin-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (424); (R)-1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (425); (R)-1-(4-(2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (426); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (427); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (428); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (429); Ethyl 2-(7-(1-(tert-Butoxycarbonyl)piperidin-4-yl)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridine-6-carboxylate (430); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-3-hydroxypropan-1-one (430); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-isopropoxyethan-1-one (431); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-isopropoxyethan-1-one (432); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-3-hydroxy-2,2-dimethylpropan-1-one (433); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-3-hydroxy-2,2-dimethylpropan-1-one (434); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxy-2-methylpropan-1-one (435); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxy-2-methylpropan-1-one (436); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-3-hydroxypropan-1-one (437); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxyethan-1-one (438); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxyethan-1-one (439); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1R,3S)-3-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (440);

[0090] (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-ethoxyethan-1-one (441); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-ethoxyethan-1-one (442); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (443); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (444); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-3-methylbutan-1-one (445); (R)-1-(4-(2-(6-(3-Aminopiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-3-methylbutan-1-one (446); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1S,3R)-3-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (447); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1S,3R)-3-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (448); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1R,3S)-3-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (449); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (450); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (451); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (452); 1-(4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (453); (S)-1-(4-(2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (454); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (455); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (456); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (457); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (458); (S)-1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (459); (R)-1-(4-(2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (460);

[0091] (R)-1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (461); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (462); ((3R,5R)-3-Amino-5-fluoropiperidine-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (463); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(thiophene-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (464); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (465); ((3R,5R)-3-Amino-5-fluoropiperidine-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (466); (4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)(3-hydroxycyclobutyl)methanone (467); Methyl (R)-4-(2-(6-(3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidine-1-carboxylate (468); Methyl 4-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidine-1-carboxylate (469); Methyl 4-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidine-1-carboxylate (470); (R)-1-(4-(2-(6-((R)-3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxypropan-1-one (471); (R)-1-(4-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxypropan-1-one (472); (2R)-1-(4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxypropan-1-one (473); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(thiophene-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (474); (4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)(thiophen-2-yl)methanone (475); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (476); 1-(4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (477); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (478); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (479); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (480);

[0092] 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (481); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (482); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (483); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (484); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (485); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (486); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (487); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (488); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (489); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (490); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (491); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (492); (R)-1-(4-(2-(6-(3-Aminopiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxy-2-methylpropan-1-one (493); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-3-methylbutan-1-one (494); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-3-methylbutan-1-one (495); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (496); (R)-1-(4-(2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (497); (R)-1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (498); (S)-1-(4-(2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (499); (S)-1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one (500);

[0093] 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxy-2-methylpropan-1-one (501); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (502); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (503); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (504); ((3R,5R)-3-Amino-5-fluoropiperidine-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (505); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (506); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)ethan-1-one (507); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (508); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (509); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (510); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (511); (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (512); 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)piperidin-1-yl)-2-methoxyethan-1-one (513); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (514); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutan-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (515); (R)-1-(3-(2-(6-(3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxy-2-methylpropan-1-one (516); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (517); 1-(3-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxy-2-methylpropan-1-one (518); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (519); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (520);

[0094] (R)-1-(3-(2-(6-(3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)ethan-1-one (521); 1-(3-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)ethan-1-one (522); (S)-1-(3-(2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxypropan-1-one (523); (S)-1-(3-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxypropan-1-one (524); (R)-1-(3-(2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxypropan-1-one (525); (R)-1-(3-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxypropan-1-one (526); 1-(3-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxyethan-1-one (527); (R)-1-(3-(2-(6-(3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxyethan-1-one (528); (R)-1-(3-(2-(6-(3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxyethan-1-one (529); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (530); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1R,3S)-3-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (531); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1R,3S)-3-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (532); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1S,3R)-3-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (533); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1S,3R)-3-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (534); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (535); (R)-1-(3-(2-(6-(3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxy-2-methylpropan-1-one (536); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (537); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (538); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (539); (R)-1-(3-(2-(6-((3R,5R)-3-amino-5-fluoropiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxypropan-1-one (540);

[0095] (R)-1-(3-(2-(6-((R)-3-aminopiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxypropan-1-one (541); (S)-1-(3-(2-(6-((3R,5R)-3-amino-5-fluoropiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxypropan-1-one (542); (S)-1-(3-(2-(6-((R)-3-aminopiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxypropan-1-one (543); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (544); ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone(545); (R)-1-(3-(2-(6-(3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxyethan-1-one(546); 1-(3-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)-2-methoxyethan-1-one(547); 1-(3-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)ethan-1-one(548); 1-(3-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)ethan-1-one(549); 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one(550); 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)-1-methylpyrrolidin-2-one(551); 4-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)-1-methylpyrrolidin-2-one (552); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)-1-methylpyrrolidin-2-one (553); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)-1-methylpyrrolidin-2-one (554); (R)-(2-(7-(2-(1H-1,2,4-Triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (555); (2-(7-(2-(1H-1,2,4-Triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (556); (2-(7-(2-(4-Amino-1H-pyrazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (557); (R)-(2-(7-(2-(4-Amino-1H-pyrazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (558); (S)-5-(((2-(6-((R)-3-Aminopiperidin-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (559); (S)-5-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (560);

[0096] (R)-5-(((2-(6-((R)-3-Aminopiperidin-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (561); 4-(((2-(6-((R)-3-Aminopiperidin-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (562); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (563); 4-(((2-(6-((R)-3-Aminopiperidin-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (564); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (565); 4-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (566); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (567); (S)-5-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (568); (S)-5-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (569); (R)-5-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (570); 4-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (571); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (572); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (573); (2-(7-(2-(1H-Imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (574); (R)-(2-(7-(2-(1H-Imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (575); 4-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)-1-methylpyrrolidin-2-one (576); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)-1-methylpyrrolidin-2-one (577); 4-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)-1-methylpyrrolidin-2-one (578); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)-1-methylpyrrolidin-2-one (579); (R)-(2-(7-(2-(1H-1,2,4-Triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (580);

[0097] (2-(7-(2-(1H-1,2,4-Triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidine-1-yl)methanone (581); (R)-(2-(7-(2-(4-Amino-1H-pyrazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (582); (2-(7-(2-(4-Amino-1H-pyrazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidine-1-yl)methanone (583); (S)-5-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (584); (S)-5-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (585); (R)-5-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (586); (R)-5-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (587); 4-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (588); 4-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (589); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one (590); 4-(((2-(6-((R)-3-Aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (591); (2-(7-(2-(1H-1,2,4-Triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (592); (R)-(2-(7-(2-(1H-1,2,4-triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (593); ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(2-(2-methyl-1H-imidazol-1-yl)ethoxy)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (594); (R)-(3-aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(2-(2-methyl-1H-imidazol-1-yl)ethoxy)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (595); (R)-(3-aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(oxetan-3-ylmethoxy)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (596); (2-(7-(2-(1H-imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (597); (R)-(2-(7-(2-(1H-imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (598); (R)-(2-(7-(2-(4H-1,2,4-triazol-4-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (599); (2-(7-(2-(4H-1,2,4-triazol-4-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (600);

[0098] 4-(((2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (601); 4-(((2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (602); 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (603); (5R)-5-(((2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (604); 4-(((2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (605); 4-(((2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (606); (5R)-5-(((2-(6-((7S)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (607); 4-(((2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (608); (R)-(2-(7-(2-(4H-1,2,4-triazol-4-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (609); (2-(7-(2-(1H-1,2,4-triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (610); ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(2-(2-methyl-1H-imidazol-1-yl)ethoxy)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (611); (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(2-(2-methyl-1H-imidazol-1-yl)ethoxy)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (612); (2-(7-(2-(4H-1,2,4-triazol-4-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (613); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (614); 4-(((2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (615); (2-(7-(2-(1H-imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (616); (R)-(2-(7-(2-(1H-Imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone (617); 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (618); 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one (619); (2-(7-(2-(4H-1,2,4-Triazol-4-yl)ethoxy)-1-methyl-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone (620); and ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(3-(cyclopropylmethyl)-4-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)benzo[b]thiophen-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone (621); or a stereoisomer, enantiomer, diastereomer, tautomer or pharmaceutically acceptable salt thereof is mentioned.

[0099] In one embodiment, the present invention uses the RFMS PAD4 functional assay disclosed herein to determine the IC 50 value is < 4.000 μM, preferably the IC 50 value is < 1.000 μM, preferably the IC 50 value is <0.500 μM, preferably, the IC 50 value is < 0.100 μM, more preferably, the IC 50 value is < 0.050 μM, more preferably, the IC 50 value is < 0.03 μM, more preferably, the IC 50 value is < 0.02 μM, even more preferably, the IC 50 value is < 0.01 μM, to provide a compound.

[0100] As defined and described above herein, X2 is selected from N and CR4. In some embodiments, X2 is N. In some embodiments, X2 is CR4. In certain embodiments, X2 is selected from those functional groups described in the examples below.

[0101] As described above, R1 is

Chemical formula

[0102] In some embodiments, R1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0103] In some embodiments, R1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0104] In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] It is. In some embodiments, R1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0105] In some embodiments, R1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0106] In some embodiments, R1 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0107] In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is [Chemistry] is. In some embodiments, R1 is

Chem.

[0108] In some embodiments, R1 is

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

Chem.

[0109] As defined and described above herein, R2 is H, F, Cl, Br, -OR b , and C 1-3 alkyl (one or more R eIt is selected from those that may be optionally replaced as desired. In some embodiments, R2 is H. In some embodiments, R2 is F, Cl, Br. In some embodiments, R2 is F. In some embodiments, R2 is C 1-3 alkyl. In some embodiments, R2 is methyl. In some embodiments, R2 is ethyl. In some embodiments, R2 is propyl. In some embodiments, R2 is OR b . In some embodiments, R2 is -OCH3. In some embodiments, R2 is -OCH2CH3. In some embodiments, R2 is OCH2CH2CH3. In certain embodiments, R2 is OCH(F)2. In certain embodiments, R2 is selected from those functional groups described in the following examples. R2 is preferably selected from H, F, Cl, CH3, and OCH3.

[0110] As defined and described above herein, R3 is selected from CH3 and CD3. In some embodiments, R3 is CH3. In some embodiments, R3 is CD3. In certain embodiments, R3 is selected from those functional groups described in the following examples. R3 is preferably selected from H, F, Cl, CH3, and CH2OH.

[0111] As defined and described above herein, R4 is H, F, Cl, Br, C 1-4 alkyl, OC 1-4 alkyl (substituted with one or more R5),

Chemical formula

Chemical formula

[0112] In some embodiments, R4 is H. In some embodiments, R4 is selected from F, Cl, and Br. In some embodiments, R4 is C 1-3 alkyl. In some embodiments, R4 is CH3.

[0113] In some embodiments, R4 is

Chemical formula

[0114] In some embodiments, R4 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0115] In some embodiments, R4 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0116] In some embodiments, R4 is

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0117] In some embodiments, R4 is

Chemical formula

Chemical formula

[0118] In some embodiments, R4 is

Chemical formula

Chemical formula

[0119] R4, alone or together with R5 and R6, is preferably H, F, Cl, C 1-5 alkyl (optionally substituted with one or more substituents selected from F, Cl, and OH), C 3-6 cycloalkyl, [Chemical formula] [Chemical formula] [Chemical formula] [Chemical formula] selected from.

[0120] As defined and described above herein, R5, independently, is H, F, Cl, Br, CN, =O, C 1-4 alkyl (optionally substituted with one or more R e ), C 2-4 alkenyl (optionally substituted with one or more R e ), C 2-4 alkynyl (optionally substituted with one or more R e ), -(CR d R d ) r OR b ,-(CR d R d ) r S(O) p R c ,-(CR d R d ) r S(O)p NR a R a ,-(CR d R d ) r NR a S(O) p R c ,-(CR d R d ) r NR a R a ,-(CR d R d ) r NR a C(=O)R b ,-(CR d R d ) r NR a C(=O)OR b ,-(CR d R d ) r NR a C(=O)NR a R a ,-(CR d R d ) r C(=O)R b ,-(CR d R d ) r C(=O)OR b ,-(CR d R d ) r C(=O)NR a R a ,-(CR d R d ) r OC(=O)R b ,-(CR d R d ) r OC(=O)OR b ,-(CR d R d ) r O(CH2) r C(=O)NR a R a ,-C 3-6 cycloalkyl (optionally substituted with one or more R e ), aryl (optionally substituted with one or more R ewhich may be optionally replaced as desired), and heterocyclyl (one or more R e which may be optionally replaced as desired).

[0121] In some embodiments, R5 is H, F, Cl, CN, C 1-4 alkyl (which may be optionally replaced with OH, NH2, and COOH), SC 1-4 alkyl, S(O)2C 1-4 alkyl, S(O)2NH-cyclopropyl, -(CH2) 0-1 NHS(O)2C 1-4 alkyl, -NR a S(O)2C 2-4 alkenyl, -(CH2) 0-1 OH, OC 1-4 alkyl, -(CH2) 0-1 NH2, -(CH2) 0-1 NHC(=O)C 1-4 alkyl, -NR a C(=O)C 2-4 alkenyl, -NHC(=O)C 2-4 alkynyl, -(CH2) 0-1 C(=O)OH, -C(=O)OC 1-4 alkyl, -NHC(=O)OC 1-4 alkyl, -NHC(=O)O(CH2)2OC 1-4 alkyl, -NHC(=O)OCH2-cyclopropyl, -NHC(=O)NH2, C(=O)NHC 1-4 alkyl, CONH(CH2) 1-2 C(=O)OH, -(CH2) 0-1 C(=O)NH2, -(CH2) 0-1 C(=O)NHC 1-4 alkyl, C(=O)NH-pyridine, -C(=O)NH(CH2)2N(C 1-4 alkyl)2, -C(=O)NH(CH2)2OH, -C(=O)NH(CH2)2S(O)2C 1-4 alkyl, and -OC(=O)C 1-4 selected from alkyl.

[0122] In some embodiments, R5 is F. In some embodiments, R5 is C 1-4 alkyl. In some embodiments, R5 is -OH or -OC 1-3 alkyl. In some embodiments, R5 is -NHS(O)2C 1-4 alkyl. In certain embodiments, R5 is selected from those functional groups described in the examples below.

[0123] In some embodiments, R4 is OC 1-3 alkyl (substituted with one or more R5); R5 is

Chemical formula

[0124] As defined and described above herein, R6 is H and C 1-3 alkyl (optionally substituted with one or more R e ), -S(O) p R c , -C(=O)R b , -(CH2) r -C(=O)NR a R a , -C(=O)(CH2) r NR a C(=O)R b , -C(=O)OR b , -S(O) p NR a R a , aryl (optionally substituted with one or more R e ), or heterocyclyl (optionally substituted with one or more R e ). In some embodiments, R6 is H. In some embodiments, R6 is methyl or isopropyl. In some embodiments, R6 is -(CH2)2OH. In certain embodiments, R6 is selected from those functional groups described in the examples below. R6 is preferably H, C 1-6Alkyl (one or more Rs e optionally substituted as desired), -S(O) p R c -S(O) p NR a R a -C(=O)R b -C(=O)OR b -C(=O)NR a R a C 3-6 Cycloalkyl (one or more Rs e optionally substituted as desired), aryl (one or more Rs e optionally substituted as desired), and heterocyclyl (one or more Rs e optionally substituted as desired). In some embodiments, R4, R5, and R6, together,

Chemical formula

[0125] As defined and described above herein, R7 is selected from H, F, Cl, Br, and C 1-4 alkyl. In some embodiments, R7 is H. In some embodiments, R7 is C 1-3 alkyl. In certain embodiments, R7 is selected from those functional groups described in the examples below. R7 is preferably selected from H, F, and Cl.

[0126] As defined and described above herein, R8 is selected from H and C 1-3 alkyl (optionally substituted with one or more substituents selected from F, Cl, and C 3-6 cycloalkyl). In some embodiments, R8 is hydrogen. In some embodiments, R8 is C 1-2 alkyl (C 3-6(substituted with cycloalkyl). In some embodiments, R8 is methyl. In some embodiments, R8 is ethyl. In some embodiments, R8 is cyclopropyl. Preferably, R8 is -CH2-cyclopropyl or -CH2-cyclobutyl. In some embodiments, R8 is -CH2-cyclobutyl (optionally substituted with methyl and / or -OH). In certain embodiments, R8 is selected from those functional groups described in the examples below.

[0127] As defined and described above herein, R a is independently H, C 1-6 alkyl (optionally substituted with one or more R e ), C 2-6 alkenyl (optionally substituted with one or more R e ), C 2-6 alkynyl (optionally substituted with one or more R e ), -(CH2) r -C 3-10 carbocyclyl (optionally substituted with one or more R e ), and -(CH2) r -heterocyclyl (optionally substituted with one or more R e ); or R a and R a together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more R e ).

[0128] As defined and described above herein, R b is independently H, C 1-6 alkyl (optionally substituted with one or more R e ), C 2-6 alkenyl (optionally substituted with one or more R e ), C 2-6 alkynyl (optionally substituted with one or more R ewhich may be optionally replaced, -(CH2) r -C 3-10 carbocyclic (one or more Rs e which may be optionally replaced), and -(CH2) r -heterocyclic (one or more Rs e which may be optionally replaced) is selected from.

[0129] As defined and described hereinabove, R c is independently selected from C 1-6 alkyl (one or more Rs e which may be optionally replaced), C 2-6 alkenyl (one or more Rs e which may be optionally replaced), C 2-6 alkynyl (one or more Rs e which may be optionally replaced), -(CH2) r -C 3-10 carbocyclic (one or more Rs e which may be optionally replaced), and -(CH2) r -heterocyclic (one or more Rs e which may be optionally replaced) is selected from. As defined and described hereinabove, R d is independently selected from H, and C 1-6 alkyl (one or more Rs e which may be optionally replaced).

[0130] As defined and described hereinabove, R e is independently selected from F, Cl, Br, CN, NH2, -NH-C 1-4 alkyl, -N(C 1-4 alkyl)2, =O, OH, -OC 1-6 alkyl, -CO2H, C 1-6 alkyl (one or more Rs f which may be optionally replaced), C 2-6 alkenyl, C 2-6 alkynyl, -(CH2) r-C 3-6 Cycloalkyl (optionally substituted with one or more R f as desired), -(CH2) r -aryl (optionally substituted with one or more R f as desired), and -(CH2) r -heterocyclyl (optionally substituted with one or more R f as desired) is selected from.

[0131] As defined and described hereinabove, R f is, independently, F, Cl, Br, CN, OH, C 1-5 alkyl (optionally substituted with OH), C 2-5 alkenyl, C 2-5 alkynyl, C 3-6 cycloalkyl, and phenyl is selected from. As defined and described hereinabove, p is, in each occurrence, independently selected from 0, 1, and 2.

[0132] As defined and described hereinabove, r is 0 - 4. In some embodiments, r is 0. In some embodiments, r is 1. In some embodiments, r is 2. In some embodiments, r is 3. In some embodiments, r is 4.

[0133] In some embodiments, the compound of formula (Ia) is selected from the following examples. In certain embodiments, the present invention also provides any of the compounds described below and herein for use in therapy, or a pharmaceutically acceptable salt or composition thereof. In some embodiments, the present invention provides any of the compounds described below and herein in isolated form. In some embodiments, the present invention provides a compound according to any one of the claims shown below.

[0134] 3. Pharmaceutical Composition In another aspect, the invention provides a composition comprising a compound of the invention, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. The amount of the compound incorporated into the composition of the invention is an amount effective to inhibit PAD4 in a biological sample or patient such that it is clearly discernible. In certain embodiments, the amount of the compound in the composition of the invention is an amount effective to visibly inhibit PAD4 in a biological sample or patient. In certain embodiments, the composition of the invention is formulated for administration to a patient in need of such a composition. In some embodiments, the composition of the invention is formulated for oral administration to a patient.

[0135] As used herein, the term "subject" is used interchangeably with the term "patient" and means an animal, preferably a mammal. In some embodiments, the subject or patient is a human. In other embodiments, the subject (or patient) is a veterinary subject (or patient). In some embodiments, the veterinary subject (or patient) is a dog, cat, or horse.

[0136] The term "pharmaceutically acceptable carrier, adjuvant, or vehicle" refers to a non-toxic carrier, adjuvant, or vehicle that does not destroy the pharmacological activity of the compound being formulated. Pharmaceutically acceptable carriers, adjuvants, or vehicles that can be used in the compounds of the present invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block copolymers, polyethylene glycol, and lanolin.

[0137] The compositions of the present invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally, or via an implanted reservoir. As used herein, the term "parenterally" includes subcutaneous, intravenous, intramuscular, intra-articular, intra-synovial, intrasternal, intramedullary, intralesional, and intracranial injection or infusion techniques. Preferably, the compositions are administered orally, intraperitoneally, or intravenously. The sterile injectable form of the compositions of the present invention may be an aqueous or oily suspension. These suspensions may be formulated according to techniques known in the art using appropriate dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent such as, for example, a solution of 1,3-butanediol. Among the acceptable vehicles and solvents that can be utilized are water, Ringer's solution, and isotonic sodium chloride solution. In addition, sterile fixed oils are commonly employed as a solvent or suspending medium.

[0138] For this purpose, any sterile fixed oil containing synthetic monoglycerides or diglycerides may be utilized. Fatty acids such as oleic acid and its glyceride derivatives are useful in the manufacture of injectables, particularly in their polyoxyethylated versions, as are natural medically acceptable oils such as olive oil or castor oil. These oily solutions or suspensions may also contain diluents or dispersants of long-chain alcohols, such as carboxymethyl cellulose or similar dispersants, which are commonly used to formulate pharmaceutically acceptable dosage forms, including emulsions and suspensions. Other commonly used surfactants, such as Tween, Span, and other emulsifiers or bioavailability enhancers, which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms, may also be used for formulation purposes.

[0139] The pharmaceutically acceptable compositions of the present invention can be orally administered in any orally acceptable dosage form, including but not limited to capsules, tablets, aqueous suspensions, or solutions. In the case of oral tablets, commonly used carriers include lactose and corn starch. Lubricants such as magnesium stearate are also typically added. For oral administration in capsule form, useful diluents include lactose and dried corn starch. When an aqueous suspension is required for oral use, the active ingredient is combined with emulsifying and suspending agents. Optionally, certain sweetening, flavoring, or coloring agents may also be added.

[0140] Alternatively, the pharmaceutically acceptable compositions of the present invention may be administered in the form of suppositories for rectal administration. These can be manufactured by mixing the agent with suitable non-irritating excipients that are solid at room temperature but liquid at rectal temperature and will thus melt in the rectum to release the drug. Such materials include cocoa butter, beeswax, and polyethylene glycol.

[0141] The pharmaceutically acceptable compositions of the present invention may also be administered topically, particularly when the target of treatment includes areas or organs that can be easily addressed by topical application, including diseases of the eye, skin or lower intestinal tract. Suitable topical formulations are readily manufactured for each of these areas or organs. Topical application to the lower intestinal tract can be effected with a rectal suppository formulation (see above) or with a suitable enema formulation. Topical transdermal patches can also be used.

[0142] In the case of topical application, the pharmaceutically acceptable compositions provided may be formulated into a suitable ointment containing the active ingredient suspended or dissolved in one or more carriers. Carriers for topical administration of the compounds of the present invention include, but are not limited to, mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene, polyoxypropylene compounds, emulsifying wax and water. Alternatively, the pharmaceutically acceptable compositions provided may be formulated into a suitable lotion or cream containing the active ingredient suspended or dissolved in one or more carriers. Suitable carriers include, but are not limited to, mineral oil, sorbitan monostearate, polysorbate 60, cetyl ester wax, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water.

[0143] When used ophthalmically, the pharmaceutically acceptable compositions provided may be formulated as a micro-suspension in isotonic, pH-adjusted, sterile saline, with or without a preservative such as benzalkonium chloride, or preferably as a solution in isotonic, pH-adjusted, sterile saline. Alternatively, when used ophthalmically, the pharmaceutically acceptable compositions may be formulated into an ointment such as petrolatum.

[0144] The pharmaceutically acceptable compositions of the present invention may also be administered by nasal aerosol or inhalation. Such compositions are manufactured according to techniques well known in the field of pharmaceutical formulations and may be manufactured as solutions in saline using benzyl alcohol or other suitable preservatives, absorption promoters to improve bioavailability, fluorocarbons, and / or other conventional solubilizing or dispersing agents.

[0145] Preferably, the pharmaceutically acceptable compositions of the present invention are formulated for oral administration. Such formulations may be administered with or without food. In some embodiments, the pharmaceutically acceptable compositions of the present invention are administered without food. In other embodiments, the pharmaceutically acceptable compositions of the present invention are administered with food.

[0146] The pharmaceutically acceptable compositions of the present invention can be administered, if desired, to humans and other animals orally, rectally, parenterally, intracapsularly, vaginally, intraperitoneally, topically (such as by powder, ointment or drops), buccally, as an oral or nasal spray, etc. In certain embodiments, the compounds of the present invention are administered orally or parenterally at a dosage level of about 0.01 mg to about 50 mg, preferably about 1 mg to about 25 mg, per kg of body weight of the subject per day, once or several times a day, to obtain the desired therapeutic effect.

[0147] Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compound, the liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizing and emulsifying agents, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (especially cottonseed, peanut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols, and fatty acid esters of sorbitan, and mixtures thereof. In addition to the inert diluents, the oral compositions may also contain adjuvants such as wetting agents, emulsifying and suspending agents, sweetening agents, flavoring and odor masking agents, and perfumes.

[0148] Injectable formulations, for example, sterile injectable aqueous or oily suspensions, may be formulated according to known techniques using suitable dispersing or wetting agents and suspending agents. Sterile injectable formulations may also be sterile injectable solutions, suspensions, or emulsions in a non-toxic parenterally acceptable diluent or solvent, such as, for example, a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be utilized are water, Ringer's solution, U.S.P., and isotonic sodium chloride solution. In addition, sterile fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil containing synthetic mono- or diglycerides may be used. In addition, fatty acids such as oleic acid may be used in the manufacture of injectable formulations.

[0149] Injectable formulations may be sterilized, for example, by filtration through a bacteria-retaining filter or by incorporating a sterilizing agent in the form of a sterile solid composition that can be dissolved or dispersed in sterile water or other sterile injectable medium immediately before use.

[0150] In order to extend the effect of the compounds of the present invention, it is often desirable to delay the absorption of the compounds from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of a crystalline or amorphous material with low water solubility. In that case, the absorption rate of the compound depends on its dissolution rate, which in turn can depend on the crystal size and crystal form. Alternatively, the delayed absorption of the form of the compound administered parenterally is achieved by dissolving or suspending the compound in an oily vehicle. Injectable depot forms are produced by forming a microcapsule-type matrix of the compound in a biodegradable polymer such as polylactide-polyglycolide. Depending on the ratio of the compound to the polymer and the properties of the particular polymer utilized, the release rate of the compound can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injection formulations are also produced by encapsulating the compound in liposomes or microemulsions that can be compatible with body tissues.

[0151] Compositions for rectal or vaginal administration are preferably suppositories, which can be produced by mixing the compounds of the present invention with a suitable non-irritating excipient or carrier, such as cocoa butter, polyethylene glycol or suppository wax, which is solid at ambient temperature but liquid at body temperature and thus melts in the rectal or vaginal cavity to release the active compound.

[0152] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is admixed with at least one inert pharmaceutically acceptable excipient or carrier such as sodium citrate or dibasic calcium phosphate, and / or (a) fillers or extenders such as starch, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia, (c) humectants such as glycerol, (d) disintegrants such as agar - agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, (e) solubilization retarders such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) wetting agents such as, for example, cetyl alcohol and glycerol monostearate, (h) absorbents such as kaolin and bentonite clay, (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also include buffering agents.

[0153] Solid compositions of the same type may also be employed as fillers in soft and hard - filled gelatin capsules using excipients such as lactose or milk sugar, and high - molecular weight polyethylene glycols and the like. Solid dosage forms of tablets, dragees, capsules, pills, and granules may be manufactured using coating agents and shells such as enteric coating agents and other coating agents well - known in the art of pharmaceutical formulation. They may optionally contain opacifying agents and may be formulated to release only the active ingredient or, preferentially, to release the active ingredient in a particular part of the intestinal tract, optionally in a delayed manner, as desired. Examples of implantable compositions that may be used include polymeric substances and waxes. Solid compositions of the same type may also be employed as fillers in soft and hard - filled gelatin capsules using excipients such as lactose or milk sugar, and high - molecular weight polyethylene glycols and the like.

[0154] The active compound can also be in microencapsulated form with one or more of the excipients described above. Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be manufactured using coating agents and shells such as enteric coating agents, release control coating agents, and other coating agents well-known in the field of pharmaceutical formulations. In such solid dosage forms, the active compound may be mixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also, as is customary in the present state of the art, contain additive substances other than inert diluents, for example lubricants for tablets such as magnesium stearate and microcrystalline cellulose and other tablet auxiliaries. In the case of capsules, tablets and pills, the dosage form may also contain buffering agents.

[0155] Dosage forms for topical or transdermal administration of the compounds of the invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active ingredient is mixed under sterile conditions with a pharmaceutically acceptable carrier and, if necessary, with the preservatives or buffering agents required. Ophthalmic preparations, ear drops, and eye drops are also considered to be within the scope of the present invention. In addition, the present invention contemplates the use of transdermal patches which have the additional advantage of providing controlled delivery of the compound to the body. Such dosage forms can be manufactured by dissolving or dispensing the compound in a suitable medium. The rate of flow of the compound across the skin can be increased using absorption promoters. The rate can be controlled either by providing a rate controlling membrane or by dispersing the compound in a polymeric matrix or gel.

[0156] The amount of the compound of the invention that can be combined with a carrier material to produce a single dosage form composition will vary depending on the host to be treated and the particular method of administration. Preferably, the compositions provided should be formulated so that an inhibitor in an amount of 0.01 - 100 mg / kg body weight / day can be administered to the patients receiving these compositions.

[0157] The compounds of the present invention can be administered alone or in combination with one or more other therapeutic compounds. Possible combination therapies can take the form of a fixed combination, or the compounds of the present invention and one or more other therapeutic compounds can be administered alternately, or independently of each other, or take the form of a combined administration of a fixed combination and one or more other therapeutic compounds. Examples of such other therapeutic agents include corticosteroids, loxapram, calphostin, cytokine-suppressive anti-inflammatory drugs (CSAIDs), interleukin-10, glucocorticoids, salicylates, nitric oxide, and other immunosuppressive agents; nuclear translocation inhibitors such as deoxyspergualin (DSG); non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, celecoxib, and rofecoxib; steroids such as prednisone or dexamethasone; antiviral agents such as abacavir; antiproliferative agents such as methotrexate, leflunomide, FK506 (tacrolimus, Prograf); cytotoxic drugs such as azathioprine and cyclophosphamide; TNF-α inhibitors such as tenizumab, anti-TNF antibodies or soluble TNF receptors, and rapamycin (sirolimus or Rapamune) or its derivatives. The compounds of the present invention can, moreover, or in addition, be administered in combination with chemotherapy, radiotherapy, immunotherapy, phototherapy, surgical intervention, or combinations thereof, particularly for tumor therapy. As described above, long-term therapy is equally possible, as is adjuvant therapy in connection with other treatment methods. Other possible treatments are therapies for maintaining the patient's condition after tumor regression, or even chemoprevention in patients, for example, in a critical condition.

[0158] These additional agents may be administered separately from the composition containing the compound of the present invention as part of a multi-dose treatment regimen. Alternatively, these agents may be part of a single-dose form and may be mixed together with the compound of the present invention in a single composition. If administered as part of a multi-dose treatment regimen, the two active agents may be administered simultaneously, sequentially, or within a certain period of time of each other, usually within 5 hours of each other.

[0159] As used herein, the terms "combination", "combined", and related terms refer to the simultaneous or sequential administration of therapeutic agents according to the present invention. For example, the compounds of the present invention may be administered simultaneously or sequentially with another therapeutic agent in separate unit dosage forms or together in a single unit dosage form. Accordingly, the present invention provides a single unit dosage form comprising a compound of the present invention, an additional therapeutic agent, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

[0160] The amounts of both the compounds of the present invention and additional therapeutic agents (the amounts in their compositions including additional therapeutic agents as described above) that can produce a single dosage form in combination with a carrier material will vary depending on the host being treated and the particular route of administration. Preferably, the compositions of the present invention should be formulated such that the compounds of the present invention can be administered at dosages between 0.01 - 100 mg / kg body weight / day.

[0161] In their compositions containing additional therapeutic agents, the additional therapeutic agent and the compounds of the present invention may act synergistically. Accordingly, the amount of the additional therapeutic agent in such compositions will be less than the amount required in a monotherapy utilizing only that therapeutic agent.

[0162] The amount of additional therapeutic agent incorporated into the compositions of the present invention will not exceed the amount that would normally be administered in a composition containing that therapeutic agent as the sole active agent. Preferably, the amount of additional therapeutic agent in the compositions disclosed herein will be in the range of about 50% - 100% of the amount generally present in a composition containing that agent as the sole therapeutically active agent.

[0163] It should also be recognized that the individual dosage amounts and treatment regimens for a particular patient will depend on a variety of factors including the activity of the individual compounds utilized, age, body weight, general health, sex, diet, duration of administration, rate of excretion, drug combination, as well as the judgment of the attending physician and the severity of the particular disease or disorder being treated. The amount of the compounds of the present invention in the composition will also depend on the individual compounds in the composition.

[0164] 4. Use of Compounds The compounds and compositions described herein are generally useful for the inhibition of PAD4. The activity of the compounds utilized in the present invention as inhibitors of PAD4 can be assayed in vitro, in vivo or in cell lines. In vitro assays include assays that measure the inhibition of PAD4. The detailed conditions for assaying the compounds utilized as inhibitors of PAD4 in the present invention are described in the following examples. In some embodiments, the provided compounds selectively inhibit PAD4 as compared to PAD2.

[0165] As used herein, the terms “treating,” “treat” and “treatment” refer to reversing, alleviating, delaying the onset of, or inhibiting the progression of a disease or disorder described herein, or one or more symptoms thereof. In some embodiments, treatment may be administered after the onset of one or more symptoms. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., taking into account the medical history of the symptoms and / or genetic or other susceptibility factors). Treatment may also be continued after the symptoms have resolved, for example, to prevent or delay their recurrence.

[0166] The provided compounds are inhibitors of PAD4 and are thus useful for treating one or more diseases or disorders associated with the activity of the PAD4 enzyme. Thus, in certain embodiments, the present invention provides a method for treating a disease or disorder associated with the activity of the PAD4 enzyme, the method comprising administering to a patient in need thereof a compound of the present invention or a pharmaceutically acceptable composition thereof.

[0167] In one embodiment, the disease or disorder associated with PAD4 enzyme activity is a disease, condition or disorder mediated by inappropriate PAD4 activity. In some embodiments, the disease or disorder associated with PAD4 enzyme activity is selected from the group consisting of rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, and psoriasis. In a further embodiment, the disease or disorder associated with PAD4 enzyme activity is rheumatoid arthritis. In a further embodiment, the disease or disorder associated with PAD4 enzyme activity is systemic lupus erythematosus. In a further embodiment, the disease or disorder associated with PAD4 enzyme activity is vasculitis. In a further embodiment, the disease or disorder associated with PAD4 enzyme activity is cutaneous lupus erythematosus. In a further embodiment, the disease or disorder associated with PAD4 enzyme activity is psoriasis.

[0168] In one embodiment, a method of treating rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, or psoriasis, the method comprising administering to a human subject in need thereof a therapeutically effective amount of a compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof.

[0169] In one embodiment, there is provided a method of treating rheumatoid arthritis, comprising administering to a human subject in need thereof a therapeutically effective amount of a provided compound, stereoisomer, enantiomer, diastereomer, tautomer, or a pharmaceutically acceptable salt thereof. In one embodiment, there is provided a method of treating systemic lupus erythematosus, comprising administering to a human subject in need thereof a therapeutically effective amount of a provided compound, stereoisomer, enantiomer, diastereomer, tautomer, or a pharmaceutically acceptable salt thereof. In one embodiment, there is provided a method of treating vasculitis, comprising administering to a human subject in need thereof a therapeutically effective amount of a provided compound, stereoisomer, enantiomer, diastereomer, tautomer, or a pharmaceutically acceptable salt thereof. In one embodiment, there is provided a method of treating cutaneous lupus erythematosus, or psoriasis, comprising administering to a human subject in need thereof a therapeutically effective amount of a provided compound, stereoisomer, enantiomer, diastereomer, tautomer, or a pharmaceutically acceptable salt thereof. In one embodiment, there is provided a method of treating psoriasis, comprising administering to a human subject in need thereof a therapeutically effective amount of a provided compound, stereoisomer, enantiomer, diastereomer, tautomer, or a pharmaceutically acceptable salt thereof.

[0170] In some embodiments, the diseases or disorders associated with PAD4 enzyme activity are acid-induced lung injury, pyogenic arthritis, pyoderma gangrenosum, acne inversa (PAPA), acute lymphocytic leukemia, acute respiratory distress syndrome, Addison's disease, adrenal hyperplasia, adrenocortical insufficiency, aging, AIDS, alcoholic hepatitis, alcoholic liver disease, allergen-induced asthma, allergic bronchopulmonary aspergillosis, allergic conjunctivitis, alopecia, Alzheimer's disease, amyloidosis, amyotrophic lateral sclerosis, weight loss, angina, angioedema, anhidrotic ectodermal dysplasia with immunodeficiency, ankylosing spondylitis, anterior uveitis, antiphospholipid syndrome, aphthous stomatitis, appendicitis, arthritis, asthma, atherosclerosis, atopic dermatitis, autoimmune disease, autoimmune pneumonia, bee sting-induced inflammation, Behçet's disease, Behçet's syndrome, Bell's palsy, beryllium poisoning, Blau syndrome, bone pain, bronchitis, burns, bursitis, cancer, cardiac hypertrophy, carpal tunnel syndrome, catabolism disorder, cataract, cerebral aneurysm, chemical irritant-induced inflammation, choroiditis, chronic heart failure, chronic lung disease of prematurity, chronic lymphocytic leukemia, chronic obstructive pulmonary disease, colitis, complex regional pain syndrome, connective tissue disease, corneal ulcer, Crohn's disease, cryopyrin-associated periodic syndrome, cryptococcosis, cystic fibrosis, deficiency of interleukin-1 receptor antagonist (DIRA), dermatitis, dermatitis endotoxemia, dermatomyositis, diffuse glioblastoma, endometriosis, endotoxemia, epiglottitis, erythroblastopenia, familial amyloidotic polyneuropathy, familial cold urticaria, familial Mediterranean fever, fetal growth retardation, glaucoma, glomerular disease, glomerulonephritis, gout, gouty arthritis, graft-versus-host disease, gut disease, head injury, headache, hearing loss, heart disease, hemolytic anemia, Henoch-Schönlein purpura, hepatitis, hereditary periodic fever syndrome, herpes zoster and herpes simplex, HIV-1, Hodgkin's disease, Huntington's disease, hyaline membrane disease, hyperammonemia, hypercalcemia, hypercholesterolemia, hyperimmunoglobulinemia D with recurrent fever (HIDS), hypoplasia and other anemias, aplastic anemia, idiopathic thrombocytopenic purpura, incontinentia pigmenti, infectious mononucleosis, inflammatory bowel disease, inflammatory lung disease, inflammatory neuropathy, inflammatory pain, insect bite-induced inflammation, iris, irritant-induced inflammation, ischemia / reperfusion, juvenile rheumatoid arthritis, keratitis, kidney disease, kidney injury caused by parasitic infection, kidney transplant rejection prevention, leptospirosis, leukemia,Selected from the group consisting of Reiter's syndrome, lung injury, lupus, lupus nephritis, lymphoma, meningitis, mesothelioma, mixed connective tissue disease, Mac-Wells syndrome (urticaria deafness amyloidosis), multiple sclerosis, muscle wasting, muscular dystrophy, myasthenia gravis, cardiomyopathy, fungating polyps, myelodysplastic syndrome, myositis, rhinosinusitis, necrotizing enteritis, neonatal onset multi-organ inflammatory disease (NOMID), nephrotic syndrome, neuritis, neuropathological diseases, non-allergen-induced asthma, obesity, eye allergy, optic neuritis, organ transplantation, osteoarthritis, otitis media, Paget's disease, pain, pancreatitis, Parkinson's disease, pemphigus, pericarditis, periodic fever, periodontitis, peritoneal endometriosis, pertussis, pharyngitis and adenitis (PFAPA syndrome), plant irritant-induced inflammation, pneumonia, pneumonitis, pneumonia infection, Rhus / urushiol oil-induced inflammation, polyarteritis nodosa, polychondritis, polycystic kidney disease, polymyositis, psoriasis, psychosocial stress disorders, lung diseases, pulmonary hypertension, pulmonary fibrosis, pyoderma gangrenosum, septic arthritis, kidney diseases, retinal diseases, rheumatic carditis, rheumatic diseases, rheumatoid arthritis, sarcoidosis, seborrhea, sepsis, severe pain, sickle cells, sickle cell anemia, silica-induced diseases, Sjögren's syndrome, skin diseases, sleep apnea, solid tumors, spinal cord injury, Stevens-Johnson syndrome, stroke, subarachnoid hemorrhage, sunburn, temporal arteritis, tenosynovitis, thrombocytopenia, thyroiditis, tissue transplantation, TNF receptor-associated periodic syndrome (TRAPS), toxoplasmosis, transplantation, traumatic brain injury, tuberculosis, type 1 diabetes, type 2 diabetes, ulcerative colitis, urticaria, uveitis, Wegener's granulomatosis, interstitial lung disease, psoriatic arthritis, juvenile idiopathic arthritis, Sjögren's syndrome, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, antiphospholipid antibody syndrome, sepsis, deep vein thrombosis, fibrosis, Alzheimer's disease, scleroderma and CREST syndrome.,

[0171] In one embodiment, the present invention provides a compound for use in therapy, or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention provides a compound for use in the treatment of a disease or disorder mediated by inappropriate PAD4 activity, or a pharmaceutically acceptable salt thereof. In another embodiment, the present invention provides a compound for use in the treatment of rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, or psoriasis, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In another embodiment, the present invention provides a compound provided for use in the treatment of rheumatoid arthritis, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In another embodiment, the present invention provides a compound for use in the treatment of systemic lupus erythematosus, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In another embodiment, the present invention provides a compound for use in the treatment of vasculitis, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In another embodiment, the present invention provides a compound for use in the treatment of cutaneous lupus erythematosus, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In another embodiment, the present invention provides a compound for use in the treatment of psoriasis, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In another embodiment, the present invention provides the use of a compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of a disorder mediated by inappropriate PAD4 activity.In another embodiment, the present invention provides the use of a compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, or psoriasis. In another embodiment, the present invention provides the use of a compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of rheumatoid arthritis. In another embodiment, the present invention provides the use of a compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of systemic lupus erythematosus. In another embodiment, the present invention provides the use of a compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of vasculitis. In another embodiment, the present invention provides the use of a compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of cutaneous lupus erythematosus. In another embodiment, the present invention provides the use of a compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in the treatment of psoriasis. In a further embodiment, the present invention provides a pharmaceutical composition for treating or preventing a disease or disorder mediated by inappropriate PAD4 activity, the pharmaceutical composition comprising the provided compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof.In a further embodiment, the present invention provides a pharmaceutical composition for treating or preventing rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosus, or psoriasis, comprising the provided compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In a further embodiment, the present invention provides a pharmaceutical composition for treating or preventing rheumatoid arthritis, comprising the provided compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In a further embodiment, the present invention provides a pharmaceutical composition for treating or preventing systemic lupus erythematosus, comprising the provided compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In a further embodiment, the present invention provides a pharmaceutical composition for treating or preventing vasculitis, comprising the provided compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In a further embodiment, the present invention provides a pharmaceutical composition for treating or preventing cutaneous lupus erythematosus, comprising the provided compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof. In a further embodiment, the present invention provides a pharmaceutical composition for treating or preventing psoriasis, comprising the provided compound, or a stereoisomer, enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt thereof.

[0172] All features of each aspect of the present invention, where appropriate, may be modified and applied mutatis mutandis to all other aspects. To better understand the invention described herein, the following examples are used to illustrate the present invention. It should be understood that these examples are for illustrative purposes only and should not be construed as limiting the present invention in any way.

[0173] 5. Examples The following examples were manufactured, isolated, and characterized using the methods disclosed herein. The following examples are illustrative of the scope of the invention and are not intended to limit the scope of the invention.

[0174] Details of the various HPLC / LC-MS methods used to analyze compounds and intermediates are described below.

[0175] Method A: Sapphire C18 (4.6x150) mm, 3.5 μm column; flow rate: 1 ml / min; gradient time: 15 minutes; 10-100% solvent B; monitored at 254 nm and 220 nm (solvent A: 5% acetonitrile (ACN), 95% water, 0.05% trifluoroacetic acid (TFA); solvent B: 95% ACN, 5% water, 0.05% TFA) Method B: X-Bridge Phenyl (4.6x150) mm, 3.5 μm column; flow rate: 1 ml / min; gradient time: 15 minutes; %10-100% solvent B; monitored at 254 nm and 220 nm (solvent A: 5% ACN, 95% water, 0.05% TFA; solvent B: 95% ACN, 5% water, 0.05% TFA) Method C: Kinetex EVO C18 (4.6x100) mm, 2.6 μm, buffer: 0.05% TFA in water, mobile phase C: buffer: ACN (95:5), mobile phase D: ACN: buffer (95:5)

[0176] Method D: Kinetex Biphenyl (4.6x100) mm, 2.6 μm, buffer: 0.05% TFA in water, mobile phase C: buffer: ACN (95:5), mobile phase D: ACN: buffer (95:5) Method E: XBridge BEH XP C18 (50x2.1) mm, 2.5 μm, time (min): 0-3% B: 0-100 buffer A: 95% water: 5% ACN; 10 mM ammonium acetate (NH4OAc); B: 5% water: 95% ACN; 10 mM NH4OAc, flow: 1.1 ml / min, temperature: 50 °C Method F: XBridge BEH XP C18 (50x2.1) mm, 2.5 μm, Time (min): 0 - 3%, B: 0 - 100, A: 95% water: 5% ACN; 0.1% TFA, B: 5% water: 95% ACN; 0.1% TFA, Flow: 1.1 ml / min, Temperature: 50 °C

[0177] Method G: ACQUITY UPLC® BEH C18 (3x50) mm, 1.7 μm, Buffer: 10 mM NH4OAc, Mobile Phase A: Buffer: ACN (95:5), Mobile Phase B: Buffer: ACN (5:95), Flow: 0.7 ml / min, Method: 0 min - 20% B, 20% - 100% B for 2 min, 2 - 2.3 min - 100% Method H: Kinetex XB C18 (75x3) mm, 2.6 μm, Mobile Phase A: 10 mM NH4OAc in water, water: ACN (98:02), Mobile Phase B: 10 mM NH4OAc in water: ACN (02:98), Gradient: 20 - 100% B over 4 min, Flow: 1.0 ml / min Method I: ACQUITY UPLC® BEH C18 (3x50) mm, 1.7 μm, Buffer: 0.05% TFA in water, Mobile Phase A: Buffer: ACN (95:5), Mobile Phase B: ACN: Buffer (95:5)

[0178] Method J: Column: HALO C18, 3x30 mm, 2.7 μm; Mobile Phase A: water + 0.05% TFA, Mobile Phase B: acetonitrile + 0.05% TFA; Flow rate: 1.5 mL / min; Gradient: 5% B - 95% B in 2.5 min, hold at 95% for 1 min, 95% B - 5% B in 0.05 min; Detection: MS and UV (254 nm) Method K: Column: Shim - pack XR - ODS, 3x50 mm, 2.2 μm; Mobile Phase A: water / 0.05% TFA, Mobile Phase B: acetonitrile / 0.05% TFA; Flow rate: 1.2000 mL / min; Gradient: 5% B - 95% B in 3.3 min, hold at 95% for 0.7 min, 95% B - 5% B in 0.1 min; Detection: MS and UV (254 nm)

[0179] The general purification method using reverse-phase HPLC (RP-HPLC) is as follows. Typically, the sample to be purified is dissolved in DCM:MeOH (2:1), 20 wt% poly(4-vinylpyridine) (Aldrich # 226963) is added to this solution, and the container containing the solution is shaken on a shaker for 2 hours. Then, the content is filtered through a 25 mm syringe filter equipped with a 0.45 μm nylon membrane (VWR # 28145-489) and placed in a clean vial, and dried using centrifugal evaporation to obtain the purified sample.

[0180] General synthetic operations: Intermediate 1 1-Amino-3-methoxy-5-(methoxycarbonyl)pyridin-1-ium 2,4-dinitrophenolate

Chemical formula

[0181] Intermediate 2 tert-Butyl 3-(1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)propionate

Chemical formula

[0182] Intermediate 3 6-Chloro-1-(cyclopropylmethyl)-2-iodo-1H-pyrrolo[2,3-b]pyridine

Chemical Structure

[0183] Intermediate 4 tert-Butyl 3-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)propionate

Chemical Structure

[0184] Intermediate 5 6-Bromo-1-(cyclopropylmethyl)-2-ethynyl-1H-indole

Chemical formula

[0185] Intermediate 6 tert-Butyl 3-(6-bromo-1-(cyclopropylmethyl)-1H-indol-2-yl)propionate

Chem.

[0186] Intermediate 7 1-(Cyclopropylmethyl)-2-(trimethylstannyl)-1H-pyrrolo[2,3-b]pyridine

Chem.

[0187] Intermediate 8 1-Amino-3-(ethoxycarbonyl)pyridin-1-ium 2,4-dinitrophenolate

Chemical Structure

[0188] Intermediate 9 1-Amino-3-fluoro-5-(methoxycarbonyl)pyridin-1-ium 2,4,6-trimethylbenzenesulfonate

Chemical Structure

[0189] Intermediate 10 1-(Cyclopropylmethyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

Chem.

[0190] Intermediate 11 1-(Cyclopropylmethyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine

Chem.

[0191] Intermediate 12 6-Bromo-1-(cyclopropylmethyl)-2-iodo-1H-indole

Chemical Structure

[0192] Intermediate 13 1-Amino-3-chloro-5-(methoxycarbonyl)pyridin-1-ium-2,4,6-trimethylbenzenesulfonate

Chemical Structure

[0193] Intermediate 14 Ethyl 6-bromo-1-(cyclopropylmethyl)-1H-indole-2-carboxylate

Chemical formula

[0194] Intermediate 15 (6-Bromo-1-(cyclopropylmethyl)-1H-indol-2-yl)methanol

Chemical formula

[0195] Intermediate 16 6-Bromo-1-(cyclopropylmethyl)-1H-indole-2-carbaldehyde

Chemical Structure

[0196] Intermediate 17 (E)-6-Bromo-1-(cyclopropylmethyl)-2-(2-nitroprop-1-en-1-yl)-1H-indole

Chemical Structure

[0197] Intermediate 18 Ethyl 2-(6-bromo-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridine-6-carboxylate [Chemical Structure] Intermediate 8 (75 mg, 0.447 mmol) and copper(I) iodide (6 mg, 0.03 mmol) were added to a stirred solution of Intermediate 17 (50 mg, 0.149 mmol) in DMF (1 mL). The reaction mixture was stirred at 80 °C for 30 h, concentrated to remove DMF, water (10 mL) was added, and the contents were extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give a crude product, which was purified by silica gel column (0 - 5% methanol in dichloromethane) to give ethyl 2-(6-bromo-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridine-6-carboxylate (20 mg, 30%). LC-MS (ES): m / z = 452.1 [M+H] + ; 11H NMR (400 MHz, DMSO-d6) δ ppm: 9.19 (s, 1H), 7.90 (s, 1H), 7.83 (d, J = 9.5 Hz, 1H), 7.62 - 7.58 (m, 2H), 7.24 - 7.20 (m, 1H), 6.91 (s, 1H), 4.50 (d, J = 7.0 Hz, 2H), 4.36 (q, J = 7.0 Hz, 2H), 2.42 (s, 3H), 1.36 (t, J = 7.0 Hz, 3H), 1.11 (m, 1H), 0.32 - 0.26 (m, 2H), 0.18 - 0.13 (m, 2H)

[0198] Intermediate 19 Ethyl 2-(6-bromo-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-6-carboxylate

Chem.

[0199] Intermediate 20 6-Chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridine

Chem.

[0200] Intermediate 21 6-Chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde

Chemical Structure

[0201] Intermediate 22 (E)-6-Chloro-1-(cyclopropylmethyl)-2-(2-nitroprop-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridine

Chem.

[0202] Intermediate 23 Ethyl 2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridine-6-carboxylate

Chem.

[0203] Intermediate 24 Methyl 2-(6-chloro-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-chloro-3-methylpyrazolo[1,5-a]pyridine-6-carboxylate

Chem.

[0204] Intermediate 25 Ethyl 7-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-2-carboxylate [Chemical formula] K2CO3 (15.46 g, 112 mmol) and PdCl2(dppf)·CH2Cl2 (3.05 g, 3.73 mmol) were added to a stirred solution of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (11.53 g, 37.3 mmol) and ethyl 7-bromo-1H-indole-2-carboxylate (10 g, 37.3 mmol) in dioxane (200 ml). The reaction mixture was purged with nitrogen for 2 minutes and then stirred at 100 °C for 3 hours, filtered through a Celite bed, and the Celite bed was thoroughly washed with ethyl acetate. The filtrates were combined and concentrated under reduced pressure to give the crude product, which was purified by silica gel column (0 - 30% ethyl acetate in petroleum ether) to give the title compound (11.3 g, 82%) as a gummy liquid. LC-MS m / z: 369.4[M-H] + ; 1 H NMR (300 MHz, DMSO-d6) δ ppm: 11.43 (s, 1H), 7.57 (d, J = 7.2 Hz, 1H), 7.21 (d, J = 4.0 Hz, 1H), 7.24 - 7.04 (m, 2H), 5.96 (brs, 1H), 4.34 (q, J = 7.1 Hz, 2H), 4.08 - 3.99 (m, 2H), 3.62 (t, J = 5.7 Hz, 2H), 1.51 - 1.45 (m, 2H), 1.46 (s, 9H), 1.34 (t, J = 7.2 Hz, 3H)

[0205] Intermediate 26 Ethyl 7-(1-(tert-butoxycarbonyl)piperidin-4-yl)-1H-indole-2-carboxylate [Chemical formula] Pd / C (7.18 g, 6.75 mmol, 50% wet) was added to a stirred solution of Intermediate 25 (5.0 g, 13.50 mmol) in methanol (100 mL) at 0 °C, purged with nitrogen, and the reaction mixture was stirred under a H2 atmosphere for 4 h. The reaction mixture was filtered through a Celite bed, and the filtrate was concentrated under reduced pressure to afford ethyl 7-(1-(tert-butoxycarbonyl)piperidin-4-yl)-1H-indole-2-carboxylate (4.95 g, 98%). LC-MS m / z: 371.4 [M-H] + ; 1 H NMR (300 MHz, DMSO-d6) δ ppm: 11.84 (s, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.21 - 7.01 (m, 3H), 4.36 (q, J = 7.1 Hz, 2H), 4.16 - 4.04 (m, 4H), 3.61 - 3.42 (m, 1H), 1.90 - 1.74 (m, 2H), 1.59 - 1.47 (m, 2H), 1.43 (s, 9H), 1.35 (t, J = 7.2 Hz, 3H)

[0206] Intermediate 27 Ethyl 7-(1-(tert-butoxycarbonyl)piperidin-4-yl)-1-(cyclopropylmethyl)-1H-indole-2-carboxylate

Chemical Structure

[0207] Intermediate 28 tert-Butyl 4-(1-(cyclopropylmethyl)-2-(hydroxymethyl)-1H-indol-7-yl)piperidine-1-carboxylate

Chemical Structure

[0208] Intermediate 29 tert-Butyl 4-(1-(cyclopropylmethyl)-2-formyl-1H-indol-7-yl)piperidine-1-carboxylate

Chemical Structure

[0209] Intermediate 30 tert-Butyl (E)-4-(1-(cyclopropylmethyl)-2-(2-nitroprop-1-en-1-yl)-1H-indol-7-yl)piperidine-1-carboxylate [Chemical formula] Ammonium acetate (0.937 g, 12.16 mmol) was added to a stirred solution of Intermediate 29 (3.1 g, 8.10 mmol) in nitroethane (20 ml, 280 mmol). The reaction mixture was heated to 80 °C, stirred for 2 hours, diluted with water, and extracted with ethyl acetate (2 x 50 ml). The combined organic layers were washed with water and brine solution, dried over anhydrous sodium sulfate, evaporated under reduced pressure to give tert-butyl (E)-4-(1-(cyclopropylmethyl)-2-(2-nitroprop-1-en-1-yl)-1H-indol-7-yl)piperidine-1-carboxylate (3.5 g, 98%). LC-MS m / z: 440.4 [M+H] + ; 11H NMR (300 MHz, chloroform-d) δ ppm: 8.23 (s, 1H), 7.53 (d, J = 6.80 Hz, 1H), 7.07 - 7.24 (m, 2H), 6.89 (s, 1H), 4.37 (brs, 1H), 4.33 (brd, J = 5.3 Hz, 2H), 3.46 - 3.59 (m, 1H), 2.78 - 2.98 (m, 2H), 2.59 (s, 3H), 2.00 - 1.90 (m, 2H), 1.86 - 1.77 (m, 1H), 1.53 - 1.63 (m, 9H), 1.22 - 1.32 (m, 1H), 1.07 - 1.21 (m, 1H), 0.83 (brd, J = 2.27 Hz, 1H), 0.53 - 0.62 (m, 2H), 0.31 (q, J = 5.16 Hz, 2H)

[0210] Intermediate 31 Ethyl 7-(1-(tert-butoxycarbonyl)-1,2,3,6-tetrahydropyridin-4-yl)-5-fluoro-1H-indole-2-carboxylate [Chemical Structure] tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (5.40 g, 17.48 mmol) and potassium carbonate (6.04 g, 43.7 mmol) were added to a stirred solution of ethyl 7-bromo-5-fluoro-1H-indole-2-carboxylate (5 g, 17.48 mmol) in 1,4-dioxane (45 ml) and water (5 ml). The reaction mixture was degassed with nitrogen for 2 minutes, and then PdCl2(dppf) (1.279 g, 1.748 mmol) was adde...

Claims

1. Formula (Ia): 【Chemical 1】 [wherein: [Chemical 2] is [Chemical Formula 3] selected from; 【Chemical 4】 is [Chemical Formula 5] selected from; X １ is independently selected from CR ２ and N; X ２ is independently selected from CR ４ , and N; X ３ is independently selected from O, and S; X ４ is independently selected from CR ２ , and N; provided that neither X １ nor X ４ is N; X ５ is independently selected from O and S; X ６ is independently selected from CR ４ , and N; provided that 1) neither X ２ nor X ６ is N; 2) when both X ２ and X ６ are CR ４ , one of R ４ is H; R １ is, independently, -NH-C １－５ alkyl (optionally substituted with one or more substituents selected from F, Cl, and NH ２ ), a 4- to 10-membered heterocyclyl (wherein the heterocyclyl contains at least one nitrogen atom and is bonded to the carbonyl group of formula (Ia) through the nitrogen atom, and the heterocyclyl is optionally substituted with one or more substituents selected from F, Cl, CN, C1-3 alkyl, =N-ORb, -(CH2)rORb, -(CH2)rNRaRa, -NRaC(=NH)C1-3 alkyl, -NRaC(=O)ORb, carbocyclic, and heterocyclyl), and -NH- a 4- to 10-membered heterocyclyl (wherein the heterocyclyl is optionally substituted with one or more substituents selected from F, Cl, CN, C １－３ alkyl, =N-OR ｂ , -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ NR ａ R ａ , -NR ａ C(=NH)C １－３ alkyl, -NR ａ C(=O)OR ｂ , carbocyclic, and heterocyclyl); R ２ is independently H, F, Cl, C １－４ alkyl (which may be substituted with one or more substituents selected from F, Cl, and OH), and -OC １－４ alkyl; R ３ is independently selected from H, F, Cl, CN, -C(=O)OR ｂ , and C １－３ alkyl optionally substituted with one or more substituents selected from F, Cl, OH, NH ２ , and N ３ ; optionally substituted with one or more substituents selected from R ４ is independently H, F, Cl, Br, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, Br, CN, ═O, C １－４ alkyl (which may be substituted with one or more R ｅ ), C ２－４ alkenyl (which may be substituted with one or more R ｅ ), C ２－４ alkynyl (which may be substituted with one or more R ｅ ), -(CR ｄ R ｄ ), ｒ OR ｂ , -(CR ｄ R ｄ ), ｒ S(O) ｐ R ｃ , -(CR ｄ R ｄ ), ｒ S(O) ｐ NR ａ R ａ , -(CR ｄ R ｄ ), ｒ NR ａ S(O) ｐ R ｃ , -(CR ｄ R ｄ ), ｒ NR ａ R ａ , -(CR ｄ R ｄ ), ｒ NR ａ C(═O)R ｂ , -(CR ｄ R ｄ ), ｒ NR ａ C(═O)OR ｂ , -(CR ｄ R ｄ ), ｒ NR ａ C(═O)NR ａ R ａ , -(CR ｄ R ｄ ), ｒ C(═O)R ｂ , -(CR ｄ R ｄ ), ｒ C(═O)OR ｂ , -(CR ｄ R ｄ ) ｒ C(=O)NR ａ R ａ 、-(CR ｄ R ｄ ) ｒ OC(=O)R ｂ 、-(CR ｄ R ｄ ) ｒ OC(=O)OR ｂ 、-(CR ｄ R ｄ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ 、C ３－６ cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ); R ６ is, independently, H, C １－６ alkyl (optionally substituted with one or more R ｅ ), -S(O) ｐ R ｃ , -S(O) ｐ NR ａ R ａ , -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ ), aryl (optionally substituted with one or more R ｅ ), and heterocyclyl (optionally substituted with one or more R ｅ ); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ cycloalkyl); R ａ independently is H, C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more R ｅ ); R ｂ independently represents H, C １－６ alkyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkenyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkynyl (which may be substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more Rs ｅ ); R ｃ is independently C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); R ｄ is independently selected from H, and C １－６ alkyl (which may be substituted with one or more R ｅ s); R ｅ is independently selected from F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), C ２－６ alkenyl, C ２－６ alkynyl, -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, OC １－５ alkyl, C １－５ alkyl (which may be substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] A compound represented by the formula, or a pharmaceutically acceptable salt thereof.

2. Formula (IIa)-(XIII): 【Chemical Formula 6】 The compound according to claim 1, represented by the formula, or a pharmaceutically acceptable salt thereof.

3. Formula (IIa): 【Chemical Formula 7】 [wherein: R １ is, independently, 【Chemical Formula 8】 selected from; R ２ is independently H, F, Cl, C １－３ alkyl (which may be substituted with one or more substituents selected from F, Cl, and OH), and OC １－３ is selected from alkyl; R ３ is independently selected from H, F, Cl, and C １－３ alkyl (which may be substituted with one or more substituents selected from F, Cl, and OH); R ４ is independently H, F, Cl, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, ═O, C １－４ alkyl (one or more R ｅ may be substituted), —(CH ２ ) ｒ OR ｂ , —(CH ２ ) ｒ S(O) ｐ R ｃ , —(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , —(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , —(CH ２ ) ｒ NR ａ R ａ , —(CH ２ ) ｒ NR ａ C(═O)R ｂ , —(CH ２ ) ｒ NR ａ C(═O)OR ｂ , —(CH ２ ) ｒ NR ａ C(═O)NR ａ R ａ , —(CH ２ ) ｒ C(═O)R ｂ , —(CH ２ ) ｒ C(═O)OR ｂ , —(CH ２ ) ｒ C(═O)NR ａ R ａ , —(CH ２ ) ｒ OC(═O)R ｂ , —(CH ２ ) ｒ OC(═O)OR ｂ , —(CH ２ ) ｒ O(CH ２ ) ｒ C(═O)NR ａ R ａ 、C ３－６ Cycloalkyl (which may be substituted with one or more Rs ｅ ), aryl (which may be substituted with one or more Rs ｅ ), and heterocyclyl (which may be substituted with one or more Rs ｅ ); R ６ is independently H, C １－６ alkyl (optionally substituted with one or more R ｅ groups), C(=O)R ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ groups), aryl (optionally substituted with one or more R ｅ groups), and heterocyclyl (optionally substituted with one or more R ｅ groups); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ ycloalkyl); R ａ is independently selected from H, and C １－６ alkyl (which may be substituted with one or more R ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (which may be substituted with one or more R ｅ ); R ｂ independently represents H, C １－６ alkyl (which may be substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more Rs ｅ ); R ｃ is independently C １－６ alkyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); R ｅ is independently selected from F, Cl, Br, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, OH, OC １－５ alkyl, C １－５ alkyl (optionally substituted with OH), C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 2, represented by the formula, or a pharmaceutically acceptable salt thereof.

4. Formula (IIIa): 【Chemical Formula 9】 [wherein: R １ is, independently, 【Chemical Formula 10】 selected from; R ２ is independently H, F, Cl, C １－３ alkyl (which may be substituted with one or more substituents selected from F, Cl, and OH), and OC １－３ alkyl; R ３ is independently selected from H, F, Cl, and C １－３ alkyl (which may be substituted with one or more substituents selected from F, Cl, and OH); R ４ is independently H, F, Cl, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, ═O, C １－４ alkyl (one or more R ｅ which may be substituted), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(═O)R ｂ , -(CH ２ ) ｒ NR ａ C(═O)OR ｂ , -(CH ２ ) ｒ NR ａ C(═O)NR ａ R ａ , -(CH ２ ) ｒ C(═O)R ｂ , -(CH ２ ) ｒ C(═O)OR ｂ , -(CH ２ ) ｒ C(═O)NR ａ R ａ , -(CH ２ ) ｒ OC(═O)R ｂ , -(CH ２ ) ｒ OC(═O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(═O)NR ａ R ａ , C ３－６ Cycloalkyl (which may be substituted with one or more Rs ｅ ), aryl (which may be substituted with one or more Rs ｅ ), and heterocyclyl (which may be substituted with one or more Rs ｅ ); and is selected from R ６ is independently H, C １－６ alkyl (optionally substituted with one or more R ｅ ), -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ ), aryl (optionally substituted with one or more R ｅ ), and heterocyclyl (optionally substituted with one or more R ｅ ); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ cycloalkyl); R ａ is independently selected from H, and C １－６ alkyl (which may be substituted with one or more Rs ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (which may be substituted with one or more Rs ｅ ); R ｂ independently represents H, C １－６ alkyl (which may be substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more Rs ｅ ); R ｃ is independently C １－６ alkyl (which may be substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more Rs ｅ ); R ｅ is independently selected from F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, OH, OC １－５ alkyl, C １－５ alkyl (optionally substituted with OH), C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 1, represented by the formula, or a pharmaceutically acceptable salt thereof.

5. R １ is, independently, 【Chemical 11】 selected from; R ２ is independently selected from H, F, Cl, CH ３ , and OCH ３ ; R ３ is independently selected from H, F, Cl, CH ３ , and CH ２ OH; R ４ is independently selected from H, F, Cl, C １－５ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ ycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ ycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, =O, C １－４ alkyl (one or more Rs ｅ may be substituted), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ２ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ２ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(=O)R ｂ , -(CH ２ ) ｒ NR ａ C(=O)OR ｂ , -(CH ２ ) ｒ NR ａ C(=O)NR ａ R ａ , -(CH ２ ) ｒ C(=O)R ｂ , -(CH ２ ) ｒ C(=O)OR ｂ , -(CH ２ ) ｒ C(=O)NR ａ R ａ , -(CH ２ ) ｒ OC(=O)R ｂ , -(CH ２ ) ｒ OC(=O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ , C ３－６ Cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ); and is selected from R ６ is independently selected from H and C １－６ alkyl (one or more R ｅ which may be substituted); R ７ is H; R ８ is C １－３ alkyl (substituted with one C ３－６ cycloalkyl); R ａ is independently selected from H, and C １－４ alkyl; R ｂ is independently selected from H, C １－４ alkyl; R ｃ is C １－４ alkyl; and r is each independently selected from 0, 1, and 2, The compound according to claim 3 or 4, or a pharmaceutically acceptable salt thereof.

6. R ４ is independently H, F, Cl, C １－５ alkyl (which may be substituted with one or more substituents selected from F, Cl, and OH), C ３－６ cycloalkyl, 【Chemical 12】 【Chemical Formula 13】 【Chemical 14】 selected from; R ５ is independently H, F, Cl, ═O, C １－４ alkyl (one or more R ｅ may be substituted), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(═O)R ｂ , -(CH ２ ) ｒ NR ａ C(═O)OR ｂ , -(CH ２ ) ｒ NR ａ C(═O)NR ａ R ａ , -(CH ２ ) ｒ C(═O)R ｂ , -(CH ２ ) ｒ C(═O)OR ｂ , -(CH ２ ) ｒ C(═O)NR ａ R ａ , -(CH ２ ) ｒ OC(═O)R ｂ , -(CH ２ ) ｒ OC(═O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(═O)NR ａ R ａ , C ３－６ Cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ); and R ６ is independently selected from H and C １－５ alkyl The compound according to claim 5, represented by the formula, or a pharmaceutically acceptable salt thereof.

7. R ４ is, independently, 【Chemical Formula 15】 【Chemical 16】 【Chemical 17】 selected from The compound according to claim 6, or a pharmaceutically acceptable salt thereof.

8. Formula (IVa): 【Chemical 18】 [wherein: R １ is, independently, 【Chemical Formula 19】 selected from; R ２ is independently H, F, Cl, C １－３ alkyl (which may be substituted with one or more substituents selected from F, Cl, and OH), and OC １－３ is selected from alkyl; R ３ is independently selected from H, F, Cl, and C １－３ alkyl (which may be substituted with one or more substituents selected from F, Cl, and OH); R ４ is independently H, F, Cl, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, ═O, C １－４ alkyl (one or more R ｅ which may be substituted), —(CH ２ ) ｒ OR ｂ , —(CH ２ ) ｒ S(O) ｐ R ｃ , —(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , —(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , —(CH ２ ) ｒ NR ａ R ａ , —(CH ２ ) ｒ NR ａ C(═O)R ｂ , —(CH ２ ) ｒ NR ａ C(═O)OR ｂ , —(CH ２ ) ｒ NR ａ C(═O)NR ａ R ａ , —(CH ２ ) ｒ C(═O)R ｂ , —(CH ２ ) ｒ C(═O)OR ｂ , —(CH ２ ) ｒ C(═O)NR ａ R ａ , —(CH ２ ) ｒ OC(═O)R ｂ , —(CH ２ ) ｒ OC(═O)OR ｂ , —(CH ２ ) ｒ O(CH ２ ) ｒ C(═O)NR ａ R ａ , C ３－６ Cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ); and is selected from R ６ is, independently, H, C １－６ alkyl (optionally substituted with one or more R ｅ groups), -S(O) ｐ R ｃ , -S(O) ｐ NR ａ R ａ , -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ groups), aryl (optionally substituted with one or more R ｅ groups), and heterocyclyl (optionally substituted with one or more R ｅ groups); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ cycloalkyl); R ａ independently is H, C １－６ alkyl (optionally substituted with one or more Rs ｅ ), —(CH ２ ) ｒ —C ３－１０ carbocyclic (optionally substituted with one or more Rs ｅ ), and —(CH ２ ) ｒ —heterocyclic (optionally substituted with one or more Rs ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more Rs ｅ ); R ｂ independently represents H, C １－６ alkyl (which may be substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more R ｅ ); R ｃ independently represents C １－６ alkyl (which may be substituted with one or more Rs ｅ ), -(CH ２ ). ｒ -C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and -(CH ２ ). ｒ -heterocyclic (which may be substituted with one or more Rs ｅ ); R ｅ is independently selected from F, Cl, Br, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, OH, OC １－５ alkyl, C １－５ alkyl (optionally substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 1, represented by the formula, or a pharmaceutically acceptable salt thereof.

9. R １ is, independently, 【Chemical 20】 selected from; R ２ is independently selected from H, F, Cl, and OCH ３ ; R ３ is independently selected from F, Cl, and CH ３ ; R ４ is, independently, H, 【Chemical 21】 selected from; R ５ is independently selected from H, =O, C １－４ alkyl, OH, and NH ２ selected from; R ６ is independently H, C １－５ alkyl (one or more Rs ｅ may be substituted), and -C(=O)R ｂ is selected from; R ７ is H; R ８ is C １－２ alkyl (which may be substituted with cyclopropyl); R ｂ is independently H, C １－６ alkyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); R ｅ is independently NH ２ and C １－５ alkyl (which may be substituted with one or more R ｆ s); and R ｆ is independently selected from F, Cl, OH, and OC １－５ alkyl The compound according to claim 8, or a pharmaceutically acceptable salt thereof.

10. R ４ is, independently, 【Chemical 22】 【Chemical 23】 selected from The compound according to claim 9, or a pharmaceutically acceptable salt thereof.

11. Formula (Va): 【Chemical 24】 [wherein: R １ is, independently, 【Chemical Formula 25】 selected from; R ２ is independently selected from H, F, Cl, CH ３ , and OCH ３ ; R ３ is independently selected from H, F, Cl, CN, CH ３ , and CH ２ OH; R ４ is independently H, F, Cl, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, ═O, C １－４ alkyl (one or more Rs ｅ may be substituted), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(═O)R ｂ , -(CH ２ ) ｒ NR ａ C(═O)OR ｂ , -(CH ２ ) ｒ NR ａ C(═O)NR ａ R ａ , -(CH ２ ) ｒ C(═O)R ｂ , -(CH ２ ) ｒ C(═O)OR ｂ , -(CH ２ ) ｒ C(═O)NR ａ R ａ , -(CH ２ ) ｒ OC(═O)R ｂ , -(CH ２ ) ｒ OC(═O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(═O)NR ａ R ａ , C ３－６ Cycloalkyl (which may be substituted with one or more Rs ｅ ), aryl (which may be substituted with one or more Rs ｅ ), and heterocyclyl (which may be substituted with one or more Rs ｅ ); and is selected from R ６ is independently selected from H, C １－６ alkyl (optionally substituted with one or more R ｅ groups), -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ groups), aryl (optionally substituted with one or more R ｅ groups), and heterocyclyl (optionally substituted with one or more R ｅ groups); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ ycloalkyl); R ａ independently is H, C １－６ alkyl (optionally substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more Rs ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more Rs ｅ ); R ｂ independently represents H, C １－６ alkyl (which may be substituted with one or more Rs ｅ ), —(CH ２ ) ｒ —C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and —(CH ２ ) ｒ —heterocyclic (which may be substituted with one or more Rs ｅ ); R ｃ independently is C １－６ alkyl (which may be substituted with one or more Rs ｅ ), —(CH ２ ) ｒ —C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and —(CH ２ ) ｒ —heterocyclic (which may be substituted with one or more Rs ｅ ); R ｅ is independently selected from F, Cl, Br, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more R ｆ ), -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more R ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more R ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more R ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, C １－５ alkyl (optionally substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 1, represented by the formula, or a pharmaceutically acceptable salt thereof.

12. R １ is, independently, 【Chemical 26】 selected from; R ２ is CH ３ and; R ３ is CH ３ and; R ４ is, independently, 【Chemical 27】 【Chemical 28】 selected from; R ７ is H; and R ８ is C １－２ alkyl (which may be substituted with cyclopropyl), The compound according to claim 11, or a pharmaceutically acceptable salt thereof.

13. Formula (VIa): 【Chemical 29】 [wherein: R １ independently, 【Chemical Formula 30】 selected from; R ３ is independently selected from H, F, and CH ３ ; R ４ is independently H, F, Cl, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, Br, CN, ═O, C １－４ alkyl (which may be substituted with one or more R ｅ s), C ２－４ alkenyl (which may be substituted with one or more R ｅ s), C ２－４ alkynyl (which may be substituted with one or more R ｅ s), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(═O)R ｂ , -(CH ２ ) ｒ NR ａ C(═O)OR ｂ , -(CH ２ ) ｒ NR ａ C(═O)NR ａ R ａ , -(CH ２ ) ｒ C(═O)R ｂ , -(CH ２ ) ｒ C(═O)OR ｂ , -(CH ２ ) ｒ C(═O)NR ａ R ａ , -(CH ２ ) ｒ OC(═O)R ｂ , -(CH ２ ) ｒ OC(═O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ , C ３－６ cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ); R ６ is independently H, C １－６ alkyl (optionally substituted with one or more R ｅ ), -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ ), aryl (optionally substituted with one or more R ｅ ), and heterocyclyl (optionally substituted with one or more R ｅ ); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ ycloalkyl); R ａ independently is H, C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more R ｅ ); R ｂ is independently selected from H, C １－６ alkyl (which may be substituted with one or more R ｅ groups), C ２－６ alkenyl (which may be substituted with one or more R ｅ groups), C ２－６ alkynyl (which may be substituted with one or more R ｅ groups), -(CH ２ ). ｒ -C ３－１０ carbocyclic (which may be substituted with one or more R ｅ groups), and -(CH ２ ). ｒ -heterocyclic (which may be substituted with one or more R ｅ groups); R ｃ is independently selected from C １－６ alkyl (which may be substituted with one or more R ｅ groups), C ２－６ alkenyl (which may be substituted with one or more R ｅ groups), C ２－６ alkynyl (which may be substituted with one or more R ｅ groups), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more R ｅ groups), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more R ｅ groups); R ｅ is independently F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), C ２－６ alkenyl, C ２－６ alkynyl, -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, C １－５ alkyl (which may be substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4] The compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by

14. R １ is, independently, 【Chemical 31】 selected from; R ３ is CH ３ and; R ４ is independently F, Cl, 【Chemical 32】 【Chemical 33】 selected from; R ７ is H; and R ８ is C １－２ alkyl (which may be substituted with cyclopropyl), The compound according to claim 13, or a pharmaceutically acceptable salt thereof.

15. Formula (VII): 【Chemical 34】 [Wherein: R １ is, independently, 【Chemical 35】 selected from; R ２ is independently selected from H, F, Cl, CH ３ , and OCH ３ ; R ３ is independently selected from H, F, and CH ３ ; R ４ is independently H, F, Cl, Br, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ ycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ ycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ s), -O-C １－６ alkyl (substituted with one or more R ５ s), -(CH ２ ) ｒ -C ３－１２ ycloalkyl (substituted with one or more R ５ s), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ s); R ５ independently represents H, F, Cl, Br, CN, =O, C １－４ alkyl (which may be substituted by one or more Rs ｅ ), C ２－４ alkenyl (which may be substituted by one or more Rs ｅ ), C ２－４ alkynyl (which may be substituted by one or more Rs ｅ ), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(=O)R ｂ , -(CH ２ ) ｒ NR ａ C(=O)OR ｂ , -(CH ２ ) ｒ NR ａ C(=O)NR ａ R ａ , -(CH ２ ) ｒ C(=O)R ｂ , -(CH ２ ) ｒ C(=O)OR ｂ , -(CH ２ ) ｒ C(=O)NR ａ R ａ , -(CH ２ ) ｒ OC(=O)R ｂ , -(CH ２ ) ｒ OC(=O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ , C ３－６ cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ); R ６ is independently H, C １－６ alkyl (optionally substituted with one or more R ｅ ), -S(O) ｐ R ｃ , -S(O) ｐ NR ａ R ａ , -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ ), aryl (optionally substituted with one or more R ｅ ), and heterocyclyl (optionally substituted with one or more R ｅ ); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ cycloalkyl); R ａ independently is H, C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more R ｅ ); R ｂ independently is H, C １－６ alkyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkenyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkynyl (which may be substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more Rs ｅ ); R ｃ is independently C １－６ alkyl (optionally substituted with one or more R ｅ groups), C ２－６ alkenyl (optionally substituted with one or more R ｅ groups), C ２－６ alkynyl (optionally substituted with one or more R ｅ groups), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ groups), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ groups); R ｅ is independently selected from F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), C ２－６ alkenyl, C ２－６ alkynyl, -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, C １－５ alkyl (optionally substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by

16. Formula (VIII): 【Chemical Formula 36】 [Wherein: R １ is, independently, 【Chemical 37】 selected from; R ２ is independently selected from H, F, and OCH ３ ; R ３ is independently selected from H, F, and CH ３ ; R ４ independently, is H, F, Cl, Br, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ ycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ ycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ s), -O-C １－６ alkyl (substituted with one or more R ５ s), -(CH ２ ) ｒ -C ３－１２ ycloalkyl (substituted with one or more R ５ s), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ s); R ５ is independently H, F, Cl, Br, CN, =O, C １－４ alkyl (which may be substituted by one or more R ｅ ), C ２－４ alkenyl (which may be substituted by one or more R ｅ ), C ２－４ alkynyl (which may be substituted by one or more R ｅ ), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(=O)R ｂ , -(CH ２ ) ｒ NR ａ C(=O)OR ｂ , -(CH ２ ) ｒ NR ａ C(=O)NR ａ R ａ , -(CH ２ ) ｒ C(=O)R ｂ , -(CH ２ ) ｒ C(=O)OR ｂ , -(CH ２ ) ｒ C(=O)NR ａ R ａ , -(CH ２ ) ｒ OC(=O)R ｂ , -(CH ２ ) ｒ OC(=O)OR ｂ ,-(CH ２ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ ,C ３－６ cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ); R ６ is independently H, C １－６ alkyl (optionally substituted with one or more R ｅ ), -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ ), aryl (optionally substituted with one or more R ｅ ), and heterocyclyl (optionally substituted with one or more R ｅ ); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ ycloalkyl); R ａ is independently H, C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more R ｅ ); R ｂ independently represents H, C １－６ alkyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkenyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkynyl (which may be substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more Rs ｅ ); R ｃ is independently selected from C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); R ｄ is independently selected from H, and C １－６ alkyl (one or more R ｅ which may be substituted); R ｅ is independently selected from F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), C ２－６ alkenyl, C ２－６ alkynyl, -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, C １－５ alkyl (which may be substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by

17. Formula (IX): 【Chemical Formula 38】 [Wherein: R １ is, independently, 【Chemical 39】 selected from; R ２ is independently selected from H, F, CH ３ , CH ２ OH, CH ２ CH ２ OH, and OCH ３ and is selected from; R ３ is independently selected from H, F, Cl, CH ３ , CH ２ OH, CH ２ CH ２ OH, CH ２ NH ３ , CH ２ CH ２ NH ２ , and CH ２ CH ２ N ３ ; and is selected from R ４ is independently H, F, Cl, Br, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, Br, CN, =O, C １－４ alkyl (which may be substituted by one or more R ｅ ), C ２－４ alkenyl (which may be substituted by one or more R ｅ ), C ２－４ alkynyl (which may be substituted by one or more R ｅ ), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(=O)R ｂ , -(CH ２ ) ｒ NR ａ C(=O)OR ｂ , -(CH ２ ) ｒ NR ａ C(=O)NR ａ R ａ , -(CH ２ ) ｒ C(=O)R ｂ , -(CH ２ ) ｒ C(=O)OR ｂ , -(CH ２ ) ｒ C(=O)NR ａ R ａ , -(CH ２ ) ｒ OC(=O)R ｂ , -(CH ２ ) ｒ OC(=O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ , C ３－６ cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ); R ６ is independently H, C １－６ alkyl (optionally substituted with one or more R ｅ ), -S(O) ｐ R ｃ , -S(O) ｐ NR ａ R ａ , -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ ), aryl (optionally substituted with one or more R ｅ ), and heterocyclyl (optionally substituted with one or more R ｅ ); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ cycloalkyl); R ａ independently is H, C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more R ｅ ); R ｂ independently is H, C １－６ alkyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkenyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkynyl (which may be substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more Rs ｅ ); R ｃ is, independently, C １－６ alkyl (optionally substituted with one or more R ｅ groups), C ２－６ alkenyl (optionally substituted with one or more R ｅ groups), C ２－６ alkynyl (optionally substituted with one or more R ｅ groups), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ groups), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ groups); R ｅ is independently F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), C ２－６ alkenyl, C ２－６ alkynyl, -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, C １－５ alkyl (optionally substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by

18. Formula (X): 【Chemical Formula 40】 [Wherein: R １ is, independently, 【Chemical 41】 selected from; R ２ is independently selected from H, F, CH ３ , CH ２ OH, CH ２ CH ２ OH, and OCH ３ and is selected from; R ３ is independently selected from H, F, CH ３ , CH ２ OH, CH ２ CH ２ OH, CH ２ NH ３ , CH ２ CH ２ NH ２ , and CH ２ CH ２ N ３ ; and is selected from R ４ is, independently, H, F, Cl, Br, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, Br, CN, =O, C １－４ alkyl (which may be substituted with one or more R ｅ ), C ２－４ alkenyl (which may be substituted with one or more R ｅ ), C ２－４ alkynyl (which may be substituted with one or more R ｅ ), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(=O)R ｂ , -(CH ２ ) ｒ NR ａ C(=O)OR ｂ , -(CH ２ ) ｒ NR ａ C(=O)NR ａ R ａ , -(CH ２ ) ｒ C(=O)R ｂ , -(CH ２ ) ｒ C(=O)OR ｂ , -(CH ２ ) ｒ C(=O)NR ａ R ａ , -(CH ２ ) ｒ OC(=O)R ｂ , -(CH ２ ) ｒ OC(=O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ , C ３－６ Cycloalkyl (which may be substituted by one or more R ｅ ), aryl (which may be substituted by one or more R ｅ ), and heterocyclyl (which may be substituted by one or more R ｅ ); R ６ independently, is H, C １－６ alkyl (optionally substituted with one or more R ｅ ), -S(O) ｐ R ｃ , -S(O) ｐ NR ａ R ａ , -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ ), aryl (optionally substituted with one or more R ｅ ), and heterocyclyl (optionally substituted with one or more R ｅ ); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ ycloalkyl); R ａ is independently selected from H, C １－６ alkyl (optionally substituted with one or more R ｅ groups), C ２－６ alkenyl (optionally substituted with one or more R ｅ groups), C ２－６ alkynyl (optionally substituted with one or more R ｅ groups), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ groups), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ groups); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more R ｅ groups); R ｂ is independently selected from H, C １－６ alkyl (which may be substituted with one or more R ｅ groups), C ２－６ alkenyl (which may be substituted with one or more R ｅ groups), C ２－６ alkynyl (which may be substituted with one or more R ｅ groups), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more R ｅ groups), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more R ｅ groups); R ｃ is, independently, C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); R ｅ is independently selected from F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more R ｆ ), C ２－６ alkenyl, C ２－６ alkynyl, -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more R ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more R ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more R ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, C １－５ alkyl (which may be substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by

19. Formula (XI): 【Chemical 42】 [Wherein: R １ is, independently, 【Chemical 43】 selected from; R ２ is independently selected from H, F, CH ３ , CH ２ OH, CH ２ CH ２ OH, and OCH ３ is selected from; R ３ is independently selected from H, F, CH ３ , CH ２ OH, CH ２ CH ２ OH, CH ２ NH ３ , CH ２ CH ２ NH ２ , and CH ２ CH ２ N ３ ; and is selected from R ４ is independently H, F, Cl, Br, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ independently represents H, F, Cl, Br, CN, ═O, C １－４ alkyl (which may be substituted by one or more Rs ｅ ), C ２－４ alkenyl (which may be substituted by one or more Rs ｅ ), C ２－４ alkynyl (which may be substituted by one or more Rs ｅ ), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(═O)R ｂ , -(CH ２ ) ｒ NR ａ C(═O)OR ｂ , -(CH ２ ) ｒ NR ａ C(═O)NR ａ R ａ , -(CH ２ ) ｒ C(═O)R ｂ , -(CH ２ ) ｒ C(═O)OR ｂ , -(CH ２ ) ｒ C(═O)NR ａ R ａ , -(CH ２ ) ｒ OC(═O)R ｂ , -(CH ２ ) ｒ OC(═O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ , C ３－６ cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ) is selected from; R ６ independently is H, C １－６ alkyl (optionally substituted with one or more R ｅ ), -S(O) ｐ R ｃ , -S(O) ｐ NR ａ R ａ , -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ ), aryl (optionally substituted with one or more R ｅ ), and heterocyclyl (optionally substituted with one or more R ｅ ); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ cycloalkyl); R ａ independently is H, C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (optionally substituted with one or more R ｅ ); R ｂ independently represents H, C １－６ alkyl (which may be substituted with one or more R ｅ groups), C ２－６ alkenyl (which may be substituted with one or more R ｅ groups), C ２－６ alkynyl (which may be substituted with one or more R ｅ groups), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more R ｅ groups), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more R ｅ groups); R ｃ is independently C １－６ alkyl (which may be substituted with one or more R ｅ s), C ２－６ alkenyl (which may be substituted with one or more R ｅ s), C ２－６ alkynyl (which may be substituted with one or more R ｅ s), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more R ｅ s), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more R ｅ s); R ｄ is independently selected from H, and C １－６ alkyl (one or more R ｅ may be substituted); R ｅ is independently F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), C ２－６ alkenyl, C ２－６ alkynyl, -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, C １－５ alkyl (which may be substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by

20. Formula (XII): 【Chemical 44】 [Wherein: R １ is, independently, 【Chemical 45】 selected from; R ２ is, independently, H, F, CH ３ , CH ２ OH, CH ２ CH ２ OH and OCH ３ selected from; R ３ is independently selected from H, F, and CH ３ , CH ２ OH, CH ２ CH ２ OH, CH ２ NH ３ , CH ２ CH ２ NH ２ , and CH ２ CH ２ N ３ ; and is selected from R ４ is independently H, F, Cl, Br, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ cycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ ), -O-C １－６ alkyl (substituted with one or more R ５ ), -(CH ２ ) ｒ -C ３－１２ cycloalkyl (substituted with one or more R ５ ), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ ); R ５ is independently H, F, Cl, Br, CN, =O, C １－４ alkyl (which may be substituted with one or more R ｅ ), C ２－４ alkenyl (which may be substituted with one or more R ｅ ), C ２－４ alkynyl (which may be substituted with one or more R ｅ ), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(=O)R ｂ , -(CH ２ ) ｒ NR ａ C(=O)OR ｂ , -(CH ２ ) ｒ NR ａ C(=O)NR ａ R ａ , -(CH ２ ) ｒ C(=O)R ｂ , -(CH ２ ) ｒ C(=O)OR ｂ , -(CH ２ ) ｒ C(=O)NR ａ R ａ , -(CH ２ ) ｒ OC(=O)R ｂ , -(CH ２ ) ｒ OC(=O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ , C ３－６ cycloalkyl (which may be substituted by one or more R ｅ ), aryl (which may be substituted by one or more R ｅ ), and heterocyclyl (which may be substituted by one or more R ｅ ); R ６ is independently H, C １－６ alkyl (optionally substituted with one or more R ｅ groups), -S(O) ｐ R ｃ , -S(O) ｐ NR ａ R ａ , -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (optionally substituted with one or more R ｅ groups), aryl (optionally substituted with one or more R ｅ groups), and heterocyclyl (optionally substituted with one or more R ｅ groups); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ cycloalkyl); R ａ independently is H, C １－６ alkyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkenyl (which may be substituted with one or more Rs ｅ ), C ２－６ alkynyl (which may be substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more Rs ｅ ); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (which may be substituted with one or more Rs ｅ ); R ｂ is independently selected from H, C １－６ alkyl (which may be substituted with one or more R ｅ groups), C ２－６ alkenyl (which may be substituted with one or more R ｅ groups), C ２－６ alkynyl (which may be substituted with one or more R ｅ groups), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more R ｅ groups), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more R ｅ groups); R ｃ is independently selected from C １－６ alkyl (which may be substituted with one or more R ｅ groups), C ２－６ alkenyl (which may be substituted with one or more R ｅ groups), C ２－６ alkynyl (which may be substituted with one or more R ｅ groups), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more R ｅ groups), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more R ｅ groups); R ｄ is independently selected from H, and C １－６ alkyl (one or more R ｅ may be substituted); R ｅ is independently selected from F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more R ｆ ), C ２－６ alkenyl, C ２－６ alkynyl, -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more R ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more R ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more R ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, C １－５ alkyl (which may be substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4]] The compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by

21. R ４ is, independently, H, F, Cl, Br, 【Chemical 46】 【Chemical 47】 【Chemical 48】 selected from, the compound according to any one of claims 16 to 19, or a pharmaceutically acceptable salt thereof.

22. Formula (XIII): 【Chemical 49】 [Wherein: R １ is, independently, 【Chemical Formula 50】 selected from; R ２ is independently selected from H, F, CH ３ , and OCH ３ ; R ３ is independently selected from H, F, and CH ３ ; R ４ is, independently, H, F, Cl, Br, -C(=O)R ｂ , C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ ycloalkyl), -NH-C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, OH, and C ３－６ ycloalkyl), -(CH ２ ) ｒ -aryl (substituted with one or more R ５ s), -O-C １－６ alkyl (substituted with one or more R ５ s), -(CH ２ ) ｒ -C ３－１２ ycloalkyl (substituted with one or more R ５ s), and -(CH ２ ) ｒ -4- to 10-membered heterocyclyl (containing a carbon atom and 1 to 5 heteroatoms selected from N, NR ６ , O, and S, and substituted with one or more R ５ s); R ５ is independently H, F, Cl, Br, CN, =O, C １－４ alkyl (which may be substituted with one or more R ｅ ), C ２－４ alkenyl (which may be substituted with one or more R ｅ ), C ２－４ alkynyl (which may be substituted with one or more R ｅ ), -(CH ２ ) ｒ OR ｂ , -(CH ２ ) ｒ S(O) ｐ R ｃ , -(CH ２ ) ｒ S(O) ｐ NR ａ R ａ , -(CH ２ ) ｒ NR ａ S(O) ｐ R ｃ , -(CH ２ ) ｒ NR ａ R ａ , -(CH ２ ) ｒ NR ａ C(=O)R ｂ , -(CH ２ ) ｒ NR ａ C(=O)OR ｂ , -(CH ２ ) ｒ NR ａ C(=O)NR ａ R ａ , -(CH ２ ) ｒ C(=O)R ｂ , -(CH ２ ) ｒ C(=O)OR ｂ , -(CH ２ ) ｒ C(=O)NR ａ R ａ , -(CH ２ ) ｒ OC(=O)R ｂ , -(CH ２ ) ｒ OC(=O)OR ｂ , -(CH ２ ) ｒ O(CH ２ ) ｒ C(=O)NR ａ R ａ , C ３－６ cycloalkyl (which may be substituted with one or more R ｅ ), aryl (which may be substituted with one or more R ｅ ), and heterocyclyl (which may be substituted with one or more R ｅ ); R ６ is, independently, H, C １－６ alkyl (which may be substituted with one or more Rs ｅ ), -S(O) ｐ R ｃ , -S(O) ｐ NR ａ R ａ , -C(=O)R ｂ , -C(=O)OR ｂ , -C(=O)NR ａ R ａ , C ３－６ cycloalkyl (which may be substituted with one or more Rs ｅ ), aryl (which may be substituted with one or more Rs ｅ ), and heterocyclyl (which may be substituted with one or more Rs ｅ ); R ７ is independently selected from H, F, and Cl; R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with one or more substituents selected from F, Cl, and C ３－６ ycloalkyl); R ａ is independently selected from H, C １－６ alkyl (which may be substituted with one or more R ｅ groups), C ２－６ alkenyl (which may be substituted with one or more R ｅ groups), C ２－６ alkynyl (which may be substituted with one or more R ｅ groups), -(CH ２ ) ｒ -C ３－１０ carbocyclic (which may be substituted with one or more R ｅ groups), and -(CH ２ ) ｒ -heterocyclic (which may be substituted with one or more R ｅ groups); or R ａ and R ａ together with the nitrogen atom to which both are attached form a heterocyclic ring (which may be substituted with one or more R ｅ groups); R ｂ independently represents H, C １－６ alkyl (optionally substituted with one or more Rs ｅ ), C ２－６ alkenyl (optionally substituted with one or more Rs ｅ ), C ２－６ alkynyl (optionally substituted with one or more Rs ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more Rs ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more Rs ｅ ); R ｃ is independently C １－６ alkyl (optionally substituted with one or more R ｅ ), C ２－６ alkenyl (optionally substituted with one or more R ｅ ), C ２－６ alkynyl (optionally substituted with one or more R ｅ ), -(CH ２ ) ｒ -C ３－１０ carbocyclic (optionally substituted with one or more R ｅ ), and -(CH ２ ) ｒ -heterocyclic (optionally substituted with one or more R ｅ ); R ｄ is independently selected from H, and C １－６ alkyl (one or more R ｅ may be substituted); R ｅ is independently selected from F, Cl, Br, CN, NH ２ , -NH-C １－４ alkyl, -N(C １－４ alkyl) ２ , =O, OH, -OC １－６ alkyl, -CO ２ H, C １－６ alkyl (which may be substituted with one or more Rs ｆ ), C ２－６ alkenyl, C ２－６ alkynyl, -(CH ２ ) ｒ -C ３－６ cycloalkyl (which may be substituted with one or more Rs ｆ ), -(CH ２ ) ｒ -aryl (which may be substituted with one or more Rs ｆ ), and -(CH ２ ) ｒ -heterocyclyl (which may be substituted with one or more Rs ｆ ); R ｆ is independently selected from F, Cl, Br, CN, OH, C １－５ alkyl (optionally substituted with OH), C ２－５ alkenyl, C ２－５ alkynyl, C ３－６ cycloalkyl, and phenyl; p is each independently selected from 0, 1, and 2; and r is each independently selected from 0, 1, 2, 3, and 4] The compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by.

23. Formula (XIV): 【Chemical Formula 51】 [Wherein: X ２ is independently selected from CR ４ and N; X ３ is independently selected from O and S; R １ is, independently, 【Chemical 52】 selected from; R ２ is independently selected from CH ２ OH, CH ２ CH ２ OH and OCH ３ and is selected from; R ３ is independently CH ２ OH, CH ２ CH ２ OH, CH ２ NH ２ , CH ２ CH ２ NH ２ , and CH ２ CH ２ N ３ selected from; R ４ is independently selected from H and -O-C １－４ alkyl (substituted with one or more R ５ ); provided that both R ４ are not both -O-C １－４ alkyl (substituted with one or more R ５ ); R ５ is independently selected from OH and heterocyclyl (which may be substituted with one or more R ｅ s); R ８ is independently selected from H, and C １－６ alkyl (optionally substituted with C ３－６ cycloalkyl); and R ｅ is independently selected from NH ２ and C １－３ alkyl The compound according to claim 1, or a pharmaceutically acceptable salt thereof, represented by.

24. Formula (XV): 【Chemical Formula 53】 [Wherein: R ４ is independently H, OCH ３ OCH ２ CH ２ OH, 【Chemical 54】 selected from; R ８ is C １－３ alkyl (C ３－６ substituted with cycloalkyl); and R ｅ is independently selected from NH ２ and C １－２ alkyl] The compound according to claim 23, or a pharmaceutically acceptable salt thereof, represented by.

25. 5-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]-heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; 5-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; 3((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; 5-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one; 6-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; 6-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-fluoro-4-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-fluoro-3-hydroxyphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; 4-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-fluorobenzamide; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-cyclopropyl-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; 6-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one; 5-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one; ((7R)-7-amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(1-hydroxyethyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-(4-aminopiperidin-1-yl)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzo[b]thiophen-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-(4-aminopiperidin-1-yl)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-3-methylbenzofuran-6-yl)methanone cyclopropylmethyl)-1H-indol-6-yl)isoindolin-1-one; 5-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)isoindolin-1-one; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-methyl-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone; 4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylbenzofuran-2-yl)-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-fluorobenzamide; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-methoxypyridin-4-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(4-methoxypiperidin-1-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(6-(4-aminopiperidin-1-yl)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-4-methoxy-3-methylbenzofuran-6-yl)methanone; ((7R)-7-Amino-2-azabicyclo[2.2.1]heptan-2-yl)(2-(1-(cyclopropylmethyl)-6-(2-hydroxypropan-2-yl)-1H-indol-2-yl)-3-methylbenzofuran-6-yl)methanone; N-[5-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)pyridin-2-yl]acetamide; (3R,5R)-1-{2-[1-(cyclopropylmethyl)-6-(4-methanesulfonylpiperidin-1-yl)-1H-indol-2-yl]-4-methoxy-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-5-fluoropiperidin-3-amine; 3-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-2-methylphenol; 5-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-N-methylpyridine-2-carboxamide; 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)morpholin-3-one; (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(4-methanesulfonylpiperidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine; (7R)-2-{2-[1-(Cyclopropylmethyl)-6-{3-methyl-[1,2,4]triazolo[4,3-a]pyridin-7-yl}-1H-indol-2-yl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine; (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine; (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine; (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine; (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-indazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine; (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(7-fluoro-1H-indazol-6-yl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine; Methyl N-[5-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)pyridin-2-yl]carbamate; 4-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)morpholin-3-one; 1-[4-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]pyrrolidin-2-one; (7R)-2-{2-[1-(cyclopropylmethyl)-6-(1H-indazol-6-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptane-7-amine; (7R)-2-{2-[1-(cyclopropylmethyl)-6-(1H-indazol-5-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridine-6-carbonyl}-2-azabicyclo[2.2.1]heptane-7-amine; N-[7-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-4-chloro-1-methyl-1H-indazol-3-yl]methanesulfonamide; 1-[2-(2-{6-[(7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)phenyl]imidazolidin-2-one; 4-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)-2-chlorobenzamide; (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(1H-pyrazol-4-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine; (7R)-2-{2-[1-(Cyclopropylmethyl)-6-(morpholin-4-yl)-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}-2-azabicyclo[2.2.1]heptan-7-amine; (3R,5R)-1-{2-[1-(Cyclopropylmethyl)-6-[4-(pyrrolidine-1-carbonyl)piperidin-1-yl]-1H-indol-2-yl]-3-methylpyrazolo[1,5-a]pyridin-6-carbonyl}-5-fluoropiperidin-3-amine; 3-[1-(2-{6-[(3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-indol-6-yl)piperidin-4-yl]-1,3-oxazolidin-2-one; 2-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-1,1-difluoropropan-2-ol; 2-(2-{6-[(7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl]-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl}-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridin-6-yl)-1,1,1-trifluoropropan-2-ol; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; (R)-1-(4-(2-(6-(3-aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one; (S)-1-(4-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; 1-(4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one; (R)-1-(4-(2-(6-(3-Aminopiperidin-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one; (R)-1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one; (R)-1-(4-(2-(6-((R)-3-Aminopiperidin-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one; 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one; 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one; 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxyethan-1-one; (R)-1-(4-(2-(6-(3-Aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxyethan-1-one; 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-ethoxyethan-1-one; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1R,3S)-3-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-Amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; 1-(4-(2-(6-((3R,5R)-3-Amino-5-fluoropiperidin-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one; 1-(4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-methoxyethan-1-one; (R)-(3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(3-hydroxy-3-(trifluoromethyl)cyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((R)-3-Aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-(tetrahydrofuran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; (4-(2-(6-((7R)-7-Amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)(3-hydroxycyclobutyl)methanone; Methyl 4-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidine-1-carboxylate; (2R)-1-(4-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)-2-hydroxypropan-1-one; (4-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)(thiophen-2-yl)methanone; 1-(4-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one; 1-(4-(2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)piperidin-1-yl)ethan-1-one; 1-(4-(2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-3-methylbutan-1-one; ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(3-hydroxycyclobutane-1-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; (R)-1-(4-(2-(6-((R)-3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-5-fluoro-1H-indol-7-yl)piperidin-1-yl)-2-methoxypropan-1-one; ((R)-3-aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-5-fluoro-7-(1-(tetrahydro-2H-pyran-2-carbonyl)piperidin-4-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1s,4s)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((3R,5R)-3-amino-5-fluoropiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((R)-3-aminopiperidin-1-yl)(2-(1-(cyclopropylmethyl)-7-(1-((1r,4r)-4-hydroxycyclohexane-1-carbonyl)azetidin-3-yl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)methanone; ((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)azetidin-1-yl)ethan-1-one; 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one; (R)-(2-(7-(2-(1H-1,2,4-triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone; (2-(7-(2-(1H-1,2,4-triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone; (2-(7-(2-(4-amino-1H-pyrazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone; (2-(6-((R)-3-aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one; (2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one; (2-(6-((R)-3-aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one; 4-(((2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one; (S)-5-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one; 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-4-fluoro-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one; (2-(7-(2-(1H-imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone; (2-(7-(2-(1H-1,2,4-triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-indol-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone; (S)-5-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one; 4-(((2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-indol-7-yl)oxy)methyl)pyrrolidin-2-one; 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one; (2-(7-(2-(1H-1,2,4-triazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone; (2-(7-(2-(1H-imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone; (R)-(2-(7-(2-(1H-imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone; (R)-(2-(7-(2-(4H-1,2,4-triazol-4-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone; (2-(7-(2-(4H-1,2,4-triazol-4-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone; 4-(((2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one; 4-(((2-(6-((3R,5R)-3-amino-5-fluoropiperidine-1-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one; (5R)-5-((((2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one; 4-((((2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one; (5R)-5-((((2-(6-((7S)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one; 4-((((2-(6-((7R)-7-amino-2-azabicyclo[2.2.1]heptane-2-carbonyl)-4-methoxy-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one; (R)-(2-(7-(2-(4H-1,2,4-triazol-4-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone; (2-(7-(2-(1H-imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)((3R,5R)-3-amino-5-fluoropiperidin-1-yl)methanone; (R)-(2-(7-(2-(1H-imidazol-1-yl)ethoxy)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-2-yl)-3-methylpyrazolo[1,5-a]pyridin-6-yl)(3-aminopiperidin-1-yl)methanone; 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one; 4-(((2-(6-((R)-3-aminopiperidine-1-carbonyl)-3-methylpyrazolo[1,5-a]pyridin-2-yl)-1-(cyclopropylmethyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)oxy)methyl)pyrrolidin-2-one The compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the above.

26. A pharmaceutical composition comprising the compound according to any one of claims 1 to 25, or a stereoisomer, enantiomer, diastereomer, tautomer thereof, or a pharmaceutically acceptable salt, and one or more pharmaceutically acceptable carriers.

27. A pharmaceutical composition for treating a disease or disorder associated with the enzymatic activity of PAD4, comprising at least one compound according to any one of claims 1 to 25, or a stereoisomer, enantiomer, diastereomer, tautomer thereof, or a pharmaceutically acceptable salt.

28. A pharmaceutical composition for treating a disease or disorder associated with the enzymatic activity of PAD4, comprising the compound according to any one of claims 1 to 25, or a stereoisomer, enantiomer, diastereomer, tautomer thereof, or a pharmaceutically acceptable salt.

29. Use of the compound according to any one of claims 1 to 25, or a stereoisomer, enantiomer, diastereomer, tautomer thereof, or a pharmaceutically acceptable salt, in the manufacture of a medicament for treating a disease or disorder associated with the enzymatic activity of PAD4.

30. A pharmaceutical composition for use in therapy, comprising the compound according to any one of claims 1 to 25, or a stereoisomer, enantiomer, diastereomer, tautomer thereof, or a pharmaceutically acceptable salt.

31. The pharmaceutical composition according to claim 27 or 28, wherein the disease or disorder associated with the enzymatic activity of PAD4 is selected from rheumatoid arthritis, Alzheimer's disease, multiple sclerosis, lupus erythematosus, Parkinson's disease, and cancer.

32. The use according to claim 29, wherein the disease or disorder associated with the enzymatic activity of PAD4 is selected from rheumatoid arthritis, Alzheimer's disease, multiple sclerosis, systemic lupus erythematosus, Parkinson's disease, and cancer.

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