FGFR inhibitors

Abstract

The present disclosure provides compounds of the formula: pharmaceutical compositions comprising these compounds, and methods of using these compounds to treat disease.

Description

120039.000209 (TYRA045PCT)FGFR INHIBITORSCROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of United States Provisional Application No. 63 / 739,224, filed December 27, 2024, the entirety of which is incorporated by reference herein.TECHNICAL FIELD

[0002] The disclosure pertains to compounds that are useful in treating cancer, pharmaceutical compositions that include one or more such compounds, and methods of using such compounds in treating cancer.BACKGROUND

[0003] Kinase inhibitors have been used to block the activity of kinases and thereby treat cancer (e.g., by inhibiting mitotic processes). These kinase inhibitors are often small molecules that target kinases to block the development, growth or spread of cancer.

[0004] Although various inhibitors of kinases are known, there remains a need for selective inhibitors to be used for the treatment of diseases such as hyper-proliferative diseases, which offer one or more advantages over current compounds. Those advantages include: improved activity and / or efficacy; beneficial kinase selectivity profile according to the respective therapeutic need; improved side effect profile, such as fewer undesired side effects, lower intensity of side effects, or reduced (cyto)toxicity; improved targeting of mutant receptors in diseased cells; improved physicochemical properties, such as solubility / stability in water, body fluids, and / or pharmaceutical formulations; improved pharmacokinetic properties, allowing e.g. for dose reduction or an easier dosing scheme; easier drug substance manufacturing e.g. by shorter synthetic routes or easier purification.SUMMARY

[0005] The disclosure provides compounds of Formula I:120039.000209 (TYRA045PCT)or pharmaceutically acceptable salts thereof,whereinR is (CR4R4)n-(CR4=R4)o-(CR4R4)p-SO2-Ci-C3alkyl, -(CR4R4)n-(CR4=R4)0-, wherein n is 0, 1, or 2; o is 0, 1, or 2; p is 0 or 1; X6is O or NH, and wherein = is a double bond or a single bond;A is a 5-6-membered heteroaryl, substituted with R1and / or R1A;or Z and A together form a fused bicyclic ring system that is a pyrazolopyrazine, an imidazopyrazine, or a pyrazolodiazepine, each substituted with R1and / or R1A;R1is hydrogen or C1-C3 alkyl;R1Ais hydrogen, halo, CN, or C1-C3 alkyl optionally substituted with one or more substituents independently selected from halo, OH, and OCH3;Xi and X2 are independently selected from N and C,wherein when one of Xi or X2is N the other is C;X3is N or CH;Y is NH, O, S or a bond;Ring B comprises X4, X5, Yi, Y2, Y3, and Y4, wherein:X4isN or CR9;X5is N or CH;Yi is absent, CR9, CHR7, CH2CHR7, CHR7CH2, CF2, CH2CF2, or CF2CH2;Y2is absent, CR9, CHR3, CH2CHR3, CHR3CH2, CF2, CH2CF2, or CF2CH2;- 2 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)Y3is O, CR4R5, CH2CR4R5, or CF2;YHs absent, CR3R4, or CF2;or Ring B may be absent if Z and A together form a fused bicyclic ring system;Z is absent, NR9A, CHR9A, CR4R4A, CR4R4ACH2, CH2CR4R4A, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo(l.l.l)pentane, bicyclo(2.1.1)hexane, azetidine, pyrrolidine or piperidine;wherein R9Atogether with R9form -CR4R4A- or -(CR4R4A)2-; or, Z and A together form a fused bicyclic ring system that is a pyrazolopyrazine, an imidazopyrazine, or a pyrazolodiazepine, each substituted with R1and / or R1A;Zi is absent , CR4R4A, CR4R4ACH2, CH2CR4R4A, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo(l.l.l)pentane, bicyclo(2.1.1)hexane, azetidine, pyrrolidine or piperidine,or Zi is -CR4R4A- or -(CR4R4A)2when Z is NR9Aor CHR9A;Z2is absent, C(O), SO2or -NR4C(O);Z3 is absent, C(O), SO2or -NR4C(O);R2is C1-C5 alkyl or R8, wherein C1-C5 alkyl is optionally substituted with one or more substituents independently selected from halo, OH, OAc, OR13, CN, oxo, -OC1-C4 alkyl, -OC3-C5 cycloalkyl, -Z2-Rn, and R10, wherein C1-C4 alky and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN;R13is a hydroxy prodrug moiety selected from ethers, esters including a- amino acid esters, phosphate esters, and sulfamate esters;R3is hydrogen, F, OH, OCH3, C1-C3 alkyl, cyclopropyl, or one R3is fused with R5or R7to form CH2, CH2-CH2, or CH2OCH2;each R4is independently hydrogen, F, Cl, CH3, or C1-C3 alkyl;R4Ais hydrogen, halo, OH, or C1-C3 alkyl;R5is hydrogen, F, OH, OCH3, CH2OCi-C3alkyl, C1-C3 alkyl, cyclopropyl, or is fused with one R3to form CH2, CH2-CH2, or CH2OCH2;- 3 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)R6is hydrogen, halo, C1-C5 alkyl, CN, 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl, wherein 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, and 5-6 membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, methyl, halomethyl, OH or OCH3 and wherein C1-C5 alkyl is optionally substituted with one or more substituents independently selected from halo, OH and OCH3;R7is hydrogen, F, OH, OCH3, C1-C3 alkyl or is fused with one R3to form CH2, CH2-CH2or CH2OCH2;R8is 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl, optionally fused to or substituted with R8A;R8Ais halo, CN, C1-C3 alkyl, C1-C3 haloalkyl, 3-6 membered cycloalkyl, 4- 6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl;R9is hydrogen, C1-C3 alkyl, or together with R9Aare CH2or CH2-CH2; each R10is independently 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl or 5-6 membered heteroaryl, each of which is optionally fused to or substituted with R8A;R11is C1-C4 alkyl, NH2, NHC1-C3 alkyl, NHC3-C5 cycloalkyl or N(Ci- C3 alkyl)2, wherein C1-C4 alkyl, C1-C3 alkyl and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN;R12is C1-C4 alkyl, C3-C5 cycloalkyl, NH2, NHC1-C3 alkyl, NHC3- C5 cycloalkyl or N(Ci-Cs alkyl)2, wherein C1-C4 alky, C1-C3 alkyl and C3- C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN; andR8, R10and R8Aare optionally substituted with one or more substituents independently selected from halo, OH, CN, -OC1-C4 alkyl, -OC3-C5 cycloalkyl and -Z3-R12wherein C1-C4 alkyl and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN.- 4 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0006] Pharmaceutical compositions comprising these compounds, and methods of using these compounds are also provided.DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0007] The disclosure may be more fully appreciated by reference to the following description, including the following definitions and examples. Certain features of the disclosed compositions and methods which are described herein in the context of separate aspects, may also be provided in combination in a single aspect. Alternatively, various features of the disclosed compositions and methods that are, for brevity, described in the context of a single aspect, may also be provided separately or in any subcombination.

[0008] When a range of carbon atoms is used herein, for example, Ci-Ce, all ranges, as well as individual numbers of carbon atoms are encompassed. For example, “C1-C3” includes C1-C3, C1-C2, C2-C3, Ci, C2, and C3. Thus, for example, a “Ci to C4alkyl” group refers to all alkyl groups having from 1 to 4 carbons (e.g., 1, 2, 3, or 4), that is, CH3-, CH3CH2-, CH3CH2CH2-, (CH3)2CH-, CH3CH2CH2CH2-, CH3CH2CH(CH3)- and (CH3)3C-. A “CI to Ce alkyl” group refers to all alkyl groups having from 1 to 6 carbons (e.g., 1, 2, 3, 4, 5, or 6).

[0009] As used herein, the term “alkyl” refers to a fully saturated aliphatic hydrocarbon group. The alkyl moiety may be branched or straight chain. Examples of branched alkyl groups include, but are not limited to, iso-propyl, sec-butyl, t-butyl and the like. Examples of straight chain alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl and the like. The alkyl group may have 1 to 30 carbon atoms (whenever it appears herein, a numerical range such as “1 to 30” refers to each integer in the given range; e.g., “1 to 30 carbon atoms” means that the alkyl group may consist of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 carbon atoms, although the present definition also covers the occurrence of the term “alkyl” where no numerical range is designated). The “alkyl” group may also be a medium size alkyl having 1 to 12 carbon atoms. The “alkyl” group could also be a lower alkyl having 1 to 6 carbon atoms. An alkyl group may be substituted or unsubstituted. By way of example only, “C1-C5 alkyl” indicates that there are one to five- 5 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)carbon atoms in the alkyl chain, i.e., the alkyl chain is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl (branched and straight-chained), etc. Typical alkyl groups include, but are in no way limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl and hexyl. In several embodiments, “Me” is methyl (e.g., CH3).

[0010] As used herein, “cycloalkyl” refers to a completely saturated (no double or triple bonds) mono- or multi- cyclic hydrocarbon ring system. When composed of two or more rings, the rings may be joined together in a fused fashion. Cycloalkyl groups may contain between 3 and 12 carbon atoms. For example, a Cs-Cecycloalkyl group indicates that there three to six carbon atoms in the ring, that is, the ring is a cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl group. A cycloalkyl group may be unsubstituted or substituted.

[0011] As used herein, the term “spirocycloalkyl ring” refers to a cycloalkyl ring that shares one carbon atom with another cyclic ring. For example, a 3-7 membered spirocycloalkyl ring indicates that there are 3, 4, 5, 6, or 7 carbon atoms in the cycloalkyl ring that shares a single carbon atom in common with another cyclic ring. By way of example, shown below are exemplary 3-7 membered spirocycloalkyl groups attached to a piperidine ring:

[0012] As used herein, “aryl” refers to a carbocyclic (all carbon) monocyclic or multicyclic aromatic ring system (including fused ring systems where two carbocyclic rings share a chemical bond) that has a fully delocalized pi-electron system throughout all the rings. The number of carbon atoms in an aryl group can vary. For example, the aryl group can be a Ce-Cu aryl group, a Ce-Cio aryl group, or a Ce aryl group. Examples of aryl groups include, but are not limited to, benzene, naphthalene and azulene. An aryl group may be substituted or unsubstituted.- 6 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0013] As used herein, “heteroaryl” refers to a monocyclic or multicyclic aromatic ring system (a ring system with fully delocalized pi-electron system) that contain(s) one or more heteroatoms, that is, an element other than carbon, including but not limited to, nitrogen, oxygen and sulfur. The number of atoms in the ring(s) of a heteroaryl group can vary. For example, the heteroaryl group can contain 4 to 14 atoms in the ring(s), 5 to 10 atoms in the ring(s) or 5 to 6 atoms in the ring(s). Furthermore, the term “heteroaryl” includes fused ring systems where two rings, such as at least one aryl ring and at least one heteroaryl ring, or at least two heteroaryl rings, share at least one chemical bond. Examples of heteroaryl rings include, but are not limited to, furan, furazan, thiophene, benzothiophene, phthalazine, pyrrole, oxazole, benzoxazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, thiazole, 1,2, 3 -thiadiazole, 1,2,4-thiadiazole, benzothiazole, imidazole, benzimidazole, indole, indazole, pyrazole, benzopyrazole, isoxazole, benzoisoxazole, isothiazole, triazole, benzotriazole, thiadiazole, tetrazole, pyridine, pyridazine, pyrimidine, pyrazine, purine, pteridine, quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline, and triazine. Heteroaryl rings may also include bridge head nitrogen atoms. For example but not limited to: pyrazolo[l,5-a]pyridine, imidazo[l,2-a]pyridine, and pyrazolo[l,5-a]pyrimidine. A heteroaryl group may be substituted or unsubstituted.

[0014] As used herein, “heterocycloalkyl” refers to three-, four-, five-, six-, seven-, eight-, nine-, ten-, up to 18-membered monocyclic, bicyclic, and tricyclic ring system wherein carbon atoms together with from 1 to 5 heteroatoms constitute said ring system. A heterocycloalkyl may optionally contain one or more unsaturated bonds situated in such a way, however, that a fully delocalized pi-electron system does not occur throughout all the rings. The heteroatom(s) is an element other than carbon including, but not limited to, oxygen, sulfur, and nitrogen. A heterocycloalkyl may further contain one or more carbonyl or thiocarbonyl functionalities, so as to make the definition include oxosystems and thio-systems such as lactams, lactones, cyclic imides, cyclic thioimides and cyclic carbamates. When composed of two or more rings, the rings may be joined together in a fused fashion. Additionally, any nitrogens in a heterocycloalkyl may be quaternized. Heterocycloalkyl groups may be unsubstituted or substituted. Examples of such “heterocycloalkyl” groups include but are not limited to, 1,3-dioxin, 1,3-dioxane, 1,4-dioxane, 1,2-di oxolane, 1,3-dioxolane, 1,4-di oxolane, 1,3-oxathiane, 1,4-oxathiin, 1,3-oxathiolane, 1,3-dithiole, 1,3 -di thiolane, 1,4-oxathiane, tetrahydro- 1,4-thiazine, 2H-1,2-- 7 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)oxazine, maleimide, succinimide, barbituric acid, thiobarbituric acid, dioxopiperazine, hydantoin, dihydrouracil, trioxane, hexahydro-1, 3, 5-triazine, imidazoline, imidazolidine, isoxazoline, isoxazolidine, oxazoline, oxazolidine, oxazolidinone, thiazoline, thiazolidine, morpholine, oxirane, piperidine A -Oxi de, piperidine, piperazine, pyrrolidine, pyrrolidone, pyrrolidione, 4-piperidone, pyrazoline, pyrazolidine, 2-oxopyrrolidine, tetrahydropyran, 4H-pyran, tetrahydrothiopyran, thiamorpholine, thiamorpholine sulfoxide, thiamorpholine sulfone, and their benzo-fused analogs (e.g., benzimidazolidinone, tetrahydroquinoline, 3 , 4-m ethyl enedi oxy phenyl) .

[0015] As used herein, the term “spiroheterocycloalkyl ring” refers to a heterocycloalkyl ring that shares one carbon atom with another cyclic ring. For example, a 3-7 membered spiroheterocycloalkyl ring indicates that there are 3, 4, 5, 6, or 7 atoms in the heterocycloalkyl ring, and only one of the carbon atoms in that heterocycloalkyl ring is also a member of another cyclic ring. By way of example, shown below are exemplary 3-7 membered spiroheterocycloalkyl groups attached to a piperidine ring:

[0016] As used herein, the term “bridged bicyclic ring”, refers to a ring system comprising two joined cycloalkyl or heterocycloalkyl rings that share at least three at least three atoms For example, a 6-9 membered bridged bicyclic ring indicates that there are 6, 7, 8, or 9 atoms in the bridged bicyclic ring. By way of example, shown below are exemplary 6-9 membered bridged bicyclic rings:6-membered 7-membered 8-membered 9-membered

[0017] As used herein, the term “amino” refers to a -NH2 group.120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0018] As used herein, the term “hydroxy” refers to a -OH group.

[0019] As used herein, the term “halogen atom” or “halogen” or “halo” refers to fluorine, chlorine, bromine and iodine.

[0020] The term “pharmaceutically acceptable salt” refers to a salt of a compound that does not cause significant irritation to an organism to which it is administered and does not abrogate the biological activity and properties of the compound. In several embodiments, the salt is an acid addition salt of the compound. Pharmaceutical salts can be obtained by reacting a compound with inorganic acids such as hydrohalic acid (e.g., hydrochloric acid or hydrobromic acid), sulfuric acid, nitric acid and phosphoric acid. Pharmaceutical salts can also be obtained by reacting a compound with an organic acid such as aliphatic or aromatic carboxylic or sulfonic acids, for example formic, acetic, succinic, lactic, malic, tartaric, citric, ascorbic, nicotinic, methanesulfonic, ethanesulfonic, p-toluensulfonic, salicylic or naphthalenesulfonic acid. Pharmaceutical salts can also be obtained by reacting a compound with a base to form a salt such as an ammonium salt, an alkali metal salt, such as a sodium or a potassium salt, an alkaline earth metal salt, such as a calcium or a magnesium salt, a salt of organic bases such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, C1-C7 alkylamine, cyclohexylamine, triethanolamine, ethylenediamine, and salts with amino acids such as arginine and lysine.

[0021] Other pharmaceutically acceptable salts include the trifluoroacetic acid salt.

[0022] It is understood that, in any compound described herein having one or more chiral centers, if an absolute stereochemistry is not expressly indicated, then each center may independently be of R-configuration or S-configuration or a mixture thereof. Thus, the compounds provided herein may be enantiomerically pure, enantiomerically enriched, racemic mixture, diastereomerically pure, diastereomerically enriched, or a stereoisomeric mixture. In addition, it is understood that, in any compound described herein having one or more double bond(s) generating geometrical isomers that can be defined as E or Z, each double bond may independently be E or Z a mixture thereof. It is understood that, in any compound described herein having one or more chiral centers, all possible diastereomers are also envisioned. It is understood that, in any compound described herein all tautomers are envisioned. It is also understood that, in any compound- 9 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)described herein, all isotopes of the included atoms are envisioned. For example, any instance of hydrogen, may include hydrogen- 1 (protium), hydrogen-2 (deuterium), hydrogen-3 (tritium) or other isotopes; any instance of carbon may include carbon-12, carbon-13, carbon- 14, or other isotopes; any instance of oxygen may include oxygen- 16, oxygen-17, oxygen-18, or other isotopes; any instance of fluorine may include one or more of fluorine-18, fluorine-19, or other isotopes; any instance of sulfur may include one or more of sulfur-32, sulfur-34, sulfur-35, sulfur-36, or other isotopes.

[0023] As used herein, the term “kinase inhibitor” means any compound, molecule or composition that inhibits or reduces the activity of a kinase. The inhibition can be achieved by, for example, blocking phosphorylation of the kinase (e.g., competing with adenosine triphosphate (ATP), a phosphorylating entity), by binding to a site outside the active site, affecting its activity by a conformational change, or by depriving kinases of access to the molecular chaperoning systems on which they depend for their cellular stability, leading to their ubiquitylation and degradation.

[0024] As used herein, “subject,” “host,” “patient,” and “individual” are used interchangeably and shall be given its ordinary meaning and shall also refer to an organism that has FGFR proteins. This includes mammals, e.g., a human, a non-human primate, ungulates, canines, felines, equines, mice, rats, and the like. The term “mammal” includes both human and non-human mammals.

[0025] The term “sample” or “biological sample” shall be given its ordinary meaning and also encompasses a variety of sample types obtained from an organism and can be used in an imaging, a diagnostic, a prognostic, or a monitoring assay. The term encompasses blood and other liquid samples of biological origin, solid tissue samples, such as a biopsy specimen or tissue cultures or cells derived therefrom and the progeny thereof. The term encompasses samples that have been manipulated in any way after their procurement, such as by treatment with reagents, solubilization, or enrichment for certain components. The term encompasses a clinical sample, and also includes cells in cell culture, cell supernatants, cell lysates, serum, plasma, biological fluids, and tissue samples.

[0026] The terms “treatment,” “treating,” “treat” and the like shall be given its ordinary meaning and shall also include herein to generally refer to obtaining a desired pharmacologic and / or physiologic effect. The effect may be prophylactic in terms of completely or partially preventing a disease or symptom thereof and / or may be therapeutic- 10 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)in terms of a partial or complete stabilization or cure for a disease and / or adverse effect attributable to the disease. “Treatment” as used herein shall be given its ordinary meaning and shall also cover any treatment of a disease in a mammal, particularly a human, and includes: (a) preventing the disease or symptom from occurring in a subject which may be predisposed to the disease or symptom but has not yet been diagnosed as having it; (b) inhibiting the disease symptom, e.g., arresting its development; and / or (c) relieving the disease symptom, e.g., causing regression of the disease or symptom.

[0027] The terms “cancer,” “neoplasm,” and “tumor” are used interchangeably herein, shall be given its ordinary meaning and shall also refer to cells which exhibit relatively autonomous growth, so that they exhibit an aberrant growth phenotype characterized by a significant loss of control of cell proliferation. In general, cells of interest for detection or treatment in the present application include precursors, precancerous e.g., benign), malignant, pre-metastatic, metastatic, and non-metastatic cells. As used herein, “FGFR related cancer” denotes those cancers that involve an increased activity in a mutant FGFR kinase, for example, the continued activation of FGFR.

[0028] The term “control” refers shall be given its ordinary meaning and shall also include a sample or standard used for comparison with a sample which is being examined, processed, characterized, analyzed, etc. In several embodiments, the control is a sample obtained from a healthy patient or a non-tumor tissue sample obtained from a patient diagnosed with a tumor. In several embodiments, the control is a historical control or standard reference value or range of values. In several embodiments, the control is a comparison to a wild-type FGFR arrangement or scenario.

[0029] With respect to the use of substantially any plural and / or singular terms herein, those having skill in the art can translate from the plural to the singular and / or from the singular to the plural as is appropriate to the context and / or application. The various singular / plural permutations may be expressly set forth herein for sake of clarity. The indefinite article “a” or “an” does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

[0030] In some aspects, the disclosure is directed to compounds of Formula I:- 11 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)or a pharmaceutically acceptable salts thereof.

[0031] In some embodiments, the disclosure is directed to compounds of Formula I.

[0032] In other embodiments, the disclosure is directed to pharmaceutically acceptable salts of compounds of Formula I.

[0033] In some aspects of the disclosure, Y in Formula I is NH, O, S or a bond.

[0034] In some aspects of the disclosure, Y in Formula I is NH.

[0035] In some aspects of the disclosure, Y in Formula I is O.

[0036] In some aspects of the disclosure, Y in Formula I is S.

[0037] In some aspects of the disclosure, Y in Formula I is a bond, z.e., R2is directly bonded to the aromatic ring.

[0038] In some aspects of the disclosure, R2in Formula I is C1-C5 alkyl or R8, wherein C1-C5 alkyl is optionally substituted with one or more substituents independently selected from halo, OH, OAc, OR13, OC(O)Ci-C6alkyl, CN, oxo, -OC1-C4 alkyl, -OC3-C5 cycloalkyl, -Z2-R11, and R10, wherein C1-C4 alkyl and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN.

[0039] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one or more substituents independently selected from halo, OH, CN, oxo, -OC1-C4 alkyl, -OC3-C5 cycloalkyl, -Z2-R11, and R10, wherein the C1-C4 alkyl and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN.

[0040] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one or more substituents independently selected from OH, and R10, wherein each R10is independently 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl, optionally fused to or substituted with R8A, and wherein each R10is optionally substituted with one or more substituents independently selected from halo, OH, CN, -OC1-C4 alkyl, -OC3-C5 cycloalkyl- 12 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)and -Z3-R12wherein C1-C4 alky and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN.

[0041] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one or more OH.

[0042] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with OAc.

[0043] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with OC(O)Ci-C6alkyl, such as, for example, OC(O)CH2CH .

[0044] In some embodiments, R2in Formula I is C1-C5 alkyl substituted with -OC1-C4 alkyl, such as, for example, wherein the -OC1-C4 alkyl is OCH2CH3, or OCH(CH3)2.

[0045] In some embodiments, R2is:

[0046] In some embodiments, R2in Formula I is C1-C5 alkyl substituted with OR13, wherein R13is a hydroxy prodrug moiety selected from ethers, esters including a-amino acid esters, phosphate esters, and sulfamate esters.

[0047] In some embodiments, R2in Formula I is C1-C5 alkyl substituted with OR13, wherein R13is a phosphate ester.

[0048] In some embodiments, R2in Formula I is C1-C5 alkyl substituted with OR13, wherein OR13is a an amino acid ester, such as, for example, an ester of glycine, dimethylglycine, alanine, dimethyl-P-alanine (DMBA), P-alanine, valine, leucine, isoleucine, dimethylaminoglycine, or lysine.

[0049] In some embodiments, R2in Formula I is C1-C5 alkyl substituted with OR13, wherein OR13is an alanine amino acid ester.

[0050] In some embodiments, R2in Formula I is C1-C5 alkyl substituted withOR13, wherein OR13isIn some embodiments, R2in Formula I is Ci-- 13 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)C5 alkyl optionally substituted with one or more R10.In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with two independently selected R10.

[0051] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one or more R10, wherein R10is 3-6 membered cycloalkyl, such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0052] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one or more R10, wherein R10is 4-6 membered heterocycloalkyl.

[0053] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one or more R10, wherein R10is oxetanyl.

[0054] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one or more R10, wherein R10is 5-6 membered aryl, such as, for example, phenyl.

[0055] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one or more R10, wherein R10is 5-6 membered heteroaryl, such as, for example pyridinyl.

[0056] In some embodiments, R2is C1-C5 alkyl substituted with OH and R10.

[0057] In some embodiments, R10is 3-6 membered cycloalkyl or 5-6 membered heteroaryl, optionally substituted with one or more halo.

[0058] In some embodiments, R10is cyclopropyl, cyclobutyl, pyridin-2-yl, or 5-fluoropyridin-2-yl.

[0059] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one 4-6 membered heterocycloalkyl and one 5-6 membered heteroaryl.

[0060] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one oxetanyl and one 5-6 membered heteroaryl.

[0061] In some embodiments, R2in Formula I is C1-C5 alkyl optionally substituted with one oxetanyl and one pyridinyl, optionally substituted with one or more halo.

[0062] In some embodiments, R2is

[0063] In some embodiments, R2is- 14 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0064] In some embodiments, R2is

[0065] In some embodiments, R2is

[0066] In some embodiments, R2is:

[0067] In some embodiments, R2is:O^

[0068] In some embodiments, R2is:

[0069] In some embodiments, R2is:

[0070] In some embodiments, R2is:

[0071] In some embodiments, R2is:- 15 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0072] In some embodiments, R2is:

[0073] In some embodiments, R2is:

[0074] In some embodiments, R2is:

[0075] In some embodiments, R2is:

[0076] In some embodiments, R2in Formula I is R8, wherein R8is 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl, optionally fused to or substituted with R8A.

[0077] In some embodiments, R2in Formula I is R8wherein R8is 3-6 membered cycloalkyl, optionally fused to or substituted with R8A.

[0078] In some embodiments, R2in Formula I is R8wherein R8is 4-6 membered heterocycloalkyl, optionally fused to or substituted with R8A.

[0079] In some embodiments, R2in Formula I is R8wherein R8is 5-6 membered aryl, optionally fused to or substituted with R8A.

[0080] In some embodiments, R2in Formula I is R8wherein R8is 5-6 membered heteroaryl, optionally fused to or substituted with R8A.

[0081] In some aspects, R8Ais halo, 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl.

[0082] In some embodiments, R8Ais halo, such as, for example, F, Cl, Br, or I.- 16 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0083] In some embodiments, R8Ais 3-6 membered cycloalkyl, such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

[0084] In some embodiments, R8Ais 4-6 membered heterocycloalkyl.

[0085] In some embodiments, R8Ais 5-6 membered aryl.

[0086] In some embodiments, R8Ais 5-6 membered heteroaryl.

[0087] In some aspects of the disclosure, Xi and X2 in Formula I are independently selected from N and C, wherein when one of Xi or X2is N the other is C.

[0088] In some embodiments, Xi and X2 are both C.

[0089] In some embodiments, Xi is N and X2is C.

[0090] In some embodiments, Xi is C and X2is N.

[0091] In some aspects of the disclosure, X3 in Formula I is N or CH.

[0092] In some embodiments, X3 is N.

[0093] In some embodiments, X3 is CH.

[0094] In some aspects of the disclosure, R6in Formula I is hydrogen, halo, Ci-C5 alkyl, CN, 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl or 5-6 membered heteroaryl, wherein 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl and 5-6 membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, methyl, halomethyl, OH or OCH3 and wherein C1-C5 alkyl is optionally substituted with one or more substituents independently selected from halo, OH and OCH3.

[0095] In some aspects of the disclosure, R6in Formula I is halo, i.e., fluoro, chloro, bromo, or iodo.

[0096] In some embodiments, R6in Formula I is chloro.

[0097] In some aspects of the disclosure, R6in Formula I is CN.

[0098] In some aspects of the disclosure, A in Formula l is a 5-6-membered heteroaryl, substituted with R1and / or R1A.

[0099] In some embodiments, A is pyrazole, triazole, thiadiazole, oxadiazole, pyridine, pyrimidine, pyrazine, or pyridazine, substituted with R1A.

[0100] In some embodiments, A is triazole or pyridine, substituted with R1A.

[0101] In some embodiments, A is pyrazole, substituted with R1A.

[0102] In some embodiments, A is triazole, substituted with R1A.

[0103] In some embodiments, A is thiadiazole, substituted with R1A.- 17 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0104] In some embodiments, A is oxadiazole, substituted with R1A.

[0105] In some embodiments, A is pyridine, substituted with R1A.

[0106] In some embodiments, A is pyrimidine, substituted with R1A.

[0107] In some embodiments, A is pyrazine, substituted with R1A.

[0108] In some embodiments, A is pyridazine, substituted with R1A.

[0109] In some embodiments, R1is hydrogen or C1-C3 alkyl.

[0110] In some embodiments, R1is hydrogen.

[0111] In some embodiments, R1is C1-C3 alkyl.

[0112] In some embodiments, R1Ais hydrogen, halo, CN, or C1-C3 alkyl optionally substituted with one or more substituents independently selected from halo, OH, and OCH3.

[0113] In some embodiments, R1Ais hydrogen.

[0114] In some embodiments, R1Ais halo, such as, for example, F, Cl, Br, or I.

[0115] In some embodiments, R1Ais CN.

[0116] In some embodiments, R1Ais C1-C3 alkyl optionally substituted with one or more substituents independently selected from halo, OH, and OCH3.

[0117] In some embodiments, R1Ais CH3.

[0118] In some aspects of the disclosure, Z in Formula I is absent, CHR9A, CR4R4A, CR4R4ACH2, CH2CR4R4A, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo(l.l.l)pentane, bicyclo(2.1.1)hexane, azetidine, pyrrolidine or piperidine, wherein R9Atogether with R9form -CR4R4A- or -(CR4R4A)2-.

[0119] In other aspects of the disclosure, Z and A together form a fused bicyclic ring system that is a pyrazolopyrazine, an imidazopyrazine, or a pyrazolodiazepine, each substituted with R1and / or R1A.

[0120] In some embodiments, Z and A together form a pyrazolopyrazine, substituted with R1and / or R1A.

[0121] In some embodiments, Z and A together form an imidazopyrazine, substituted with R1and / or R1A.

[0122] In some embodiments, Z and A together form an pyrazolodiazepine, substituted with R1and / or R1A.

[0123] In some embodiments, Z in Formula I is absent.- 18 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0124] In some embodiments, Z in Formula I is CHR9A, wherein R9Atogether with R9form -CR4R4A- or -(CR4R4A)2-.

[0125] In some embodiments, Z in Formula I is CR4R4A.

[0126] In some embodiments, Z in Formula I is CR4R4ACH2.

[0127] In some embodiments, Z in Formula I is CH2CR4R4A.

[0128] In some embodiments, Z in Formula I is cyclobutyl.

[0129] In some embodiments, Z in Formula I is cyclopentyl.

[0130] In some embodiments, Z in Formula I is cyclohexyl.

[0131] In some embodiments, Z in Formula I is bicyclo(l.l.l)pentane.

[0132] In some embodiments, Z in Formula I is bicyclo(2.1.1)hexane.

[0133] In some embodiments, Z in Formula I is azetidine.

[0134] In some embodiments, Z in Formula I is pyrrolidine.

[0135] In some embodiments, Z in Formula I is piperidine.

[0136] In other aspects of the disclosure, Zi is absent , CR4R4A, CR4R4ACH2, CH2CR4R4A, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo(l.l.l)pentane, bicyclo(2.1. l)hexane, azetidine, pyrrolidine or piperidine, or Zi is -CR4R4A- or -(CR4R4A)2When Z is CHR9A;

[0137] In some embodiments, Zi in Formula I is absent.

[0138] In some embodiments, Zi in Formula I is CR4R4A.

[0139] In some embodiments, Zi in Formula I is CR4R4ACH2.

[0140] In some embodiments, Zi in Formula I is CH2CR4R4A.

[0141] In some embodiments, Zi in Formula I is cyclobutyl.

[0142] In some embodiments, Zi in Formula I is cyclopentyl.

[0143] In some embodiments, Zi in Formula I is cyclohexyl.

[0144] In some embodiments, Zi in Formula I is bicyclo(l.l.l)pentane.

[0145] In some embodiments, Zi in Formula I is bicyclo(2.1.1)hexane.

[0146] In some embodiments, Zi in Formula I is azetidine.

[0147] In some embodiments, Zi in Formula I is pyrrolidine.

[0148] In some embodiments, Zi in Formula I is piperidine.

[0149] In some aspects of the disclosure, Zi is -CR4R4A- or -(CR4R4A)2when Z is CHR9A.- 19 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0150] In some aspects of the disclosure, R4Ais hydrogen, halo, OH, or Ci-C3 alkyl.

[0151] In some embodiments, R4Ais hydrogen.

[0152] In some embodiments, R4Ais halo, such as F, Cl, Br, or I.

[0153] In some embodiments, R4Ais OH.

[0154] In some embodiments, R4Ais C1-C3 alkyl, such as, for example, Ci alkyl, C2 alkyl, C3 alkyl, methyl, ethyl, propyl, and the like.

[0155] In some aspects of the disclosure, Z and Zi in Formula I are both absent.

[0156] In some aspects of the disclosure, Ring B comprises X4, X5, Yi, Y2, Y3, and Y4, wherein:X4isN or CR9;X5is N or CH;Yi is absent, CHR7, CH2CHR7, CHR7CH2, CF2, CH2CF2, or CF2CH2; Y2is absent, CHR3, CH2CHR3, CHR3CH2, CF2, CH2CF2, or CF2CH2;Y3is O, CR4R5or CF2;Y4is CR3R4, or CF2;or Ring B may be absent if Z and A together form a fused bicyclic ring system.

[0157] In some aspects, X4 in Ring B is N or CR9.

[0158] In some embodiments, X4 in Ring B is N.

[0159] In some embodiments, X4 in Ring B is CR9.

[0160] In some embodiments, X4 in Ring B is CH.

[0161] In some aspects, X5 in Ring B is N or CH.

[0162] In some embodiments, X5 in Ring B is N.

[0163] In some embodiments, X5 in Ring B is CH.

[0164] In some embodiments, X5 is N and X4 is CH.

[0165] In some embodiments, X5 is CH and X4 is N.

[0166] In some embodiments, X5 is N and X4 is N.

[0167] In some aspects, Yi in Ring B is absent, CHR7, CH2CHR7, CHR7CH2, CF2, CH2CF2, or CF2CH2.

[0168] In some embodiments, Yi is absent or CHR7.

[0169] In some embodiments, Yi is CH2.- 20 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0170] In some aspects, Yi in Ring B is absent.

[0171] In some embodiments, Yi in Ring B is CHR7.

[0172] In some embodiments, Yi in Ring B is CH2CHR7.

[0173] In some embodiments, Yi in Ring B is CHR7CH2.

[0174] In some embodiments, Yi in Ring B is CF2.

[0175] In some embodiments, Yi in Ring B is CH2CF2.

[0176] In some embodiments, Yi in Ring B is CF2CH2.

[0177] In some aspects, Y?in Ring B is absent, CHR3, CH2CHR3, CHR3CH2, CF2, CH2CF2, or CF2CH2.

[0178] In some embodiments, Y2is absent or CHR3.

[0179] In some aspects, Y?in Ring B is absent.

[0180] In some embodiments, Y2 in Ring B is CHR3.

[0181] In some embodiments, Y2is absent or CH2.

[0182] In some embodiments, Y2 in Ring B is CH2CHR3.

[0183] In some embodiments, Y2 in Ring B is CHR3CH2.

[0184] In some embodiments, Y2 in Ring B is CF2.

[0185] In some embodiments, Y2 in Ring B is CH2CF2.

[0186] In some embodiments, Y2 in Ring B is CF2CH2.

[0187] In some aspects, Y3 in Ring B is O, CR4R5or CF2.

[0188] In some embodiments, Y3 in Ring B is CR4R5.

[0189] In some embodiments, Y3 in Ring B is CF2.

[0190] In some embodiments, Y3 in Ring B is O.

[0191] In some aspects, Y4 in Ring B is CR3R4or CF2.

[0192] In some embodiments, Y4 in Ring B is CR3R4.

[0193] In some embodiments, Y4 in Ring B is CF2.- 21 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0194] In some embodiments, ring B is:

[0195] In some aspects, each R3in Formula I is independently hydrogen, F, OH, OCH3, C1-C3 alkyl, cyclopropyl, or one R3is fused with R5or R7to form CH2, CH2-CH2, or CH2OCH2.

[0196] In some embodiments, R3is hydrogen.

[0197] In some embodiments, R3is F.

[0198] In some embodiments, R3is OH.

[0199] In some embodiments, R3is OCH3.

[0200] In some embodiments, R3is C1-C3 alkyl.

[0201] In some embodiments, R3is cyclopropyl.

[0202] In some embodiments, one R3is fused with R5or R7to form CH2, CH2- CH2, or CH2OCH2.

[0203] In some aspects, each R4is independently hydrogen, F, Cl, CH3, OH, C3-C5 cycloalkyl, or C1-C3 alkyl.- 22 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0204] In some aspects, each R4in Formula I is independently hydrogen or Ci-C3 alkyl.

[0205] In some embodiments, R4is hydrogen or CH3.

[0206] In some embodiments, R4is hydrogen.

[0207] In some embodiments, R4is C1-C3 alkyl, such as, for example, Ci alkyl, C2 alkyl, C3 alkyl, methyl, ethyl, propyl, and the like.

[0208] In some embodiments, R4is CH3.

[0209] In some embodiments, R4is F.

[0210] In some embodiments, R4is Cl.

[0211] In some embodiments, R4is OH.

[0212] In some embodiments, R4is C3-C5 cycloalkyl, such as, for example, Cscycloalkyl, C4 cycloalkyl, C5 cycloalkyl, cyclopropyl, cyclobutyl, cyclopentyl, and the like.

[0213] In some embodiments, R4is cyclopropyl.

[0214] In some aspects, R5in Formula I is hydrogen, F, OH, OCH3, CH2OC1-Csalkyl, C1-C3 alkyl, cyclopropyl, or is fused with one R3to form CH2, CH2-CH2, or CH2OCH2.

[0215] In some embodiments, R5in Formula I is hydrogen, CH3, or CH2OC1-Csalkyl.

[0216] In some embodiments, R5in Formula I is hydrogen.

[0217] In some embodiments, R5in Formula I is F.

[0218] In some embodiments, R5in Formula I is OH.

[0219] In some embodiments, R5in Formula I is CH3.

[0220] In some embodiments, R5in Formula I is OCH3.

[0221] In some embodiments, R5in Formula I is QbOCi-Csalkyl, such as, for example, CH2OC1 alkyl, CH2OC2 alkyl, CH2OC3 alkyl, CH2O-CH3, CH2O-CH2CH3, CH2O-propyl, and the like.

[0222] In some embodiments, R5in Formula I is CH2O-CH3.

[0223] In some embodiments, R5in Formula I is C1-C3 alkyl, such as, for example, Ci alkyl, C2 alkyl, C3 alkyl, methyl, ethyl, propyl, and the like.

[0224] In some embodiments, R5in Formula I is cyclopropyl.- 23 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0225] In some embodiments, R5in Formula I is with one R3to form CH2, CH2-CH2, or CH2OCH2., wherein n is 0, 1, or 2; o is 0, 1, or 2; p is 0 or 1; X6is O or NH, and wherein is a double bond or a single bond.

[0227] In some aspects, R in FormulaCi-Csalkyl,wherein n is 0, 1, or 2; o is 0 or 1; p is 0 or 1; and wherein = is a double bond or a single bond.

[0228] In some embodiments, R in Formula I is -(CR4R4)n-(CR4=R4)0-(CR4R4)p-SC>2-Ci-C3alkyl wherein n is 0, 1, or 2; o is 0 or 1; p is 0 or 1.

[0229] In some embodiments, R in Formula I is -(CR4R4)n-(CR4=R4)0-(CR4R4)p-SC>2-Ci-C3alkyl wherein n is 0, 1, or 2; o is 0, 1 or 2; p is 0 or 1.

[0230] In some embodiments, R in Formula I is -(CR4R4)n-(CR4=R4)0-(CR4R4)p-C(O)N(Ci-C3alkyl)2 wherein n is 0, 1, or 2; o is 0, 1 or 2; p is 0 or 1.

[0231] In some aspects, R in Formulawherein X6is O or NH.

[0232] In some aspects, R in Formulawherein X6is O or NH; n is 0, 1, or 2; o is 0, 1, or 2; and wherein = is a double bond or a single bond.

[0233] In some embodiments, X6is O.- 24 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0234] In some embodiments, X6is NH.

[0235] In some aspects, R in Formula, wherein n is 0, 1, or 2; o is 0 or 1; and wherein = is a double bond or a single bond.

[0236] In some embodiments, is a double bond.

[0237] In some embodiments, is a single bond.

[0238] In some embodiments of R, n is 0.

[0239] In some embodiments of R, n is 1.

[0240] In some embodiments of R, n is 2.

[0241] In some embodiments of R, o is 0.

[0242] In some embodiments of R, o is 1.

[0243] In some embodiments of R, o is 2.

[0244] In some embodiments of R, p is 0.

[0245] In some embodiments of R, p is 1.

[0246] In some embodiments of R, n=l, o=l, p=0.

[0247] In some embodiments, each R4in R is independently hydrogen or CH3.

[0248] In some embodiments, each R4in R is hydrogen.

[0249] In some embodiments, at least one R4in R is CH3.

[0250] In some embodiments, at least two R4in R are CH3.

[0251] In some embodiments, R is:

[0253] In some embodiments, R is:

[0254] In some embodiments, R is:- 25 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0255] In some embodiments, R is:

[0256] In some embodiments, R is:

[0257] In some embodiments, R is:

[0258] In some embodiments, R is:

[0259] In some embodiments, R is:

[0260] In some embodiments, R is:

[0261] In some embodiments, R is:

[0262] In some embodiments of R, n=l or 2, o=0, p=l.

[0263] In some embodiments of R, n=l or 2, o=0, p=land each R4is hydrogen.- 26 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0264] In some embodiments, R is:

[0265] In some embodiments, R is:

[0266] In some embodiments, R is:

[0267] In some embodiments, R is:

[0268] In some embodiments, R is:

[0269] In some embodiments, R is:

[0270] In some embodiments, R is

[0271] In other embodiments, R is

[0272] In other embodiments, R is- 27 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0273] In other embodiments, R is9

[0274] In other embodiments, R is

[0275] In other embodiments, R is

[0276] In some aspects of the disclosure, Z2is absent, C(O), SChor -NR4C(O).

[0277] In some embodiments, Z2is absent.

[0278] In some embodiments, Z2is C(O).

[0279] In some embodiments, Z2is SO2.

[0280] In some embodiments, Z2is -NR4C(O).

[0281] In some aspects of the disclosure, Z3 is absent, C(O), SO2 or -NR4C(O).

[0282] In some embodiments, Z3 is absent.

[0283] In some embodiments, Z3 is C(O).

[0284] In some embodiments, Z3 is SO2.

[0285] In some embodiments, Z3 is -NR4C(O).

[0286] In some aspects of the disclosure, R7is hydrogen, F, OH, OCH3, Ci-C3 alkyl or is fused with one R3to form CH2, CH2-CH2 or CH2OCH2.- 28 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0287] In some aspects of the disclosure, R8is 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl, optionally fused to or substituted with R8A;

[0288] In some aspects of the disclosure, R8Ais halo, 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl;

[0289] In some aspects of the disclosure, R9is hydrogen, C1-C3 alkyl, or together with R9Aare CH2 or CH2-CH2;

[0290] In some aspects of the disclosure, R10is 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl or 5-6 membered heteroaryl, optionally fused to or substituted with R8A;

[0291] In some aspects of the disclosure, R11is C1-C4 alkyl, NH2, NHCi-C3 alkyl, NHC3-C5 cycloalkyl or N(Ci-Cs alkyl)2, wherein C1-C4 alkyl, C1-C3 alkyl and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN;

[0292] In some aspects of the disclosure, R12is C1-C4 alkyl, C3-C5 cycloalkyl, NH2, NHC1-C3 alkyl, NHC3-C5 cycloalkyl or N(Ci-Cs alkyl)2, wherein C1-C4 alky, Ci-C3 alkyl and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN; and

[0293] In some aspects of the disclosure, R8, R10and R8Aare optionally substituted with one or more substituents independently selected from halo, OH, CN, -OC1-C4 alkyl, -OC3-C5 cycloalkyl and -Z3-R12wherein Ci-C4alky and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN.

[0294] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IA-0:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.- 29 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0295] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IA:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0296] In some aspects of the disclosure, the compound of Formula IA is a compound of Formula IA-1:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0297] In some aspects of the disclosure, the compound of Formula IA is a compound of Formula IA-2:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0298] In some aspects of the disclosure, the compound of Formula IA is a compound of Formula IA-3:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.- 30 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0299] In some embodiments, the compound of Formula IA-3 is a compound of Formula IA-4:pharmaceutically acceptable salt thereof.

[0300] In some embodiments, the compound of Formula IA-3 is a compound of Formula IA-5:pharmaceutically acceptable salt thereof.

[0301] In some embodiments, the compound of Formula IA is a compound ofpharmaceutically acceptable salt thereof.

[0302] In some embodiments, the compound of Formula IA is a compound of Formula IA-7:pharmaceutically acceptable salt thereof.- 31 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0303] In some embodiments, R1Ais hydrogen or CH3.

[0304] In some aspects of the disclosure, the compound of Formula I is a

[0305] In some aspects of the disclosure, the compound of Formula I is awherein the variables are as defined herein.

[0306] In some aspects of the disclosure, the compound of Formula IB is a compound of Formula IB-1:wherein the variables are as defined herein.

[0307] In some embodiments of the compounds of Formula IB, and subgenera thereof, X4 is N.- 32 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0308] In some embodiments of the compounds of Formula IB, and subgenera thereof, X5 is N.

[0309] In some embodiments of the compounds of Formula IB, and subgenera thereof, X5 is CH.

[0310] In some aspects of the disclosure, the compound of Formula IB is a compound of Formula IB-2:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0311] In some aspects of the disclosure, the compound of Formula IB is a compound of Formula IB-3:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0312] In some aspects of the disclosure, the compound of Formula IB is a compound of Formula IB-4:- 33 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0313] In some embodiments of Formula I, Z is piperidine and Zi is absent.

[0314] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IC-0:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0315] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IC:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0316] In some aspects of the disclosure, the compound of Formula IC is a compound of Formula IC-1:- 34 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0317] In some embodiments of Formula I, Z and A together form a fused bicyclic ring system that is a pyrazolopyrazine, an imidazopyrazine, or apyrazolodi azepine, each substituted with R1and / or R1A.

[0318] In some embodiments of Formula I, Ring B is absent.

[0319] In some aspects of the disclosure, the compound of Formula I is a compound of Formula ID-0, IE-0, or IF-0:wherein the variables are as defined herein.

[0320] In some aspects of the disclosure, the compound of Formula I is a compound of Formula ID, IE, or IF:- 35 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)wherein the variables are as defined herein.

[0321] In some embodiments, the compound of Formula I is a compound of Formula ID.

[0322] In some embodiments, the compound of Formula I is a compound of Formula IE.

[0323] In some embodiments, the compound of Formula I is a compound of Formula IF.

[0324] In some embodiments of formula ID, IE, or IF, R1Ais hydrogen or CH3.

[0325] In some embodiments of Formula I, Zi is absent.

[0326] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IG-0 or IH-0:- 36 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)0), or a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0327] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IG or IH:a pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0328] In some embodiments, the compound of Formula I is a compound of Formula IG.

[0329] In some embodiments, the compound of Formula I is a compound of Formula IH.

[0330] In some embodiments, the compound of Formula IH is a compound of Formula IH-1- 37 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0331] In some embodiments, R1Ais hydrogen or CH3.

[0332] In some aspects of Formula I, X4 is CR9.

[0333] In some embodiments, R9is H.

[0334] In some embodiments, X4 is CR9, Z is CHR9A, wherein R9Atogether with R9form -CR4R4A- or -(CR4R4A)2-; and Zi is -CR4R4A- or -(CR4R4A)2.

[0335] In some easpects of the disclosure, the compound of Formula I is a compound of Formula IJ-0:

[0336] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IJ:thereof, wherein the variables are as defined herein.

[0337] In some easpects of the disclosure, the compound of Formula IJ is a compound of Formula IJ-1 :- 38 -l20039.000209\4905-l 100-04521thereof, wherein the variables are as defined herein.

[0338] In some aspects of the disclosure, the compound of Formula IJ is a compound of Formula IJ-4:pharmaceutically acceptable salt thereof, wherein the variables are as defined herein.

[0339] In some aspects of the disclosure, Yi and Y2 are both absent, and the compound of Formula IJ is a compound of Formula IJ-2:

[0340] In some embodiments, the compound of Formula IJ-2 is a compound of Formula IJ-3 :- 39 - 120039.000209\4905-l 100-0452.1

[0341] In some aspects of the disclosure, the compound of Formula I is a

[0342] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IK-1:pharmaceutically acceptable salt thereof.

[0343] In some aspects of the disclosure, the compound of Formula I is a- 40 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0344] In some aspects, the disclosure is directed to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein X4 is N or CH, Yi is CR9, Z is CHR9A, wherein R9Atogether with R9form -CR4R4A- or -(CR4R4A)2-; and Zi is -CR4R4A- or -(CR4R4A)2.

[0345] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IL-0:

[0346] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IL-1:

[0347] In some aspects of the disclosure, the compound of Formula I is a

[0348] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IL-5:- 41 - 120039.000209\4905-l 100-0452.1

[0349] In some aspects of the disclosure, the compound of Formula I wherein

[0350] In some aspects of the disclosure, the compound of Formula I is a

[0351] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IL-3-1:pharmaceutically acceptable salt thereof- 42 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0352] In some aspects of the disclosure, the compound of Formula I is a

[0353] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IM-0:thereof.

[0354] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IM:pharmaceutically acceptable salt thereof.

[0355] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IM-1:pharmaceutically acceptable salt thereof.

[0356] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IM-2:- 43 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)pharmaceutically acceptable salt thereof.

[0357] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IQ-0:thereof.

[0358] In some aspects of the disclosure, the compound of Formula I is a

[0359] In some aspects of the disclosure, the compound of Formula I is a- 44 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0360] In some aspects of the disclosure, the compound of Formula I is a compound of Formula IQ-3:pharmaceutically acceptable salt thereof.

[0361] In some embodiments of compounds of Formula IM and IQ, and subgenera thereof, each R4is H and each R4Ais H.

[0362] In some aspects, the disclosure is directed to a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is3-(4-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(E)-3 -chloro-4-methoxy-6-(5 -methyl- 1 -(1 -(4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide- 45 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide(R,E)-3-chloro-6-(6-(4-(2-(methylsulfonyl)vinyl)piperidin-l-yl)pyridin-3-yl)-4-(l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;(2R)-2-[3-chloro-6-[l-[(2S,4S)-2-(methoxymethyl)-l-[(E)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy- 2-(5 -fluoro-2-pyridyl)ethanol ;(2S)-2-[3-chloro-6-[l-[(2S,4S)-2-(methoxymethyl)-l-[(E)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5 -fluoro-2-pyridyl)ethanol ;3-(4-(4-(3-chloro-4-((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R)-2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyri din-2 -yl)ethan- 1 -ol;(R)-2-((3 -chloro-6-(5 -methyl- 1 -(1 -((R,E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyri din-2 -yl)ethan- 1 -ol;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((S,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyri din-2 -yl)ethan- 1 -ol;- 46 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((R,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyri din-2 -yl)ethan- 1 -ol;3-(4-(4-(3-chloro-4-((R)-l-cyclobutylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-cyclobutylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-cyclobutylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(R)-2-((3 -chloro-6-( 1 -((2 S,4 S)-2-(methoxymethyl)- 1 -((E)-3 - (methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chloro-6-( 1 -((2S,4S)-2-(m ethoxymethyl)- 1 -((E)-3 -(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R,E)-3-chloro-6-(5-methyl-l-(l-(3-(methylsulfonyl)allyl)-piperidin-4-yl)-lH-l,2,3-triazol-4-yl)-4-(l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;3-(4-(4-(3-chloro-4-((R)-l-cyclopropylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-cyclopropylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-cyclopropylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;-47 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R,E)-3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-6-(6-(4-(2-(methylsulfonyl)-vinyl)piperidin-l-yl)pyridin-3-yl)pyrazolo[l,5-a]pyridine;(R)-3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-(3-(methylsulfonyl)propyl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(pyridin-2-yl)ethoxy)pyrazolo[ 1 , 5-a]pyridine;3-chloro-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(pyridin-2-yl)ethoxy)pyrazolo[ 1 , 5-a]pyridine;3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(pyridin-2-yl)ethoxy)pyrazolo[ 1 , 5-a]pyridine;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -( 1 -((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -( 1 -((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;(R,E)-3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-(3-(methylsulfonyl)allyl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-cyclobutylethoxy)-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-cyclobutylethoxy)-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-cyclobutylethoxy)-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-6-(l-((2S,4S)-2-(methoxymethyl)-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;- 48 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(l-((2S,4S)-2-(methoxymethyl)-l-((E)-3-(methylsulfonyl)-allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;(R)-2-((3-chloro-6-(l-((2R,4S)-2-(methoxymethyl)-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chloro-6-( 1 -((2R,4 S)-2-(methoxymethyl)- 1 -((E)-3 -(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;3-chloro-4-((R)-l-cyclopropylethoxy)-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-cyclopropylethoxy)-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-cyclopropylethoxy)-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(l-((2R,4S)-2-(methoxymethyl)-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[ 1 ,5 -a]pyridine;3-chloro-6-(l-((2R,4S)-2-(methoxymethyl)-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(l-((2S,4S)-2-(methoxymethyl)-1 -((E)-3 -(methyl sulfonyl)allyl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1,5-a]pyridine;3-chloro-6-(l-((2S,4S)-2-(methoxymethyl)-l-((E)-3- (m ethyl sulfonyl)allyl)piperidin-4-yl)-lH- 1,2, 3 -tri azol -4-yl)-4-((R)-l -(pyri din-2 -yl)ethoxy)pyrazolo[l,5-a]pyridine;-49 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(l-((2R,4S)-2- (m ethoxymethyl)- 1 -((E)-3 -(methylsulfonyl)allyl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -(2-(methylsulfonyl)-ethyl)piperidin-4-yl)-lH- 1.2.3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol; or (R)-2-((3-chloro-6-(5-methyl-l-(l-(2-(methylsulfonyl)-ethyl)piperidin-4-yl)-lH- 1.2.3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol.

[0363] In other aspects, the disclosure is directed to a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is3-chloro-6-(l-((2R,4S)-2-(methoxymethyl)-l-((E)-3- (m ethyl sulfonyl)allyl)piperidin-4-yl)-lH- 1,2, 3 -tri azol -4-yl)-4-((R)-l -(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;(R,E)-2-((3-chloro-6-(5-methyl-l-(l-(3-(methylsulfonyl)allyl)piperidin-4-yl)-lH- 1.2.3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S,E)-2-((3-chloro-6-(5-methyl-l-(l-(3-(methylsulfonyl)allyl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -(3 -(methylsulfonyl)propyl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R)-2-((3 -chloro-6-(5 -methyl- 1 -( 1 -(3 -(methyl sulfonyl)propyl)piperidin-4-yl)- 1 H-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R)-2-((3-chloro-6-(l-(2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(R)-2-((3-chloro-6-(l-(2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;- 50 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3-chloro-6-(l-(2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer C;(S)-2-((3-chloro-6-(l-(2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanollsomer D;(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1 -di oxide Isomer A;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer B;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer C;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer D;(E)-3-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)propan-l-ol Isomer A;(E)-3-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)propan-l-ol Isomer B;2-((3-chloro-6-(l-(l-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;2-((3-chloro-6-(l-(l-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyri din-2 -yl)ethanol Isomer B;2-((3-chloro-6-(l-(l-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer C;- 51 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2-((3-chloro-6-(l-(l-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer D;2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cyclobutylethanol Isomer A;2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cyclobutylethanol Isomer B;2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cyclobutylethanol Isomer C;2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cyclobutylethanol Isomer D;(E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)ethanol Isomer A;(E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)ethanol Isomer B;2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cyclopropylethanol Isomer A;2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cyclopropylethanol Isomer B;2-((3-chloro-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cyclopropylethanol Isomer C;2-((3-chloro-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cyclopropylethanol Isomer D;4-[ 1 -(5 -fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl- 1 -[ 1 -[(E)-3 -methylsulfonylallyl]-4-piperidyl]-triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;4-[l-(5-fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;- 52 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(E)-l-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperi din-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-methylpropan-2-ol Isomer A;(E)-l-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-methylpropan-2-ol Isomer B;3-chloro-5-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-7-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)imidazo[l,2-a]pyridine Isomer A;3-chloro-5-((S)-l-(5-fluoropyridin-2-yl)ethoxy)-7-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)imidazo[l,2-a]pyridine Isomer B;3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-1H- 1 ,2,3-triazol-4-yl)-4-(((R)-tetrahydrofuran-3 -yl)oxy)pyrazolo[ 1 ,5-a]pyridine;4-[ 1 -(5 -fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl- 1 -[ 1 -[(E)-3 -methylsulfonylallyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;4-[ 1 -(5 -fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl- 1 -[ 1 -[(E)-3 -methylsulfonylallyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;(E)-3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)pyrazolo[l,5-a]pyridine;3-chloro-N-((R)-l-(5-fluoropyridin-2-yl)ethyl)-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-amine;(S,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl obuty 1 ethanol ;(R,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl obuty 1 ethanol ;(S,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl opropy 1 ethanol ;- 53 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl opropy 1 ethanol ;3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)-4-(((S)-tetrahydrofuran-3-yl)oxy)pyrazolo[l,5-a]pyridine;(E)-3-chloro-4-(2-methoxyethoxy)-6-(5-methyl-l-(l-(4-(methylsulfonyl)-but-3-en-2-yl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 ,5-a]pyridine;2-[3-chloro-6-[3-methyl-5-[(E)-3-methylsulfonylallyl]-6,7-dihydro- 4Hpyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-5-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[5-methyl-l-[l-[l-[(E)-3-methylsulfonylallyl]azetidin-3-yl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-7-(3-methylsulfonylpropyl)-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[5-methyl-l-[7-[(E)-3-methylsulfonylallyl]-7-azaspiro-[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-7-[(E)-3-methylsulfonylallyl]-6,8-dihydro- 5Himidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(E)-3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)-4-(2-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;(E)-3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)-4-(2-(pyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridine;2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H-imidazof 1 ,2-a]pyrazin-2-yl]pyrazolo[ 1 ,5 -a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;4-[(lS)-l-(5-fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl-l-[l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;- 54 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)4-[(lS)-l-(5-fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl-l-[l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;(E)-3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)-4-((l-(pyridin-2-yl)propan-2-yl)oxy)pyrazolo[l,5-a]pyridine;(E)-2-((3-chloro-7-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)imidazo[l,2-a]pyridin-5-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol Isomer B;(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol Isomer C;(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol Isomer D;2-[3-chloro-6-[3-methyl-5-[(E,R)-3-methylsulfonylallyl]-6,7-dihydro-4Hpyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-5-[(E,S)-3-methylsulfonylallyl]-6,7-dihydro-4Hpyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-5-[l-[(E)-3-methylsulfonylallyl]pyrrolidin-3-yl]-6,7-dihydro-4H-pyrazolo[l,5-a]-pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-7-(3-methylsulfonylpropyl)-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol Isomer A;2-[3-chloro-6-[3-methyl-7-(3-methylsulfonylpropyl)-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol Isomer B;- 55 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2-[3-chloro-6-[5-methyl-l-[7-[(E, R)-3-methylsulfonylallyl]-7-azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[5-methyl-l-[7-[(E, S)-3-methylsulfonylallyl]-7-azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(E)-4-((3-fluoropyridin-2-yl)thio)-6-(5-methyl-l-(l-(4-(methylsulfonyl)-but-3-en-2-yl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 ,5-a]pyridine-3 -carbonitrile;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer D;6-(l-(l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile;2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol Isomer A;2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol Isomer B;2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol Isomer C;2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol Isomer D;- 56 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(E)-4-((2-cyanophenyl)thio)-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3-carbonitrile;2-[3-chloro-6-[3-methyl-7-[(E)-3-methylsulfonylallyl]-6,8-dihydro-5Himidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)-ethanol Isomer A;2-[3-chloro-6-[3-methyl-7-[(E)-3-methylsulfonylallyl]-6,8-dihydro-5Himidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)-ethanol Isomer B;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer D;6-(l-(-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxy ethoxy )pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;6-(l-(-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxy ethoxy )pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;6-(l-(l -(1, 1-dioxi do-2, 3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l, 2, 3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;6-(l-(l -(1, 1-dioxi do-2, 3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l, 2, 3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;- 57 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol Isomer A;(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol Isomer B;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol Isomer C;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol Isomer D;6-(l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer C;6-(l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer D;6-(l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;6-(l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;6-(l-(l-(l,l-dioxidotetrahydro-2H-thiopyran-4-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile;6-(l-(-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxy ethoxy )pyrazolo[l, 5-a]pyridine-3-carbonitrile Isomer A;6-(l-(-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxy ethoxy )pyrazolo[l, 5-a]pyridine-3-carbonitrile Isomer B;6-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer C;- 58 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)6-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer D;6-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;6-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;(R)-4-(4-(4-(3-chloro-4-(2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin-l -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide Isomer A;(S)-4-(4-(4-(3 -chloro-4-(2-hydroxy- 1 -(pyri din-2 -yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin-l -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide Isomer B;6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-triazol-4-yl]-4-(2-pyridylsulfanyl)-pyrazolo[l,5-a]pyridine-3-carbonitrile;(E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)benzonitrile;4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)-6-(5-m ethyl- 1 -(1 -((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile Isomer A;4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)-6-(5-m ethyl- 1 -(1 -((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile Isomer B;4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile Isomer C;4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile Isomer D;- 59 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)4-((S)-2-hydroxy- 1 -(pyridin-2-yl)ethoxy)-6-(5-methyl- 1 -( 1 -((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile Isomer A;4-((S)-2-hydroxy- 1 -(pyridin-2-yl)ethoxy)-6-(5-methyl- 1 -( 1 -((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile Isomer B;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer D;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer B;4-[(3-fluoro-2-pyridyl)sulfanyl]-6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;4-(2-cyanophenyl)sulfanyl-6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonylallyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;6-(l-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;6-(l-(l-(l,l-dioxidotetrahydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;4-[(lS)-l-(3-fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;6-[l-[l-(l,l-dioxothian-4-yl)-4-piperidyl]-5-methyl-triazol-4-yl]-4-[(lS)-2-hydroxy-l-(2-pyridyl)-ethoxy]pyrazolo[l,5-a]pyridine-3-carbonitrile;- 60 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)6-[l-[l-(l,l-dioxothiolan-3-yl)-4-piperidyl]-5-methyl-triazol-4-yl]-4-[(lS)-2-hydroxy-l-(2-pyridyl)ethoxy]-pyrazolo[l,5-a]pyridine-3-carbonitrile;3-(4-(4-(3-chloro-4-((R)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer D;3-(4-(4-(3-chloro-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(R)-2-((3-chloro-6-(5-methyl-l-(l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3-fluoropyridin-2-yl)ethanol Isomer A;(R)-2-((3-chloro-6-(5-methyl-l-(l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3-fluoropyridin-2-yl)ethanol Isomer B;(S)-2-((3-chloro-6-(5-methyl-l-(l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3-fluoropyridin-2-yl)ethanol Isomer C;(S)-2-((3-chloro-6-(5-methyl-l-(l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3-fluoropyridin-2-yl)ethanol Isomer D;3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer A;- 61 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene- 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene- 1,1-dioxide Isomer D;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene- 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene- 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;3-(4-(4-(3-chloro-4-(l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(4-fluoropyridin-2-yl)ethanol;(E)-4-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)pent-2-enenitrile;3-(3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;3-(4-(4-(3-chloro-4-(l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide;- 62 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)4-(2-cyanophenoxy)-6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer B;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer D;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro-thiophene- 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro-thiophene- 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro-thiophene- 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro-thiophene- 1,1-dioxide Isomer D;- 63 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-((R)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer D;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(E)-4-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-N,N-dimethylpent-2-enamide;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer B;(R)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer B;- 64 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer D;(R)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide;(R)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin-l -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide Isomer A;(S)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin-l -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide Isomer B;3 - [2 - (4 - { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyridin-2-yl)-2-hy droxy-ethoxy]pyrazolo[ 1 , 5-a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3-triazol- 1 -y l)-7 -azaspiro[3.5 ]nonan-7-yl]-2, 3 -dihydro- 1 l6-thiophene- 1 , 1 -di one Isomer A;3 - [2 - (4 - { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyridin-2-yl)-2-hy droxy-ethoxy]pyrazolo[ 1 , 5-a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3-triazol- 1 -y l)-7 -azaspiro[3.5 ]nonan-7-yl]-2, 3 -dihydro- 1 l6-thiophene- 1 , 1 -di one Isomer B ;3-(3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer C;- 65 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer D;3-(4-(4-(3-chloro-4-(-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-(-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-(-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-(-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer D;4-(4-(4-(3-chloro-4-(l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydro-2H-thiopyran 1, 1-dioxide Isomer A;4-(4-(4-(3-chloro-4-(l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydro-2H-thiopyran 1, 1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-pyrazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-pyrazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer B;(S)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)- 1 -iminothietane 1 -oxide;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer D;- 66 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)- 1 -iminothietane 1 -oxide;3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thiolane-1,1 -di one Isomer A;3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thiolane-1,1 -di one Isomer B;3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thietane-l,l-dione;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;(R)-4-(4-(4-(3-chloro-4-(l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide ;(S)-4-(4-(4-(3-chloro-4-(l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;- 67 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer D;3-(4-(4-(3-chloro-4-(l-(6-methylpyridazin-3-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;3-(4-(4-(3-chloro-4-(l-(5-fluoropyrimidin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(S)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)-3-fluoropyridin-2-yl)piperazin-l-yl)thietane 1,1-dioxide;(S)-3 -(4-(4-(3 -chloro-4-(2-hydroxy- 1 -phenylethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-phenylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)- 1 -iminothietane 1 -oxide;(R)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)pyridin-2-yl)piperazin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(6-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-3-fluoropyridin-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)thietane 1,1-dioxide;(S)-3-(6-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)pyridin-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)thietane 1,1-dioxide;(S)-3-(6-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)-3-fluoropyridin-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)thietane 1,1-dioxide;- 68 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)4-[4-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl]-ll6-thiane-1,1 -di one;3-(4-(4-(3-chloro-4-(l-(5-fluoropyrimidin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)thietane 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-(l-(5-fluoropyrimidin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)thietane 1,1-dioxide Isomer B;(R)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-3-fluoropyridin-2-yl)piperazin-l-yl)thietane 1, 1 -di oxide;(S)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)pyri din-2 -yl)piperazin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(6-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)pyridin-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)thietane 1,1-dioxide;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro-[3.5]nonan-7-yl]-2,3-dihydro-ll6-thiophene-l,l-dione Isomer A;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro-[3.5]nonan-7-yl]-2,3-dihydro-ll6-thiophene-l,l-dione Isomer B;(2S)-2-{[3-chloro-6-(l-{7-[(2S,3E)-4-methanesulfonylbut-3-en-2-yl]-7-azaspiro[3.5]nonan-2-yl}-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl]oxy}-2-(5-fluoropyridin-2-yl)ethan-l-ol;(2S)-2-[3-chloro-6-[5-methyl-l-[7-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-7-azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thietane-1,1 -di one;[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-pyrazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thietanel,l-dioxide;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-phenylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide;- 69 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;(2S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-phenylethanol;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thiolane-1,1 -di one Isomer A;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thiolane-1,1 -di one Isomer B;(S)-2-[3-chloro-6-[l-[l-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(2-pyridyl)ethanol Isomer A;(S)-2-[3-chloro-6-[l-[l-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(2-pyridyl)ethanol Isomer B;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer B;3-[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thiolane 1,1-dioxide Isomer A;3-[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thiolane 1,1-dioxide Isomer B;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[2-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-2-azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;(2S)-2-[3-chloro-6-[l-[2-(l,l-dioxothiolan-3-yl)-2-azaspiro[3.3]heptan-6-yl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;- 70 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1 -di oxide Isomer A;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer B;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer A;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer B;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer B;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer C;3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer D;- 71 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(4-fluorophenyl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer A;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer B;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer A;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer C;- 72 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide Isomer D;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((R)- 1 -((E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((R)- 1 -((E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyri din-2 -yl)ethanol Isomer B;3-(2-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-5-yl)-ll6-thietane-l,l -dione;2-[(lR)-l-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2S,3E)-4-methanesulfonyl-but-3-en-2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine;2-[(lR)-l-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2R,3E)-4-methanesulfonyl-but-3-en-2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine;3-[6-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo-[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-2-azaspiro-[3.3]heptan-2-yl]-2,3-dihydro-ll6-thiophene- 1 , 1 -di one;(2S)-2-[3-chloro-6-[l-[2-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-2-azaspiro[3.3]heptan-6-yl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3 -(2- { 3 -chloro-4-[ 1 -(5 -fluoropyrimidin-2-yl)ethoxy]-pyrazolo[ 1 ,5-a]pyridin-6-yl } -3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-5-yl)-ll6-thietane-l,l-dione;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;- 73 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(2S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(4-fluorophenyl)ethanol;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[ 1,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer A;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer B;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((S)- 1 -((E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((S)- 1 -((E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyri din-2 -yl)ethanol Isomer B;3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-6-(5-m ethyl- 1 -((S)- 1 -((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-6-(5-m ethyl- 1 -((S)- 1 -((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1 -di oxide Isomer A;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((R)-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;- 74 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((R)-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer B;3-((R)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer B;3 -(2- { 3 -chi oro-4- [( 1 R)- 1 -(5-fluoropyrimidin-2-yl)-2-hydroxy-ethoxy]pyrazolo[l,5-a]pyridin-6-yl}-3-methyl-4H,5H,6H,7Hpyrazolo[l,5-a]pyrazin-5-yl)-1 X hi etane- 1 , 1 -di one;3 -(2- { 3 -chi oro-4- [( 1 S)- 1 -(5 -fluoropyrimidin-2-yl)-2-hy droxy-ethoxy ]pyrazolo[ 1 , 5 -a]pyridin-6-yl}-3-methyl-4H,5H,6H,7Hpyrazolo[l,5-a]pyrazin-5-yl)-ll6-thietane-l,l-dione;3 - [(3 S,4 S)-4-(4- { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 -a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-l-yl]-2,3-dihydro-ll6-thiophene-l,l-dione Isomer A;3 - [(3 S,4 S)-4-(4- { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 -a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-l-yl]-2,3-dihydro-ll6-thiophene-l,l-dione Isomer B;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-2-azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thietane 1,1-dioxide;- 75 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(2S)-2-[3-chloro-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethan- 1 -ol ;(2S)-2-[(3-chloro-6-{l-[(2S,4S)-l-[(2S,3E)-4-methanesulfonylbut-3-en-2-yl]-2-methylpiperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}-pyrazolo[l,5-a]pyridin-4-yl)oxy]-2-(5 -fluoropyri din-2 -yl)ethan- 1 -ol ;3-chloro-4-methoxy-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methyl-sulfonylallyl]-2-azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;(2S)-2-[3-chloro-6-[5-methyl-l-[(2R,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2 S)-2- [3 -chloro-6-[5-methyl- 1 -[(2R,4S)-2-methyl- 1 -[(E, 1 S)- 1 -methyl-3 -methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2R)-2- [(3 -chi oro-6- { 1 - [(3R,4 S)-3 -fluoro- 1 - [(2 S, 3E)-4-methane-sulfonylbut-3 -en-2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethan-l-ol;(2S)-2-[(3-chloro-6-{l-[(3R,4S)-3-fluoro-l-[(2S,3E)-4-methane-sulfonylbut-3-en-2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]-2-(5-fluoropyri din-2 -yl)ethan- 1 -ol;3 -(2- { 3 -chi oro-4- [( 1 S)- 1 -(5 -fluoropyridin-2-yl)-2-hy droxy ethoxy ] -py razolof 1 , 5 -a]pyridin-6-yl}-3-methyl-4H,5H,6H,7Hpyrazolo[l,5-a]pyrazin-5-yl)-ll6-thietane-l,l-dione;3-chloro-6-[l-[(3R,4S)-3-fluoro-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridine;3-chloro-6-[l-[(3R,4S)-3-fluoro-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridine;(S)-3-(4-(4-(3-chloro-4-(l-(4-fluorophenyl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;- 76 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-m ethoxy ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-m ethoxy ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;2-((3-chloro-6-(l-((R)-l-((R)-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate Isomer A;2-((3-chloro-6-(l-((R)-l-((R)-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)thietane 1 , 1 -dioxide;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl- 1-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;(2S)-2-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2R,3E)-4-methanesulfonylbut-3-en- 2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]-2-(5-fluoropyri din-2 -yl)ethan- 1 -ol;(2S)-2-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2S,3E)-4-methane-sulfonylbut-3-en-2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]-2-(5-fluoropyri din-2 -yl)ethan- 1 -ol;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-[(2R,3E)-4-methanesulfonyl-but-3-en-2-yl]-7-azaspiro[3.5 ]nonane;- 77 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-[(2S,3E)-4-methanesulfonylbut-3-en-2-yl]-7-azaspiro[3.5 ]nonane;3-[(2R,4S)-4-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol- 1 -yl]-2-methyl- 1 -piperidyl]thiolane 1 , 1 -dioxide;3 - [(3R,4 S)-4-(4- { 3 -chloro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 -a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-l-yl]-ll6-thiolane-l,l-dione;(S)-2-((3 -chloro-6-( 1 -(1 -(-2,2-dimethyl- 1 -((E)-4-(methylsulfonyl)but-3 -en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3 -chloro-6-( 1 -(1 -(-2,2-dimethyl- 1 -((E)-4-(methylsulfonyl)but-3 -en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;(S)-2-((3 -chloro-6-( 1 -(1 -(-2,2-dimethyl- 1 -((E)-4-(methylsulfonyl)but-3 -en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer C;(S)-2-((3 -chloro-6-( 1 -(1 -(-2,2-dimethyl- 1 -((E)-4-(methylsulfonyl)but-3 -en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer D;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-m ethoxy ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(S)-2-((3-chloro-6-(l-((R)-l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate Isomer A;(S)-2-((3-chloro-6-(l-((R)-l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate Isomer B;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -( 1 , 1 -di oxidothi etan-3 -yl)piperi din-3 -yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate;- 78 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2R,4S)-2-methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2R,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3 - [(2 S,4 S)-4-(4- { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 -a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-2-methylpiperidin-l-yl]-ll6-thiolane-l,l-dione;3 - [(3 S,4 S)-4-(4- { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 -a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-l-yl]-ll6-thiolane-l,l-dione;3-chloro-4-isopropoxy-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-2-azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-chloro-4-ethoxy-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methylsulfonylallyl]-2-azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;(2S)-2-[3-chloro-6-[l-[2-(l,l-dioxothietan-3-yl)-2-azaspiro[3.3]heptan-6-yl]-5-methyl-pyrazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[5-methyl-l-[2-[(E,lS)-l-methyl-3-methylsulfonylallyl]-2-azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5-a]pyridine Isomer A;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5-a]pyridine Isomer B;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5-a]pyridine Isomer C;- 79 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5-a]pyridine Isomer D;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-m ethoxy ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1 -di oxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-m ethoxy ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((3R)-l-(4-(methylsulfonyl)butan-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;(2S)-2-((3-chloro-6-(5-methyl-l-((3R)-l-(4-(methylsulfonyl)butan-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5-a]pyridine Isomer A;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5-a]pyridine Isomer B;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5-a]pyridine Isomer C;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5-a]pyridine Isomer D;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-isopropoxypyrazolo[l,5-a]pyridine Isomer A;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-isopropoxypyrazolo[l,5-a]pyridine Isomer B;- 80 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-isopropoxypyrazolo[l,5-a]pyridine Isomer C;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-isopropoxypyrazolo[l,5-a]pyridine Isomer D;(2S)-2-[3-chloro-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methyl-sulfonylallyl]-2-azaspiro-[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[l-[2-(l,l-dioxothietan-3-yl)-2-azaspiro[3.3]heptan-6-yl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-[(3S,4S)-4-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-l-yl]-ll6-thiolane-l,l-di one Isomer A;3-[(3S,4S)-4-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-l-yl]-ll6-thiolane-l,l-dione Isomer B;3 - [(3R,4 S)-4-(4- { 3 -chloro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 -a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-l-yl]-2,3-dihydro-ll6-thiophene- 1 , 1 -di one;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer B;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer C;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer D;- 81 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)tetrahydrothiophene 1,1 -di oxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)tetrahydrothiophene 1,1 -di oxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;2-[(lR)-l-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2R)-4-methanesulfonyl-butan-2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]ethyl]- 5-fluoropyridine;[6-[4-[3-chloro-4-[(lS)-l-(5-fluoro-2-pyridyl)-2-methoxyethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]-2,3-dihydrothiophene 1,1-dioxide;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -( 1 - (4 -(methylsulfonyl)butan-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -( 1 - (4 -(methylsulfonyl)butan-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3-[7-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin- 6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-2-azaspiro[3.5]nonan-2-yl]-2,3-dihydro-ll6-thiophene- 1 , 1 -di one;(7-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-2-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-2-azaspiro[3.5 ]nonane;- 82 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-[(2R)-4-methanesulfonylbutan-2-yl]-7-azaspiro[3.5 ]nonane;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[6-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-6-azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(E)- 4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)- 2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;3 -((7R, 8aS)-7-(4-(3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)pyrazolo [ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)hexahydropyrrolo[ 1 ,2-a]pyrazin-2(lH)-yl)-2,3 -dihydrothiophene 1 , 1 -dioxide;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(E)- 4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3-chloro-6-(l-(l-(4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 -yl)ethoxy)pyrazolo[ 1,5-a]pyridine Isomer A;- 83 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-6-(l-(l-(4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 -yl)ethoxy)pyrazolo[ 1,5-a]pyridine Isomer B;3-chloro-6-(l-(l-(4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 -yl)ethoxy)pyrazolo[ 1,5-a]pyridine Isomer C;3-chloro-6-(l-(l-(4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5-methyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 -yl)ethoxy)pyrazolo[ 1,5-a]pyridine Isomer D;3-chloro-6-[l-[(3S,4S)-3-fluoro-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]-4-[(lS)-l-(5-fluoro-2-pyridyl)-2 -methoxy-ethoxy]pyrazolo[ 1 , 5-a]pyridine;[(2S)-2-[3-chloro-6-[l-[(3S,4S)-3-fluoro-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethyl] acetate;(2S)-2-[3-chloro-6-[5-methyl-l-[6-[(E,lR)-l-methyl-3-methylsulfonylallyl]-6-azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-{[3-chloro-6-(l-{6-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-6-azaspiro[3.5]nonan-2-yl}-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl]oxy}-2-(5-fluoropyridin-2-yl)ethan-l-ol;[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]-2,3-dihydrothiophene 1,1-dioxide;3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]thiolane 1,1-dioxide;3-[7-[4-(3-chloro-4-methoxy-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-triazol-l-yl]-2-azaspiro[3.5]nonan-2-yl]-2,3-dihydrothiophene 1,1-dioxide;3-chloro-4-methoxy-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methylsulfonylallyl]-2-azaspiro[3.5]nonan-7-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-((7S,8aS)-7-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)hexahydropyrrolo[ 1 ,2-a]pyrazin-2(lH)-yl)-2,3 -dihydrothiophene 1 , 1 -dioxide;- 84 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -(( 1 R, 3 S, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5 -fluoropy ridin-2-yl)ethoxy)-pyrazolo[ 1,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)-2,3-dihydrothiophene 1,1 -di oxide Isomer A;3 -(( 1 R, 3 S, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5 -fluoropy ridin-2-yl)ethoxy)pyrazol o[ 1 , 5 -a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;3 -(( 1 R, 3 S, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5 -fluoropy ridin-2-yl)ethoxy)pyrazol o[ 1 , 5 -a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3 -(( 1 R, 3 S, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5 -fluoropy ridin-2-yl)ethoxy)pyrazol o[ 1 , 5 -a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-6-azaspiro[3.5]nonan-6-yl]-2,3-dihydro-ll6-thiophene- 1 , 1 -di one;3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-6-azaspiro[3.5]nonan-6-yl]-ll6-thiolane-l,l-dione;3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]thiolane-l,l-dioxide Isomer A;3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]thiolane-l,l-dioxide Isomer B;3-chloro-4-ethoxy-6-[5-methyl-l-[7-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-7-azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrrolo[l,2-b]pyridazine;2-[(lR)-l-[(3-chloro-6-{l-[(3R,4S)-3-fluoro-l-[(2R)-4-methanesulfonyl-butan-2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine;- 85 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(2 S)-2- { [3 -chloro-6-( 1 - { 7- [(2R)-4-methanesulfonylbutan-2-yl]-7-azaspiro[3.5]nonan-2-yl}-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl]oxy}-2-(5-fluoropyridin-2-yl)ethan-l-ol;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[6-[(lR)-l-methyl-3-methylsulfonyl-propyl]-6-azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]-2,3-dihydrothiophene 1,1-dioxide Isomer A;3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]-2,3-dihydrothiophene 1,1-dioxide Isomer B;2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-6-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-6-azaspiro[3.5 ]nonane;6-[l-[(3aR,6aS)-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-3,3a,4,5,6,6ahexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4-yl]-3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridine;-[l-[(3aS,6aR)-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4-yl]-3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridine;-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3-methyl-5-[(3S)-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]pyrrolidin-3-yl]-6,7-dihydro-4H-pyrazolo[ 1 , 5-a]pyrazine;2S)-2-[6-[l-[(3aS,6aR)-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4-yl]-3-chloro-pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;S)-2-[6-[l-[(3aR,6aS)-2-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4-yl]-3-chloro-pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methylsulfonylallyl]-2-azaspiro-[3.5]nonan-7-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;- 86 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(2S)-2-[6-[l-[(3aS,6aR)-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-3,3a,4,5,6,6a-hexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4-yl]-3-chloro-pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-[(3aR,5S,6aS)-5-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-octahydrocyclo-penta[c]pyrrol-2-yl]-2,3 -dihydro- 1 l6-thiophene- 1 , 1 -di one;3-chloro-6-(l-(l-(E)-l-cyclopropyl-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 -yl)ethoxy)pyrazolo[ 1,5-a]pyridine Isomer A;3-chloro-6-(l-(l-(E)-l-cyclopropyl-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 -yl)ethoxy)pyrazolo[ 1,5-a]pyridine Isomer B;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-[2,2-dimethyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]azetidin-3-yl]-3-methyl-6,7-dihy dro-4H-pyrazolo[ 1 , 5 -a]pyrazine;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-[2,2-dimethyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]azetidin-3-yl]-3-methyl-6,7-dihy dro-4H-pyrazolo[ 1 , 5 -a]pyrazine;3-((7S,8aS)-7-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3 -triazol- 1 -yl)hexahydropyrrolo[ 1 ,2-a]pyrazin-2(lH)-yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer A;3-((7S,8aS)-7-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3 -triazol- 1 -yl)hexahydropyrrolo[ 1 ,2-a]pyrazin-2(lH)-yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer B;2-[(lR)-l-[(3-chloro-6-{5-[(3S)-l-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]pyrrolidin-3-yl]-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-2-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine;3 - [(3 aR, 5R,6aS)-5-(4-{3 -chi oro-4- [( 1 S)- 1 -(5 -fluoropyri din-2 -yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-octahydrocyclo-penta[c]pyrrol-2-yl]-4-hydroxy- 1 l6-thiolane- 1 , 1 -di one Isomer A;- 87 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 - [(3 aR, 5R,6aS)-5 -(4- { 3 -chi oro-4- [( 1 S)- 1 -(5 -fluoropyri din-2 -yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-octahydrocyclo-penta[c]pyrrol-2-yl]-4-hydroxy- 1 l6-thiolane- 1 , 1 -di one Isomer B;3-((7R,8aS)-7-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3 -triazol- 1 -yl)hexahydropyrrolo[ 1 ,2-a]pyrazin-2(lH)-yl)-2, 3 -dihydrothiophene 1,1-dioxide;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((7S,8aS)-2-((E)-4-(methylsulfonyl)but-3-en-2-yl)octahydropyrrolo[l,2-a]pyrazin-7-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3-methyl-5-[l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazine;2-[(lR)-l-[(3-chloro-6-{5-[(4S)-2-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-l,2-oxazolidin-4-yl]-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-2-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine;(lR,5S,7R)-7-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-9-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-3-oxa-9-azabicyclo-[3.3.1 ]nonane;(2S)-2-[3-chloro-6-[3-methyl-5-[(3R)-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]pyrr°lidin-3-yl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl] oxy-2-(5 -fluoro-2-pyridyl)ethanol ;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene- 1,1 -dioxi de Isomer A;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene- 1,1 -dioxi de Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene 1,1 -di oxide Isomer A;- 88 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer B;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1-dioxide Isomer A;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1-dioxide Isomer B;3-((R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1 , 1 -dioxide Isomer A;3-((R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer B;(R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidine Isomer A;(R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidine Isomer B;(lR,5S,7S)-7-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-9-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)-3-oxa-9-azabicyclo[3.3.1]nonane ;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer B;- 89 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3 -chloro-6-( 1 -((R)- 1 -(- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3 -yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl propionate Isomer A;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -(- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3 -yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl propionate Isomer B;(2S)-2-[3-chloro-6-[3-methyl-5-[l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5 -fluoro-2-pyridyl)ethanol ;(2S)-2-[3-chloro-6-[5-[(3 R)-l -(1,1 -di oxothiolan-3-yl)pyrrolidin-3-yl]-3 -methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro- 2-pyridyl)ethanol;3 - [(2R,4 S)-4-(4- { 3 -chloro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 -a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-2-methylpiperidin-l-yl]-ll6-thietane-l,l-dione;(2S)-2-[3-chloro-6-[5-[(3S)-l-(l,l-dioxothiolan-3-yl)pyrrolidin-3-yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-[(2S,4S)-4-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol- 1 -yl]-2-methyl- 1 -piperidyl]thietane 1 , 1 -dioxide;(4R)-4-[2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-5-yl]-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]isoxazolidine;(S)-2-((3-chloro-6-(5-methyl-l-((lR,5S,7R)-9-((R,E)-4-(methyl-sulfonyl)but-3-en-2-yl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin- 4-yl)oxy)-2-(5-fluoro-pyridin-2-yl)ethanol;3-((S)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydrothiophene 1 , 1 -dioxide Isomer A;3-((S)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydrothiophene 1,1 -di oxide Isomer B;- 90 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -( 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3 -yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate Isomer A;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -( 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3 -yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate Isomer B;3-[(lR,5S,7r)-7-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-oxa-9-azabicy clo[3.3.1 ]nonan-9-yl]- 1 X hi etane- 1 , 1 -di one;(lR,5S)-7-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-9-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-3-oxa-9-azabicyclo-[3.3.1 ]nonane;2S)-2-[(3-chloro-6-{5-[(4S)-2-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-l,2-oxazolidin-4-yl]-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-2-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethan-l-ol;3-[(lR,5S)-7-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-3-oxa-9-azabicyclo[3.3.1]nonan-9-yl]thietane 1,1-dioxide;3-[(4S)-4-(2-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-5-yl)-l,2-oxazolidin-2-yl]-2,3-dihydro-ll6-thiophene-l,l-dione;(S)-2-((3-chloro-6-(5-methyl-l-((R)-2-(E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;- 91 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3-chloro-6-(5-methyl-l-((R)-2-(E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyri din-2 -yl)ethanol Isomer B;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer C;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer D;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;(2S)-2-((3-chloro-6-(5-methyl-l-((7S,8aS)-2-((E)-4-(methylsulfonyl)-but-3-en-2-yl)octahydropyrrolo[l,2-a]pyrazin-7-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-(l-((S)-l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)pyrrolidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate Isomer A;(S)-2-((3-chloro-6-(l-((S)-l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)pyrrolidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate Isomer B;- 92 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)tetrahydrothiophene 1,1 -di oxide Isomer A;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4-(methylsulfonyl)-but-3-en-2-yl)-8-azabicyclo-[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-( 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[ 1,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)thietane 1 , 1 -dioxide Isomer A;3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-( 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[ 1,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)thietane 1,1-dioxide Isomer B;(2S)-2-[3-chloro-6-[5-[l-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-4-piperidyl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-chloro-6-[l-[(2R,6R)-2,6-dimethyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridine;3-[4-[2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-5-yl]-l-piperidyl]-2,3-dihydrothiophene 1 , 1 -dioxide;(2S)-2-[3-chloro-6-[5-[(4S)-2-(l,l-dioxo-2,3-dihydrothiophen-3-yl)isoxazolidin-4-yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;- 93 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(2S)-2-[3-chloro-6-[3-methyl-5-[(3S)-l-[(E,lR)-l-methyl-3-methyl-sulfonylallyl]pyrrolidin-3-yl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-[(4R)-4-[2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-5-yl]isoxazolidin-2-yl]-2,3 -dihydrothiophene 1 , 1 -dioxide;(2S)-2-[3-chloro-6-[3-methyl-5-[(4R)-2-[(E,lR)-l-methyl-3-methyl-sulfonyl-allyl]isoxazolidin-4-yl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-( 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[ 1,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)thietane 1 , 1 -dioxide Isomer A;3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-( 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[ 1,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)thietane 1,1 -di oxide Isomer B;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((7R,8aS)-2-((E)-4-(methylsulfonyl)but-3-en-2-yl)octahydropyrrolo[l,2-a]pyrazin-7-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;(S)-2-((3-chloro-6-(5-methyl-l-((S)-2-((E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-((S)-2-((E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyri din-2 -yl)ethanol Isomer B;3-((R)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer B;- 94 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((R)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer C;3-((R)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer D;3-((R)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)isoxazolidin-2-yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-((R)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)isoxazolidin-2-yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer B;3-((R)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)isoxazolidin-2-yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer C;3-((R)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)isoxazolidin-2-yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer D;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer C;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer D;- 95 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(2S)-2-[3-chloro-6-[5-methyl-l-[(lR,5S)-9-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5 -fluoro-2-pyridyl)ethanol ;(2S)-2-[3-chloro-6-[l-[(2R,6R)-2,6-dimethyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5 -fluoro-2-pyridyl)ethanol ;3-((R)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide Isomer A;3-((R)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer B;(S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidine Isomer A;(S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidine Isomer B;3-((S)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1 , 1 -dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1 , 1 -dioxide Isomer B;3-((S)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1 , 1 -dioxide Isomer C;3-((S)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1 , 1 -dioxide Isomer D;- 96 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)isoxazolidin-2-yl)-2, 3 -dihydro-thiophene 1 , 1 -dioxide Isomer A;3-((S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)isoxazolidin-2-yl)-2, 3 -dihydro-thiophene 1 , 1 -dioxide Isomer B;3-((S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)isoxazolidin-2-yl)-2, 3 -dihydro-thiophene 1 , 1 -dioxide Isomer C;3-((S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)isoxazolidin-2-yl)-2, 3 -dihydro-thiophene 1 , 1 -dioxide Isomer D;(R)-3-((S)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide Isomer A;(R)-3-((S)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer B;3-chloro-4-[l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-[l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine Isomer B;3-chloro-4-[l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-[l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine Isomer B;- 97 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3-methyl-5-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-6,7-dihy dro-4H-pyrazolo[ 1 , 5 -a]pyrazine;(2S)-2-[3-chloro-6-[3-methyl-5-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-;yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[3-methyl-5-[(2S,4R)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo-[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-((S)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene- 1,1 -di oxide Isomer A;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydrothio-phene- 1,1 -di oxide Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer B;4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-3-methyl-6-[5-methyl-l-[(2S,4S)-2-;- 98 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)methyl- 1 -[(E, 1R)- 1 -methyl-3 -methylsulfonyl-allyl]-4-piperidyl]triazol-4-; yl]pyrazolo[ 1 ,5 -a]pyridine;4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-3-methyl-6-[5-methyl-l-[(2S,4S)-2-; methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-y 1 ] py razol o [ 1 , 5 -a] py ri dine ;3-((R)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer B;3 -chloro-4-(l -(5 -fluoropyridin-2-yl)-2-(oxetan-3 -yl)ethoxy)-6-(5-m ethyl- 1 -(1 -(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3 -chloro-4-(l -(5 -fluoropyridin-2-yl)-2-(oxetan-3 -yl)ethoxy)-6-(5-m ethyl- 1 -(1 -(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3 -chloro-4-(l -(5 -fluoropyridin-2-yl)-2-(oxetan-3 -yl)ethoxy)-6-(5-m ethyl- 1 -(1 -(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer C;3 -chloro-4-(l -(5 -fluoropyridin-2-yl)-2-(oxetan-3 -yl)ethoxy)-6-(5-m ethyl- 1 -(1 -(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer D;(2S)-2-[(3-chloro-6-(l-[(2S,4S)-l-[(2S,3E)-4-methanesulfonylbut-3-en-2-yl]-2-methylpiperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl-pyrazolo[l,5-a]pyridin-4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethyl (2S)-2-aminopropanoate;(2S)-2-[(3-chloro-6-{l-[(2S,4S)-l-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-2-methylpiperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl-pyrazolo[l,5-a]pyridin-4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethyl (2S)-2-aminopropanoate;(2S)-2-(5-fluoro-2-pyridyl)-2-[3-methyl-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl] oxy-ethanol;- 99 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(2S)-2-(5-fluoro-2-pyridyl)-2-[3-methyl-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-ethano;[(2S)-2-[3-chloro-6-[5-methyl-l-[(2R,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethyl] (2S)-2-aminopropanoate;[(2S)-2-[3-chloro-6-[5-methyl-l-[(2R,4S)-2-methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethyl] (2S)-2-aminopropanoate; orl-[3-chloro-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methyl-sulfonyl-allyl]-4-piperidyl]-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)propan-2-ol.

[0364] In some aspects, the compounds listed above include multiple stereoisomers of the same constitutional isomer. For such compounds, the disclosure contemplates each of the possible stereoisomers.

[0365] In some aspects, the disclosure is directed to the following compounds, or a pharmaceutically acceptable salt thereof:(R)-2-((3-chloro-6-(l-((S)-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R)-2-((3-chloro-6-(l-((R)-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chloro-6-( 1 -((S)-2,2-dimethyl- 1 -((E)-3 -(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-(l-((R)-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;- 100 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(S, E)-3-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)propan-l-ol;(R, E)-3-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- 1H- 1,2,3 -tri azol -4-yl)pyrazolo[ 1 , 5-a]pyridin-4-yl)oxy)propan- 1 -ol;(R)-2-((3-chloro-6-(l-(l-((S)-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R)-2-((3 -chloro-6-( 1 -( 1 -((R)-2,2-dimethyl- 1 -((E)-3 - (methylsulfonyl)allyl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chloro-6-( 1 -(1 -((S)-2,2-dimethyl- 1 -((E)-3 -(methyl sulfonyl )al lyl )azeti din-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R)-2-((3 -chloro-6-(5 -methyl- 1 -(1 -((R, E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl obuty 1 ethanol ;(R)-2-((3-chloro-6-(5-methyl-l-(l-((S, E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl obuty 1 ethanol ;- 101 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((R, E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl obuty 1 ethanol ;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((S, E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl obuty 1 ethanol ;(R, E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)ethanol;(S, E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)ethanol;(R)-2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl opropy 1 ethanol ;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((S,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl opropy 1 ethanol ;(R)-2-((3 -chloro-6-(5 -methyl- 1 -(1 -((R,E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl opropy 1 ethanol ;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((R,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-cy cl opropy 1 ethanol ;(S, E)-l-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-methylpropan-2-ol;(R, E)- 1 -((3 -chloro-6-(5-methyl- 1 -( 1 -(4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-methylpropan-2-ol;3-chloro-5-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-7-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)imidazo[l,2-a]pyridine;3-chloro-5-((S)-l-(5-fluoropyridin-2-yl)ethoxy)-7-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)imidazo[l,2-a]pyridine;- 102 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-5-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-7-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)imidazo[l,2-a]pyridine;3-chloro-5-((S)-l-(5-fluoropyridin-2-yl)ethoxy)-7-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)imidazo[l,2-a]pyridine;4-[ 1 -(5 -fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl- 1 -[ 1 -[(R,E)-3 -methylsulfonylallyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;4-[ 1 -(5 -fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl- 1 -[ 1 -[(S,E)-3 -methylsulfonylallyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((R,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((S,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol;(R)-2-((3 -chloro-6-(5 -methyl- 1 -(1 -((R,E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol;(R)-2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol;2-[3-chloro-6-[3-methyl-5-[(E,R)-3-methylsulfonylallyl]-6,7-dihydro-4Hpyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-5-[(E,S)-3-methylsulfonylallyl]-6,7-dihydro-4Hpyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(S)-2-[3-chloro-6-[3-methyl-5-[l-[(S,E)-3-methylsulfonylallyl]pyrrolidin-3-yl]-6,7-dihydro-4H-pyrazolo[l,5-a]-pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;- 103 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-[3-chloro-6-[3-methyl-5-[l-[(R,E)-3-methylsulfonylallyl]pyrrolidin-3-yl]- 6,7-dihydro-4H-pyrazolo[l,5-a]-pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(R)-2-[3-chloro-6-[3-methyl-5-[l-[(S,E)-3-methylsulfonylallyl]pyrrolidin-3-yl]- 6,7-dihydro-4H-pyrazolo[l,5-a]-pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(R)-2-[3-chloro-6-[3-methyl-5-[l-[(R,E)-3-methylsulfonylallyl]pyrrolidin-3-yl]- 6,7-dihydro-4H-pyrazolo[l,5-a]-pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(S)-2-[3-chloro-6-[3-methyl-7-(3-methylsulfonylpropyl)-6,8-dihydro-5H-imidazof 1 ,2-a]pyrazin-2-yl]pyrazolo[ 1 ,5 -a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(R)-2-[3-chloro-6-[3-methyl-7-(3-methylsulfonylpropyl)-6,8-dihydro-5H-imidazof 1 ,2-a]pyrazin-2-yl]pyrazolo[ 1 ,5 -a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[5-methyl-l-[7-[(E, R)-3-methylsulfonylallyl]-7-azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[5-methyl-l-[7-[(E, S)-3-methylsulfonylallyl]-7-azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(S,E)-4-((3-fluoropyridin-2-yl)thio)-6-(5-methyl-l-(l-(4-(methylsulfonyl)-but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3-carbonitrile;(R,E)-4-((3-fluoropyridin-2-yl)thio)-6-(5-methyl-l-(l-(4-(methylsulfonyl)-but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3-carbonitrile;(S)-3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;- 104 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-2-[3-chloro-6-[3-methyl-7-[(R,E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(S)-2-[3-chloro-6-[3-methyl-7-[(S,E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(R)-2-[3-chloro-6-[3-methyl-7-[(R,E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(R)-2-[3-chloro-6-[3-methyl-7-[(S,E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H-imidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-7-[(S,E)-3-methylsulfonylallyl]-6,8-dihydro-5Himidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)-ethanol;2-[3-chloro-6-[3-methyl-7-[(R,E)-3-methylsulfonylallyl]-6,8-dihydro-5Himidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)-ethanol;(S)-3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;- 105 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;6-(l-(l-((S)-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-1 ,2,3 -triazol-4-yl)-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1,5-a]pyridine-3 -carbonitrile;6-(l-(l-((R)-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-1 ,2,3 -triazol-4-yl)-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1,5-a]pyridine-3 -carbonitrile;(S)-6-(l-(l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile;(R)-6-(l-(l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH- 1.2.3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile;(R)-2-((3 -chloro-6-(5 -methyl- 1 -(1 -((R,E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol;(R)-2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((R,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((S,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2-yl)ethanol;6-(l-(l-((R)-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH- 1.2.3-triazol-4-yl)-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile;6-(l-(l-((S)-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile;- 106 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)6-(l-(l-((R)-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH- 1 ,2,3 -triazol-4-yl)-4-((S)-2-hydroxy- 1 -(pyri din-2 -yl)ethoxy)pyrazolo[ 1 ,5-a]pyridine-3 -carbonitrile;6-(l-(l-((S)-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH- 1 ,2,3 -triazol-4-yl)-4-((S)-2-hydroxy- 1 -(pyri din-2 -yl)ethoxy)pyrazolo[ 1 ,5-a]pyridine-3 -carbonitrile;6-(l-(l-((S)-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH- 1 ,2,3 -triazol-4-yl)-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1,5-a]pyridine-3 -carbonitrile;6-(l-(l-((R)-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH- 1 ,2,3 -triazol-4-yl)-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1,5-a]pyridine-3 -carbonitrile;6-(l-(l-((S)-l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3 -carbonitrile;6-(l-(l-((R)-l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3 -carbonitrile;6-(l-(l-((S)-l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3 -carbonitrile;6-(l-(l-((R)-l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3 -carbonitrile;6-(l-(l-((S)-l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3 -carbonitrile;6-(l-(l-((R)-l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridine-3 -carbonitrile;(R)-4-(4-(4-(3-chloro-4-(2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide;- 107 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-4-(4-(4-(3 -chloro-4-(2-hydroxy- 1 -(pyri din-2 -yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide;4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)-6-(5-m ethyl- 1 -(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3-carbonitrile;4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)-6-(5-m ethyl- 1 -(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile;4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile;4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile;4-((S)-2-hydroxy- 1 -(pyridin-2-yl)ethoxy)-6-(5-methyl- 1 -( 1 -((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile;4-((S)-2-hydroxy- 1 -(pyridin-2-yl)ethoxy)-6-(5-methyl- 1 -( 1 -((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3 -carbonitrile;(S)-3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;- 108 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-6-(l-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile;(R)-6-(l-(l-(l,l-dioxidotetrahydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3-carbonitrile;(R)-3-(4-(4-(3-chloro-4-((R)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((S)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1 , 1 -dioxide;(R)-2-((3 -chloro-6-(5 -methyl- 1 -(1 -(R,E)-(4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3-fluoropyridin-2-yl)ethanol;(R)-2-((3-chloro-6-(5-methyl-l-(l-(S,E)-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -(R,E)-(4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -(S,E)-(4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3-fluoropyridin-2-yl)ethanol;(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1 , 1 -dioxide;- 109 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene-1, 1-dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene-1, 1-dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene-1, 1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene-1, 1-dioxide;(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3 -chi oro-4-((R)-l-(4-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;- 110 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-(4-(4-(3 -chi oro-4-((S)-l-(4-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro-thiophene- 1 , 1 -dioxide;(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro-thiophene- 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro-thiophene- 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro-thiophene- 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((S)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;- Ill - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(S)-3 -(4-(4-(3 -chloro-4-((R)- 1 -(4-fluoropyri din-2 -yl)ethoxy)pyrazolo[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide;(S)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide;(S)-3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)-2-hydroxy-ethoxy]pyrazolo[ 1 , 5-a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-7 -azaspiro[3.5 ]nonan-7-yl]-2, 3 -dihydro- 1 l6-thiophene- 1 , 1 -di one;(R)-3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)-2-hydroxy-ethoxy]pyrazolo[ 1 , 5-a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-7 -azaspiro[3.5 ]nonan-7-yl]-2, 3 -dihydro- 1 l6-thiophene- 1 , 1 -di one;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;- 112 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-methylpyridin-2-yl)ethoxy)pyrazolo[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-4-(4-(4-(3-chloro-4-(l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide;(S)-4-(4-(4-(3-chloro-4-(l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;- 113 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)propoxy)pyrazolo[ 1,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(S)-3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thiolane-l,l-dione;(R)-3 - [2 -(4- { 3 -chloro-4-[( 1R)- 1 -(5 -fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thiolane-l,l-dione;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((R,E)-4-(m ethyl sulfonyl )but-3 -en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((S,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)propoxy)pyrazolo[ 1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyrimidin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;- 114 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyrimidin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-3-fluoropyridin-2-yl)piperazin-l-yl)thietane 1, 1 -di oxide;(S)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5-a]pyridin-6-yl)pyri din-2 -yl)piperazin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(6-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)pyridin-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)thietane 1,1-dioxide;(S)-3 - [2-(4- { 3 -chloro-4-[(l S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-7-azaspiro-[3.5]nonan-7 -y 1 ] -2, 3 -dihydro- 1 l6-thiophene- 1 , 1 -dione;(R)-3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-7-azaspiro-[3.5]nonan-7 -y 1 ] -2, 3 -dihydro- 1 l6-thiophene- 1 , 1 -dione;(R)-3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thiolane-l,l-dione;(S)-3 - [2-(4- { 3 -chloro-4-[(l S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-7-azaspiro[3.5]nonan-7-yl]-ll6-thiolane-l,l-dione;(S)-2-[3-chloro-6-[l-[l-((R)-l,l-dioxo-2,3-dihydrothiophen-3-yl)-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(2-pyridyl)ethanol;(S)-2-[3-chloro-6-[l-[l-((S)-l,l-dioxo-2,3-dihydrothiophen-3-yl)-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(2-pyridyl)ethanol;(R)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thiolane 1,1-dioxide;- 115 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thiolane 1,1-dioxide;(S)-3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3 -((R)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-((S)-3-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;- 116 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(S)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(R)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(S)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(R)-3-((R)-3-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(R)-3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(4-fluoropyridin-2-yl)ethoxy)py razolo- [1,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydrothiophene 1,1-dioxide;- 117 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((R)- 1 -((R, E)-4-(methyl sulfonyl )but-3 -en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((S)- 1 -((R, E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R)-3 -((R)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(2S)-2-((3-chloro-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(4-fluorophenyl)ethanol;(2S)-2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(4-fluorophenyl)ethanol;(R)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1-dioxide;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((S)- 1 -((S,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((S)- 1 -((R, E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;- 118 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-6-(5-m ethyl- 1 -((S)- 1 -((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-6-(5-m ethyl- 1 -((S)- 1 -((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;(R)-3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1 , 1 -dioxide;(S)-3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxy ethoxy )-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1 , 1 -dioxide;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -((R)- 1 -(R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((R)-l-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;(R)-3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(R)-3-((R)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-[(3S,4S)-4-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-l-yl]-2,3-dihydro- 1 l6-thiophene- 1 , 1 -di one;(R)-3-[(3S,4S)-4-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-l-yl]-2,3-dihydro- 1 l6-thiophene- 1 , 1 -di one;- 119 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3 -((R)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-m ethoxy ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-m ethoxy ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -((R)- 1 , 1 -di oxidotetrahydrothi ophen-3 -yl)piperi din-3 -yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate;(R)-2-((3-chloro-6-(l-((R)-l-((R)-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate;(S)-2-((3 -chloro-6-( 1 -(1 -((S)-2,2-dimethyl- 1 -((S,E)-4-(methylsulfonyl)but-3 -en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chloro-6-( 1 -(1 -((S)-2,2-dimethyl- 1 -((R, E)-4-(m ethyl sulfonyl)but-3 -en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -((R)- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)piperidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin- 2-yl)ethyl acetate;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -((S)- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)piperidin- 3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate;- 120 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-6-(l-(l-((S)-2,2-dimethyl-l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((S)-2,2-dimethyl-l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5-a]pyridine;(R)-3 -((R)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-m ethoxy ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-m ethoxy ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;3-chloro-6-(l-(l-((S)-2,2-dimethyl-l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((S)-2,2-dimethyl-l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5-a]pyridine;- 121 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-6-(l-(l-((S)-2,2-dimethyl-l-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-isopropoxypyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((S)-2,2-dimethyl-l-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-isopropoxypyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-isopropoxypyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-isopropoxypyrazolo[l,5-a]pyridine;(S)-3 -[(3 S,4S)-4-(4- { 3 -chloro-4-[( 1R)- 1 -(5-fluoropyridin-2-yl)ethoxy]pyrazolo[ 1 ,5-a]pyridin-6-yl } -5-m ethyl- 1EI- 1 ,2 -tri azol- 1 -yl)-3 -fluoropiperi din-1 -yl] - 1 l6-thi olane- 1 , 1 -di one;(R)-3-[(3S,4S)-4-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-fluoropiperidin-1 -yl] - 1 l6-thi olane- 1 , 1 -di one;3-chloro-6-(l-(l-((S)-2,2-dimethyl-l-(S,E)-4-(methylsulfonyl)but-3-en-2-yl-azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((S)-2,2-dimethyl-l-(R,E)-4-(methylsulfonyl)but-3-en-2-yl-azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-(S,E)-4-(methylsulfonyl)but-3-en-2-yl-azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R)-2,2-dimethyl-l-(R,E)-4-(methylsulfonyl)but-3-en-2-yl-azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;- 122 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3 -((R)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3 -((R)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;3-chloro-4-((R)-l -(5-fluoropyri din-2-yl)ethoxy)-6-(5-methyl-l-(l-((S)-4-(methylsulfonyl)butan-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -( 1 -((R)-4-(methylsulfonyl)butan-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5 -fluoropyri din-2 -yl)ethanol ;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5 -fluoropyri din-2 -yl)ethanol ;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;- 123 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;3-chloro-6-(l-(l-((S,E)-4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((S,Z)-4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R,E)-4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-chloro-6-(l-(l-((R,Z)-4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;(R)-3-((lR,3S,5S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-3-((lR,3S,5S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)-2,3-dihydrothiophene 1,1-dioxide;(S)-3-((lR,3S,5S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)-2,3-dihydrothiophene 1,1-dioxide;(R)-3-((lR,3S,5S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)-2,3-dihydrothiophene 1,1-dioxide;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5 -fluoropyri din-2 -yl)ethanol ;- 124 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5 -fluoropyri din-2 -yl)ethanol ;(S)-3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]thiolane-l,l-dioxide;(R)-3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol- 1 -yl]-6-azaspiro[3.5]nonan-6-yl]thiolane- 1 , 1 -dioxide;(S)-3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]-2,3-dihydrothiophene 1,1-dioxide;(R)-3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]-2,3-dihydrothiophene 1,1-dioxide;3-chloro-6-(l-(l-(S,E)-l-cyclopropyl-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1,5-a]pyridine;3-chloro-6-(l-(l-(R,E)-l-cyclopropyl-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1,5-a]pyridine;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-[2,2-dimethyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]azetidin-3-yl]-3-methyl-6,7-dihy dro-4H-pyrazolo[ 1 , 5 -a]pyrazine;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5-[2,2-dimethyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]azetidin-3-yl]-3-methyl-6,7-dihy dro-4H-pyrazolo[ 1 , 5 -a]pyrazine;(S)-3-((7S,8aS)-7-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-1H- 1 ,2,3-triazol- 1 -yl)hexahydropyrrolo[ 1 ,2-a]pyrazin-2(lH)-yl)-2,3-dihydrothiophene 1,1-dioxide;(R)-3-((7S,8aS)-7-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-1H- 1 ,2,3-triazol- 1 -yl)hexahydropyrrolo[ 1 ,2-a]pyrazin-2(lH)-yl)-2,3-dihydrothiophene 1,1-dioxide;- 125 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2-[(lR)-l-[(3-chloro-6-{5-[(3S)-l-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]pyrrolidin-3-yl]-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-2-yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine;3(S)-[(3aR,5R,6aS)-5-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-octahydrocyclo-penta[c]pyrrol-2-yl]-4-hydroxy- 1 l6-thiolane- 1 , 1 -di one;3(R)-[(3aR,5R,6aS)-5-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-octahydrocyclo-penta[c]pyrrol-2-yl]-4-hydroxy- 1 l6-thiolane- 1 , 1 -di one;(S)-3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene- 1 , 1 -dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene- 1 , 1 -dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(R)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(S)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1-dioxide;(R)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1-dioxide;(S)-3-((R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;- 126 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-((R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidine;(R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidine;(S)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo-[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo-[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -((S)- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin- 2-yl)ethyl propionate;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -((R)- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin- 3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl propionate;(4R)-4-[2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-5-yl]-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]isoxazolidine;(S)-2-((3-chloro-6-(5-methyl-l-((lR,5S,7R)-9-((R,E)-4-(methyl-sulfonyl)but-3-en-2-yl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin- 4-yl)oxy)-2-(5-fluoro-pyridin-2-yl)ethanol;(S)-3-((S)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydrothiophene 1,1 -di oxide;- 127 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-((S)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydrothiophene 1,1 -di oxide;(S)-3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -((S)- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin- 2-yl)ethyl acetate;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -((R)- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin- 3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate;(S)-2-((3-chloro-6-((4S)-5-methyl-l-((R)-2-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-((4R)-5-methyl-l-((R)-2-(E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;- 128 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-1H- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 , 5-a]pyridine;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-1H- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 , 5-a]pyridine;(S)-2-((3 -chloro-6-( 1 -((S)- 1 -((S)- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin- 2-yl)ethyl acetate;(S)-2-((3 -chloro-6-( 1 -((S)- 1 -((R)- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin- 3-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethyl acetate;(S)-3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)tetrahydrothiophene 1 , 1 -dioxide;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-1 ,2,3 -triazol-4-yl)pyrazolo[ 1 ,5-a]pyridine;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(R,E)-4-(methylsulfonyl)-but-3-en-2-yl)-8-azabicyclo-[3.2.1]octan-3-yl)-1H- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 , 5-a]pyridine;3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-((S)- 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)thietane 1 , 1 -dioxide;- 129 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)thietane 1 , 1 -dioxide;3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-((S)- 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)thietane 1 , 1 -dioxide;3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8-yl)thietane 1 , 1 -dioxide;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((7R,8aS)-2-((E)-4-(methylsulfonyl)but-3-en-2-yl)octahydropyrrolo[l,2-a]pyrazin-7-yl)-lH-l,2,3-triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine ;(S)-2-((3-chloro-6-(5-methyl-l-((S)-2-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-(5-methyl-l-((S)-2-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(R)-3 -((R)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)propoxy)-pyrazolo[ 1 ,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide;- 130 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-((R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydrothiophene 1,1 -di oxide;(R)-3 -((R)-4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)propoxy)-pyrazolo-[ 1,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydrothiophene 1,1 -di oxide;(S)-3-((R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydrothiophene 1,1 -di oxide;(S)-3-((R)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydrothiophene 1,1 -di oxide;3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyraz°l°[l,5-a]pyridine;3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyraz°l°[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyraz°lo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyraz°lo[l,5-a]pyridine;(S)-3-((R)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(R)-3-((R)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;- 131 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidine;(S)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)isoxazolidine;(R)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1-dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1-dioxide;(S)-3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1-dioxide;(S)-3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)propoxy)-pyrazolo[ 1 ,5-a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1-dioxide;(R)-3-((S)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(R)-3-((S)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(S)-3-((S)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(S)-3 -((S)-4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyri din-2 -yl)propoxy)-pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;- 132 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-((S)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(S)-3-((S)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxy ethoxy )-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro-thiophene 1,1 -di oxide;3-chloro-4-[(S)-l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-chloro-4-[(R)-l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-chloro-4-[(S)-l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-chloro-4-[(R)-l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3-methyl-5-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-6,7-dihy dro-4H-pyrazolo[ 1 , 5 -a]pyrazine;(2S)-2-[3-chloro-6-[3-methyl-5-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[3-methyl-5-[(2S,4R)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo-[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(S)-3-((S)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3 -dihydrothiophene 1 , 1 -dioxide;- 133 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-((S)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3 -dihydrothiophene 1 , 1 -dioxide;(S)-3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-isopropoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene- 1 , 1 -dioxide;(R)-3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydrothio-phene- 1 , 1 -dioxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(R)-3 -((R)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2-isopropoxy-ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l-yl)-2,3-dihydro-thiophene 1,1 -di oxide;(S)-3-((R)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1 -dioxide;(R)-3-((R)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydro-thiophene 1,1 -dioxide;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-(oxetan-3-yl)ethoxy)-6-(5-methyl-l-(l-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-(oxetan-3-yl)ethoxy)-6-(5-methyl-l-(l-(R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-(oxetan-3-yl)ethoxy)-6-(5-methyl-l-(l-(S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine; or 3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-(oxetan-3-yl)ethoxy)-6-(5-m ethyl- 1 -( 1 -(S,E)-4-(methylsulfonyl)but-3 -en-2-yl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-y l)py razol o [ 1 , 5 -a] py ri dine .- 134 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0366] In some aspects, the disclosure is directed to the following compounds:>>- 135 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)""- 136 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)"">> <"">- 137 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0367] In other aspects, the disclosure is directed to the following compounds:- 138 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)- 139 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)"- 140 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0368] References herein to Formula (I) or subgenera thereof are meant to encompass the identified formula and any subgenera of those formula disclosed herein.

[0369] Stereoisomers of compounds of Formula (I) are also contemplated by the present disclosure. Thus, the disclosure encompasses all stereoisomers of any compound disclosed or claimed herein, including all enantiomers and diastereomers, or mixtures thereof.

[0370] Pharmaceutically acceptable salts and solvates of the compounds of Formula (I) are also within the scope of the disclosure.- 141 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0371] It is to be appreciated that certain features of the invention which are, for clarity, described herein in the context of separate embodiments, may also be provided in combination in a single embodiment. That is, unless obviously incompatible or specifically excluded, each individual embodiment is deemed to be combinable with any other embodiment s) and such a combination is considered to be another embodiment. Conversely, various features of the invention that are, for brevity, described in the context of a single embodiment, may also be provided separately or in any sub-combination. While an embodiment may be described as part of a series of steps or part of a more general structure, each said step may also be considered an independent embodiment in itself, combinable with others.Pharmaceutical compositions and methods of administration

[0372] In some aspects, the disclosure is directed to pharmaceutical compositions comprising a compound of the disclosure, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0373] The subject pharmaceutical compositions are typically formulated to provide a therapeutically effective amount of a compound of the present disclosure as the active ingredient, or a pharmaceutically acceptable salt, ester, prodrug, solvate, hydrate or derivative thereof. In some embodiments, the pharmaceutical compositions contain a compound of the present disclosure or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients, carriers, including inert solid diluents and fillers, diluents, including sterile aqueous solution and various organic solvents, permeation enhancers, solubilizers and adjuvants.

[0374] The subject pharmaceutical compositions can be administered alone or in combination with one or more other agents, which are also typically administered in the form of pharmaceutical compositions. Where desired, the one or more compounds of the invention and other agent(s) may be mixed into a preparation or both components may be formulated into separate preparations to use them in combination separately or at the same time.

[0375] In some embodiments, the concentration of one or more compounds provided in the pharmaceutical compositions of the present invention is less than 100%, 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%,- 142 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, 0.01%, 0.009%, 0.008%, 0.007%, 0.006%, 0.005%, 0.004%, 0.003%, 0.002%, 0.001%, 0.0009%, 0.0008%, 0.0007%, 0.0006%, 0.0005%, 0.0004%, 0.0003%, 0.0002%, or 0.0001% (or a number in the range defined by and including any two numbers above) w / w, w / v or v / v.

[0376] In some embodiments, the concentration of one or more compounds of the invention is greater than 90%, 80%, 70%, 60%, 50%, 40%, 30%, 20%, 19.75%, 19.50%, 19.25%, 19%, 18.75%, 18.50%, 18.25% 18%, 17.75%, 17.50%, 17.25% 17%, 16.75%, 16.50%, 16.25%, 16%, 15.75%, 15.50%, 15.25% 15%, 14.75%, 14.50%, 14.25% 14%, 13.75%, 13.50%, 13.25%, 13%, 12.75%, 12.50%, 12.25%, 12%, 11.75%, 11.50%, 11.25% 11%, 10.75%, 10.50%, 10.25% 10%, 9.75%, 9.50%, 9.25%, 9%, 8.75%, 8.50%, 8.25% 8%, 7.75%, 7.50%, 7.25%, 7%, 6.75%, 6.50%, 6.25%, 6%, 5.75%, 5.50%, 5.25%, 5%, 4.75%, 4.50%, 4.25%, 4%, 3.75%, 3.50%, 3.25%, 3%, 2.75%, 2.50%, 2.25%, 2%, 1.75%, 1.50%, 1.25% , 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, 0.01%, 0.009%, 0.008%, 0.007%, 0.006%, 0.005%, 0.004%, 0.003%, 0.002%, 0.001%, 0.0009%, 0.0008%, 0.0007%, 0.0006%, 0.0005%, 0.0004%, 0.0003%, 0.0002%, or 0.0001% (or a number in the range defined by and including any two numbers above) w / w, w / v, or v / v.

[0377] In some embodiments, the concentration of one or more compounds of the invention is in the range from approximately 0.0001% to approximately 50%, approximately 0.001% to approximately 40%, approximately 0.01% to approximately 30%, approximately 0.02% to approximately 29%, approximately 0.03% to approximately 28%, approximately 0.04% to approximately 27%, approximately 0.05% to approximately 26%, approximately 0.06% to approximately 25%, approximately 0.07% to approximately 24%, approximately 0.08% to approximately 23%, approximately 0.09% to approximately 22%, approximately 0.1% to approximately 21%, approximately 0.2% to approximately 20%, approximately 0.3% to approximately 19%, approximately 0.4% to approximately 18%, approximately 0.5% to approximately 17%, approximately 0.6% to approximately 16%, approximately 0.7% to approximately 15%, approximately 0.8% to approximately 14%, approximately 0.9% to approximately 12%, approximately 1% to approximately 10% w / w, w / v or v / v.- 143 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0378] In some embodiments, the concentration of one or more compounds of the invention is in the range from approximately 0.001% to approximately 10%, approximately 0.01% to approximately 5%, approximately 0.02% to approximately 4.5%, approximately 0.03% to approximately 4%, approximately 0.04% to approximately 3.5%, approximately 0.05% to approximately 3%, approximately 0.06% to approximately 2.5%, approximately 0.07% to approximately 2%, approximately 0.08% to approximately 1.5%, approximately 0.09% to approximately 1%, approximately 0.1% to approximately 0.9% w / w, w / v or v / v.

[0379] In some embodiments, the amount of one or more compounds of the invention is equal to or less than 10 g, 9.5 g, 9.0 g, 8.5 g, 8.0 g, 7.5 g, 7.0 g, 6.5 g, 6.0 g, 5.5 g, 5.0 g, 4.5 g, 4.0 g, 3.5 g, 3.0 g, 2.5 g, 2.0 g, 1.5 g, 1.0 g, 0.95 g, 0.9 g, 0.85 g, 0.8 g, 0.75 g, 0.7 g, 0.65 g, 0.6 g, 0.55 g, 0.5 g, 0.45 g, 0.4 g, 0.35 g, 0.3 g, 0.25 g, 0.2 g, 0.15 g, 0.1 g, 0.09 g, 0.08 g, 0.07 g, 0.06 g, 0.05 g, 0.04 g, 0.03 g, 0.02 g, 0.01 g, 0.009 g, 0.008 g, 0.007 g, 0.006 g, 0.005 g, 0.004 g, 0.003 g, 0.002 g, 0.001 g, 0.0009 g, 0.0008 g, 0.0007 g, 0.0006 g, 0.0005 g, 0.0004 g, 0.0003 g, 0.0002 g, or 0.0001 g (or a number in the range defined by and including any two numbers above).

[0380] In some embodiments, the amount of one or more compounds of the invention is more than 0.0001 g, 0.0002 g, 0.0003 g, 0.0004 g, 0.0005 g, 0.0006 g, 0.0007 g, 0.0008 g, 0.0009 g, 0.001 g, 0.0015 g, 0.002 g, 0.0025 g, 0.003 g, 0.0035 g, 0.004 g, 0.0045 g, 0.005 g, 0.0055 g, 0.006 g, 0.0065 g, 0.007 g, 0.0075 g, 0.008 g, 0.0085 g, 0.009 g, 0.0095 g, 0.01 g, 0.015 g, 0.02 g, 0.025 g, 0.03 g, 0.035 g, 0.04 g, 0.045 g, 0.05 g, 0.055 g, 0.06 g, 0.065 g, 0.07 g, 0.075 g, 0.08 g, 0.085 g, 0.09 g, 0.095 g, 0.1 g, , 0.15 g, 0.2 g, , 0.25 g, 0.3 g, , 0.35 g, 0.4 g, , 0.45 g, 0.5 g, 0.55 g, 0.6 g, , 0.65 g, 0.7 g, 0.75 g, 0.8 g, 0.85 g, 0.9 g, 0.95 g, 1 g, 1.5 g, 2 g, 2.5, 3 g, 3.5, 4 g, 4.5 g, 5 g, 5.5 g, 6 g, 6.5g, 7 g, 7.5g, 8 g, 8.5 g, 9 g, 9.5 g, or 10 g (or a number in the range defined by and including any two numbers above).

[0381] In some embodiments, the amount of one or more compounds of the invention is in the range of 0.0001-10 g, 0.0005-9 g, 0.001-8 g, 0.005-7 g, 0.01-6 g, 0.05-5 g, 0.1-4 g, 0.5-4 g, or 1-3 g.

[0382] In some embodiments, the compounds according to the invention are effective over a wide dosage range. For example, in the treatment of adult humans, dosages from 0.01 to 1000 mg, from 0.5 to 100 mg, from 1 to 50 mg per day, and from 5- 144 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)to 40 mg per day are examples of dosages that may be used. An exemplary dosage is 10 to 30 mg per day. The exact dosage will depend upon the route of administration, the form in which the compound is administered, the subject to be treated, the body weight of the subject to be treated, and the preference and experience of the attending physician.

[0383] Unless otherwise noted, the amounts of the compounds described herein are set forth on a free base basis. That is, the amounts indicate that amount of the compound administered, exclusive of, for example, solvent (such as in solvates) or counterions (such as in pharmaceutically acceptable salts).

[0384] Described below are non- limiting exemplary pharmaceutical compositions and methods for preparing the same.Pharmaceutical compositions for oral administration.

[0385] In some embodiments, the invention provides a pharmaceutical composition for oral administration containing a compound of the invention, and a pharmaceutical excipient suitable for oral administration.

[0386] In some embodiments, the invention provides a solid pharmaceutical composition for oral administration containing: (i) an effective amount of a compound of the invention; optionally (ii) an effective amount of a second agent; and (iii) a pharmaceutical excipient suitable for oral administration. In some embodiments, the composition further contains: (iv) an effective amount of a third agent.

[0387] In some embodiments, the pharmaceutical composition may be a liquid pharmaceutical composition suitable for oral consumption. Pharmaceutical compositions of the invention suitable for oral administration can be presented as discrete dosage forms, such as capsules, cachets, or tablets, or liquids or aerosol sprays each containing a predetermined amount of an active ingredient as a powder or in granules, a solution, or a suspension in an aqueous or non-aqueous liquid, an oil-in- water emulsion, or a water-in-oil liquid emulsion. Such dosage forms can be prepared by any of the methods of pharmacy, but all methods include the step of bringing the active ingredient into association with the carrier, which constitutes one or more necessary ingredients. In general, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into the desired presentation. For example, a tablet can be- 145 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)prepared by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing in a suitable machine the active ingredient in a free- flowing form such as powder or granules, optionally mixed with an excipient such as, but not limited to, a binder, a lubricant, an inert diluent, and / or a surface active or dispersing agent. Molded tablets can be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent.

[0388] This invention further encompasses anhydrous pharmaceutical compositions and dosage forms comprising an active ingredient, since water can facilitate the degradation of some compounds. For example, water may be added (e.g., 5%) in the pharmaceutical arts as a means of simulating long-term storage in order to determine characteristics such as shelf- life or the stability of formulations over time. Anhydrous pharmaceutical compositions and dosage forms of the invention can be prepared using anhydrous or low moisture containing ingredients and low moisture or low humidity conditions. Pharmaceutical compositions and dosage forms of the invention which contain lactose can be made anhydrous if substantial contact with moisture and / or humidity during manufacturing, packaging, and / or storage is expected. An anhydrous pharmaceutical composition may be prepared and stored such that its anhydrous nature is maintained. Accordingly, anhydrous compositions may be packaged using materials known to prevent exposure to water such that they can be included in suitable formulary kits. Examples of suitable packaging include, but are not limited to, hermetically sealed foils, plastic or the like, unit dose containers, blister packs, and strip packs.

[0389] An active ingredient can be combined in an intimate admixture with a pharmaceutical carrier according to conventional pharmaceutical compounding techniques. The carrier can take a wide variety of forms depending on the form of preparation desired for administration. In preparing the compositions for an oral dosage form, any of the usual pharmaceutical media can be employed as carriers, such as, for example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, and the like in the case of oral liquid preparations (such as suspensions, solutions, and elixirs) or aerosols; or carriers such as starches, sugars, micro-crystalline cellulose, diluents, granulating agents, lubricants, binders, and disintegrating agents can be used in the case of oral solid preparations, in some embodiments without employing the use of lactose. For example, suitable carriers include powders, capsules, and tablets, with the- 146 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)solid oral preparations. If desired, tablets can be coated by standard aqueous or nonaqueous techniques.

[0390] Binders suitable for use in pharmaceutical compositions and dosage forms include, but are not limited to, corn starch, potato starch, or other starches, gelatin, natural and synthetic gums such as acacia, sodium alginate, alginic acid, other alginates, powdered tragacanth, guar gum, cellulose and its derivatives (e.g., ethyl cellulose, cellulose acetate, carboxymethyl cellulose calcium, sodium carboxymethyl cellulose), polyvinyl pyrrolidone, methyl cellulose, pre-gelatinized starch, hydroxypropyl methyl cellulose, microcrystalline cellulose, and mixtures thereof.

[0391] Examples of suitable fillers for use in the pharmaceutical compositions and dosage forms disclosed herein include, but are not limited to, talc, calcium carbonate (e.g., granules or powder), microcrystalline cellulose, powdered cellulose, dextrates, kaolin, mannitol, silicic acid, sorbitol, starch, pre-gelatinized starch, and mixtures thereof.

[0392] Disintegrants may be used in the compositions of the invention to provide tablets that disintegrate when exposed to an aqueous environment. Too much of a disintegrant may produce tablets which may disintegrate in the bottle. Too little may be insufficient for disintegration to occur and may thus alter the rate and extent of release of the active ingredient(s) from the dosage form. Thus, a sufficient amount of disintegrant that is neither too little nor too much to detrimentally alter the release of the active ingredient(s) may be used to form the dosage forms of the compounds disclosed herein. The amount of disintegrant used may vary based upon the type of formulation and mode of administration, and may be readily discernible to those of ordinary skill in the art. About 0.5 to about 15 weight percent of disintegrant, or about 1 to about 5 weight percent of disintegrant, may be used in the pharmaceutical composition. Disintegrants that can be used to form pharmaceutical compositions and dosage forms of the invention include, but are not limited to, agar-agar, alginic acid, calcium carbonate, microcrystalline cellulose, croscarmellose sodium, crospovidone, polacrilin potassium, sodium starch glycolate, potato or tapioca starch, other starches, pre-gelatinized starch, other starches, clays, other algins, other celluloses, gums or mixtures thereof.

[0393] Lubricants which can be used to form pharmaceutical compositions and dosage forms of the invention include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, light mineral oil, glycerin, sorbitol, mannitol, polyethylene glycol,- 147 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)other glycols, stearic acid, sodium lauryl sulfate, talc, hydrogenated vegetable oil (e.g., peanut oil, cottonseed oil, sunflower oil, sesame oil, olive oil, com oil, and soybean oil), zinc stearate, ethyl oleate, ethyl laureate, agar, or mixtures thereof. Additional lubricants include, for example, a syloid silica gel, a coagulated aerosol of synthetic silica, or mixtures thereof. A lubricant can optionally be added, in an amount of less than about 1 weight percent of the pharmaceutical composition.

[0394] When aqueous suspensions and / or elixirs are desired for oral administration, the active ingredient therein may be combined with various sweetening or flavoring agents, coloring matter or dyes and, if so desired, emulsifying and / or suspending agents, together with such diluents as water, ethanol, propylene glycol, glycerin and various combinations thereof.

[0395] The tablets can be uncoated or coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monostearate or glyceryl distearate can be employed. Formulations for oral use can also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example, peanut oil, liquid paraffin or olive oil.

[0396] Surfactant which can be used to form pharmaceutical compositions and dosage forms of the invention include, but are not limited to, hydrophilic surfactants, lipophilic surfactants, and mixtures thereof. That is, a mixture of hydrophilic surfactants may be employed, a mixture of lipophilic surfactants may be employed, or a mixture of at least one hydrophilic surfactant and at least one lipophilic surfactant may be employed.

[0397] A suitable hydrophilic surfactant may generally have an HLB value of at least 10, while suitable lipophilic surfactants may generally have an HLB value of or less than about 10. An empirical parameter used to characterize the relative hydrophilicity and hydrophobicity of non-ionic amphiphilic compounds is the hydrophilic-lipophilic balance (" HLB" value). Surfactants with lower HLB values are more lipophilic or hydrophobic, and have greater solubility in oils, while surfactants with higher HLB values are more hydrophilic, and have greater solubility in aqueous solutions.- 148 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0398] Hydrophilic surfactants are generally considered to be those compounds having an HLB value greater than about 10, as well as anionic, cationic, or zwitterionic compounds for which the HLB scale is not generally applicable. Similarly, lipophilic (i.e., hydrophobic) surfactants are compounds having an HLB value equal to or less than about 10. However, HLB value of a surfactant is merely a rough guide generally used to enable formulation of industrial, pharmaceutical and cosmetic emulsions.

[0399] Hydrophilic surfactants may be either ionic or non-ionic. Suitable ionic surfactants include, but are not limited to, alkylammonium salts; fusidic acid salts; fatty acid derivatives of amino acids, oligopeptides, and polypeptides; glyceride derivatives of amino acids, oligopeptides, and polypeptides; lecithins and hydrogenated lecithins; lysolecithins and hydrogenated lysolecithins; phospholipids and derivatives thereof; lysophospholipids and derivatives thereof; carnitine fatty acid ester salts; salts of alkylsulfates; fatty acid salts; sodium docusate; acyl lactylates; mono- and di-acetylated tartaric acid esters of mono- and di-glycerides; succinylated mono- and di-glycerides; citric acid esters of mono- and di-glycerides; and mixtures thereof.

[0400] Within the aforementioned group, ionic surfactants include, by way of example: lecithins, lysolecithin, phospholipids, lysophospholipids and derivatives thereof; carnitine fatty acid ester salts; salts of alkyl sulfates; fatty acid salts; sodium docusate; acylactylates; mono- and di-acetylated tartaric acid esters of mono- and di-glycerides; succinylated mono- and di-glycerides; citric acid esters of mono- and di-glycerides; and mixtures thereof.

[0401] Ionic surfactants may be the ionized forms of lecithin, lysolecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, phosphatidylserine, lysophosphatidyl choline, lysophosphatidylethanolamine, lysophosphatidylglycerol, lysophosphatidic acid, lysophosphatidylserine, PEG-phosphatidylethanolamine, PVP -phosphatidylethanolamine, lactylic esters of fatty acids, stearoyl-2-lactylate, stearoyl lactylate, succinylated monoglycerides, mono / diacetylated tartaric acid esters of mono / diglycerides, citric acid esters of mono / diglycerides, cholyl sarcosine, caproate, caprylate, caprate, laurate, myristate, palmitate, oleate, ricinoleate, linoleate, linolenate, stearate, lauryl sulfate, teracecyl sulfate, docusate, lauroyl carnitines, palmitoyl carnitines, myristoyl carnitines, and salts and mixtures thereof.- 149 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0402] Hydrophilic non-ionic surfactants may include, but are not limited to, alkylglucosides; alkylmaltosides; alkylthioglucosides; lauryl macrogolglycerides; polyoxyalkylene alkyl ethers such as polyethylene glycol alkyl ethers; polyoxyalkylene alkylphenols such as polyethylene glycol alkyl phenols; polyoxyalkylene alkyl phenol fatty acid esters such as polyethylene glycol fatty acids monoesters and polyethylene glycol fatty acids di esters; polyethylene glycol glycerol fatty acid esters; polyglycerol fatty acid esters; poly oxy alkylene sorbitan fatty acid esters such as polyethylene glycol sorbitan fatty acid esters; hydrophilic transesterification products of a polyol with at least one member of the group consisting of glycerides, vegetable oils, hydrogenated vegetable oils, fatty acids, and sterols; polyoxyethylene sterols, derivatives, and analogues thereof; polyoxyethylated vitamins and derivatives thereof; polyoxyethylene-polyoxypropylene block copolymers; and mixtures thereof; polyethylene glycol sorbitan fatty acid esters and hydrophilic transesterification products of a polyol with at least one member of the group consisting of triglycerides, vegetable oils, and hydrogenated vegetable oils. The polyol may be glycerol, ethylene glycol, polyethylene glycol, sorbitol, propylene glycol, pentaerythritol, or a saccharide.

[0403] Other hydrophilic-non-ionic surfactants include, without limitation, PEG- 10 laurate, PEG- 12 laurate, PEG-20 laurate, PEG-32 laurate, PEG-32 dilaurate, PEG- 12 oleate, PEG- 15 oleate, PEG-20 oleate, PEG-20 dioleate, PEG-32 oleate, PEG-200 oleate, PEG-400 oleate, PEG- 15 stearate, PEG-32 distearate, PEG-40 stearate, PEG-100 stearate, PEG-20 dilaurate, PEG-25 glyceryl trioleate, PEG-32 di oleate, PEG-20 glyceryl laurate, PEG-30 glyceryl laurate, PEG-20 glyceryl stearate, PEG-20 glyceryl oleate, PEG-30 glyceryl oleate, PEG-30 glyceryl laurate, PEG-40 glyceryl laurate, PEG-40 palm kernel oil, PEG-50 hydrogenated castor oil, PEG-40 castor oil, PEG-35 castor oil, PEG-60 castor oil, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-60 com oil, PEG-6 caprate / caprylate glycerides, PEG-8 caprate / caprylate glycerides, polyglyceryl- 10 laurate, PEG-30 cholesterol, PEG-25 phyto sterol, PEG-30 soya sterol, PEG-20 trioleate, PEG-40 sorbitan oleate, PEG-80 sorbitan laurate, polysorbate 20, polysorbate 80, POE-9 lauryl ether, POE-23 lauryl ether, POE- 10 oleyl ether, POE-20 oleyl ether, POE-20 stearyl ether, tocopheryl PEG- 100 succinate, PEG-24 cholesterol, polyglyceryl-lOoleate, Tween 40, Tween 60, sucrose monostearate, sucrose mono laurate,- 150 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)sucrose monopalmitate, PEG 10-100 nonyl phenol series, PEG 15-100 octyl phenol series, and poloxamers.

[0404] Suitable lipophilic surfactants include, by way of example only: fatty alcohols; glycerol fatty acid esters; acetylated glycerol fatty acid esters; lower alcohol fatty acids esters; propylene glycol fatty acid esters; sorbitan fatty acid esters; polyethylene glycol sorbitan fatty acid esters; sterols and sterol derivatives; polyoxyethylated sterols and sterol derivatives; polyethylene glycol alkyl ethers; sugar esters; sugar ethers; lactic acid derivatives of mono- and di-glycerides; hydrophobic transesterification products of a polyol with at least one member of the group consisting of glycerides, vegetable oils, hydrogenated vegetable oils, fatty acids and sterols; oil-soluble vitamins / vitamin derivatives; and mixtures thereof. Within this group, preferred lipophilic surfactants include glycerol fatty acid esters, propylene glycol fatty acid esters, and mixtures thereof, or are hydrophobic transesterification products of a polyol with at least one member of the group consisting of vegetable oils, hydrogenated vegetable oils, and triglycerides.

[0405] In one embodiment, the composition may include a solubilizer to ensure good solubilization and / or dissolution of the compound of the present invention and to minimize precipitation of the compound of the present invention. This can be especially important for compositions for non-oral use, e.g., compositions for injection. A solubilizer may also be added to increase the solubility of the hydrophilic drug and / or other components, such as surfactants, or to maintain the composition as a stable or homogeneous solution or dispersion.

[0406] Examples of suitable solubilizers include, but are not limited to, the following: alcohols and polyols, such as ethanol, isopropanol, butanol, benzyl alcohol, ethylene glycol, propylene glycol, butanediols and isomers thereof, glycerol, pentaerythritol, sorbitol, mannitol, transcutol, dimethyl isosorbide, polyethylene glycol, polypropylene glycol, polyvinylalcohol, hydroxypropyl methylcellulose and other cellulose derivatives, cyclodextrins and cyclodextrin derivatives; ethers of polyethylene glycols having an average molecular weight of about 200 to about 6000, such as tetrahydrofurfuryl alcohol PEG ether (glycofurol) or methoxy PEG ; amides and other nitrogen-containing compounds such as 2-pyrrolidone, 2-piperidone, s-caprolactam, N-alkylpyrrolidone, N-hydroxyalkylpyrrolidone, N-alkylpiperidone, N-alkylcaprolactam, dimethylacetamide and polyvinylpyrrolidone; esters such as ethyl propionate,- 151 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)tributylcitrate, acetyl tri ethyl citrate, acetyl tributyl citrate, tri ethyl citrate, ethyl oleate, ethyl caprylate, ethyl butyrate, triacetin, propylene glycol monoacetate, propylene glycol diacetate, s-caprolactone and isomers thereof, 6-valerolactone and isomers thereof, P-butyrolactone and isomers thereof; and other solubilizers known in the art, such as dimethyl acetamide, dimethyl isosorbide, N-methyl pyrrolidones, monooctanoin, diethylene glycol monoethyl ether, and water.

[0407] Mixtures of solubilizers may also be used. Examples include, but not limited to, triacetin, tri ethyl citrate, ethyl oleate, ethyl caprylate, dimethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl cyclodextrins, ethanol, polyethylene glycol 200-100, glycofurol, transcutol, propylene glycol, and dimethyl isosorbide. Particularly preferred solubilizers include sorbitol, glycerol, triacetin, ethyl alcohol, PEG-400, glycofurol and propylene glycol.

[0408] The amount of solubilizer that can be included is not particularly limited. The amount of a given solubilizer may be limited to a bioacceptable amount, which may be readily determined by one of skill in the art. In some circumstances, it may be advantageous to include amounts of solubilizers far in excess of bioacceptable amounts, for example to maximize the concentration of the drug, with excess solubilizer removed prior to providing the composition to a subject using conventional techniques, such as distillation or evaporation. Thus, if present, the solubilizer can be in a weight ratio of 10%, 25%o, 50%), 100%o, or up to about 200%> by weight, based on the combined weight of the drug, and other excipients. If desired, very small amounts of solubilizer may also be used, such as 5%>, 2%>, 1%) or even less. Typically, the solubilizer may be present in an amount of about 1%> to about 100%, more typically about 5%> to about 25%> by weight.

[0409] The composition can further include one or more pharmaceutically acceptable additives and excipients. Such additives and excipients include, without limitation, detackifiers, anti-foaming agents, buffering agents, polymers, antioxidants, preservatives, chelating agents, viscomodulators, tonicifiers, flavorants, colorants, odorants, opacifiers, suspending agents, binders, fillers, plasticizers, lubricants, and mixtures thereof.

[0410] In addition, an acid or a base may be incorporated into the composition to facilitate processing, to enhance stability, or for other reasons. Examples of- 152 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)pharmaceutically acceptable bases include amino acids, amino acid esters, ammonium hydroxide, potassium hydroxide, sodium hydroxide, sodium hydrogen carbonate, aluminum hydroxide, calcium carbonate, magnesium hydroxide, magnesium aluminum silicate, synthetic aluminum silicate, synthetic hydrocalcite, magnesium aluminum hydroxide, diisopropylethylamine, ethanolamine, ethylenediamine, triethanolamine, triethylamine, triisopropanolamine, trimethylamine, tri s(hydroxymethyl)aminom ethane (TRIS) and the like. Also suitable are bases that are salts of a pharmaceutically acceptable acid, such as acetic acid, acrylic acid, adipic acid, alginic acid, alkanesulfonic acid, amino acids, ascorbic acid, benzoic acid, boric acid, butyric acid, carbonic acid, citric acid, fatty acids, formic acid, fumaric acid, gluconic acid, hydroquinosulfonic acid, isoascorbic acid, lactic acid, maleic acid, oxalic acid, para-bromophenylsulfonic acid, propionic acid, p-toluenesulfonic acid, salicylic acid, stearic acid, succinic acid, tannic acid, tartaric acid, thioglycolic acid, toluenesulfonic acid, uric acid, and the like. Salts of polyprotic acids, such as sodium phosphate, di sodium hydrogen phosphate, and sodium dihydrogen phosphate can also be used. When the base is a salt, the cation can be any convenient and pharmaceutically acceptable cation, such as ammonium, alkali metals, alkaline earth metals, and the like. Example may include, but not limited to, sodium, potassium, lithium, magnesium, calcium and ammonium.

[0411] Suitable acids are pharmaceutically acceptable organic or inorganic acids. Examples of suitable inorganic acids include hydrochloric acid, hydrobromic acid, hydriodic acid, sulfuric acid, nitric acid, boric acid, phosphoric acid, and the like.Examples of suitable organic acids include acetic acid, acrylic acid, adipic acid, alginic acid, alkanesulfonic acids, amino acids, ascorbic acid, benzoic acid, boric acid, butyric acid, carbonic acid, citric acid, fatty acids, formic acid, fumaric acid, gluconic acid, hydroquinosulfonic acid, isoascorbic acid, lactic acid, maleic acid, methanesulfonic acid, oxalic acid, para-bromophenylsulfonic acid, propionic acid, p-toluenesulfonic acid, salicylic acid, stearic acid, succinic acid, tannic acid, tartaric acid, thioglycolic acid, toluenesulfonic acid, uric acid and the like.Pharmaceutical compositions for injection.

[0412] In some embodiments, the invention provides a pharmaceutical composition for injection containing a compound of the present invention and a- 153 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)pharmaceutical excipient suitable for injection. Components and amounts of agents in the compositions are as described herein.

[0413] The forms in which the novel compositions of the present invention may be incorporated for administration by injection include aqueous or oil suspensions, or emulsions, with sesame oil, com oil, cottonseed oil, or peanut oil, as well as elixirs, mannitol, dextrose, or a sterile aqueous solution, and similar pharmaceutical vehicles.

[0414] Aqueous solutions in saline are also conventionally used for injection. Ethanol, glycerol, propylene glycol, liquid polyethylene glycol, and the like (and suitable mixtures thereof), cyclodextrin derivatives, and vegetable oils may also be employed. The proper fluidity can be maintained, for example, by the use of a coating, such as lecithin, for the maintenance of the required particle size in the case of dispersion and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like.

[0415] Sterile injectable solutions are prepared by incorporating the compound of the present invention in the required amount in the appropriate solvent with various other ingredients as enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, certain desirable methods of preparation are vacuum-drying and freeze- drying techniques which yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0416] Pharmaceutical compositions for topical (e.g. transdermal) delivery.

[0417] In some embodiments, the invention provides a pharmaceutical composition for transdermal delivery containing a compound of the present invention and a pharmaceutical excipient suitable for transdermal delivery.

[0418] Compositions of the present invention can be formulated into preparations in solid, semisolid, or liquid forms suitable for local or topical administration, such as gels, water soluble jellies, creams, lotions, suspensions, foams, powders, slurries, ointments, solutions, oils, pastes, suppositories, sprays, emulsions, saline solutions,- 154 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)dimethylsulfoxide (DMSO)-based solutions. In general, carriers with higher densities are capable of providing an area with a prolonged exposure to the active ingredients. In contrast, a solution formulation may provide more immediate exposure of the active ingredient to the chosen area.

[0419] The pharmaceutical compositions also may comprise suitable solid or gel phase carriers or excipients, which are compounds that allow increased penetration of, or assist in the delivery of, therapeutic molecules across the stratum corneum permeability barrier of the skin. There are many of these penetration- enhancing molecules known to those trained in the art of topical formulation.

[0420] Examples of such carriers and excipients include, but are not limited to, humectants (e.g., urea), glycols (e.g., propylene glycol), alcohols (e.g., ethanol), fatty acids (e.g., oleic acid), surfactants (e.g., isopropyl myristate and sodium lauryl sulfate), pyrrolidones, glycerol monolaurate, sulfoxides, terpenes (e.g., menthol), amines, amides, alkanes, alkanols, water, calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols.

[0421] Another exemplary formulation for use in the methods of the present invention employs transdermal delivery devices ("patches"). Such transdermal patches may be used to provide continuous or discontinuous infusion of a compound of the present invention in controlled amounts, either with or without another agent.The construction and use of transdermal patches for the delivery of pharmaceutical agents is well known in the art. See, e.g., U.S. Pat. Nos. 5,023,252, 4,992,445 and 5,001,139. Such patches may be constructed for continuous, pulsatile, or on demand delivery of pharmaceutical agents.Pharmaceutical compositions for inhalation.

[0422] Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as described supra. Preferably the compositions are administered by the oral or nasal respiratory route for local or systemic effect.Compositions in preferably pharmaceutically acceptable solvents may be nebulized by use of inert gases. Nebulized solutions may be inhaled directly from the nebulizing device or the nebulizing device may be attached to a face mask tent, or intermittent positive pressure- 155 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)breathing machine. Solution, suspension, or powder compositions may be administered, preferably orally or nasally, from devices that deliver the formulation in an appropriate manner.Other pharmaceutical compositions.

[0423] Pharmaceutical compositions may also be prepared from compositions described herein and one or more pharmaceutically acceptable excipients suitable for sublingual, buccal, rectal, intraosseous, intraocular, intranasal, epidural, or intraspinal administration. Preparations for such pharmaceutical compositions are well-known in the art. See, e.g., Anderson, Philip O.; Knoben, James E.; Troutman, William G, eds., Handbook of Clinical Drug Data, Tenth Edition, McGraw-Hill, 2002; Pratt and Taylor, eds., Principles of Drug Action, Third Edition, Churchill Livingston, New York, 1990; Katzung, ed., Basic and Clinical Pharmacology, Ninth Edition, McGraw Hill, 20037ybg; Goodman and Gilman, eds., The Pharmacological Basis of Therapeutics, Tenth Edition, McGraw Hill, 2001 ; Remingtons Pharmaceutical Sciences, 20th Ed., Lippincott Williams & Wilkins., 2000; Martindale, The Extra Pharmacopoeia, Thirty-Second Edition (The Pharmaceutical Press, London, 1999); all of which are incorporated by reference herein in their entirety.

[0424] Administration of the compounds or pharmaceutical composition of the present invention can be effected by any method that enables delivery of the compounds to the site of action. These methods include oral routes, intraduodenal routes, parenteral injection (including intravenous, intraarterial, subcutaneous, intramuscular, intravascular, intraperitoneal or infusion), topical (e.g. transdermal application), rectal administration, via local delivery by catheter or stent or through inhalation. Compounds can also be administered intraadiposally or intrathecally.

[0425] The amount of the compound administered will be dependent on the subject being treated, the severity of the disorder or condition, the rate of administration, the disposition of the compound and the discretion of the prescribing physician. However, an effective dosage is in the range of about 0.001 to about 100 mg per kg body weight per day, preferably about 1 to about 35 mg / kg / day, in single or divided doses. For a 70 kg human, this would amount to about 0.05 to 7 g / day, preferably about 0.05 to about 2.5 g / day. In some instances, dosage levels below the lower limit of the aforesaid range may- 156 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)be more than adequate, while in other cases still larger doses may be employed without causing any harmful side effect, e.g. by dividing such larger doses into several small doses for administration throughout the day.

[0426] In some embodiments, a compound of the invention is administered in a single dose.

[0427] Typically, such administration will be by injection, e.g., intravenous injection, in order to introduce the agent quickly. However, other routes may be used as appropriate. A single dose of a compound of the invention may also be used for treatment of an acute condition.

[0428] In some embodiments, a compound of the invention is administered in multiple doses. Dosing may be about once, twice, three times, four times, five times, six times, or more than six times per day. Dosing may be about once a month, once every two weeks, once a week, or once every other day. In another embodiment a compound of the invention and another agent are administered together about once per day to about 6 times per day. In another embodiment the administration of a compound of the invention and an agent continues for less than about 7 days. In yet another embodiment the administration continues for more than about 6, 10, 14, 28 days, two months, six months, or one year. In some cases, continuous dosing is achieved and maintained as long as necessary.

[0429] Administration of the compounds of the invention may continue as long as necessary. In some embodiments, a compound of the invention is administered for more than 1, 2, 3, 4, 5, 6, 7, 14, or 28 days. In some embodiments, a compound of the invention is administered for less than 28, 14, 7, 6, 5, 4, 3, 2, or 1 day. In some embodiments, a compound of the invention is administered chronically on an ongoing basis, e.g., for the treatment of chronic effects.

[0430] An effective amount of a compound of the invention may be administered in either single or multiple doses by any of the accepted modes of administration of agents having similar utilities, including rectal, buccal, intranasal and transdermal routes, by intra-arterial injection, intravenously, intraperitoneally, parenterally, intramuscularly, subcutaneously, orally, topically, or as an inhalant.

[0431] The compositions of the invention may also be delivered via an impregnated or coated device such as a stent, for example, or an artery -inserted cylindrical polymer. Such a method of administration may, for example, aid in the prevention or- 157 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)amelioration of restenosis following procedures such as balloon angioplasty. Without being bound by theory, compounds of the invention may slow or inhibit the migration and proliferation of smooth muscle cells in the arterial wall which contribute to restenosis. A compound of the invention may be administered, for example, by local delivery from the struts of a stent, from a stent graft, from grafts, or from the cover or sheath of a stent. In some embodiments, a compound of the invention is admixed with a matrix. Such a matrix may be a polymeric matrix, and may serve to bond the compound to the stent. Polymeric matrices suitable for such use, include, for example, lactone-based polyesters or copolyesters such as polylactide, polycaprolactonglycolide, polyorthoesters, polyanhydrides, polyaminoacids, polysaccharides, polyphosphazenes, poly (ether-ester) copolymers (e.g. PEO-PLLA); polydimethyl siloxane, poly(ethylene-vinylacetate), acrylate-based polymers or copolymers (e.g. polyhydroxyethyl methylmethacrylate, polyvinyl pyrrolidinone), fluorinated polymers such as polytetrafluoroethylene and cellulose esters. Suitable matrices may be nondegrading or may degrade with time, releasing the compound or compounds. Compounds of the invention may be applied to the surface of the stent by various methods such as dip / spin coating, spray coating, dipcoating, and / or brush-coating. The compounds may be applied in a solvent and the solvent may be allowed to evaporate, thus forming a layer of compound onto the stent.Alternatively, the compound may be located in the body of the stent or graft, for example in microchannels or micropores. When implanted, the compound diffuses out of the body of the stent to contact the arterial wall. Such stents may be prepared by dipping a stent manufactured to contain such micropores or microchannels into a solution of the compound of the invention in a suitable solvent, followed by evaporation of the solvent. Excess drug on the surface of the stent may be removed via an additional brief solvent wash. In yet other embodiments, compounds of the invention may be covalently linked to a stent or graft. A covalent linker may be used which degrades in vivo, leading to the release of the compound of the invention. Any bio-labile linkage may be used for such a purpose, such as ester, amide or anhydride linkages. Compounds of the invention may additionally be administered intravascularly from a balloon used during angioplasty. Extravascular administration of the compounds via the pericard or via advential application of formulations of the invention may also be performed to decrease restenosis.- 158 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)

[0432] A variety of stent devices which may be used as described are disclosed, for example, in the following references, all of which are hereby incorporated by reference: U.S. Pat. No. 5451233; U.S. Pat. No. 5040548; U.S. Pat. No. 5061273; U.S. Pat. No. 5496346; U.S. Pat. No. 5292331; U.S. Pat. No. 5674278; U.S. Pat. No. 3657744; U.S. Pat. No. 4739762; U.S. Pat. No. 5195984; U.S. Pat. No. 5292331; U.S. Pat. No. 5674278; U.S. Pat. No. 5879382; U.S. Pat. No. 6344053.

[0433] The compounds of the invention may be administered in dosages. It is known in the art that due to intersubject variability in compound pharmacokinetics, individualization of dosing regimen is necessary for optimal therapy. Dosing for a compound of the invention may be found by routine experimentation in light of the instant disclosure.

[0434] When a compound of the invention is administered in a composition that comprises one or more agents, and the agent has a shorter half- life than the compound of the invention unit dose forms of the agent and the compound of the invention may be adjusted accordingly.

[0435] The subject pharmaceutical composition may, for example, be in a form suitable for oral administration as a tablet, capsule, pill, powder, sustained release formulations, solution, suspension, for parenteral injection as a sterile solution, suspension or emulsion, for topical administration as an ointment or cream or for rectal administration as a suppository. The pharmaceutical composition may be in unit dosage forms suitable for single administration of precise dosages. The pharmaceutical composition will include a conventional pharmaceutical carrier or excipient and a compound according to the invention as an active ingredient. In addition, it may include other medicinal or pharmaceutical agents, carriers, adjuvants, etc.

[0436] Exemplary parenteral administration forms include solutions or suspensions of active compound in sterile aqueous solutions, for example, aqueous propylene glycol or dextrose solutions. Such dosage forms can be suitably buffered, if desired.Methods of use

[0437] The FGFR receptors (FGFR1, FGFR2, FGFR3, and FGFR4) share several structural features in common, including three extracellular immunoglobulin-like- 159 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(Ig) domains, a hydrophobic transmembrane domain, and an intracellular tyrosine kinase domain split by a kinase insert domain, followed by a cytoplasmic c-terminal tail (Johnson et al., Adv. Cancer Res. 60:1-40, 1993; and Wilkie et al., Curr. Biol. 5:500-507, 1995). In FGFR1, the kinase insert domain spans positions 582 to 595 of the alpha Al isoform of FGFR1. In FGFR2, the kinase insert domain spans positions 585 to 598 of the FGFR2 Ille isoform. In FGFR3, the kinase insert domain spans positions 576 to 589 of the FGFR3 Ille isoform. In FGFR4, the kinase insert domain spans positions 571 to 584 of FGFR4 isoform 1. The c-terminal tail of FGFRs begins following the end of the tyrosine kinase domain and extends to the c-terminus of the protein. Several isoforms of each FGFR have been identified and are the result of alternative splicing of their mRNAs (Johnson et al., Mol. Cell. Biol. 11:4627-4634, 1995; and Chellaiah et al., J. Biol. Chem. 269:11620-11627, 1994).

[0438] A few of the receptor variants that result from this alternative splicing have different ligand binding specificities and affinities (Zimmer et al., J. Biol. Chem. 268:7899-7903, 1993; Cheon et al., Proc. Natl. Acad. Sci. U.S.A. 91:989-993, 1994; and Miki et al., Proc. Natl. Acad. Sci. U.S.A. 89:246-250, 1992). Protein sequences for FGFR proteins and nucleic acids encoding FGFR proteins are known in the art. Signaling by FGFRs regulates key biological processes including cell proliferation, survival, migration, and differentiation. Dysregulation of a FGFR gene, a FGFR protein, or expression or activity, or level of the same, has been associated with many types of cancer. For example, dysregulation of FGFRs can occur by multiple mechanisms, such as FGFR gene overexpression, FGFR gene amplification, activating mutations (e.g., point mutations or truncations), and chromosomal rearrangements that lead to FGFR fusion proteins.Dysregulation of a FGFR gene, a FGFR protein, or expression or activity, or level of the same, can result in (or cause in part) the development of a variety of different FGFR-associated cancers.

[0439] FGFR fusion proteins are known in the art. See, e.g., Baroy et al., PloS One; 1 l(9):e0163859. doi: 10.1371 / journal. pone.0163859, 2016; Ren et al., Int. J.Cancer, 139(4):836-40, 2016; Marchwicka et al., Cell Biosci., 6:7. doi: 10.1186 / sl3578-016-0075-9, 2016; PCT Patent Application Publication No. WO 2014 / 071419A2; U.S. Patent Application Publication No. 2015 / 0366866A1; PCT Patent Application Publication No. WO 2016 / 084883 Al; PCT Patent Application Publication No. WO 2016 / 030509 Al;- 160 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)PCT Patent Application Publication No. WO 2015 / 150900A2; PCT Patent Application Publication No. WO 2015 / 120094A2; Kasaian et al., BMC Cancer., 15:984, 2015; Vakil et al., Neuro-Oncology, 18:Supp. Supplement 3, pp. iii93. Abstract Number: LG-64, 17thInternational Symposium on Pediatric Neuro-Oncology, Liverpool, United Kingdom, 2016; Astsaturov et al., Journal of Clinical Oncology, 34:Supp. Supplement 15, Abstract Number: 11504, 2016 Annual Meeting of the American Society of Clinical Oncology, Chicago, IL; Heinrich et al., Journal of Clinical Oncology, 34:Supp. Supplement 15, Abstract Number: 11012, 2016 Annual Meeting of the American Society of Clinical Oncology, Chicago, IL; Hall et al., Molecular Cancer Therapeutics, Vol. 14, No. 12, Supp.2, Abstract Number: B151, AACR-NCI-EORTC International Conference:Molecular Targets and Cancer Therapeutics, 2015; Reuther et al., Journal of Molecular Diagnostics, Vol. 17, No. 6, pp. 813, Abstract Number: ST02, 2015 Annual Meeting of the Association for Molecular Pathology, Austin, TX; Moeini et al., Clin. Cancer. Res., 22(2):291-300, 2016; Schrock et al, J Thorac. Oneal. pii SI 556-0864(18)30674-9, 2018. doi: 10.1016 / j.jtho.2018.05.027; Pekmezci et al, Acta Nurotapho / . Commun. 6(1):47. doi: 10.1186 / s40478-018-0551-z; Lowery et al. Clin Cancer Res. pii: clincanres.0078.2018. doi: 10.1158 / 1078-0432. CCR-18-0078; Ryland et al. J Clin Patho / pii: jclinpath-2018-205195, 2018. doi: 10.1136 / jclinpath-2018-205195; Ferguson et al. J Neuropatho / Exp Neural 77(6) :437-442, 2018. doi: 10.1093 / jnen / nly022; Wu et al, BMC Cancer 18(1):343, 2018. doi: 10.1186 / sl2885-018-4236-6; Shibata et al, Cancer Sci 109(5): 1282-1291, 2018. doi: 10.1111 / cas.13582; Papdopoulos et al, Br J Cancer, 1117(11): 1592- 1599, 2017. doi: 10.1038 / bjc.2017.330; Hall et al, PLoS One, 1 l(9):el062594, 2016. doi:10.1371 / joumal. pone.0162594; Johnson et al, Oncologist, 22(12): 1478-1490, 2017. doi: 10.1634 / theoncologist.2017-0242; Yang et al, Am J Hum Genet, 98(5):843-856, 2016. doi: 10.1016 / j.ajhg.2016.03.017; U.S. Patent Application Publication No. 2013 / 009621;Babina and Turner, Nat Rev Cancer 17(5):318-332, 2017. doi: 10.1038 / nrc.2017.8;Ryland et al, J Clin Patho / ., 2018 May 14. pii: jclinpath-2018-205195. doi:10.1136 / jclinpath-2018-205195; Kumar et al, Am J Clin Patho / . 143(5):738-748, 2015. doi: 10.1309 / AJCPUD6W1JLQQMNA; Grand et al, Genes Chromosomes Cancer40(l):78-83, 2004. doi: 10.1002 / gcc.20023; Reeser, et al, JMo / Diagn, 19(5):682-696, 2017. doi: 10.1016 / j.jmoldx.2017.05.006; Basturk, et al, Mod Patho 30(12): 1760- 1772, 2017. doi: 10.1038 / modpathol.2017.60; Wang, et al, Cancer 123(20):3916-3924,- 161 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2017. doi: 10.1002 / cncr.30837; Kim, et al, Oncotarget, 8(9):15014-15022, 2017. doi: 10.18632 / oncotarget.l4788; Busse, et al, Genes Chromosomes Cancer, 56(10):730-749, 2017. doi: 10.1002 / gcc.22477; Shi, et al, J Transl Med., 14(1):339, 2016. doi:10.1186 / sl2967-016-1075-6, each of which is incorporated by reference herein.FGFR point mutations are known in the art. See, e.g., UniParc entry UPI00000534B8; UniParc entry UPI0000001COF; UniParc entry UPI000002A99A; UniParc entry UPI000012A72A; UniParc entry UPI000059D1C2; UniParc entry UPI000002A9AC; Uniparc entry UPI000012A72C; Uniparc entry UPI000012A72D; Uniparc entry UPI000013EOB8; Uniparc entry UPI0001CE06A3; Gen bank entry BAD92868.1; Ang et al., Diagn. Mo / . Patho / . Feb 24, 2014; U.S. Patent Application Publication No.2011 / 0008347; Gallo et al., Cytokine Growth Factor Rev. 26:425-449, 2015; Davies et al., J. Cancer Res. 65:7591, 2005; Kelleher et al., Carcinogenesis 34:2198, 2013; Cazier et al., Nat. Commun. 5:3756, 2014; Liu et al., Genet. Mo / . Res. 13:1109, 2014; Trudel et al., Blood 107:4039, 2006; Gallo et al., Cytokine Growth Factor Rev. 26:425, 2015; Liao et al., Cancer Res. 73:5195-5205, 2013; Martincorena et al., Science 348:880 (2015); U.S. Patent Application Publication No. US2016 / 0235744 Al; U.S. Patent No. 9254288B2; U.S. Patent No. 9267176B2; U.S. Patent Application Publication No. S2016 / 0215350A1;European Patent Application Publication No. EP3023101 Al; PCT Patent Application Publication No. W02016105503A1; Rivera et al., Acta. Neuropatho / .,131(6):847-63, 2016; Lo lacono et al., Oncotarget., 7(12): 14394-404, 2016; Deeken et al., Journal of Clinical Oncology, 34:Supp. Supplement 15, pp. iii93. Abstract Number: el 7520, 2016 Annual Meeting of the American Society of Clinical Oncology, Chicago, IL; Sullivan et al., Journal of Clinical Oncology, 34:Supp. Supplement 15, pp. iii93. Abstract Number: 11596, 2016 Annual Meeting of the American Society of Clinical Oncology, Chicago, IL; Nguyen et al., Molecular Cancer Therapeutics, Vol. 14, No. 12, Supp.2, Abstract Number: C199, AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, 2015; Li et al., Hum. Patho / ., 55:143-50, 2016; European Patent No.EP2203449B1; Yoza et al., Genes Cells., (10): 1049-1058, 2016; U.S. Patent No.9,254,288B2; European Patent Application Publication No. 3023101 Al; PCT Application Publication No. WO 2015 / 099127A1; European Patent No. EP2203449B1; Yoza et al., Genes Cells., (10):1049-1058, 2016; Bunney et al., EbioMedicine, 2(3):194-204, 2015; Byron et al., Neop / asia, 15(8):975-88, 20...

Claims

120039.000209 (TYRA045PCT)What is claimed:

1. A compound of Formula I:or a pharmaceutically acceptable salt thereof,whereinR is -(CR4R4)n-(CR4=R4)o-(CR4R4)p-SO2-Ci-C3alkyl, -(CR4R4)n-(CR4=R4)0- O X6,<>(CR4R4)p-C(O)N(Ci-C3alkyl)2,, , wherein n is 0, 1, or 2; o is 0, 1, or 2; p is 0 or 1; X6is O or NH, and wherein is a double bond or a single bond;A is a 5-6-membered heteroaryl, substituted with R1and / or R1A;or Z and A together form a fused bicyclic ring system that is a pyrazolopyrazine, an imidazopyrazine, or a pyrazolodiazepine, each substituted with R1and / or R1A;R1is hydrogen or C1-C3 alkyl;R1Ais hydrogen, halo, CN, or C1-C3 alkyl optionally substituted with one or more substituents independently selected from halo, OH, and OCH3;Xi and X2 are independently selected from N and C,wherein when one of Xi or X2is N the other is C;X3is N or CH;Y is NH, O, S or a bond;Ring B comprises X4, X5, Yi, Y2, Y3, and Y4, wherein:X4isN or CR9;X5is N or CH;- 508 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)Yi is absent, CR9, CHR7, CH2CHR7, CHR7CH2, CF2, CH2CF2, or CF2CH2;Y2is absent, CR9, CHR3, CH2CHR3, CHR3CH2, CF2, CH2CF2, or CF2CH2;Y3is O, CR4R5, CH2CR4R5, or CF2;Y4is absent, CR3R4, or CF2;or Ring B may be absent if Z and A together form a fused bicyclic ring system;Z is absent, NR9A, CHR9A, CR4R4A, CR4R4ACH2, CH2CR4R4A, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo(l.l.l)pentane, bicyclo(2.1.1)hexane, azetidine, pyrrolidine or piperidine;wherein R9Atogether with R9form -CR4R4A- or -(CR4R4A)2-; or, Z and A together form a fused bicyclic ring system that is a pyrazolopyrazine, an imidazopyrazine, or a pyrazolodiazepine, each substituted with R1and / or R1A;Zi is absent , CR4R4A, CR4R4ACH2, CH2CR4R4A, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo(l.l.l)pentane, bicyclo(2.1.1)hexane, azetidine, pyrrolidine or piperidine,or Zi is -CR4R4A- or -(CR4R4A)2when Z is NR9Aor CHR9A;Z2is absent, C(O), SO2or -NR4C(O);Z3 is absent, C(O), SO2or -NR4C(O);R2is C1-C5 alkyl or R8, wherein C1-C5 alkyl is optionally substituted with one or more substituents independently selected from halo, OH, OAc, OC(O)Ci- C6alkyl, OR13, CN, oxo, -OC1-C4 alkyl, -OC3-C5 cycloalkyl, -Z2-Rn, and R10, wherein Ci-C4alky and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN;R13is a hydroxy prodrug moiety selected from ethers, esters including a- amino acid esters, phosphate esters, and sulfamate esters;R3is hydrogen, F, OH, OCH3, C1-C3 alkyl, cyclopropyl, or one R3is fused with R5or R7to form CH2, CH2-CH2, or CH2OCH2;- 509 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)each R4is independently hydrogen, F, Cl, CH3, OH, C3-C5 cycloalkyl, or C1-C3 alkyl;R4Ais hydrogen, halo, OH, or C1-C3 alkyl;R5is hydrogen, F, OH, OCH3, OHhOCi-Csalkyl, CH3, C1-C3 alkyl, cyclopropyl, or is fused with one R3to form CH2, CH2-CH2, or CH2OCH2;R6is hydrogen, halo, C1-C5 alkyl, CN, 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl or 5-6 membered heteroaryl, wherein 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl and 5-6 membered heteroaryl are optionally substituted with one or more substituents independently selected from halo, methyl, halomethyl, OH or OCH3 and wherein C1-C5 alkyl is optionally substituted with one or more substituents independently selected from halo, OH and OCH3;R7is hydrogen, F, OH, OCH3, C1-C3 alkyl or is fused with one R3to form CH2, CH2-CH2or CH2OCH2;R8is 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl, optionally fused to or substituted with R8A;R8Ais halo, CN, C1-C3 alkyl, C1-C3 haloalkyl, 3-6 membered cycloalkyl, 4- 6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl;R9is hydrogen, C1-C3 alkyl, or together with R9Aare -CR4R4A- or - (CR4R4A)2-;each R10is independently 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered aryl, or 5-6 membered heteroaryl, each of which is optionally fused to- or substituted with- R8A;R11is C1-C4 alkyl, NH2, NHC1-C3 alkyl, NHC3-C5 cycloalkyl or N(Ci- C3 alkyl)2, wherein C1-C4 alkyl, C1-C3 alkyl and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN;R12is C1-C4 alkyl, C3-C5 cycloalkyl, NH2, NHC1-C3 alkyl, NHC3- C5 cycloalkyl or N(Ci-Cs alkyl)2, wherein C1-C4 alky, C1-C3 alkyl and C3- C5 cycloalkyl are optionally substituted with one or more substituents- 510 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN; andR8, R10and R8Aare optionally substituted with one or more substituents independently selected from halo, OH, CN, -OC1-C4 alkyl, -OC3-C5 cycloalkyl and -Z3-R12wherein C1-C4 alkyl and C3-C5 cycloalkyl are optionally substituted with one or more substituents independently selected from halo, OH, OCH3, methylamine, N,N-dimethylamine and CN.

2. The compound of claim 1, wherein A is pyrazole, triazole, thiadiazole, oxadiazole, pyridine, pyrimidine, pyrazine, or pyridazine.

3. The compound of claim 2, wherein A is triazole, pyrazole, or pyridine.

4. The compound of claim 2, wherein A is triazole or pyridine.

5. The compound of claim 2, wherein A is triazole.

6. The compound of claim 2, wherein A is pyrazole.

7. The compound of claim 2, wherein A is pyridine.

8. The compound of any preceding claim, wherein Y is O.

9. The compound of any one of claims 1-7, wherein Y is S.

10. The compound of any preceding claim, wherein R6is halo or CN.

11. The compound of any preceding claim, wherein R6is halo.

12. The compound of claim 11, wherein R6is Cl.

13. The compound of claim 10, wherein R6is CN.

14. The compound of any preceding claim, wherein Xi is N.

15. The compound of any preceding claim, wherein X2 is C.

16. The compound of any one of claims 1-13, wherein Xi is C.

17. The compound of any one of claims 1-13 or 16, wherein X2 is N.

18. The compound of any preceding claim, wherein X3 is CH.

19. The compound of any preceding claim, wherein Z is absent.

20. The compound of any preceding claim, wherein Zi is absent.

21. The compound of any preceding claim, or a pharmaceutically acceptable salt thereof, wherein Z and Zi are both absent.

22. The compound of claim 21, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IA-0:- 511 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)23. The compound of claim 22, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IA:

24. The compound of claim 23, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IA is a compound of Formula IA-1 :

25. The compound of claim 23, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IA is a compound of Formula IA-2:

26. The compound of claim 23, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IA is a compound of Formula IA-6:- 512 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)27. The compound of claim 23, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IA is a compound of Formula IA-7:

28. The compound of any one of claims 22-27, wherein R1Ais hydrogen or CH3.

29. The compound of claim 22, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IA-0 is a compound of Formula IA-3:

30. The compound of claim 29, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IA-3 is a compound of Formula IA-4:

31. The compound of claim 29, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IA-3 is a compound of Formula IA-5:- 513 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)32. The compound of any one of claims 1-18 or 20, wherein Z is piperidinyl.

33. The compound of claim 32, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IC-0:

34. The compound of claim 33, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IC-0 is a compound of Formula IC:

35. The compound of claim 34, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IC is a compound of Formula IC-1:

36. The compound of claim 35, wherein each of R4and R5is methyl.

37. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X4 is CR9, Z is CHR9A, wherein R9Atogether with R9form -CR4R4A- or - (CR4R4A)2-; and Zi is -CR4R4A- or -(CR4R4A)2.

38. The compound of claim 37, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IJ-0:- 514 -l20039.000209\4905-l 100-04521120039.000209 (TYRA045PCT)39. The compound of claim 37, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IJ:

40. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IJ is a compound of Formula IJ-1 :

41. The compound of claim 38, or a pharmaceutically acceptable salt thereof, wherein Yi and Y2 are both absent, and the compound is a compound of Formula IJ-2:

42. The compound of claim 41, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IJ-2 is a compound of Formula IJ-3 :- 515 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)43. The compound of any one of claims 37-39 or 41-42, or a pharmaceutically acceptable salt thereof, wherein each R4is H and each R4Ais H.

44. The compound of claim 39, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IJ is a compound of Formula IJ-4:

45. The compound of claim 37, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IK-0:

46. The compound of claim 45, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IK-0 is a compound of Formula IK-1:

47. The compound of claim 46, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IK-1 is a compound of Formula IK-2:- 516 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)48. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X4 is N or CH, Yi is CR9, Z is CHR9A, wherein R9Atogether with R9form - CR4R4A- or -(CR4R4A)2-; and Zi is -CR4R4A- or -(CR4R4A)2.

49. The compound of claim 48, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IL-0:

50. The compound of claim 49, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IL-0 is a compound of Formula IL-1:

51. The compound of claim 50, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IL-1 is a compound of Formula IL-4:- 517 -l20039.000209\4905-l 100-04521120039.000209 (TYRA045PCT)52. The compound of claim 50, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IL-1 is a compound of Formula IL-5:

53. The compound of claim 49, or a pharmaceutically acceptable salt thereof, wherein Y2 is absent and the compound of Formula IL-0 is a compound of Formula IL-2:

54. The compound of claim 53, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IL-2 is a compound of Formula IL-3:

55. The compound of claim 54, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IL-3 is a compound of Formula IL-3-1:

56. The compound of claim 54, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IL-3 is a compound of Formula IL-3-2:- 518 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)57. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IM-0:

58. The compound of claim 57, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IM-0 is a compound of Formula IM:

59. The compound of claim 58, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IM is a compound of Formula IM-1:

60. The compound of claim 58, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IM is a compound of Formula IM-2:- 519 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)61. The compound of claim 37, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IQ-0:

62. The compound of claim 61, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IQ-0 is a compound of Formula IQ-1:

63. The compound of claim 62, or a pharmaceutically acceptable salt thereof, wherein Yi and Y2 are both absent, and the compound is a compound of Formula IQ-2:

64. The compound of claim 63, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IQ-2 is a compound of Formula IQ-3:- 520 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)65. The compound of any one of claims 61 to 64, or a pharmaceutically acceptable salt thereof, wherein each R4is H and each R4Ais H.

66. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IB-0:

67. The compound of claim 66, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IB-0 is a compound of Formula IB:

68. The compound of claim 67, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IB is a compound of Formula IB-1:- 521 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)69. The compound of claim 68, or a pharmaceutically acceptable salt thereof, wherein X4is N.

70. The compound of claim 68 or claim 69, or a pharmaceutically acceptable salt thereof, wherein X5 is N.

71. The compound of claim 68 or claim 69, or a pharmaceutically acceptable salt thereof, wherein X5 is CH.

72. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IB-2:

73. The compound of claim 72, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IB-2 is a compound of Formula IB-3:

74. The compound of claim 73, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IB-3 is a compound of Formula IB-4:- 522 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)75. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Z and A together form a fused bicyclic ring system that is a pyrazolopyrazine, an imidazopyrazine, or a pyrazolodiazepine, each substituted with R1and / or R1A.

76. The compound of claim 75, or a pharmaceutically acceptable salt thereof, wherein Ring B is absent.

77. The compound of claim 76, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula ID-0, IE-0, or IF-0:

78. The compound of claim 77, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula ID, IE, or IF:- 523 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)79. The compound of claim 78, wherein the compound of Formula I is a compound of Formula ID.

80. The compound of claim 78, wherein the compound of Formula I is a compound of Formula IE.

81. The compound of claim 78, wherein the compound of Formula I is a compound of Formula IF.

82. The compound of any one of claims 22-81, wherein R1Ais hydrogen or CH3.

83. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Zi is absent.

84. The compound of claim 83, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IG-0 or H4-0:- 524 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)85. The compound of claim 84, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IG or IH:

86. The compound of claim 85, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula IG.

87. The compound of claim 85, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is a compound of Formula H4.

88. The compound of claim 87, or a pharmaceutically acceptable salt thereof, wherein the compound of Formula IH is a compound of Formula IH-1- 525 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)89. The compound of any one of the preceding claims, wherein R1Ais hydrogen or CH3.

90. The compound of any preceding claim, wherein X4 is CR9.

91. The compound of claim 90, wherein R9is H.

92. The compound of any one of the preceding claims, wherein Yi is absent or CHR7.

93. The compound of claim 92, wherein R7is H.

94. The compound of any one of the preceding claims, wherein Y2 is absent or CHR3.

95. The compound of claim 94, wherein R3is H.

96. The compound of any one of the preceding claims, wherein Y3 is CR4R5.

97. The compound of any one of the preceding claims, wherein Y4 is CR3R4.

98. The compound of claim 97, wherein R3is H.

99. The compound of any one of claims 96-98, wherein R4is hydrogen or CH3.

100. The compound of claim 99, wherein R4is hydrogen.

101. The compound of claim 99, wherein R4is CH3.

102. The compound of any one of claims 96-101, wherein R5is hydrogen, CH3, or CH2OCi-C3alkyl.

103. The compound of claim 102, wherein R5is hydrogen.

104. The compound of claim 102, wherein R5is CH3.

105. The compound of claim 102, wherein R5is CH2OCH3.

106. The compound of any preceding claim, wherein X5 is N.

107. The compound of any one of claims 1-105, wherein X5 is CH.

108. The compound of any preceding claim, wherein X4 is N.

109. The compound of any one of claims 1-107, wherein X4 is CH.

110. The compound of any one of claims 1-106 or 109, wherein X5 is N and X4 is CH.

111. The compound of any one of claims 1-105 or 108, wherein X5 is CH and X4 is N.

112. The compound of any one of claims 1-106 or 108, wherein X5 is N and X4 is N.- 526 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)113. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R2is C1-C5 alkyl optionally substituted with one or more substituents independently selected from OH, OAc, OR13, and R10.

114. The compound of claim 113, or a pharmaceutically acceptable salt thereof, wherein R2is C1-C5 alkyl, methyl, ethyl, propyl, or isopropyl.

115. The compound of claim 113, or a pharmaceutically acceptable salt thereof, wherein R2is C1-C5 alkyl substituted with -OH.

116. The compound of claim 115, or a pharmaceutically acceptable salt thereof, wherein R2is 3-hydroxypropyl, 2-hydroxyethyl, or 2-hydroxy-2-m ethylpropanol.

117. The compound of claim 113, or a pharmaceutically acceptable salt thereof, wherein R2is C1-C5 alkyl substituted with -OC1-C4 alkyl, such as 2-methoxy ethyl.

118. The compound of claim 113, or a pharmaceutically acceptable salt thereof, wherein R2is C1-C5 alkyl substituted with -OC1-C4 alkyl and R10.

119. The compound of claim 118, wherein R2is120. The compound of claim 113, or a pharmaceutically acceptable salt thereof, wherein R2is C1-C5 alkyl substituted with OAc and R10.

121. The compound of claim 120, wherein R2is122. The compound of claim 113, or a pharmaceutically acceptable salt thereof, wherein R2is C1-C5 alkyl substituted with R10.

123. The compound of claim 122, or a pharmaceutically acceptable salt thereof, wherein R2is124. The compound of any one of claims 113 or 118-123, or a pharmaceutically acceptable salt thereof, wherein R10is 3-6 membered cycloalkyl, 5-6 membered- 527 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)aryl, or 5-6 membered heteroaryl, each optionally substituted with one or more halo, CN, CH3, and CF3.

125. The compound of claim 124, or a pharmaceutically acceptable salt thereof, wherein R10is cyclopropyl, cyclobutyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 5- fluoropyri din-2 -yl, 3-fluoropyridin-2-yl, 4-fluoropyri din-2 -yl, pyridazinyl, methylpyridazinyl, pyrimidinyl, methylpyrimidinyl, phenyl, fluorophenyl, 2- fluorophenyl, 3 -fluorophenyl, of 4-fluorophenyl,126. The compound of claim 113, or a pharmaceutically acceptable salt thereof, wherein R2is:

128. The compound of any one of claims 1-112, or a pharmaceutically acceptable salt thereof, wherein R2is R8.- 528 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)129. The compound of claim 128, or a pharmaceutically acceptable salt thereof, wherein R8is 4-6 membered heterocycloalkyl.

130. The compound of claim 129, or a pharmaceutically acceptable salt thereof, wherein131. The compound of claim 128, or a pharmaceutically acceptable salt thereof, wherein R8is 5-6 membered aryl, optionally fused to or substituted with R8A.

132. The compound of claim 131, or a pharmaceutically acceptable salt thereof, wherein R8is cyanophenyl or fluorophenyl.

133. The compound of claim 128, or a pharmaceutically acceptable salt thereof, wherein R8is 5-6 membered heteroaryl, optionally fused to or substituted with R8A.

134. The compound of claim 133, or a pharmaceutically acceptable salt thereof, wherein R8is fluoropyridinyl or pyridinyl.

135. The compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein R is -(CR4R4)n-(CR4=R4)o-(CR4R4)p-SO2-Ci- Csalkyl, wherein n is 0, 1, or 2; o is 0, 1, or2; p is 0 or 1.

136. The compound of claim 135, wherein n=l, o=l, p=0 and each R4is independently hydrogen, CH3, orF.

137. The compound of claim 136, wherein R is:

138. The compound of claim 136, wherein R is:

139. The compound of claim 135, wherein n=l or 2, o=0, p=l and each R4is hydrogen.

140. The compound of claim 139, wherein R is:- 529 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)141. The compound of any one of claims 1-134, or a pharmaceutically acceptable salt thereof, wherein R iswherein n is 0, 1, or 2; o is 0, 1, or 2; and wherein is a double bond or a single bond.

142. The compound claim 141, wherein R is143. The compound of claim 141, wherein R is144. The compound claim 141, wherein R is145. The compound of any one of claims 1-134, or a pharmaceutically acceptable saltthereof, wherein146. The compound claim 145, or a pharmaceutically acceptable salt thereof, wherein R is- 530 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)147. The compound of any one of claims 141-146, or a pharmaceutically acceptable salt thereof, wherein X6is O.

148. The compound of any one of claims 141-146, or a pharmaceutically acceptable salt thereof, wherein X6is NH.

149. The compound of any one of claims 1-134, or a pharmaceutically acceptable salt thereof, wherein R is -(CR4R4)n-(CR4=R4)o-(CR4R4)p-C(O)N(Ci-C3alkyl)2.

150. The compound of claim 149, or a pharmaceutically acceptable salt thereof, wherein151. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is3-(4-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3- triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide;(E)-3 -chloro-4-methoxy-6-(5 -methyl- 1 -(1 -(4-(m ethyl sulfonyl)but-3 -en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide- 531 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide(R,E)-3-chloro-6-(6-(4-(2-(methylsulfonyl)vinyl)piperidin-l-yl)pyridin-3-yl)-4-(l- (pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;(2R)-2-[3-chloro-6-[l-[(2S,4S)-2-(methoxymethyl)-l-[(E)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5- a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[l-[(2S,4S)-2-(methoxymethyl)-l-[(E)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5- a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-(4-(4-(3-chloro-4-((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1- dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1- dioxide(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethanol;(R)-2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyri din-2 -yl)ethan- 1 -ol;(R)-2-((3 -chloro-6-(5 -methyl- 1 -(1 -((R,E)-4-(m ethyl sulfonyl)but-3 -en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyri din-2 -yl)ethan- 1 -ol(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethanol;- 532 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((S,E)-4-(methylsulfonyl)but-3 -en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyri din-2 -yl)ethan- 1 -ol;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -((R.,E)-4-(m ethyl sulfonyl )but-3 -en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyri din-2 -yl)ethan- 1 -ol;3-(4-(4-(3-chloro-4-((R)-l-cyclobutylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-cyclobutylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-cyclobutylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;(R)-2-((3 -chloro-6-( 1 -((2 S,4 S)-2-(methoxymethyl)- 1 -((E)-3 - (methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chloro-6-( 1 -((2S,4S)-2-(m ethoxymethyl)- 1 -((E)-3 - (methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(R,E)-3-chloro-6-(5-methyl-l-(l-(3-(methylsulfonyl)allyl)-piperidin-4-yl)-lH- l,2,3-triazol-4-yl)-4-(l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6- yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1 -di oxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1 , 1 -dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1 , 1 -dioxide;- 533 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-((R)-l-cyclopropylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;(R)-3-(4-(4-(3-chloro-4-((R)-l-cyclopropylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;(S)-3-(4-(4-(3-chloro-4-((R)-l-cyclopropylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;(R,E)-3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-6-(6-(4-(2-(methylsulfonyl)- vinyl)piperidin-l-yl)pyridin-3-yl)pyrazolo[l,5-a]pyridine;(R)-3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-(3- (methylsulfonyl)propyl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5- a]pyridine;3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(pyridin-2-yl)ethoxy)pyrazolo[ 1,5- a]pyridine;3-chloro-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(pyridin-2-yl)ethoxy)pyrazolo[ 1,5- a]pyridine;3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(pyridin-2-yl)ethoxy)pyrazolo[ 1,5- a]pyridine;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -( 1 -((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -( 1 -((R,E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-((S,E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;- 534 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R,E)-3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-(3- (methylsulfonyl)allyl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5- a]pyridine;3-chloro-4-((R)-l-cyclobutylethoxy)-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but- 3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine; 3-chloro-4-((R)-l-cyclobutylethoxy)-6-(5-methyl-l-(l-((R,E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;3-chloro-4-((R)-l-cyclobutylethoxy)-6-(5-methyl-l-(l-((S,E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;3-chloro-6-(l-((2S,4S)-2-(methoxymethyl)-l-((E)-3- (methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4- ((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(l-((2S,4S)-2-(methoxymethyl)- l-((E)-3-(methylsulfonyl)-allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol- 4-yl)pyraz°l° [ 1 , 5 -a]pyri dine;(R)-2-((3-chloro-6-(l-((2R,4S)-2-(methoxymethyl)-l-((E)-3- (methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3 -chloro-6-( 1 -((2R,4 S)-2-(methoxymethyl)- 1 -((E)-3 - (methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;3-chloro-4-((R)-l-cyclopropylethoxy)-6-(5-methyl-l-(l-((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;3-chloro-4-((R)-l-cyclopropylethoxy)-6-(5-methyl-l-(l-((R,E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;3-chloro-4-((R)-l-cyclopropylethoxy)-6-(5-methyl-l-(l-((S,E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;- 535 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(l-((2R,4S)-2- (methoxymethyl)-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)-5-methyl- lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine;3-chloro-6-(l-((2R,4S)-2-(methoxymethyl)-l-((E)-3- (methylsulfonyl)allyl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4- ((R)-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(l-((2S,4S)-2-(methoxymethyl)- 1 -((E)-3 -(methylsulfonyl)allyl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;3-chloro-6-(l-((2S,4S)-2-(methoxymethyl)-l-((E)-3- (m ethyl sulfonyl)allyl)piperidin-4-yl)-lH- 1,2, 3 -tri azol -4-yl)-4-((R)-l- (pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(l-((2R,4S)-2- (m ethoxymethyl)- 1 -((E)-3 -(methylsulfonyl)allyl)piperidin-4-yl)- 1H- 1,2,3- triazol-4-yl)pyrazolo[ 1 ,5 -a]pyridine;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -(2-(methylsulfonyl)-ethyl)piperidin-4-yl)-lH- l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2- yl)ethanol;(R)-2-((3-chloro-6-(5-methyl-l-(l-(2-(methylsulfonyl)-ethyl)piperidin-4-yl)-lH- l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2- yl)ethanol;3-chloro-6-(l-((2R,4S)-2-(methoxymethyl)-l-((E)-3- (m ethyl sulfonyl)allyl)piperidin-4-yl)-lH- 1,2, 3 -tri azol -4-yl)-4-((R)-l- (pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine;(R,E)-2-((3-chloro-6-(5-methyl-l-(l-(3-(methylsulfonyl)allyl)piperidin-4-yl)-lH- l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2- yl)ethanol;(S,E)-2-((3-chloro-6-(5-methyl-l-(l-(3-(methylsulfonyl)allyl)piperidin-4-yl)-lH- l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2- yl)ethanol;- 536 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -( 1 -(3 -(methylsulfonyl)propyl)piperidin-4-yl)-lH- l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2- yl)ethanol;(R)-2-((3 -chloro-6-(5 -methyl- 1 -( 1 -(3 -(methyl sulfonyl)propyl)piperidin-4-yl)- 1 H- l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2- yl)ethanol;(R,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyridin-2-yl)ethanol;(S,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyridin-2-yl)ethanol;(R)-2-((3-chloro-6-(l-(2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)- 5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethanol Isomer A;(R)-2-((3-chloro-6-(l-(2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)- 5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethanol Isomer B;(S)-2-((3-chloro-6-(l-(2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)- 5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethanol Isomer C;(S)-2-((3-chloro-6-(l-(2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)piperidin-4-yl)- 5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyri din-2 -yl)ethanollsomer D;(S)-3 -(4-(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1 -di oxide Isomer A;(R)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer B;- 537 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer C;(S)-3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer D;(E)-3-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)propan-l-ol Isomer A;(E)-3-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)propan-l-ol Isomer B;2-((3-chloro-6-(l-(l-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4- yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;2-((3-chloro-6-(l-(l-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4- yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;2-((3-chloro-6-(l-(l-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4- yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer C;2-((3-chloro-6-(l-(l-2,2-dimethyl-l-((E)-3-(methylsulfonyl)allyl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4- yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer D;2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cyclobutylethanol Isomer A;2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cyclobutylethanol Isomer B;- 538 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cyclobutylethanol Isomer C;2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cyclobutylethanol Isomer D;(E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)ethanol Isomer A;(E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)ethanol Isomer B;2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cyclopropylethanol Isomer A;2-((3-chloro-6-(5-methyl-l-(l-((S,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cyclopropylethanol Isomer B;2-((3-chloro-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cyclopropylethanol Isomer C;2-((3-chloro-6-(5-methyl-l-(l-((R,E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cyclopropylethanol Isomer D;4-[ 1 -(5 -fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl- 1 -[ 1 -[(E)-3 - methylsulfonylallyl]-4-piperidyl]-triazol-4-yl]pyrazolo[l,5-a]pyridine-3- carbonitrile;4-[l-(5-fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl-l-[l-[(E)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3- carbonitrile;- 539 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(E)-l-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperi din-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-methylpropan- 2-ol Isomer A;(E)-l-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-methylpropan- 2-ol Isomer B;3-chloro-5-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-7-(5-methyl-l-(l-((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)imidazo[l,2-a]pyridine Isomer A;3-chloro-5-((S)-l-(5-fluoropyridin-2-yl)ethoxy)-7-(5-methyl-l-(l-((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)imidazo[l,2-a]pyridine Isomer B;3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- 1H- 1 ,2,3-triazol-4-yl)-4-(((R)-tetrahydrofuran-3 -yl)oxy)pyrazolo[ 1,5- a]pyridine;4-[ 1 -(5 -fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl- 1 -[ 1 -[(E)-3 - methylsulfonylallyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3- carbonitrile Isomer A;4-[ 1 -(5 -fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl- 1 -[ 1 -[(E)-3 - methylsulfonylallyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3- carbonitrile Isomer B;(E)-3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- lH-l,2,3-triazol-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)pyrazolo[l,5- a]pyridine;3-chloro-N-((R)-l-(5-fluoropyridin-2-yl)ethyl)-6-(5-methyl-l-(l-((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridin-4-amine;(S,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cy cl obuty 1 ethanol ;- 540 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cy cl obuty 1 ethanol ;(S,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cy cl opropy 1 ethanol ;(R,E)-2-((3-chloro-6-(5-methyl-l-(l-(2-methyl-4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- cy cl opropy 1 ethanol ;3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- lH-l,2,3-triazol-4-yl)-4-(((S)-tetrahydrofuran-3-yl)oxy)pyrazolo[l,5- a]pyridine;(E)-3-chl oro-4-(2 -methoxy ethoxy)-6-(5-methyl-l-(l-(4-(methylsulfonyl)-but-3-en- 2-yl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 ,5-a]pyridine;2-[3-chloro-6-[3-methyl-5-[(E)-3-methylsulfonylallyl]-6,7-dihydro- 4Hpyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5- fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-5-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,7-dihydro-4H- pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;2-[3-chloro-6-[5-methyl-l-[l-[l-[(E)-3-methylsulfonylallyl]azetidin-3-yl]-4- piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;2-[3-chloro-6-[3-methyl-7-(3-methylsulfonylpropyl)-6,8-dihydro-5H-imidazo[l,2- a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;2-[3-chloro-6-[5-methyl-l-[7-[(E)-3-methylsulfonylallyl]-7-azaspiro-[3.5]nonan-2- yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;2-[3-chloro-6-[3-methyl-7-[(E)-3-methylsulfonylallyl]-6,8-dihydro- 5Himidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro- 2-pyridyl)ethanol;- 541 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(E)-3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- lH-l,2,3-triazol-4-yl)-4-(2-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine; (E)-3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- lH-l,2,3-triazol-4-yl)-4-(2-(pyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridine; 2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H- imidazof 1 ,2-a]pyrazin-2-yl]pyrazolo[ 1 ,5 -a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;4-[(lS)-l-(5-fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl-l-[l-[(E,lS)-l- methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5- a]pyridine-3 -carbonitrile;4-[(lS)-l-(5-fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl-l-[l-[(E,lR)-l- methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5- a]pyridine-3 -carbonitrile;(E)-3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)- lH-l,2,3-triazol-4-yl)-4-((l-(pyridin-2-yl)propan-2-yl)oxy)pyrazolo[l,5- a]pyridine;(E)-2-((3-chloro-7-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)imidazo[l,2-a]pyridin-5-yl)oxy)-2-(5- fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2- yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2- yl)ethanol Isomer B;(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2- yl)ethanol Isomer C;(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2- yl)ethanol Isomer D;- 542 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2-[3-chloro-6-[3-methyl-5-[(E,R)-3-methylsulfonylallyl]-6,7-dihydro- 4Hpyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5- fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-5-[(E,S)-3-methylsulfonylallyl]-6,7-dihydro- 4Hpyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5- fluoro-2-pyridyl)ethanol;2-[3-chloro-6-[3-methyl-5-[l-[(E)-3-methylsulfonylallyl]pyrrolidin-3-yl]-6,7- dihydro-4H-pyrazolo[l,5-a]-pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy- 2-(5 -fluoro-2-pyridyl)ethanol ;2-[3-chloro-6-[3-methyl-7-(3-methylsulfonylpropyl)-6,8-dihydro-5H-imidazo[l,2- a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol Isomer A;2-[3-chloro-6-[3-methyl-7-(3-methylsulfonylpropyl)-6,8-dihydro-5H-imidazo[l,2- a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol Isomer B;2-[3-chloro-6-[5-methyl-l-[7-[(E, R)-3-methylsulfonylallyl]-7-azaspiro[3.5]nonan- 2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;2-[3-chloro-6-[5-methyl-l-[7-[(E, S)-3-methylsulfonylallyl]-7-azaspiro[3.5]nonan- 2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;(E)-4-((3-fluoropyridin-2-yl)thio)-6-(5-methyl-l-(l-(4-(methylsulfonyl)-but-3-en- 2-yl)piperidin-4-yl)- 1H- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 ,5-a]pyridine-3 - carbonitrile;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer B;- 543 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer C;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer D;6-(l-(l -(1, 1-dioxi do-2, 3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l, 2,3- triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3- carbonitrile;2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H- imidazof 1 ,2-a]pyrazin-2-yl]pyrazolo[ 1 ,5 -a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol Isomer A;2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H- imidazof 1 ,2-a]pyrazin-2-yl]pyrazolo[ 1 ,5 -a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol Isomer B;2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H- imidazof 1 ,2-a]pyrazin-2-yl]pyrazolo[ 1 ,5 -a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol Isomer C;2-[3-chloro-6-[3-methyl-7-[(E)-l-methyl-3-methylsulfonyl-allyl]-6,8-dihydro-5H- imidazof 1 ,2-a]pyrazin-2-yl]pyrazolo[ 1 ,5 -a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol Isomer D;(E)-4-((2-cyanophenyl)thio)-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine-3- carbonitrile;2-[3-chloro-6-[3-methyl-7-[(E)-3-methylsulfonylallyl]-6,8-dihydro- 5Himidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro- 2-pyridyl)-ethanol Isomer A;2-[3-chloro-6-[3-methyl-7-[(E)-3-methylsulfonylallyl]-6,8-dihydro- 5Himidazo[l,2-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro- 2-pyridyl)-ethanol Isomer B;- 544 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide Isomer D;6-(l-(-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3- triazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;6-(l-(-l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3- triazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;6-(l-(l -(1, 1-dioxi do-2, 3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l, 2,3- triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3- carbonitrile Isomer A;6-(l-(l -(1, 1-dioxi do-2, 3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l, 2,3- triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3- carbonitrile Isomer B;(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2- yl)ethanol Isomer A;(R)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2- yl)ethanol Isomer B;- 545 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2- yl)ethanol Isomer C;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(pyridin-2- yl)ethanol Isomer D;6-(l-(l, 1-dioxi do-2, 3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l, 2, 3- triazol-4-yl)-4-((R)-2-hy droxy- 1 -(pyri din-2 -yl)eth oxy )pyrazolo[ 1,5- a]pyridine-3 -carbonitrile Isomer C;6-(l-(l, 1-dioxi do-2, 3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l, 2, 3- tri azol -4-yl)-4-((R)-2-hy droxy- 1 -(pyri din-2 -yl)eth oxy )pyrazolo[ 1,5- a]pyridine-3 -carbonitrile Isomer D;6-(l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3- triazol-4-yl)-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyridine-3 -carbonitrile Isomer A;6-(l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3- triazol-4-yl)-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyridine-3 -carbonitrile Isomer B;6-(l-(l -(1, 1-dioxi dotetrahydro-2H-thiopyran-4-yl)piperidin-4-yl)-5-methyl-lH- l,2,3-triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3- carbonitrile;6-(l-(-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3- triazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;6-(l-(-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3- triazol-4-yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;6-(l-(l, 1-dioxi dotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4- yl)-4-((R)-l-(5-fluoropyri din-2 -yl)-2-hy droxy ethoxy)-pyrazolo[ 1,5- a]pyridine-3 -carbonitrile Isomer C;- 546 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)6-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4- yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyridine-3 -carbonitrile Isomer D;6-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4- yl)-4-((R)-l-(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)-pyrazolo[ 1,5- a]pyridine-3 -carbonitrile Isomer A;6-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-pyrazol-4- yl)-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyridine-3 -carbonitrile Isomer B;(R)-4-(4-(4-(3-chloro-4-(2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H- thiopyran 1,1 -di oxide Isomer A;(S)-4-(4-(4-(3 -chloro-4-(2-hydroxy- 1 -(pyri din-2 -yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H- thiopyran 1,1-dioxide Isomer B;6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-triazol-4-yl]- 4-(2-pyridylsulfanyl)-pyrazolo[l,5-a]pyridine-3-carbonitrile;(E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)benzonitrile; 4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)-6-(5-m ethyl- 1 -(1 -((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;4-((S)- 1 -(5-fluoropyri din-2 -yl)-2-hydroxyethoxy)-6-(5-m ethyl- 1 -(1 -((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer C;4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)-6-(5-methyl-l-(l-((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer D;- 547 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)4-((S)-2-hydroxy- 1 -(pyridin-2-yl)ethoxy)-6-(5-methyl- 1 -( 1 -((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer A;4-((S)-2-hydroxy- 1 -(pyridin-2-yl)ethoxy)-6-(5-methyl- 1 -( 1 -((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine-3-carbonitrile Isomer B;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin-l -yl)tetrahydrothiophene 1,1 -di oxide Isomer C;3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin-l -yl)tetrahydrothiophene 1,1 -di oxide Isomer D;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin-l -yl)tetrahydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-2-hydroxy-l-(pyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl- 1H- 1 ,2,3-triazol- 1 -yl)piperidin-l -yl)tetrahydrothiophene 1,1 -di oxide Isomer B;4-[(3-fluoro-2-pyridyl)sulfanyl]-6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonyl- allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;4-(2-cyanophenyl)sulfanyl-6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonylallyl]- 4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;6-(l-(l-(l,l-dioxidotetrahydro-thiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3- triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3- carbonitrile Isomer A;6-(l-(l-(l,l-dioxidotetrahydrothiophen-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3- triazol-4-yl)-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridine-3- carbonitrile Isomer B;4-[(lS)-l-(3-fluoro-2-pyridyl)-2-hydroxy-ethoxy]-6-[5-methyl-l-[l-[(E)-l-methyl- 3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3- carbonitrile;- 548 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)6-[l-[l-(l,l-dioxothian-4-yl)-4-piperidyl]-5-methyl-triazol-4-yl]-4-[(lS)-2- hydroxy-l-(2-pyridyl)-ethoxy]pyrazolo[l,5-a]pyridine-3-carbonitrile; 6-[l-[l-(l,l-dioxothiolan-3-yl)-4-piperidyl]-5-methyl-triazol-4-yl]-4-[(lS)-2- hydroxy-l-(2-pyridyl)ethoxy]-pyrazolo[l,5-a]pyridine-3-carbonitrile; 3-(4-(4-(3-chloro-4-((R)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1 -di oxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer D;3-(4-(4-(3-chloro-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;(R)-2-((3-chloro-6-(5-methyl-l-(l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3- fluoropyridin-2-yl)ethanol Isomer A;(R)-2-((3-chloro-6-(5-methyl-l-(l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3- fluoropyridin-2-yl)ethanol Isomer B;(S)-2-((3-chloro-6-(5-methyl-l-(l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3- fluoropyridin-2-yl)ethanol Isomer C;(S)-2-((3-chloro-6-(5-methyl-l-(l-(E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(3- fluoropyridin-2-yl)ethanol Isomer D;- 549 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-methyl-lH-pyrazol-l-yl)piperidin-l-yl)-2,3- dihydrothiophene 1,1 -di oxide Isomer A;3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-methyl-lH-pyrazol-l-yl)piperidin-l-yl)-2,3- dihydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene- 1, 1-dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene-1, 1-dioxide Isomer D;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene-1, 1-dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene-1, 1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((3-fluoropyridin-2-yl)thio)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide;3-(4-(4-(3-chloro-4-(l-(3-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1 , 1 -dioxide;(E)-2-((3-chloro-6-(5-methyl-l-(l-(4-(methylsulfonyl)but-3-en-2-yl)piperidin-4- yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(4- fluoropyridin-2-yl)ethanol;(E)-4-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)- pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l- yl)pent-2-enenitrile;- 550 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1 , 1 -dioxide;3-(4-(4-(3-chloro-4-(l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1- dioxide;4-(2-cyanophenoxy)-6-[5-methyl-l-[l-[(E)-l-methyl-3-methylsulfonyl-allyl]-4- piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridine-3-carbonitrile;3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1 -di oxide Isomer A;3-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer D;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro- thiophene- 1,1 -di oxide Isomer A;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro- thiophene- 1,1 -di oxide Isomer B;- 551 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro- thiophene- 1,1 -di oxide Isomer C;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 -dihydro- thiophene- 1,1 -di oxide Isomer D;3-(4-(4-(3-chloro-4-((R)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer D;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6- yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;(E)-4-(4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin- 1 -yl)-N,N-dimethylpent-2-enamide;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer B;- 552 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1,1 -di oxide;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer C;3-(4-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer D;(R)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl-lH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1,1- dioxide;(R)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H- thiopyran 1,1 -di oxide Isomer A;(S)-4-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H- thiopyran 1,1-dioxide Isomer B;3 - [2 - (4 - { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyridin-2-yl)-2-hy droxy- ethoxy]pyrazolo[ 1 , 5-a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-7 - azaspiro[3.5 ]nonan-7-yl]-2, 3 -dihydro- 1 l6-thiophene- 1 , 1 -di one Isomer A; 3 - [2 - (4 - { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyridin-2-yl)-2-hy droxy- ethoxy]pyrazolo[ 1 , 5-a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-7 - azaspiro[3.5 ]nonan-7-yl]-2, 3 -dihydro- 1 l6-thiophene- 1 , 1 -di one Isomer B ;- 553 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1 , 1 -dioxide;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1 -di oxide Isomer A;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer C;3-(4-(4-(3-chloro-4-(l-(5-(trifluoromethyl)pyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer D;3-(4-(4-(3-chloro-4-(-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer A;3-(4-(4-(3-chloro-4-(-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer B;3-(4-(4-(3-chloro-4-(-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer C;3-(4-(4-(3-chloro-4-(-l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer D;4-(4-(4-(3-chloro-4-(l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1,1- dioxide Isomer A;- 554 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)4-(4-(4-(3-chloro-4-(l-(5-methylpyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1,1- dioxide Isomer B;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl-lH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer A;3-(4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl-lH-pyrazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer B;(S)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)- 1 - iminothietane 1 -oxide;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer A;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer B;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer C;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)tetrahydrothiophene 1,1- dioxide Isomer D;(S)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)thietane 1,1- dioxide;(S)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1,1- dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;- 555 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)- 1 -iminothietane 1 -oxide; 3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5- a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7- yl]-ll6-thiolane-l, 1-dione Isomer A;3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5- a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7- yl]-ll6-thiolane-l, 1-dione Isomer B;3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin- 6-yl} -5-methyl-lH- 1,2, 3-tri azol- l-yl)-7-azaspiro[3.5]nonan-7-yl]-ll6- thietane-l,l-dione;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin- 2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2-yl)piperidin- 4-yl)-lH-pyrazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin- 2-yl)ethanol Isomer B;(R)-4-(4-(4-(3-chloro-4-(l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1.1 -di oxide ;(S)-4-(4-(4-(3-chloro-4-(l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)tetrahydro-2H-thiopyran 1.1 -di oxide;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1- dioxide Isomer A;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1- dioxide Isomer B;- 556 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1- dioxide Isomer C;3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1- dioxide Isomer D;3-(4-(4-(3-chloro-4-(l-(6-methylpyridazin-3-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide; 3-(4-(4-(3-chloro-4-(l-(5-fluoropyrimidin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(S)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)-3-fluoropyridin-2-yl)piperazin-l-yl)thietane 1,1 -di oxide; (S)-3 -(4-(4-(3 -chloro-4-(2-hydroxy- 1 -phenylethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)- 5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-phenylethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- IH-pyrazol- 1 -yl)piperidin- 1 -yl)- 1 -iminothietane 1 -oxide; (R)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6- yl)pyridin-2-yl)piperazin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(6-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6- yl)-3 -fluoropyridin-2-yl)-2,6-diazaspiro[3.3 ]heptan-2-yl)thietane 1,1- dioxide;(S)-3-(6-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)pyridin-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)thietane 1,1- dioxide;(S)-3-(6-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)-3-fluoropyridin-2-yl)-2,6-diazaspiro[3.3]heptan-2- yl)thietane 1 , 1 -dioxide;- 557 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)4-[4-(4-{3-chloro-4-[(l S)-l -(5-fluoropyri din-2 -yl)-2-hydroxy ethoxy]- pyrazolof 1 , 5-a]pyridin-6-yl } -5-methyl- 1H- 1,2,3 -tri azol- 1 -yl)piperidin- 1 - y 1 ] - 1 X hi ane- 1 , 1 -di one;3-(4-(4-(3-chloro-4-(l-(5-fluoropyrimidin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide Isomer A;3-(4-(4-(3-chloro-4-(l-(5-fluoropyrimidin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide Isomer B;(R)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5-a]pyridin-6- yl)-3-fluoropyridin-2-yl)piperazin-l-yl)thietane 1, 1 -di oxide;(S)-3-(4-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyridin-6-yl)pyri din-2 -yl)piperazin- 1 -yl)thietane 1 , 1 -dioxide;(R)-3-(6-(5-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)pyridin-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)thietane 1,1-dioxide;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5- a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro-[3.5]nonan-7- yl]-2,3-dihydro-ll6-thiophene-l, 1-dione Isomer A;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5- a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro-[3.5]nonan-7- yl]-2,3-dihydro-ll6-thiophene-l, 1-dione Isomer B;(2S)-2-{[3-chloro-6-(l-{7-[(2S,3E)-4-methanesulfonylbut-3-en-2-yl]-7- azaspiro[3.5]nonan-2-yl}-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5- a]pyridin-4-yl]oxy}-2-(5-fluoropyridin-2-yl)ethan-l-ol;(2S)-2-[3-chloro-6-[5-methyl-l-[7-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-7- azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5- fluoro-2-pyridyl)ethanol;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5- a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7- y 1 ] - 1 X hi etane- 1 , 1 -di one;[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]- 5-methyl-pyrazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thietanel,l-dioxide;- 558 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-(4-(4-(3-chloro-4-((S)-2-hydroxy-l-phenylethoxy)pyrazolo[l,5-a]pyridin-6-yl)- 5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1- dioxide;3-(4-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6-yl)-5- methyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)-2, 3 -dihydrothiophene 1,1- dioxide;3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)-6-(5-methyl-l-(l-((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;(2S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- phenyl ethanol;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5- a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7- yl]-ll6-thiolane-l, 1-dione Isomer A;3-[2-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy]pyrazolo[l,5- a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-azaspiro[3.5]nonan-7- yl]-ll6-thiolane-l, 1-dione Isomer B;(S)-2-[3-chloro-6-[l-[l-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-4-piperidyl]-5- methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(2-pyridyl)ethanol Isomer A;(S)-2-[3-chloro-6-[l-[l-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-4-piperidyl]-5- methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(2-pyridyl)ethanol Isomer B;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1 -di oxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer B;- 559 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thiolane 1,1-dioxide Isomer A;3-[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thiolane 1,1-dioxide Isomer B;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[2-[(E,lS)-l- methyl-3-methylsulfonyl-allyl]-2-azaspiro[3.3]heptan-6-yl]triazol-4- yl]pyrazolo[ 1 ,5 -a]pyridine;(2S)-2-[3-chloro-6-[l-[2-(l,l-dioxothiolan-3-yl)-2-azaspiro[3.3]heptan-6-yl]-5- methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer A;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer B;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 , 5- a]pyridin-6-yl)-5-methyl-lH-pyrazol-l-yl)piperidin-l-yl)-2,3- dihydrothiophene 1,1-dioxide Isomer A;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 , 5- a]pyridin-6-yl)-5-methyl-lH-pyrazol-l-yl)piperidin-l-yl)-2,3- dihydrothiophene 1,1-dioxide Isomer B;- 560 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)thietane 1,1- dioxide;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1 -di oxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer B;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer C;3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer D;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5- a]pyridin-6-yl)-5-methyl-lH-pyrazol-l-yl)piperidin-l-yl)-2,3- dihydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5- a]pyridin-6-yl)-5-methyl-lH-pyrazol-l-yl)piperidin-l-yl)-2,3- dihydrothiophene 1,1-dioxide Isomer B;3-(4-(4-(3-chloro-4-((S)-l-(4-fluorophenyl)-2-hydroxyethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1 , 1 -dioxide;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)thietane 1,1- dioxide;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer A;- 561 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)pyrazolo[ 1 ,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer B;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer A;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer C;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(4-fluoropyridin-2-yl)ethoxy)pyrazolo-[ 1,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer D;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((R)- 1 -((E)-4-(m ethyl sulfonyl)but-3 -en-2- yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((R)- 1 -((E)-4-(m ethyl sulfonyl)but-3 -en-2- yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyridin-2-yl)ethanol Isomer B;3-(2-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6- yl}-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-5-yl)-ll6-thietane-l,l- dione;- 562 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2-[(lR)-l-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2S,3E)-4-methanesulfonyl-but-3- en-2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5- a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine;2-[(lR)-l-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2R,3E)-4-methanesulfonyl-but-3- en-2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5- a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine;3-[6-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo-[l,5-a]pyridin- 6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-2-azaspiro-[3.3]heptan-2-yl]-2,3- dihydro- 1 l6-thiophene- 1 , 1 -di one;(2S)-2-[3-chloro-6-[l-[2-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-2- azaspiro[3.3]heptan-6-yl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4- yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3 -(2- { 3 -chloro-4-[ 1 -(5 -fluoropyrimidin-2-yl)ethoxy]-pyrazolo[ 1 ,5-a]pyridin-6-yl } - 3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-5-yl)-ll6-thietane-l,l- dione;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;(2S)-2-((3-chloro-6-(5-methyl-l-(l-((E)-4-(methylsulfonyl)but-3-en-2- yl)piperidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (4-fluoropheny 1 )ethanol ;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[ 1,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer A;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[ 1,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)piperidin- 1 - yl)tetrahydrothiophene 1,1-dioxide Isomer B;- 563 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((S)- 1 -((E)-4-(m ethyl sulfonyl)but-3 -en-2- yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3 -chi oro-6-(5-m ethyl- 1 -((S)- 1 -((E)-4-(m ethyl sulfonyl)but-3 -en-2- yl)piperidin-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2- (5-fluoropyridin-2-yl)ethanol Isomer B;3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-6-(5-m ethyl- 1 -((S)- 1 -((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer A;3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-6-(5-m ethyl- 1 -((S)- 1 -((E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer B;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)- pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l- yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)- pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l- yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((R)-l-(E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((R)-l-(E)-4- (methylsulfonyl)but-3-en-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer B;3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyri din-6- yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1 , 1 -dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyri din-6- yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;- 564 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((R)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1 , 1 -dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((R)-l-(4-fluorophenyl)ethoxy)pyrazolo[l,5-a]pyridin-6- yl)-5-methyl-lH-l,2,3-triazol-l-yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1 -di oxide Isomer B;3 -(2- { 3 -chi oro-4- [( 1 R)- 1 -(5-fluoropyrimidin-2-yl)-2-hydroxy- ethoxy]pyrazolo[l,5-a]pyridin-6-yl}-3-methyl-4H,5H,6H,7Hpyrazolo[l,5- a]pyrazin-5-yl)- 1 X hi etane- 1 , 1 -di one;3 -(2- { 3 -chi oro-4- [( 1 S)- 1 -(5 -fluoropyrimidin-2-yl)-2-hy droxy-ethoxy ]pyrazolo[ 1 , 5 - a]pyridin-6-yl}-3-methyl-4H,5H,6H,7Hpyrazolo[l,5-a]pyrazin-5-yl)-ll6- thietane-l,l-dione;3 - [(3 S,4 S)-4-(4- { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 - a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-3 -fluoropiperidin- 1 -y 1] - 2, 3 -dihydro- ll6-thiophene-l, 1-dione Isomer A;3 - [(3 S,4 S)-4-(4- { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 - a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-3 -fluoropiperidin- 1 -y 1] - 2, 3 -dihydro- ll6-thiophene-l, 1-dione Isomer B;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[2-[(E,lR)-l- methyl-3-methylsulfonyl-allyl]-2-azaspiro[3.3]heptan-6-yl]triazol-4- yl]pyrazolo[ 1 ,5 -a]pyridine;3-[6-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]thietane 1,1-dioxide; (2S)-2-[3-chloro-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4- yl]oxy-2-(5-fluoro-2-pyridyl)ethan-l-ol;(2S)-2-[(3-chloro-6-{l-[(2S,4S)-l-[(2S,3E)-4-methanesulfonylbut-3-en-2-yl]-2- methylpiperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}-pyrazolo[l,5- a]pyridin-4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethan-l-ol;3-chloro-4-methoxy-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methyl-sulfonylallyl]-2- azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;- 565 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(2S)-2-[3-chloro-6-[5-methyl-l-[(2R,4S)-2-methyl-l-[(E,lR)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4- yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2 S)-2- [3 -chloro-6-[5-methyl- 1 -[(2R,4S)-2-methyl- 1 -[(E, 1 S)- 1 -methyl-3 - methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4- yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2R)-2- [(3 -chi oro-6- { 1 - [(3R,4 S)-3 -fluoro- 1 - [(2 S, 3E)-4-methane-sulfonylbut-3 -en- 2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin- 4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethan-l-ol;(2S)-2-[(3-chloro-6-{l-[(3R,4S)-3-fluoro-l-[(2S,3E)-4-methane-sulfonylbut-3-en- 2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin- 4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethan-l-ol;3 -(2- { 3 -chi oro-4- [( 1 S)- 1 -(5 -fluoropyridin-2-yl)-2-hy droxy ethoxy ] -py razolof 1 , 5 - a]pyridin-6-yl}-3-methyl-4H,5H,6H,7Hpyrazolo[l,5-a]pyrazin-5-yl)-ll6- thietane-l,l-dione;3-chloro-6-[l-[(3R,4S)-3-fluoro-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4- piperidyl]-5-methyl-triazol-4-yl]-4-[(lR)-l-(5-fluoro-2- pyridyl)ethoxy]pyrazolo[ 1 , 5-a]pyridine;3-chloro-6-[l-[(3R,4S)-3-fluoro-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4- piperidyl]-5-methyl-triazol-4-yl]-4-[(lR)-l-(5-fluoro-2- pyridyl)ethoxy]pyrazolo[ 1 , 5-a]pyridine;(S)-3-(4-(4-(3-chloro-4-(l-(4-fluorophenyl)-2-hydroxyethoxy)-pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -triazol- 1 -yl)piperidin- 1 -yl)thietane 1,1- dioxide;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- methoxyethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3-triazol- 1 - yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- methoxyethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3-triazol- 1 - yl)piperidin-l-yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;- 566 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)2-((3-chloro-6-(l-((R)-l-((R)-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-3-yl)- 5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl acetate Isomer A;2-((3-chloro-6-(l-((R)-l-((R)-l,l-dioxidotetrahydrothiophen-3-yl)piperidin-3-yl)- 5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl acetate Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin- 1 -yl)thietane 1 , 1 -dioxide;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl- 1-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[ 1 ,5 -a]pyridine;(2S)-2-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2R,3E)-4-methanesulfonylbut-3-en- 2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin- 4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethan-l-ol;(2S)-2-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2S,3E)-4-methane-sulfonylbut-3-en- 2-yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin- 4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethan-l-ol;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl- 1-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[ 1 ,5 -a]pyridine;2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6- yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-[(2R,3E)-4-methanesulfonyl-but-3- en-2-yl]-7-azaspiro[3.5]nonane;(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6- yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-[(2S,3E)-4-methanesulfonylbut-3-en- 2-yl]-7-azaspiro[3 ,5]nonane;3-[(2R,4S)-4-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-pyrazolo[l,5- a]pyridin-6-yl]-5-methyl-triazol- 1 -yl]-2-methyl- 1 -piperidyl]thiolane 1,1- dioxide;- 567 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 - [(3R,4 S)-4-(4- { 3 -chloro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 - a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-3 -fluoropiperidin- 1 -y 1 ] - 1 l6-thiolane- 1 , 1 -di one;(S)-2-((3 -chloro-6-( 1 -(1 -(-2,2-dimethyl- 1 -((E)-4-(methylsulfonyl)but-3 -en-2- yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3 -chloro-6-( 1 -(1 -(-2,2-dimethyl- 1 -((E)-4-(methylsulfonyl)but-3 -en-2- yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;(S)-2-((3 -chloro-6-( 1 -(1 -(-2,2-dimethyl- 1 -((E)-4-(methylsulfonyl)but-3 -en-2- yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer C;(S)-2-((3 -chloro-6-( 1 -(1 -(-2,2-dimethyl- 1 -((E)-4-(methylsulfonyl)but-3 -en-2- yl)azetidin-3-yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer D;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- methoxyethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3-triazol- 1 - yl)piperidin- 1 -yl)thietane 1 , 1 -dioxide;(S)-2-((3-chloro-6-(l-((R)-l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-3- yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl acetate Isomer A;(S)-2-((3-chloro-6-(l-((R)-l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)piperidin-3- yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl acetate Isomer B;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -( 1 , 1 -di oxidothi etan-3 -yl)piperi din-3 -yl)-5-methyl- 1H- l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2- yl)ethyl acetate;- 568 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2R,4S)-2-methyl- l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[ 1 ,5 -a]pyridine;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2R,4S)-2-methyl- l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[ 1 ,5 -a]pyridine;3 - [(2 S,4 S)-4-(4- { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 - a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-2-methylpiperidin- 1 -y 1 ] - 1 l6-thiolane- 1 , 1 -di one;3 - [(3 S,4 S)-4-(4- { 3 -chi oro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 - a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-3 -fluoropiperidin- 1 -y 1 ] - 1 l6-thiolane- 1 , 1 -di one;3-chloro-4-isopropoxy-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methylsulfonyl- allyl]-2-azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine; 3-chloro-4-ethoxy-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methylsulfonylallyl]-2- azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;(2S)-2-[3-chloro-6-[l-[2-(l,l-dioxothietan-3-yl)-2-azaspiro[3.3]heptan-6-yl]-5- methyl-pyrazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;(2S)-2-[3-chloro-6-[5-methyl-l-[2-[(E,lS)-l-methyl-3-methylsulfonylallyl]-2- azaspiro[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5- fluoro-2-pyridyl)ethanol;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5- a]pyridine Isomer A;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5- a]pyridine Isomer B;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5- a]pyridine Isomer C;- 569 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-methoxypyrazolo[l,5- a]pyridine Isomer D;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- methoxyethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3-triazol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1 -di oxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- methoxyethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3-triazol- 1 - yl)piperidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((3R)-l-(4- (methylsulfonyl)butan-2-yl)piperidin-3-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[ 1 ,5 -a]pyridine;(2S)-2-((3-chloro-6-(5-methyl-l-((3R)-l-(4-(methylsulfonyl)butan-2-yl)piperidin- 3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethanol;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5- a]pyridine Isomer A;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5- a]pyridine Isomer B;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5- a]pyridine Isomer C;3-chloro-6-(l-(l-(2,2-dimethyl-l-((E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-ethoxypyrazolo[l,5- a]pyridine Isomer D;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4- isopropoxypyrazolo[l,5-a]pyridine Isomer A;- 570 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4- isopropoxypyrazolo[l,5-a]pyridine Isomer B;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4- isopropoxypyrazolo[l,5-a]pyridine Isomer C;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4- isopropoxypyrazolo[l,5-a]pyridine Isomer D;(2S)-2-[3-chloro-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methyl-sulfonylallyl]-2- azaspiro-[3.3]heptan-6-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2- (5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[l-[2-(l,l-dioxothietan-3-yl)-2-azaspiro[3.3]heptan-6-yl]-5- methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2- pyridyl)ethanol;3-[(3S,4S)-4-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo[l,5- a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-3 -fluoropiperidin- 1-yl]- ll6-thiolane-l,l-dione Isomer A;3-[(3S,4S)-4-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo[l,5- a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-3 -fluoropiperidin- 1-yl]- ll6-thiolane-l,l-dione Isomer B;3 - [(3R,4 S)-4-(4- { 3 -chloro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 - a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -y l)-3 -fluoropiperidin- 1 -y 1 ] - 2,3 -dihydro- 1 X hi ophene- 1 , 1 -di one;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5- fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5- fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer B;- 571 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5- fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer C;3-chloro-6-(l-(l-(2,2-dimethyl-l-(E)-4-(methylsulfonyl)but-3-en-2-yl)azetidin-3- yl)piperidin-4-yl)-5-methyl-lH-l,2,3-triazol-4-yl)-4-((R)-l-(5- fluoropyridin-2-yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer D;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer B;2-[(lR)-l-[(3-chloro-6-{l-[(3S,4S)-3-fluoro-l-[(2R)-4-methanesulfonyl-butan-2- yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4- yl)oxy]ethyl]-5-fluoropyridine;[6-[4-[3-chloro-4-[(lS)-l-(5-fluoro-2-pyridyl)-2-methoxyethoxy]pyrazolo[l,5- a]pyridin-6-yl]-5-methyl-triazol-l-yl]-2-azaspiro[3.3]heptan-2-yl]-2,3- dihydrothiophene 1 , 1 -dioxide;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -( 1 -(4- (methylsulfonyl)butan-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer A;3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)-6-(5 -methyl- 1 -( 1 -(4- (methylsulfonyl)butan-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer B;- 572 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-[7-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin- 6-yl } -5-methyl- 1H- 1 ,2 -triazol- 1 -yl)-2-azaspiro[3.5]nonan-2-yl]-2,3 - dihydro- 1 l6-thiophene- 1 , 1 -di one;(7-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl}-5-methyl-lH-l,2,3-triazol-l-yl)-2-[(2R,3E)-4-methanesulfonylbut-3- en-2-yl]-2-azaspiro[3.5]nonane;2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl}-5-methyl-lH-l,2,3-triazol-l-yl)-7-[(2R)-4-methanesulfonylbutan-2-yl]- 7-azaspiro[3.5]nonane;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[6-[(E,lR)-l- methyl-3-methylsulfonyl-allyl]-6-azaspiro[3.5]nonan-2-yl]triazol-4- yl]pyrazolo[ 1 ,5 -a]pyridine;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(E)- 4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(E)- 4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2- yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5- a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2- yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5- a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;3 -((7R, 8aS)-7-(4-(3 -chloro-4-((R)- 1 -(5 -fluoropyridin-2-yl)ethoxy)pyrazolo [ 1,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)hexahydropyrrolo[ 1 ,2- a]pyrazin-2(lH)-yl)-2,3-dihydrothiophene 1, 1-dioxide;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(E)- 4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;- 573 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((lR,3S,5S)-8-(E)- 4-(methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3-chloro-6-(l-(l-(4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5- methyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 - yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-6-(l-(l-(4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5- methyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 - yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer B;3-chloro-6-(l-(l-(4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5- methyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 - yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer C;3-chloro-6-(l-(l-(4-fluoro-4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-5- methyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 - yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer D;3-chloro-6-[l-[(3S,4S)-3-fluoro-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4- piperidyl]-5-methyl-triazol-4-yl]-4-[(lS)-l-(5-fluoro-2-pyridyl)-2- methoxy-ethoxy]pyrazolo[l,5-a]pyridine;[(2S)-2-[3-chloro-6-[l-[(3S,4S)-3-fluoro-l-[(E,lR)-l-methyl-3-methylsulfonyl- allyl]-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2- (5-fluoro-2-pyridyl)ethyl] acetate;(2S)-2-[3-chloro-6-[5-methyl-l-[6-[(E,lR)-l-methyl-3-methylsulfonylallyl]-6- azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5- fluoro-2-pyridyl)ethanol;(2S)-2-{[3-chloro-6-(l-{6-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-6- azaspiro[3.5]nonan-2-yl}-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5- a]pyridin-4-yl]oxy}-2-(5-fluoropyridin-2-yl)ethan-l-ol;[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]- 5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]-2,3-dihydrothiophene 1,1 -di oxide;3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]thiolane 1,1 -di oxide;- 574 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-[7-[4-(3-chloro-4-methoxy-pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-triazol-l-yl]- 2-azaspiro[3.5]nonan-2-yl]-2,3-dihydrothiophene 1,1-dioxide;3-chloro-4-methoxy-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methylsulfonylallyl]-2- azaspiro[3.5]nonan-7-yl]triazol-4-yl]pyrazolo[l,5-a]pyridine;3-((7S,8aS)-7-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)pyrazolo[l,5- a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)hexahydropyrrolo[ 1 ,2- a]pyrazin-2(lH)-yl)-2,3-dihydrothiophene 1, 1-dioxide;3 -(( 1 R, 3 S, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5 -fluoropy ridin-2-yl)ethoxy)-pyrazolo[ 1,5- a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8- yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3 -(( 1 R, 3 S, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5 -fluoropy ridin-2-yl)ethoxy)pyrazol o[ 1 , 5 - a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8- yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;3 -(( 1 R, 3 S, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5 -fluoropy ridin-2-yl)ethoxy)pyrazol o[ 1 , 5 - a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8- yl)-2,3-dihydrothiophene 1,1-dioxide Isomer A;3 -(( 1 R, 3 S, 5 S)-3 -(4-(3 -chloro-4-((R)- 1 -(5 -fluoropy ridin-2-yl)ethoxy)pyrazol o[ 1 , 5 - a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8- yl)-2,3-dihydrothiophene 1,1-dioxide Isomer B;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2- yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5- a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-((lR,3S,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2- yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5- a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin- 6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-6-azaspiro[3.5]nonan-6-yl]-2,3- dihydro- 1 l6-thiophene- 1 , 1 -di one;3-[2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin- 6-yl} -5-methyl-lH- 1,2, 3-tri azol- l-yl)-6-azaspiro[3.5]nonan-6-yl]-ll6- thiolane-l,l-dione;- 575 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]thiolane-l,l-dioxide Isomer A;3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]thiolane-l,l-dioxide Isomer B;3-chloro-4-ethoxy-6-[5-methyl-l-[7-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-7- azaspiro[3.5]nonan-2-yl]triazol-4-yl]pyrrolo[l,2-b]pyridazine;2-[(lR)-l-[(3-chloro-6-{l-[(3R,4S)-3-fluoro-l-[(2R)-4-methanesulfonyl-butan-2- yl]piperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl}pyrazolo[l,5-a]pyridin-4- yl)oxy]ethyl]-5-fluoropyridine;(2 S)-2- { [3 -chloro-6-( 1 - { 7- [(2R)-4-methanesulfonylbutan-2-yl]-7- azaspiro[3.5]nonan-2-yl}-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5- a]pyridin-4-yl]oxy}-2-(5-fluoropyridin-2-yl)ethan-l-ol;3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[6-[(lR)-l -methyl- 3-methylsulfonyl-propyl]-6-azaspiro[3.5]nonan-2-yl]triazol-4- yl]pyrazolo[ 1 ,5 -a]pyridine;3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]-2,3-dihydrothiophene 1 , 1 -dioxide Isomer A;3-[2-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl]-5-methyl-triazol-l-yl]-6-azaspiro[3.5]nonan-6-yl]-2,3-dihydrothiophene 1,1 -di oxide Isomer B;2-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5-a]pyridin-6- yl}-5-methyl-lH-l,2,3-triazol-l-yl)-6-[(2R,3E)-4-methanesulfonylbut-3- en-2-yl]-6-azaspiro[3.5]nonane;6-[l-[(3aR,6aS)-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]- 3,3a,4,5,6,6ahexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4- yl]-3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridine; -[l-[(3aS,6aR)-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-3,3a,4,5,6,6a- hexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4-yl]-3-chloro-4- [(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridine;- 576 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3- methyl-5-[(3S)-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]pyrrolidin-3-yl]- 6,7 -dihy dro-4H-pyrazolo[ 1 , 5 -a]py razine;2S)-2-[6-[l-[(3aS,6aR)-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-3,3a,4,5,6,6a- hexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4-yl]-3-chloro- pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;S)-2-[6-[l-[(3aR,6aS)-2-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-3,3a,4,5,6,6a- hexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4-yl]-3-chloro- pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[5-methyl-l-[2-[(E,lR)-l-methyl-3-methylsulfonylallyl]-2- azaspiro-[3.5]nonan-7-yl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5- fluoro-2-pyridyl)ethanol;(2S)-2-[6-[l-[(3aS,6aR)-2-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-3,3a,4,5,6,6a- hexahydro-lH-cyclopenta[c]pyrrol-5-yl]-5-methyl-triazol-4-yl]-3-chloro- pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-[(3aR,5S,6aS)-5-(4-{3-chloro-4-[(lS)-l-(5-fluoropyridin-2-yl)-2- hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)-octahydrocyclo-penta[c]pyrrol-2-yl]-2,3-dihydro-ll6-thiophene-l,l- dione;3-chloro-6-(l-(l-(E)-l-cyclopropyl-3-(methylsulfonyl)allyl)piperidin-4-yl)-5- methyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 - yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-6-(l-(l-(E)-l-cyclopropyl-3-(methylsulfonyl)allyl)piperidin-4-yl)-5- methyl- 1H- 1 ,2,3 -triazol-4-yl)-4-((R)- 1 -(5-fluoropyri din-2 - yl)ethoxy)pyrazolo[l,5-a]pyridine Isomer B;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5- [2,2-dimethyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]azetidin-3-yl]-3- methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazine;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-5- [2,2-dimethyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]azetidin-3-yl]-3- methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazine;- 577 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((7S,8aS)-7-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3 -tri azol- 1 -yl)hexahy dropyrrolof 1 ,2-a]pyrazin-2(lH)-yl)-2,3 - dihydrothiophene 1,1 -di oxide Isomer A;3-((7S,8aS)-7-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3 -tri azol- 1 -yl)hexahy dropyrrolof 1 ,2-a]pyrazin-2(lH)-yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer B;2-[(lR)-l-[(3-chloro-6-{5-[(3S)-l-[(2R,3E)-4-methanesulfonylbut-3-en-2- yl]pyrrolidin-3-yl]-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-2- yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine;3 - [(3 aR, 5R,6aS)-5-(4-{3 -chi oro-4- [( 1 S)- 1 -(5 -fluoropyri din-2 -yl)-2- hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)-octahydrocyclo-penta[c]pyrrol-2-yl]-4-hydroxy-ll6-thiolane-l,l-dione Isomer A;3 - [(3 aR, 5R,6aS)-5-(4-{3 -chi oro-4- [( 1 S)- 1 -(5 -fluoropyri din-2 -yl)-2- hydroxyethoxy]pyrazolo[ 1 ,5 -a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)-octahydrocyclo-penta[c]pyrrol-2-yl]-4-hydroxy-ll6-thiolane-l,l-dione Isomer B;3-((7R,8aS)-7-(4-(3-chloro-4-methoxypyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH- 1 ,2,3 -tri azol- 1 -yl)hexahy dropyrrolof 1 ,2-a]pyrazin-2(lH)-yl)-2,3 - dihydrothiophene 1 , 1 -dioxide;3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((7S,8aS)-2-((E)-4- (methylsulfonyl)but-3-en-2-yl)octahydropyrrolo[l,2-a]pyrazin-7-yl)-lH- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 ,5-a]pyridine;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3- methyl-5-[l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]-6,7- dihydro-4H-pyrazolo[l,5-a]pyrazine;2-[(lR)-l-[(3-chloro-6-{5-[(4S)-2-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-l,2- oxazolidin-4-yl]-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-2- yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]ethyl]-5-fluoropyridine; (lR,5S,7R)-7-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5- a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-9-[(2R,3E)-4- methanesulfonylbut-3-en-2-yl]-3-oxa-9-azabicyclo-[3.3.1]nonane;- 578 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(2S)-2-[3-chloro-6-[3-methyl-5-[(3R)-l-[(E,lR)-l-methyl-3-methylsulfonyl- allyl]pyrr°lidin-3-yl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2- yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)- pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l- yl)-2 -dihydro-thiophene- 1,1 -di oxide Isomer A;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy-ethoxy)- pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)pyrrolidin-l- yl)-2,3-dihydro-thiophene-l,l-dioxide Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy- ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydro-thiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-methoxy- ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydro-thiophene 1,1-dioxide Isomer B;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[ 1,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3 - dihydro-thiophene 1,1-dioxide Isomer A;3 -((R)-3 -(4-(3 -chloro-4-((R)- 1 -(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[ 1,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3 - dihydro-thiophene 1,1-dioxide Isomer B;3-((R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5- a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3- dihydro-thiophene 1,1-dioxide Isomer A;3-((R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5- a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3- dihydro-thiophene 1,1-dioxide Isomer B;(R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((E)-4-(methylsulfonyl)but-3-en-2- yl)isoxazolidine Isomer A;- 579 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((E)-4-(methylsulfonyl)but-3-en-2- yl)isoxazolidine Isomer B;(lR,5S,7S)-7-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-9-((S,E)-4- (methylsulfonyl)but-3-en-2-yl)-3-oxa-9-azabicyclo[3.3.1]nonane ;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo-[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3 - dihydrothiophene 1,1 -di oxide Isomer A;3-((S)-3-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo-[l,5- a]pyri din-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer B;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -(- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3 - yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl propionate Isomer A;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -(- 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3 - yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl propionate Isomer B;(2S)-2-[3-chloro-6-[3-methyl-5-[l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4- piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5- a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[5-[(3 R)-l -(1,1 -di oxothiolan-3-yl)pyrrolidin-3-yl]-3 -methyl- 6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4- yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3 - [(2R,4 S)-4-(4- { 3 -chloro-4- [( 1 R)- 1 -(5 -fluoropyri din-2 -yl)ethoxy ] -py razol o[ 1 , 5 - a]pyridin-6-yl } -5-methyl- 1H- 1 ,2,3 -tri azol- 1 -yl)-2-methylpiperidin- 1 -y 1 ] - 1 X hi etane- 1 , 1 -di one;(2S)-2-[3-chloro-6-[5-[(3S)-l-(l,l-dioxothiolan-3-yl)pyrrolidin-3-yl]-3-methyl- 6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5-a]pyridin-4- yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;- 580 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-[(2S,4S)-4-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-pyrazolo[l,5- a]pyridin-6-yl]-5-methyl-triazol- 1 -yl]-2-methyl- 1 -piperidyl]thietane 1,1- dioxide;(4R)-4-[2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin- 6-yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-5-yl]-2-[(E,lR)-l- methyl-3-methylsulfonyl-allyl]isoxazolidine;(S)-2-((3-chloro-6-(5-methyl-l-((lR,5S,7R)-9-((R,E)-4-(methyl-sulfonyl)but-3-en- 2-yl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoro-pyridin-2-yl)ethanol; 3-((S)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5- a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3- dihydrothiophene 1,1 -di oxide Isomer A;3-((S)-4-(4-(3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5- a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3- dihydrothiophene 1,1-dioxide Isomer B;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer A;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer A;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -( 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3 - yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl acetate Isomer A;(S)-2-((3 -chloro-6-( 1 -((R)- 1 -( 1 , 1 -di oxido-2, 3 -dihydrothi ophen-3 -yl)pyrrolidin-3 - yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl acetate Isomer B;3-[(lR,5S,7r)-7-(4-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]- pyrazolo[l,5-a]pyridin-6-yl}-5-methyl-lH-l,2,3-triazol-l-yl)-3-oxa-9- azabicy clo[3.3.1 ]nonan-9-yl]- 1 X hi etane- 1 , 1 -di one;- 581 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(lR,5S)-7-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5- a]pyridin-6-yl]-5-methyl-triazol-l-yl]-9-[(E,lR)-l-methyl-3- methylsulfonyl-allyl]-3-oxa-9-azabicyclo-[3.3.1]nonane;2S)-2-[(3-chloro-6-{5-[(4S)-2-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-l,2- oxazolidin-4-yl]-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-2- yl}pyrazolo[l,5-a]pyridin-4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethan-l-ol; 3-[(lR,5S)-7-[4-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-pyrazolo[l,5- a]pyridin-6-yl]-5-methyl-triazol-l-yl]-3-oxa-9-azabicyclo[3.3.1]nonan-9- yl]thietane 1,1 -di oxide;3-[(4S)-4-(2-{3-chloro-4-[(lR)-l-(5-fluoropyridin-2-yl)ethoxy]-pyrazolo[l,5- a]pyridin-6-yl}-3-methyl-4H,5H,6H,7H-pyrazolo[l,5-a]pyrazin-5-yl)-l,2- oxazolidin-2-yl]-2, 3 -dihydro- 1 l6-thiophene- 1 , 1 -di one;(S)-2-((3-chloro-6-(5-methyl-l-((R)-2-(E)-4-(methylsulfonyl)but-3-en-2- yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4- yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-((R)-2-(E)-4-(methylsulfonyl)but-3-en-2- yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4- yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4- (methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4- (methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4- (methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer C;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-(E)-4- (methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer D;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l- ((lR,3R,5S)-8-((E)-4-(methylsulfonyl)but-3-en-2-yl)-8-- 582 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l- ((lR,3R,5S)-8-((E)-4-(methylsulfonyl)but-3-en-2-yl)-8- azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;(2S)-2-((3-chloro-6-(5-methyl-l-((7S,8aS)-2-((E)-4-(methylsulfonyl)-but-3-en-2- yl)octahydropyrrolo[ 1 ,2-a]pyrazin-7-yl)- 1H- 1,2,3 -tri azol -4- yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol;(S)-2-((3-chloro-6-(l-((S)-l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)pyrrolidin-3- yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl acetate Isomer A;(S)-2-((3-chloro-6-(l-((S)-l-(l,l-dioxido-2,3-dihydrothiophen-3-yl)pyrrolidin-3- yl)-5-methyl-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4-yl)oxy)-2-(5- fluoropyridin-2-yl)ethyl acetate Isomer B;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer A;3 -((S)-3 -(4-(3 -chloro-4-((S)- 1 -(5-fluoropyridin-2-yl)-2- hydroxyethoxy)pyrazolo[ 1 ,5 -a]pyridin-6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)tetrahydrothiophene 1,1-dioxide Isomer B;3-chloro-4-((S)- l-(5-fluoropyri din-2 -yl)-2-methoxy ethoxy)-6-(5-methyl-l - ((lR,3R,5S)-8-(E)-4-(methylsulfonyl)but-3-en-2-yl)-8- azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-((S)-l-(5-fluoropyri din-2 -yl)-2-methoxyethoxy)-6-(5-methyl-l- ((lR,3R,5S)-8-(E)-4-(methylsulfonyl)-but-3-en-2-yl)-8-azabicyclo- [3.2.1 ]octan-3 -yl)- 1H- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 ,5-a]pyridine Isomer B ; 3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-( 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[ 1,5- a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8- yl)thietane 1,1-dioxide Isomer A;- 583 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-( 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[ 1,5- a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8- yl)thietane 1,1-dioxide Isomer B;(2S)-2-[3-chloro-6-[5-[l-(l,l-dioxo-2,3-dihydrothiophen-3-yl)-4-piperidyl]-3- methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5- a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-chloro-6-[l-[(2R,6R)-2,6-dimethyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]- 4-piperidyl]-5-methyl-triazol-4-yl]-4-[(lR)-l-(5-fluoro-2- pyridyl)ethoxy]pyrazolo[ 1 , 5-a]pyridine;3-[4-[2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6- yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-5-yl]-l-piperidyl]- 2,3 -dihydrothiophene 1 , 1 -dioxide;(2S)-2-[3-chloro-6-[5-[(4S)-2-(l,l-dioxo-2,3-dihydrothiophen-3-yl)isoxazolidin-4- yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2-yl]pyrazolo[l,5- a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[3-methyl-5-[(3S)-l-[(E,lR)-l-methyl-3-methyl- sulfonylallyl]pyrrolidin-3-yl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2- yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-[(4R)-4-[2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5- a]pyridin-6-yl]-3-methyl-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-5- yl]isoxazolidin-2-yl]-2,3-dihydrothiophene 1,1-dioxide;(2S)-2-[3-chloro-6-[3-methyl-5-[(4R)-2-[(E,lR)-l-methyl-3-methyl-sulfonyl- allyl]isoxazolidin-4-yl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin-2- yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-( 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[ 1,5- a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8- yl)thietane 1,1-dioxide Isomer A;3 -(( 1 R, 3 s, 5 S)-3 -(4-(3 -chloro-4-( 1 -(5 -fluoropyridin-2-yl)propoxy)-pyrazolo[ 1,5- a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)-8-azabicyclo[3.2.1]octan-8- yl)thietane 1,1-dioxide Isomer B;- 584 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-chloro-4-((R)-l-(5-fluoropyridin-2-yl)ethoxy)-6-(5-methyl-l-((7R,8aS)-2-((E)-4- (methylsulfonyl)but-3-en-2-yl)octahydropyrrolo[l,2-a]pyrazin-7-yl)-lH- 1 ,2,3 -triazol-4-yl)pyrazolo[ 1 ,5-a]pyridine;(S)-2-((3-chloro-6-(5-methyl-l-((S)-2-((E)-4-(methylsulfonyl)but-3-en-2- yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4- yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer A;(S)-2-((3-chloro-6-(5-methyl-l-((S)-2-((E)-4-(methylsulfonyl)but-3-en-2- yl)isoxazolidin-4-yl)-lH-l,2,3-triazol-4-yl)pyrazolo[l,5-a]pyridin-4- yl)oxy)-2-(5-fluoropyridin-2-yl)ethanol Isomer B;3-((R)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1 , 1 -dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer B;3-((R)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer C;3-((R)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer D;3-((R)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)isoxazolidin-2-yl)-2,3 - dihydrothiophene 1,1 -di oxide Isomer A;3-((R)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)isoxazolidin-2-yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer B;3-((R)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)isoxazolidin-2-yl)-2,3 - dihydrothiophene 1,1-dioxide Isomer C;- 585 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3-((R)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo-[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)isoxazolidin-2-yl)-2,3 - dihydrothiophene 1,1 -di oxide Isomer D;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4- (methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4- (methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer B;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4- (methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer C;3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-6-(5-methyl-l-((lR,3R,5S)-8-((E)-4- (methylsulfonyl)but-3-en-2-yl)-8-azabicyclo[3.2.1]octan-3-yl)-lH-l,2,3- triazol-4-yl)pyrazolo[l,5-a]pyridine Isomer D;(2S)-2-[3-chloro-6-[5-methyl-l-[(lR,5S)-9-[(E,lR)-l-methyl-3-methylsulfonyl- allyl]-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl]triazol-4-yl]pyrazolo[l,5- a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[l-[(2R,6R)-2,6-dimethyl-l-[(E,lR)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]-5-methyl-triazol-4-yl]pyrazolo[l,5- a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-((R)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)- pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2- yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer A;3-((R)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)- pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2- yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer B;(S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6- yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((R,E)-4-(methylsulfonyl)but-3-en-2- yl)isoxazolidine Isomer A;- 586 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)ethoxy)-pyrazolo[l,5-a]pyridin-6- yl)-5-methyl-lH-l,2,3-triazol-l-yl)-2-((R,E)-4-(methylsulfonyl)but-3-en-2- yl)isoxazolidine Isomer B;3-((S)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1 -di oxide Isomer A;3-((S)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer B;3-((S)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer C;3-((S)-3-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-m ethyl- 1H- 1 ,2,3 -tri azol- 1 -yl)pyrrolidin- 1 -yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer D;3-((S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro- thiophene 1,1-dioxide Isomer A;3-((S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro- thiophene 1,1-dioxide Isomer B;3-((S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro- thiophene 1,1-dioxide Isomer C;3-((S)-4-(4-(3-chloro-4-(l-(5-fluoropyridin-2-yl)propoxy)-pyrazolo[l,5-a]pyridin- 6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2-yl)-2,3-dihydro- thiophene 1,1-dioxide Isomer D;(R)-3-((S)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)- pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2- yl)-2,3-dihydro-thiophene 1,1-dioxide Isomer A; or- 587 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)(R)-3-((S)-4-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-hydroxyethoxy)- pyrazolo[l,5-a]pyridin-6-yl)-5-methyl-lH-l,2,3-triazol-l-yl)isoxazolidin-2- yl)-2 -dihydro-thiophene 1,1-dioxide Isomer B;3-chloro-4-[l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l- [(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-[l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l- [(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[l,5-a]pyridine Isomer B;3-chloro-4-[l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l- [(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[l,5-a]pyridine Isomer A;3-chloro-4-[l-(5-fluoro-2-pyridyl)propoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l- [(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[l,5-a]pyridine Isomer B;2-[3-chloro-4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]pyrazolo[l,5-a]pyridin-6-yl]-3- methyl-5-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4- piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazine;(2S)-2-[3-chloro-6-[3-methyl-5-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin- 2-;yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;(2S)-2-[3-chloro-6-[3-methyl-5-[(2S,4R)-2-methyl-l-[(E,lR)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]-6,7-dihydro-4H-pyrazolo[l,5-a]pyrazin- 2-yl]pyrazolo-[l,5-a]pyridin-4-yl]oxy-2-(5-fluoro-2-pyridyl)ethanol;3-((S)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2- yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer A;3-((S)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2- yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydrothiophene 1,1-dioxide Isomer B;- 588 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)- l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5- a]pyridine;4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lS)- l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5- a]pyridine;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy- ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydro-thiophene- 1,1 -di oxide Isomer A;3-((S)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy- ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2,3-dihydrothio-phene-l,l-dioxide Isomer B;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy- ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydro-thiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-l-(5-fluoropyridin-2-yl)-2-isopropoxy- ethoxy)pyrazolo[ 1 , 5-a]pyridin-6-yl)-5-methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydro-thiophene 1,1-dioxide Isomer B;4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-3-methyl-6-[5-methyl-l-[(2S,4S)-2-; methyl- 1 -[(E, 1R)- 1 -methyl-3 -methylsulfonyl-allyl]-4-piperidyl]triazol-4-; yl]pyrazolo[ 1 ,5 -a]pyridine;4-[(lR)-l-(5-fluoro-2-pyridyl)ethoxy]-3-methyl-6-[5-methyl-l-[(2S,4S)-2-; methyl-l-[(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[ 1 ,5 -a]pyridine;3-((R)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2- yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydro-thiophene 1,1-dioxide Isomer A;3-((R)-3-(4-(3-chloro-4-((S)-2-ethoxy-l-(5-fluoropyridin-2- yl)ethoxy)pyrazolo[ 1 ,5-a]pyridin-6-yl)-5 -methyl- 1H- 1 ,2,3 -tri azol- 1 - yl)pyrrolidin-l-yl)-2, 3 -dihydro-thiophene 1,1-dioxide Isomer B;- 589 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)3 -chloro-4-(l -(5 -fluoropyridin-2-yl)-2-(oxetan-3 -yl)ethoxy)-6-(5-m ethyl- 1 -(1 -(E)- 4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer A;3 -chloro-4-(l -(5 -fluoropyridin-2-yl)-2-(oxetan-3 -yl)ethoxy)-6-(5-m ethyl- 1 -(1 -(E)- 4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer B;3 -chloro-4-(l -(5 -fluoropyridin-2-yl)-2-(oxetan-3 -yl)ethoxy)-6-(5-m ethyl- 1 -(1 -(E)- 4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer C;3 -chloro-4-(l -(5 -fluoropyridin-2-yl)-2-(oxetan-3 -yl)ethoxy)-6-(5-m ethyl- 1 -(1 -(E)- 4-(methylsulfonyl)but-3-en-2-yl)piperidin-4-yl)-lH-l,2,3-triazol-4- yl)pyrazolo[l,5-a]pyridine Isomer D;(2S)-2-[(3-chloro-6-(l-[(2S,4S)-l-[(2S,3E)-4-methanesulfonylbut-3-en-2-yl]-2- methylpiperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl-pyrazolo[l,5- a]pyridin-4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethyl (2S)-2-aminopropanoate; (2S)-2-[(3-chloro-6-{l-[(2S,4S)-l-[(2R,3E)-4-methanesulfonylbut-3-en-2-yl]-2- methylpiperidin-4-yl]-5-methyl-lH-l,2,3-triazol-4-yl-pyrazolo[l,5- a]pyridin-4-yl)oxy]-2-(5-fluoropyridin-2-yl)ethyl (2S)-2-aminopropanoate; (2S)-2-(5-fluoro-2-pyridyl)-2-[3-methyl-6-[5-methyl-l-[(2S,4S)-2-methyl-l- [(E,lR)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- y 1 ] py razol o [ 1 , 5 -a] py ri din-4-y 1 ] oxy-ethanol ;(2S)-2-(5-fluoro-2-pyridyl)-2-[3-methyl-6-[5-methyl-l-[(2S,4S)-2-methyl-l- [(E,lS)-l-methyl-3-methylsulfonyl-allyl]-4-piperidyl]triazol-4- yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-ethano;[(2S)-2-[3-chloro-6-[5-methyl-l-[(2R,4S)-2-methyl-l-[(E,lR)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4- yl]oxy-2-(5-fluoro-2-pyridyl)ethyl] (2S)-2-aminopropanoate;[(2S)-2-[3-chloro-6-[5-methyl-l-[(2R,4S)-2-methyl-l-[(E,lS)-l-methyl-3- methylsulfonyl-allyl]-4-piperidyl]triazol-4-yl]pyrazolo[l,5-a]pyridin-4- yl]oxy-2-(5-fluoro-2-pyridyl)ethyl] (2S)-2-aminopropanoate; or- 590 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)l-[3-chloro-6-[5-methyl-l-[(2S,4S)-2-methyl-l-[(E,lR)-l-methyl-3-methyl- sulfonyl-allyl]-4-piperidyl]-triazol-4-yl]pyrazolo[l,5-a]pyridin-4-yl]oxy-2- (5-fluoro-2-pyridyl)propan-2-ol.

152. A pharmaceutical composition comprising a compound of any one of claims 1- 151, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

153. A method for treating cancer in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of claims 1- 151 or a pharmaceutically acceptable salt thereof.

154. The method of claim 153, wherein the cancer is an FGFR-associated cancer.

155. The method of claim 154, wherein the FGFR-associated cancer is selected from the group consisting of: bladder cancer, brain cancer, breast cancer, cholangiocarcinoma, head and neck cancer, lung cancer, multiple myeloma, rhabdomyosarcoma, urethral cancer, and uterine cancer.

156. The method of claim 154, wherein the FGFR-associated cancer is a FGFR fusion lung cancer, a FGFR fusion breast cancer, a FGFR fusion bladder cancer, a FGFR fusion biliary tract cancer, a FGFR fusion urethral cancer, a FGFR fusion head and neck cancer, or a FGFR fusion multiple myeloma.

157. The method of claim 155 or claim 156, wherein the lung cancer is small cell lung carcinoma, non small cell lung cancer, squamous cell lung cancer, or lung adenocarcinoma.

158. The method of any one of claims 153-157, wherein the compound or a pharmaceutically acceptable salt thereof is orally administered.

159. The method of any one of claims 153-158, wherein the method further comprises administering an additional therapy or therapeutic agent to the subject.

160. Use of a compound of any one of claims 1-151 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating a FGFR-associated cancer in a subject.

161. The use of claim 160, wherein the FGFR-associated cancer is selected from the group consisting of: bladder cancer, brain cancer, breast cancer,- 591 - 120039.000209\4905-l 100-0452.1120039.000209 (TYRA045PCT)cholangiocarcinoma, head and neck cancer, lung cancer, multiple myeloma, rhabdomyosarcoma, urethral cancer, and uterine cancer.

162. The use of claim 160, wherein the FGFR-associated cancer is a FGFR fusion lung cancer, a FGFR fusion breast cancer, a FGFR fusion bladder cancer, a FGFR fusion biliary tract cancer, a FGFR fusion urethral cancer, a FGFR fusion head and neck cancer, or a FGFR fusion multiple myeloma.

163. The use of claim 161 or claim 162, wherein the lung cancer is small cell lung carcinoma, non-small cell lung cancer, squamous cell lung cancer, or lung adenocarcinoma.

164. The use of any one of claims 160-163 wherein the compound or a pharmaceutically acceptable salt thereof is formulated for oral administration.- 592 - 120039.000209\4905-l 100-0452.1

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