Fused azines for the treatment of inflammatory diseases

Abstract

The present invention relates to compounds, compositions containing them, and to their use in the treatment of various disorders, in particular autoimmune, autoinflammatory or immune-mediated conditions, such as systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE) and lupus nephritis.

Description

[0001] COMPOUNDS FIELD OF THE INVENTION The present invention relates to compounds, compositions containing them, and to their use in the treatment of various disorders, in particular autoimmune, autoinflammatory or immune-mediated conditions, such as systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis, Sjogren’s syndrome, dermatomyositis, scleroderma, amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD), acute kidney injury, chronic kidney disease, diabetic kidney disease or injury, APOL1 nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, idiopathic pulmonary fibrosis, interstitial lung disease, myocardial infarction, stroke, heart hypertrophy / heart failure, non-alcoholic steatohepatitis (NASH) and non- alcoholic fatty liver disease (NAFLD), particularly systemic lupus erythematosus, cutaneous lupus erythematosus and lupus nephritis. BACKGROUND TO THE INVENTION Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that mediates the production of type I interferons and inflammatory cytokines in response to dsDNA (Sun et al. Science, 33(6121) 786-791, 2013; Cai et al. Mol Cell, 54(2) 289-296, 2014). In the absence of DNA, cGAS exists in an autoinhibited state. Binding to DNA induces a conformational change in the active site, which catalyzes the synthesis of cyclic GMP-AMP (cGAMP) from ATP and GTP (Zhang et al. Cell Rep, 6(3) 421-430, 2014; Gao et al. Cell, 153(5) 1094-1107, 2013; Civril et al. Nature, 498(7454) 332-337, 2013). The generated cGAMP functions as a second messenger that binds and activates stimulator of interferon genes (STING). Activated STING recruits TANK-binding kinase 1 (TBK1), which phosphorylates STING and subsequently the transcription factor IFN regulatory factor 3 (IRF3). Phosphorylated IRF3 dimerizes and translocates into the nucleus, where it functions together with nuclear factor kB (NF-kB), a transcription factor also activated by STING, to turn on the expression of type I IFNs and inflammatory cytokines (Ablasser and Chen, Science, 363(6431) eaat8657, 2019). While the cGAS-STING pathway has evolved as a major defense mechanism for the detection of microbial infection, activation of cGAS by self-DNA has been linked to a number of monogenic diseases (AGS, FCL, RVCL) as well as multifactorial autoimmune / inflammatory diseases. Therapeutic targeting of the cGAS-STING pathway with small molecule cGAS inhibitors could be beneficial in a broad array of autoinflammatory, autoimmune and immune- mediated diseases. Therefore, there exists a need for novel chemical compounds which are capable of inhibiting the cGAS pathway. SUMMARY OF THE INVENTION In a first aspect, the present invention provides a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof, wherein R1is hydrogen or a R2is selected from the group consisting of hydrogen, halo, cyano, nitro, C1-3alkyl, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -SO2R7, -C(O)NR7R8, -NR7C(O)R8, and -CO2R7, wherein C1-3alkyl, halo(C1-3)alkyl, and halo(C1-3)alkoxy is optionally substituted by hydroxyl, -NR7R8, or C3-4cycloalkyl; R3is a 5- or 6-membered heteroaryl optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety; ring A is a 5- or 6-membered heteroaryl or 5- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S; p is 0, 1, 2, or 3; each X is independently selected from oxo and L-Y; each L is independently selected from a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, - O(CRaRb)n-, -(CRaRb)nO(CRaRb)m-, -SO2-, -SO2(CRaRb)n-, -C(O)O-, -OC(O)-, - C(O)O(CRaRb)n-, -(CRaRb)nC(O)O-, -C(O)NH(CRaRb)n-, -NRaC(O)(CRaRb)n-, or - NH(CRaRb)n-, wherein each n or m is independently selected from 1, 2, or 3; each Raand Rbis independently selected from hydrogen, halo, or C1-4alkyl; each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, thio(C1-4)alkyl, hydroxy(C1-6)alkyl, cyano(C1-4)alkyl, halo(C1-4)alkyl, halo(C2-4)alkenyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -C(O)SR10, -CO2R10, - C(O)R10, -CHCHC(O)OR10, -OSO2R10, -S(O)R10, -N(R10)SO2R10, -P(O)(Ph)OR10, - P(O)(OR10)2, -P(S)(Ph)OR10, phenyl, 5- or 6-membered heteroaryl, and 3- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, phenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; or two X substituents taken together with the carbon atoms to which they are attached form a ring selected from phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8-membered heteroaryl, or a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8-membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, C1-4alkyl, oxo, -C(O)R10, -SO2R10, -C1-3alkylene-NR9R10, and -C1-3alkylene-OR10; R7and R8are independently selected from hydrogen and C1-3alkyl; R9is independently selected from the group consisting of hydrogen, hydroxy, C1-4alkyl, -C(O)C1-4alkyl, and halo(C1-4)alkyl; and R10is independently selected from hydrogen and C1-6alkyl; or wherein R9and R10taken together with the nitrogen atom to which they are attached form a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; with the proviso that the compound of Formula I is not a compound of Formula (II), wherein R1, R2, R3, X, and with Formula (I). In a second aspect, the present invention provides a pharmaceutical composition comprising a compound of the invention, and a pharmaceutically acceptable excipient. In a third aspect, the present invention provides a method of treatment of an autoimmune, autoinflammatory or immune-mediated condition in a human in need thereof comprising administering to said human a therapeutically effective amount of a compound of the invention as disclosed herein. In a fourth aspect, the present invention provides a compound of the invention as disclosed herein, for use in therapy. In a fifth aspect, the present invention provides the use of a compound of the invention disclosed herein in the manufacture of a medicament for use in the treatment of an autoimmune, autoinflammatory or immune-mediated condition. DETAILED DESCRIPTION Definitions As used herein, the term halo refers to chloro, fluoro, bromo, or iodo substituents. As used herein, the term cyano refers to the group -CN. As used herein, the term nitro refers to the group -NO2. As used herein, the term hydroxyl refers to the group -OH. As used herein, the term amino refers to the group -NH2. As used herein, the term “oxo” represents a double-bonded oxygen moiety; for example, if attached directly to a carbon atom forms a carbonyl moiety (C = O). As used herein, “Ph” refers to a phenyl group. As used herein, the term “prodrug” refers to compounds that readily undergo chemical changes under physiological conditions to provide a pharmacologically active parent compound. The term “prodrug moiety” refers to the chemical moiety of a prodrug that is released under physiological conditions to form the active parent compound. As used herein, the term “alkyl” refers to a saturated hydrocarbon radical, straight or branched, having the specified number of carbon atoms. For example, the term “C1-6alkyl” refers to an alkyl group having 1 to 6 carbon atoms. Exemplary groups include, but are not limited to, methyl, ethyl, propyl (n-propyl and isopropyl), butyl (n-butyl, sec-butyl, isobutyl and tert-butyl), pentyl, and hexyl. The term “C1-4alkyl” refers to an alkyl group having 1 to 4 carbon atoms. As used herein, the term “cycloalkyl” refers to a non-aromatic, saturated, monocyclic, hydrocarbon ring containing the specified number of carbon atoms. For example, “C3-7cycloalkyl” refers to a cycloalkyl group containing 3 to 7 carbon atoms. Exemplary groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl. As used herein, the term “cycloalkenyl” refers to a non-aromatic, unsaturated, monocyclic, hydrocarbon ring containing the specified number of carbon atoms and at least 1 double bond. For example, “C5-7cycloalkenyl” refers to a cycloalkyl group containing 5 to 7 carbon atoms. Exemplary groups include cyclopentenyl, cyclohexenyl, and cycloheptenyl. As used herein, the term “alkylene” refers to a divalent radical derived from a straight or branched, saturated hydrocarbon group of, for example, 1 to 6 carbon atoms (C1-6alkylene). Exemplary groups include, but are not limited to, -CH2- (methylene), -CH2CH2- (ethylene), - CH2CH2CH2- (propylene), and -CH2CH(CH3)2- (iso-butylene). As used herein, the term “C2-4alkenyl” refers to a straight or branched hydrocarbon radical containing the specified number of carbon atoms and at least 1 double bond. For example, “C2-4alkenyl” has 2 to 4 carbon atoms. Exemplary groups include, but are not limited to, ethenyl and propenyl. As used herein, the term "alkynyl" refers to a straight or branched hydrocarbon radical containing the specified number of carbon atoms and at least one triple bond. For example, “C2-4alkynyl” has 2 to 6 carbon atoms. Exemplary groups include, but are not limited to, ethynyl and propynyl. As used herein, the term “alkoxy” refers to an -O-alkyl group, i.e. an alkyl group which is attached through an oxygen linking atom, wherein “alkyl” is defined above. For example, the term “C1-4alkoxy” refers to an alkoxy group having 1 to 4 carbon atoms. Exemplary groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, s- butoxy, isobutoxy, and t-butoxy. As used herein, the term “halo(C1-4)alkyl” is intended to mean a radical having one or more halogen atoms, which may be the same or different, at one or more carbon atoms of an alkyl moiety containing from 1 to 4 carbon atoms, which is a straight or branched chain carbon radical. Exemplary groups include, but are not limited to, -CF3(trifluoromethyl), - CF2H (difluoromethyl), -CCl3(trichloromethyl), -CF2Cl (chlorodifluoromethyl), 1,1- difluoroethyl, 2,2,2-trifluoroethyl, and hexafluoroisopropyl. It follows that the term halo(C1-2)alkyl refers to a radical having one or more halogen atoms, which may be the same or different, at one or more carbon atoms of an alkyl moiety containing from 1 to 2 carbon atoms. As used herein, the term “halo(C1-4)alkoxy” refers to a straight or branched chain hydrocarbon radical, having at least 1 and up to 4 carbon atoms with one or more halogen atoms, which may be the same or different, attached to one or more carbon atoms, which radical is attached through an oxygen linking atom. Exemplary groups include, but are not limited to, -OCHF2(difluoromethoxy), -OCF3(trifluoromethoxy), and -OCH(CF3)2(hexafluoroisopropoxy). As used herein, the term “thio(C1-4)alkyl” refers to refers to an -S-alkyl group, i.e., an alkyl group which is attached through a sulfur linking atom, wherein “alkyl” is defined above. For example, the term “C1-4thioalkyl” refers to a thioalkyl group having 1 to 4 carbon atoms. Exemplary groups include, but are not limited to, thiomethyl, thioethyl, thiopropyl, and thio- isopropyl, and so on. As used herein, the term “hydroxy(C1-6)alkyl” is intended to mean a radical having one or more hydroxyl groups at one or more carbon atoms of an alkyl moiety containing from 1 to 6 carbon atoms, which is a straight or branched chain carbon radical. Exemplary groups include, but are not limited to, hydroxymethyl (-CH2OH), 2-hydroxyethyl (-CH2CH2OH), 2- hydroxybutanol (-CH2C(OH)CH2CH3), and hydroxy-isopropyl. As used herein, the term “cyano(C1-4)alkyl” is intended to mean a radical having one or more cyano groups at one or more carbon atoms of an alkyl moiety containing 1 to 4 carbon atoms, which is a straight or branched chain carbon radical. As used herein, the term “halo(C2-4)alkenyl” refers to a straight or branched chain hydrocarbon radical, having at least 2 and up to 4 carbon atoms and at least one double bond, with one or more halogen atoms, which may be the same or different, attached to one or more carbon atoms. Exemplary groups include, but are not limited to, -CH=CHF, - CH=CF2, and -CF=CF2. As used herein, the term "hydroxy(C2-4)alkynyl" refers to a straight or branched hydrocarbon radical, having at least 2 and up to 4 carbon atoms and at least one triple bond, with one or more hydroxyl atoms attached to one or more carbon atoms. Exemplary groups include, but are not limited to, -CH≡C-OH, -CH2C≡C-OH, and -C≡C-CH2OH. As used herein, the term “heteroaryl” refers to a group or moiety comprising an aromatic monovalent monocyclic radical, containing the specified number of ring atoms, including at least one carbon atom and at least one heteroatom independently selected from nitrogen, oxygen and sulfur. As used herein, the term “5- or 6-membered heteroaryl” refers to a group or moiety comprising an aromatic monovalent monocyclic radical, containing 5 or 6 ring atoms, including at least one carbon atom and at least one heteroatom independently selected from nitrogen, oxygen and sulfur. Selected 5-membered heteroaryl groups contain one nitrogen, oxygen, or sulfur ring heteroatom, and optionally contain 1, 2, or 3 additional nitrogen ring atoms. Selected 6-membered heteroaryl groups contain 1, 2, or 3 nitrogen ring heteroatoms. Exemplary groups include, but are not limited to furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, and triazinyl. As used herein, the term “5-membered nitrogen containing heteroaryl” refers to a group or moiety comprising an aromatic monovalent monocyclic radical, containing 5 ring atoms, containing at least one carbon atom, at least one nitrogen and optionally at least one other heteroatom independently selected from nitrogen, oxygen, and sulfur. Exemplary groups include, but are not limited to, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, and thiadiazolyl. As used herein, the term “heteroarylene” refers to a group or moiety comprising an aromatic divalent monocyclic or bicyclic radical, containing 5 to 10 ring atoms, including at least one heteroatom independently selected from nitrogen, oxygen and sulfur. For example, the term “heteroarylene” refers to a group or moiety comprising an aromatic divalent monocyclic or bicyclic radical, containing 5 to 10 ring atoms, including one or two heteroatoms independently selected from nitrogen, oxygen, and sulfur. As used herein, the term “heterocycloalkyl” refers to a saturated or unsaturated monocyclic or bicyclic ring containing the specified number of atoms and including at least one heteroatom independently selected from nitrogen, oxygen and sulfur (the other atoms being carbon). For example, the term “5- to 7-membered heterocycloalkyl” refers to a heterocycloalkyl group having 5 to 7 atoms. Bicyclic heterocycloalkyl groups may be bridged, fused or spiro bicyclic groups. For the avoidance of doubt, heterocycloalkyl groups are not aromatic. As used herein, the term “3- to 7- membered heterocycloalkyl” refers to a saturated or unsaturated 3- to 7-membered monocyclic ring, which must contain 1 or 2 non-carbon atoms, which are selected from nitrogen, oxygen, and sulfur. Exemplary groups include, but are not limited to, oxiranyl, oxetanyl, azetidinyl, pyrrolidinyl, pyrazolidinyl, pyrazolinyl, imidazolidinyl, imidazolinyl, oxazolinyl, thiazolinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, dihydrofuranyl, 1,3-dioxolanyl, tetrahydro-2H-pyranyl, dihydropyranyl, morpholinyl, morpholinyl-3-one, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-oxathiolanyl, 1,3-oxathianyl, 1,3- dithianyl, 1,4-oxathiolanyl, 1,4-oxathianyl, 1,4-dithianyl, piperidyl-2-one, pyrimidinyl- 2,4(1H,3H)-dione, thiomorpholinyl, thiomorpholinyl 1,1-dioxide, tetrahydropyridinyl, pyrrolidinyl-2-one, and 2-oxa-5-azabicyclo[2.2.1]heptyl. As used herein, the term “5- to 7- membered heterocycloalkyl” refers to a saturated or unsaturated 5- to 7-membered monocyclic ring, which must contain 1 or 2 non-carbon atoms, which are selected from nitrogen, oxygen, and sulfur. Exemplary groups include, but are not limited to, pyrrolidinyl, pyrazolidinyl, pyrazolinyl, imidazolidinyl, imidazolinyl, oxazolinyl, thiazolinyl, piperidinyl, piperazinyl, tetrahydrofuranyl, dihydrofuranyl, 1,3- dioxolanyl, tetrahydro-2H-pyranyl, dihydropyranyl, morpholinyl, morpholinyl-3-one, 1,3- dioxanyl, 1,4-dioxanyl, 1,3-oxathiolanyl, 1,3-oxathianyl, 1,3-dithianyl, 1,4-oxathiolanyl, 1,4- oxathianyl, 1,4-dithianyl, piperidyl-2-one, pyrimidinyl-2,4(1H,3H)-dione, thiomorpholinyl, thiomorpholinyl 1,1-dioxide, azepanyl, tetrahydroazepinyl, dihydrooxazinyl, tetrahydropyrazinyl, oxazepanyl, dihydrooxazepinyl, tetrahydropyridinyl, oxazolidinyl, 2,3- dihydropyrrolyl, tetrahydropyridinyl, dihydropyridinyl, dihydropyrrolyl, and 5H-pyrrolyl. As used herein, the term “bicyclic ring” may refer to a bridged, fused or spiro bicyclic group. For the avoidance of doubt, all bicyclic ring systems may be attached at any suitable position on either ring. As used herein, the term “optionally substituted” indicates that a group may be unsubstituted or substituted with one or more substituents as defined herein. The term “substituted” in reference to a group indicates that a hydrogen atom attached to a member atom within a group is replaced by one of the defined substituents. In the case where groups may be selected from a number of alternative groups, the selected groups may be the same or different. The term “independently selected” means that where more than one substituent is selected from a number of possible substituents, those substituents may be the same or different. Thus, each substituent is separately selected from the entire group of recited possible substituents. As used herein, the term “pharmaceutically acceptable salt” refers to salts that retain the desired biological activity of the subject compound and exhibit minimal undesired toxicological effects. Such pharmaceutically acceptable salt may be prepared in situ during the final isolation and purification of the compound, or by separately reacting the purified compound in its free acid or free base form with a suitable base or acid, respectively. The term “treatment” refers to ameliorating or stabilising the specified condition, reducing, or eliminating the symptoms of the condition, slowing, or eliminating the progression of the condition, and preventing or delaying reoccurrence of the condition in a previously afflicted patient or subject. The term “prevention” refers to avoidance of the stated disease in a subject who is not suffering from the stated disease. The term “compound(s) of the invention” refers to a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof. The term “therapeutically effective amount” refers to the quantity of a compound of the invention, which will elicit the desired biological response in a human body. It may vary depending on the compound, the disease and its severity, and the age and weight of the subject to be treated. A reference to a compound of Formula (I) encompasses a reference to any one of Formulae (IA), (IAA), (IB), (IBB), (IC) (ICC), (ID), (IE), (IEE), (IF), (IH), (IHH), (IJ), or (IJJ). Statement of Invention In a first aspect, the present invention provides a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof, wherein 1 R is hydrogen or a prodrug R2is selected from the group consisting of hydrogen, halo, cyano, nitro, C1-3alkyl, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -SO2R7, -C(O)NR7R8, -NR7C(O)R8, and -CO2R7, wherein C1-3alkyl, halo(C1-3)alkyl, and halo(C1-3)alkoxy is optionally substituted by hydroxyl, -NR7R8, or C3-4cycloalkyl; R3is a 5- or 6-membered heteroaryl optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety; ring A is a 5- or 6-membered heteroaryl or 5- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S; p is 0, 1, 2, or 3; each X is independently selected from oxo and L-Y; each L is independently selected from a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, - O(CRaRb)n-, -(CRaRb)nO(CRaRb)m-, -SO2-, -SO2(CRaRb)n-, -C(O)O-, -OC(O)-, - C(O)O(CRaRb)n-, -(CRaRb)nC(O)O-, -C(O)NH(CRaRb)n-, -NRaC(O)(CRaRb)n-, or - NH(CRaRb)n-, wherein each n or m is independently selected from 1, 2, or 3; each Raand Rbis independently selected from hydrogen, halo, or C1-4alkyl; each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, thio(C1-4)alkyl, hydroxy(C1-6)alkyl, cyano(C1-4)alkyl, halo(C1-4)alkyl, halo(C2-4)alkenyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -C(O)SR10, -CO2R10, - C(O)R10, -CHCHC(O)OR10, -OSO2R10, -S(O)R10, -N(R10)SO2R10, -P(O)(Ph)OR10, - P(O)(OR10)2, -P(S)(Ph)OR10, phenyl, 5- or 6-membered heteroaryl, and 3- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, phenyl, heteroaryl and heterocycloalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; or two X substituents taken together with the carbon atoms to which they are attached form a ring selected from phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8-membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8-membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, C1-4alkyl, oxo, -C(O)R10, -SO2R10, -C1-3alkylene-NR9R10, and -C1-3alkylene-OR10; R7and R8are independently selected from hydrogen and C1-3alkyl; R9is independently selected from the group consisting of hydrogen, hydroxyl, C1-4alkyl, -C(O)C1-4alkyl, and halo(C1-4)alkyl; and R10is independently selected from hydrogen and C1-6alkyl; or wherein R9and R10taken together with the nitrogen atom to which they are attached form a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; with the proviso that the compound of Formula I is not a compound of Formula (II), wherein R1, R2, R3, X, with Formula (I). In an alternative aspect, the present invention provides a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof, wherein R1is hydrogen or a prodrug moiety; R2is selected from the group consisting of hydrogen, halo, cyano, nitro, C1-3alkyl, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -SO2R7, -C(O)NR7R8, -NR7C(O)R8, and -CO2R7, wherein C1-3alkyl, halo(C1-3)alkyl, and halo(C1-3)alkoxy is optionally substituted by hydroxyl, -NR7R8, or C3-4cycloalkyl; R3is a 5- or 6-membered heteroaryl optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety; ring A is a 5- or 6-membered heteroaryl or 5- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S; p is 0, 1, 2, or 3; each X is independently selected from oxo and L-Y; each L is independently selected from a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, - O(CRaRb)n-, -(CRaRb)nO(CRaRb)m-, -SO2-, -SO2(CRaRb)n-, -C(O)O-, -OC(O)-, - C(O)O(CRaRb)n-, -(CRaRb)nC(O)O-, -C(O)NH(CRaRb)n-, -NRaC(O)(CRaRb)n-, or - NH(CRaRb)n-, wherein each n or m is independently selected from 1, 2 or 3; each Raand Rbis independently selected from hydrogen, halo, or C1-4alkyl; each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2 - -4alkenyl, C2-6alkynyl, thio(C1-4)alkyl, hydroxy(C1-6)alkyl, cyano(C1-4)alkyl, halo(C1-4)alkyl, halo(C2-4)alkenyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -C(O)SR10, -CO2R10, - C(O)R10, -CHCHC(O)OR10, -OSO2R10, -S(O)R10, -N(R10)SO2R10, -P(O)(Ph)OR10, - P(O)(OR10)2, -P(S)(Ph)OR10, phenyl, 5- or 6-membered heteroaryl, and 3- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, phenyl, heteroaryl and heterocycloalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; or two X substituents taken together with the carbon atoms to which they are attached form a ring selected from phenyl, C5-8 cycloalkyl, C5-8 cycloalkenyl, 5- to 8-membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8-membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, C1-4alkyl, oxo, -C(O)R10, -SO2R10, -C1-3alkylene-NR9R10, and -C1-3alkylene-OR10; R7and R8are independently selected from hydrogen and C1-3alkyl; R9is independently selected from the group consisting of hydrogen, hydroxyl, C1-4alkyl, -C(O)C1-4alkyl, and halo(C1-4)alkyl; and R10is independently selected from hydrogen and C1-6alkyl; or wherein R9and R10taken together with the nitrogen atom to which they are attached form a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; wherein ring A is not wherein X and p are as with Formula (I). In an alternative aspect, the present invention provides a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof, wherein R1is hydrogen or a prodrug moiety; R2is selected from the group consisting of hydrogen, halo, cyano, nitro, C1-3alkyl, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -SO2R7, -C(O)NR7R8, -NR7C(O)R8, and -CO2R7, wherein C1-3alkyl, halo(C1-3)alkyl, and halo(C1-3)alkoxy is optionally substituted by hydroxyl, -NR7R8, or C3-4cycloalkyl; R3is a 5- or 6-membered heteroaryl optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety; ring A is a 5- or 6-membered heteroaryl or 5- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S; p is 0, 1, 2, or 3; each X is independently selected from oxo and L-Y; each L is independently selected from a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, - O(CRaRb)n-, -(CRaRb)nO(CRaRb)m-, -SO2-, -SO2(CRaRb)n-, -C(O)O-, -OC(O)-, - C(O)O(CRaRb)n-, -(CRaRb)nC(O)O-, -C(O)NH(CRaRb)n-, -NRaC(O)(CRaRb)n-, or - NH(CRaRb)n-, wherein each n or m is independently selected from 1, 2 or 3; each Raand Rbis independently selected from hydrogen, halo, or C1-4alkyl; each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, thio(C1-4)alkyl, hydroxy(C1-6)alkyl, cyano(C1-4)alkyl, halo(C1-4)alkyl, halo(C2-4)alkenyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -C(O)SR10, -CO2R10, - C(O)R10, -CHCHC(O)OR10, -OSO2R10, -S(O)R10, -N(R10)SO2R10, -P(O)(Ph)OR10, - P(O)(OR10)2, -P(S)(Ph)OR10, phenyl, 5- or 6-membered heteroaryl, and 3- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, phenyl, heteroaryl and heterocycloalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; or two X substituents taken together with the carbon atoms to which they are attached form a ring selected from phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8-membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8-membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, C1-4alkyl, oxo, -C(O)R10, -SO2R10, -C1-3alkylene-NR9R10, and -C1-3alkylene-OR10; R7and R8are independently selected from hydrogen and C1-3alkyl; R9is independently selected from the group consisting of hydrogen, hydroxyl, C1-4alkyl, -C(O)C1-4alkyl, and halo(C1-4)alkyl; and R10is independently selected from hydrogen and C1-6alkyl; or wherein R9and R10taken together with the nitrogen atom to which they are attached form a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; wherein ring A in combination with the adjacent imidazolyl ring is not imidazo[1,2- a]pyrimidinyl. In an embodiment, only one of R1and R3comprises a prodrug moiety. In an embodiment, a prodrug moiety is at R1and not at R3. In another embodiment, a prodrug moiety is at R3and not at R1. In an embodiment, R1is a prodrug moiety and R3is a 5-membered heteroaryl optionally substituted by C1-3alkyl or -C(O)R8. In an embodiment, R1is a prodrug moiety and R3is a 5-membered nitrogen containing heteroaryl optionally substituted by C1-3alkyl or -C(O)R8. In an embodiment, R1is a prodrug moiety and R3is imidazolyl or pyrazolyl, where R3is optionally substituted by C1-3alkyl or -C(O)R8. In an embodiment, R1is a prodrug moiety. In an embodiment, the prodrug moiety is a phosphate ester, ester, or an amino acid-type prodrug. In an embodiment, the prodrug moiety is a phosphate ester. In an embodiment, R1is a phosphate ester prodrug. In an embodiment, each prodrug moiety is independently selected from the group consisting of -CH(Rc)O-P(O)(ORd)(ORe), -CH(Rc)O-C(O)-C1-6alkylene-O-P(O)(ORd)(ORe), -CH(Rc)O- C(O)-C1-6alkylene-P(O)(ORd)(ORe), -CH(Rc)O-C(O)-C1-6alkylene-CO2H, -CH(Rc)O-C(O)Rd, -CH(Rc)O-C(O)ORd, -CH(Rc)O-C(O)O-C1-6alkylene-CO2H, -CH(Rc)O-C(O)-C1-6alkylene- NRdRe, -CH(Rc)O-C(O)O-C1-6alkylene-NRdRe, -C(O)Rd, -CH(Rc)O-C(O)-C1-6alkylene- heterocycloalkyl, -CH(Rc)O-C(O)-C1-6alkylene-heterocycloalkyl and -CRdRe-O-(C(O)-NRd- heteroarylene-CH2O-C(O)-CH2-NRdRe; wherein Rcis independently selected from hydrogen and methyl; Rdand Reare each independently hydrogen or C1-6alkyl; each heterocycloalkyl is 4- to 6-membered and contains one or two heteroatoms independently selected from N, O, and S; and each heteroarylene is 5- or 6-membered and contains one or two heteroatoms independently selected from N, O, and S. In an embodiment, Rcis independently selected from hydrogen, halo, and C1-3alkyl. In an embodiment, Rcis independently selected from hydrogen, fluoro, and methyl. In an embodiment, Rcis independently selected from hydrogen and methyl. In an embodiment, Rcis hydrogen. In an embodiment, each prodrug moiety is independently selected from the group consisting of -CH2O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-6alkylene-O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-6alkylene-P(O)(ORd)(ORe), -CH2O-C(O)-C1-6alkylene-CO2H, -CH2O-C(O)Rd, -CH2O- C(O)ORd, -CH2O-C(O)O-C1-6alkylene-CO2H, -CH2O-C(O)-C1-6alkylene-NRdRe, -CH2O- C(O)O-C1-6alkylene-NRdRe, -C(O)Rd, -CH2O-C(O)-C1-6alkylene-heterocycloalkyl, -CH2O- C(O)-C1-6alkylene-heterocycloalkyl and -CRdRe-O-(C(O)-NRd-heteroarylene-CH2O-C(O)- CH2-NRdRe; wherein Rdand Reare each independently hydrogen or C1-6alkyl; each heterocycloalkyl is 4- to 6-membered and contains one or two heteroatoms independently selected from N, O, and S; and each heteroarylene is 5- or 6-membered and contains one or two heteroatoms independently selected from N, O, and S. In an embodiment, each prodrug moiety is independently selected from the group consisting of -CH2O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-6alkylene-O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-6alkylene-P(O)(ORd)(ORe), -CH2O-C(O)-C1-6alkylene-CO2H, -CH2O-C(O)Rd, -CH2O- C(O)ORd, -CH2O-C(O)O- C1-6alkylene-CO2H, -CH2O-C(O)-C1-6alkylene-NRdRe, -CH2O- C(O)O-C1-6alkylene-NRdReand -C(O)Rd. In an embodiment, each prodrug moiety is independently selected from the group consisting of -CH2O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-6alkylene-O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-6alkylene-P(O)(ORd)(ORe), -CH2O-C(O)-C1-6alkylene-CO2H, -CH2O-C(O)O- C1-6alkylene- CO2H, -CH2O-C(O)-C1-6alkylene-NRdReand -CH2O-C(O)O-C1-6alkylene-NRdRe. In an embodiment, each prodrug moiety is independently selected from the group consisting of -CH2O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-3 alkylene-O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-3 alkylene-P(O)(ORd)(ORe), -CH2O-C(O)-C1-3alkylene-CO2H, -CH2O-C(O)Rd, -CH2O- C(O)ORd, -CH2O-C(O)O-C1-3alkylene-CO2H, -CH2O-C(O)-C1-3alkylene-NRdRe, -CH2O- C(O)O-C1-3alkylene-NRdRe, -C(O)Rd, -CH2O-C(O)-C1-3alkylene-heterocycloalkyl, -CH2O- C(O)-C1-3alkylene-heterocycloalkyl and -CRdRe-O-(C(O)-NRd-heteroarylene-CH2O-C(O)- CH2-NRdRe; wherein Rdand Reare each independently hydrogen or C1-6alkyl; each heterocycloalkyl is 4- to 6-membered and contains one or two heteroatoms independently selected from N, O, and S; and each heteroarylene is 5- or 6-membered and contains one or two heteroatoms independently selected from N, O, and S. In an embodiment, each prodrug moiety is independently selected from the group consisting of -CH2O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-3alkylene-O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-3alkylene-P(O)(ORd)(ORe), -CH2O-C(O)-C1-3alkylene-CO2H, -CH2O-C(O)Rd, -CH2O- C(O)ORd, -CH2O-C(O)O-C1-3alkylene-CO2H, -CH2O-C(O)-C1-3alkylene-NRdRe, -CH2O- C(O)O-C1-3alkylene-NRdReand -C(O)Rd. In an embodiment, each prodrug moiety is independently selected from the group consisting of -CH2O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-3alkylene-O-P(O)(ORd)(ORe), -CH2O-C(O)-C1-3alkylene-P(O)(ORd)(ORe), -CH2O-C(O)-C1-3alkylene-CO2H, -CH2O-C(O)O- C1-3alkylene- CO2H, -CH2O-C(O)-C1-3alkylene-NRdReand -CH2O-C(O)O-C1-3alkylene-NRdRe. In an embodiment, each prodrug moiety is independently selected from the group consisting of -CH2O-C(O)-C1-3alkylene-CO2H, -CH2O-C(O)Rd-, -CH2O-C(O)ORd, -CH2O-C(O)-C1-4alkylene-NRdRe, and CH2O-P(O)(ORd)(ORe). In an embodiment, each prodrug moiety is independently selected from . (ORe), where Rdand Reare as defined above. In an embodiment, each prodrug moiety is . of Formula (I) is a compound of Formula (IA) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: wherein R2, R3, X, p, and ring in relation to Formula (I), with the proviso that the compound of Formula IA is not a compound of Formula (IIA), wherein R2, R3, X, and p are as defined in accordance with Formula (I). In an embodiment, R1is hydrogen. In an embodiment, the compound of Formula (I) is a compound of Formula (IAA) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: wherein R2, R3, X, p, and ring in relation to Formula (I), with the proviso that the compound of Formula IAA is not a compound of Formula (IIAA), wherein R2, R3, X, and p are as defined in accordance with Formula (I). In an embodiment, R2is selected from the group consisting of hydrogen, halo, cyano, C1-3alkyl, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -C(O)NR7R8and CO2R7, wherein halo(C1-3)alkyl is optionally substituted by hydroxyl, -NR7R8, or cyclopropyl. In an embodiment, R2is selected from the group consisting of hydrogen, halo, cyano, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -C(O)NR7R8and CO2R7, wherein halo(C1-3)alkyl is optionally substituted by hydroxyl, -NR7R8, or cyclopropyl. In an embodiment, R2is selected from the group consisting of hydrogen, bromo, cyano, - C(O)NH2, -CF2CH2NH2, -CF2CH2CH2NH2, -CHFCH2NH2, -CF2CH2NHCH3, -CF2CH2OH, - CH2F, -CHF2, -CF3, -CF2CF3, -CF2CH3, -CF2CH(OH)CH3, -CF2CH(NH2)CH3, -CF2CHF2, - OCHF2, -S(O)CH3, -C(O)OCH2CH3, -CClF2, -CH3, and -CF2-cyclopropyl. In an embodiment, R2is selected from the group consisting of hydrogen, bromo, cyano, - C(O)NH2, -CF2CH2NH2, -CF2CH2CH2NH2, -CHFCH2NH2, -CF2CH2NHCH3, -CF2CH2OH, - CH2F, -CHF2, -CF3, -CF2CF3, -CF2CH3, -CF2CH(OH)CH3, -CF2CH(NH2)CH3, -CF2CHF2, - OCHF2, -S(O)CH3, -C(O)OCH2CH3, -CClF2, and -CF2-cyclopropyl. In an embodiment, R2is selected from the group consisting of hydrogen, bromo, cyano, - C(O)NH2, -CF2CH2NH2,-CF2CH2OH, -CH2F, -CHF2, -CF3, -CF2CHF2, -OCHF2, -S(O)CH3, - C(O)OCH2CH3, -CClF2, -CH3, and -CF2-cyclopropane. In an embodiment, R2is selected from the group consisting of hydrogen, bromo, cyano, - C(O)NH2, -CF2CH2NH2,-CF2CH2OH, -CH2F, -CHF2, -CF3, -CF2CHF2, -OCHF2, -S(O)CH3, - C(O)OCH2CH3, -CClF2, and -CF2-cyclopropane. In an embodiment, R2is selected from the group consisting of halo, cyano, -C(O)NH2, halo(C1-3)alkoxy, halo(C1-3)alkyl, -CF2CH2NH2, -CF2CH2OH, and -S(O)CH3. In an embodiment, R2is selected from the group consisting of bromo, cyano, -C(O)NH2, - CF2CH2NH2, -CF2CH2OH, -CH2F, -CHF2, -CF3, -CF2CF3, -CF2CH3, -CF2CHF2, -OCHF2and -S(O)CH3. In an embodiment, R2is selected from the group consisting of hydrogen, halo, C1-3alkyl, halo(C1-3)alkyl, and halo(C1-3)alkoxy. In a particular embodiment, R2is selected from the group consisting of halo and C1-3alkyl. In an embodiment, R2is selected from the group consisting of bromo, -CF3, and -CHF2. In an embodiment, R2is selected from the group consisting of Br and -CF3. In an embodiment, R2is -CF3. In an embodiment, the compound of Formula (I) is a compound of Formula (IB) or Formula (IBB) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: wherein R3, with the proviso that the compound of Formula (IB) or (IBB) is not a compound of Formula (IIB) or Formula (IIBB), wherein R3, X, and p are as defined in accordance with Formula (I). In an embodiment, R3is a 5- or 6-membered heteroaryl optionally substituted by -C(O)R8or a prodrug moiety. In an embodiment, R3is a 5-membered heteroaryl. In an embodiment, R3is a 5-membered heteroaryl optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety. In an embodiment, R3is a 5-membered heteroaryl optionally substituted by -C(O)R8or a prodrug moiety. In an embodiment, R3is a 5- membered heteroaryl optionally substituted by a prodrug moiety. In an embodiment, R3is a 5-membered nitrogen containing heteroaryl. In an embodiment, R3is a 5-membered nitrogen containing heteroaryl optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety. In an embodiment, R3is a 5-membered nitrogen containing heteroaryl optionally substituted by -C(O)R8or a prodrug moiety. In an embodiment, R3is a 5-membered nitrogen containing heteroaryl optionally substituted by a prodrug moiety. In an embodiment, R3is a 5-membered nitrogen containing heteroaryl optionally containing one, two, or three additional heteroatoms selected from N, O, and S, wherein the heteroaryl is optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety. In an embodiment, R3is a 5-membered nitrogen containing heteroaryl optionally containing one, two, or three additional heteroatoms selected from N, O, and S, wherein the heteroaryl is optionally substituted by -C(O)R8or a prodrug moiety. In an embodiment, R3is a 5-membered nitrogen containing heteroaryl optionally containing one, two, or three additional heteroatoms selected from N, O, and S, wherein the heteroaryl is optionally substituted by a prodrug moiety. In an embodiment, R3is imidazolyl or pyrazolyl, where R3is optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety. In an embodiment, R3is imidazolyl or pyrazolyl, where R3is optionally substituted by a prodrug moiety. In an embodiment, R3is imidazolyl or pyrazolyl. In an embodiment, R3is imidazolyl. For the avoidance of doubt, in an embodiment, R3is unsubstituted imidazolyl. In an embodiment, R3is imidazolyl or pyrazolyl linked through carbon, i.e., a C-linked imidazolyl or C-linked pyrazolyl. In an embodiment, R3is a C-linked imidazolyl. In an embodiment, R3is imidazol-4-yl or imidazol-5-yl. In an embodiment, R3is imidazol-5-yl. In an embodiment, R1is a prodrug moiety and R3is imidazolyl, in particular C-linked imidazolyl. In an embodiment, R1is H and R3is substituted by a prodrug moiety. In a particular embodiment, R1is and R3is imidazolyl, in particular C-linked imidazolyl. Alternatively, R1is hydrogen and R3is imidazolyl, in particular C-linked imidazolyl. In an embodiment, the compound of Formula (I) is a compound of Formula (IC) or Formula (ICC) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: (IC) (ICC) wherein X, p, and ring A are as defined herein in relation to Formula (I), with the proviso that the compound of Formula (IC) or (ICC) is not a compound of Formula (IIC) or (IICC), wherein In an embodiment, ring A is selected from any of the embodiments disclosed herein. For the avoidance of doubt, ring A is fused to the adjacent imidazolyl ring. For example, when ring A , the compound of Formula (I) is a compound of Formula (ID) . In an embodiment, ring A is Xp(as defined in accordance with any of the embodiments disclosed herein). In an embodiment, ring A is 6-membered heteroaryl. In an embodiment, ring A is selected from by -Xp(as defined in accordance with any of the embodiments disclosed herein). In an embodiment, the compound of Formula (I) is a compound of Formula (ID) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: wherein R1, R2, R3, X, and p to Formula (I). In an embodiment, the compound of Formula (I) is a compound of Formula (ID) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: wherein R1is hydrogen or a prodrug moiety; R2is selected from the group consisting of hydrogen, halo, cyano, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -C(O)NR7R8, and CO2R7, wherein halo(C1-3)alkyl is optionally substituted by hydroxyl, -NR7R8, or cyclopropyl; R3is a 5-membered heteroaryl optionally substituted by a prodrug moiety; p is 0, 1, 2, or 3; each X is L-Y; each L is a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, -O(CRaRb)n-, -(CRaRb)nO(CRaRb)m-, - SO2-, -SO2(CRaRb)n-, -C(O)O-, -OC(O)-, -C(O)O(CRaRb)n-, -C(O)NH(CRaRb)n-, or - NH(CRaRb)n-, wherein each n is independently 1, 2 or 3; each Raand Rbis independently selected from hydrogen, halo, or C1-4alkyl; each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, hydroxy(C1-6)alkyl, halo(C1-4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, - CO2R10, -COR10, -OSO2R10, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one or two substituents independently selected from halo, amino, C1-4alkyl, C1-4alkoxy, and hydroxy(C1-4)alkyl; two substituents taken together with the carbon atoms to which they are attached form a ring selected from C5-8cycloalkyl or a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the C5-8cycloalkyl or 5- to 8-membered heterocycloalkyl ring is optionally substituted with one or two substituents independently selected from oxo and C1-4alkyl; R7and R8are independently selected from hydrogen and C1-3alkyl; R9is independently selected from the group consisting of hydrogen, hydroxyl, and C1-4alkyl; and R10is independently selected from hydrogen and C1-6alkyl; or wherein R9and R10taken together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N and O. In an embodiment, the compound of Formula (I) is a compound of Formula (IE) or Formula (IEE) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: wherein R2, In an embodiment, the compound of Formula (I) is a compound of Formula (IF) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: wherein R1, R3, X, and p are to Formula (I). In an embodiment, the compound of Formula (I) is a compound of Formula (IG) or Formula (IGG) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: wherein R3, X, and p are as defined herein in relation to Formula (I). In an embodiment, the compound of Formula (I) is a compound of Formula (IH) or Formula (IHH) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: Wherein R2, In an embodiment, the compound of Formula (I) is a compound of Formula (IJ) or Formula (IJJ) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof: wherein X In an alternative aspect, the present invention provides a compound of Formula (III) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof, wherein R1is hydrogen or a prodrug moiety; R2is selected from the group consisting of hydrogen, halo, cyano, nitro, C1-3alkyl, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -SO2R7, -C(O)NR7R8, -NR7C(O)R8, and -CO2R7, wherein C1-3alkyl, halo(C1-3)alkyl, and halo(C1-3)alkoxy are optionally substituted by hydroxyl, -NR7R8, or C3-4cycloalkyl; R3is a 5- or 6-membered heteroaryl optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety; represents a single bond or double bond; q is 0, 1, 2, or 3; X1, X2, X3, and X4are independently selected from O, S, N, NRh, CRi, and CRhRi; each Rhand Riis independently L-Y or Rhand Ritaken together are oxo; each L is independently selected from a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, - O(CRaRb)n-, -(CRaRb)nO(CRaRb)m-, -SO2-, -SO2(CRaRb)n-, -C(O)O-, -OC(O)-, - C(O)O(CRaRb)n-, -(CRaRb)nC(O)O-, -C(O)NH(CRaRb)n-, or -NH(CRaRb)n-, wherein each n or m is independently 1, 2 or 3; each Raand Rbis independently selected from hydrogen, halo, or C1-4alkyl; each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, thio(C1-4)alkyl, hydroxy(C1-6)alkyl, cyano(C1-4)alkyl, halo(C1-4)alkyl, halo(C2-4)alkenyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -C(O)SR10, -CO2R10, - C(O)R10, -CHCHC(O)OR10, -OSO2R10, -S(O)R10, -N(R10)SO2R10, -P(O)(Ph)OR10, - P(O)(OR10)2, -P(S)(Ph)OR10, phenyl, 5- or 6-membered heteroaryl, and 3- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, phenyl, heteroaryl and heterocycloalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; or two Rhor Ritaken together with the atoms to which they are attached form a ring selected from phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8-membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8- membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, C1-4 alkyl, oxo, - C(O)R10, -SO2R10, -C1-3alkylene-NR9R10, and -C1-3alkylene-OR10; R7and R8are independently selected from hydrogen and C1-3alkyl; R9is independently selected from the group consisting of hydrogen, hydroxyl, C1-4alkyl, -C(O)C1-4alkyl, and halo(C1-4)alkyl; and R10is independently selected from hydrogen and C1-6alkyl; or wherein R9and R10taken together with the nitrogen atom to which they are attached form a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; with the proviso that when q is 1 and X1is N, X2, X3, and X4are not all CRi. For the avoidance of doubt, when any one of X1-X4is CRhRi, and Rhand Ritaken together are oxo, this means that any one of X1-X4is C=O. In an embodiment, each Raand Rbis independently selected from hydrogen, halo, or methyl. In an embodiment, each Raand Rbis independently selected from hydrogen, fluoro, or methyl. In an embodiment, each Raand Rbis independently selected from hydrogen or fluoro. In an embodiment, each Raand Rbis hydrogen. In an embodiment, X is independently selected from oxo and L-Y. In an embodiment, each L is a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, -O(CRaRb)n-, - (CRaRb)nO(CRaRb)m-, -SO2-, -SO2CH2-, -C(O)O-, -OC(O)-, -C(O)O(CRaRb)n-, - C(O)NH(CRaRb)n-, or -NH(CRaRb)n- and each Y is independently selected from the group consisting of hydrogen halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, hydroxy(C1-6)alkyl, halo(C1-4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -CO2R10, -COR10, -OSO2R10, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, amino, C1-4alkyl, C1-4alkoxy, and hydroxy(C1-4)alkyl; or two adjacent X substituents (or Rhand Riwhere relevant) taken together with the carbon atoms to which they are attached form a ring selected from C5-8cycloalkyl, or a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N or O, wherein the C5-8cycloalkyl or 5 to 8-membered heterocycloalkyl ring is optionally substituted with one or two substituents independently selected from oxo and C1-4alkyl. In an embodiment, each L is a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, -O(CRaRb)n-, - (CRaRb)nO(CRaRb)m-, -SO2-, -SO2CH2-, -C(O)O-, -OC(O)-, -C(O)O(CRaRb)n-, - C(O)NH(CRaRb)n-, or -NH(CRaRb)n- and each Y is independently selected from the group consisting of hydrogen halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, hydroxy(C1-6)alkyl, halo(C1-4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10,-CO2R10, -COR10, -OSO2R10, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one, two, or three substituents independently selected from halo, amino, C1-4alkyl, C1-4alkoxy, and hydroxy(C1-4)alkyl. In an embodiment, two X substituents (or Rhand Riwhere relevant) taken together with the carbon atoms to which they are attached form a ring selected from C5-8cycloalkylor a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N or O, wherein the C5-8cycloalkyl or 5- to 8-membered heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from C1-4alkyl, oxo, -C1-3alkylene-NR9R10, and -C1-3alkylene-OR10. In an embodiment, two adjacent X substituents (or Rhand Riwhere relevant) taken together with the carbon atoms to which they are attached form a ring selected from cyclohexyl or 5- or 6-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N or O, wherein the cyclohexyl or 5- or 6-membered heterocycloalkyl ring is optionally substituted with one or two substituents independently selected from oxo and C1-4alkyl. In an embodiment, two adjacent X substituents (or Rhand Riwhere relevant) taken together with the carbon atoms to which they are attached form a 5-membered heterocycloalkyl ring containing one heteroatom selected from N and O. In an embodiment, two X substituents taken together with the carbon atoms to which they are attached form a 6-membered heterocycloalkyl ring containing one heteroatom selected from N and O. In an embodiment, two X substituents taken together with the carbon atoms to which they are attached form a cyclohexyl ring. In an embodiment, each R9is independently selected from hydrogen and C1-4alkyl. In an embodiment, each R9is hydrogen. In an embodiment, each R10is independently selected from hydrogen and C1-6alkyl. In an embodiment, each R10is independently selected from hydrogen and C1-4alkyl. In an embodiment, each R10is C1-4alkyl. In an embodiment, R9and R10taken together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N and O, wherein the heterocycloalkyl ring is optionally substituted with one or two substituents independently selected from halo, amino, C1-4alkyl, and halo(C1-4)alkyl. In an embodiment, R9and R10taken together with the nitrogen atom to which they are attached form a 6-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N and O. In an embodiment, each R9is independently selected from hydrogen and C1-4alkyl; and each R10is independently selected from hydrogen and C1-4alkyl; or wherein R9and R10taken together with the nitrogen atom to which they are attached form a 6-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N and O. In an embodiment, each X is independently L-Y. In an embodiment, each X is independently L-Y, and each L is independently selected from a bond, -(CRaRb)n-, -(CRaRb)nO-, -O(CRaRb)n-, -C(O)O-, and -C(O)O(CRaRb)n-. In an embodiment, each X is independently L-Y, and each L is independently selected from a bond and -(CRaRb)n-. In an embodiment, each X is independently L-Y, and each L is a bond. In an embodiment, each L is a bond; and each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, hydroxy(C1-6)alkyl, cyano(C1-4)alkyl, halo(C1-4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -C(O)SR10, -CO2R10, -C(O)R10, - CHCHC(O)OR10, -OSO2R10, -P(O)(Ph)OR10, -P(O)(OH)OR10, -P(S)(Ph)OR10, -P(O)(CH3)2, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one or two substituents independently selected from C1-4alkyl and hydroxy(C1-4)alkyl; or two adjacent X substituents (or Rhand Riwhere relevant) taken together with the carbon atoms to which they are attached form a ring selected from C5-8cycloalkyl or a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N or O, wherein the C5-8cycloalkyl or 5- to 8-membered heterocycloalkyl ring ring is optionally substituted with one, two, or three substituents independently selected from C1-4 alkyl, oxo, -C1-3 alkylene-NR9R10, and -C1-3 alkylene-OR10. In an embodiment, each L is a bond; and each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, hydroxy(C1-6)alkyl, cyano(C1-4)alkyl, halo(C1-4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -C(O)SR10, -CO2R10, -C(O)R10, - CHCHC(O)OR10, -OSO2R10, -P(O)(Ph)OR10, -P(O)(OH)OR10, -P(S)(Ph)OR10, -P(O)(CH3)2, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one or two substituents independently selected from C1-4alkyl and hydroxy(C1-4)alkyl. In an embodiment, each L is a bond; and each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-6cycloalkyl, cyclohexenyl, C2-4alkenyl, C2-6alkynyl, hydroxy(C1-6)alkyl, halo(C1-4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -CO2R10, -C(O)R10, -OSO2R10, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-6cycloalkyl, cyclohexenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one C1-3alkyl; or two adjacent X substituents (or Rhand Riwhere relevant) taken together with the carbon atoms to which they are attached form a cyclohexyl or 5- or 6-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N or O, wherein the cyclohexyl or 5- or 6-membered heterocycloalkyl ring is optionally substituted with one or two substituents independently selected from oxo and C1-4alkyl. In an embodiment, each L is a bond; and each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-6cycloalkyl, cyclohexenyl, C2-4alkenyl, C2-6alkynyl, hydroxy(C1-6)alkyl, halo(C1-4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, -CO2R10, -C(O)R10, -OSO2R10, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-6cycloalkyl, cyclohexenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one C1-3alkyl. In an embodiment, each X is independently L-Y, and each L is independently selected from a bond and -(CRaRb)n-; and each Y is independently selected from hydrogen, halo, hydroxyl, cyano, C1-3alkyl, -CO2R10, -COR10, halo(C1-3)alkyl, C1-3alkoxy, phenyl, and -NR9R10. In an embodiment, each Y is independently selected from hydrogen, halo, hydroxyl, cyano, C1-3alkyl, -CO2R10, -COR10, halo(C1-3)alkyl, C1-3alkoxy, phenyl, and -NR9R10. In an embodiment, each Y is independently selected from hydrogen, bromo, fluoro, chloro, hydroxyl, cyano, methyl, ethyl, -CO2Me, -CO2Et,-C(O)Me, -CF3, -OMe, phenyl, and - NHCH3. In an embodiment, each Y is independently selected from hydrogen, halo, -CO2R10, and halo(C1-4)alkyl. In an embodiment, each L is a bond, and each Y is independently selected from hydrogen, halo, hydroxyl, cyano, C1-3alkyl, -CO2R10, -COR10, halo(C1-3)alkyl, C1-3alkoxy, and phenyl. In an embodiment, each Y is independently selected from hydrogen, halo, cyano, C1-4alkyl, and -CO2R10. In an embodiment, each Y is independently selected from hydrogen, fluoro, cyano, methyl, and -CO2Me. In an embodiment, Y is hydrogen. In an embodiment, L is a bond and Y is hydrogen. In an embodiment, Y is cyano. In an embodiment, L is a bond and Y is cyano. In an embodiment, each Y is halo or C1-4alkyl. In an embodiment, each Y is fluoro or methyl. In an embodiment, L is a bond, and each Y is fluoro or methyl. In an embodiment, Y is halo. In an embodiment, Y is fluoro. In an embodiment, L is a bond and Y is halo, in particular fluoro. In an embodiment, Y is -CO2R10. In an embodiment, Y is -CO2Me. In an embodiment, L is a bond and Y is -CO2R10, in particular Y is -CO2Me. In an embodiment, each L is a bond, and each Y is independently selected from hydrogen, cyano, C1-4alkyl, halo, and -CO2R10. In an embodiment, each L is a bond, and each Y is hydrogen. In an embodiment, each L is a bond, and each Y is halo. In an embodiment, each L is a bond, and each Y is fluoro. In an embodiment, each L is a bond, and each Y is halo or C1-4alkyl. In an embodiment, each L is a bond, and each Y is fluoro or methyl. In an embodiment, each L is a bond, and each Y is cyano. In an embodiment, each L is a bond, and each Y is -CO2R10. In an embodiment, each L is a bond, and each Y is -CO2Me. In an embodiment, p is 0, 1 or 2. In an embodiment, p is 0. In an embodiment, p is 1 or 2. In an embodiment, p is 1. In an embodiment, p is 2. In an embodiment, the present invention provides a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof, wherein R1is hydrogen or a prodrug moiety; R2is halo(C1-3)alkyl; R3is imidazolyl or pyrazolyl; ring A is selected from ; X L-Y; each L is independently selected from a bond or -CF2CH2-; each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-3alkyl, -CO2R10, -COR10, halo(C1-3)alkyl, C1-3alkoxy, -NHCH3, and phenyl; and R10is independently selected from hydrogen and C1-6alkyl. In an alternative aspect, the present invention provides a compound of Formula (IV) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof, wherein R1is hydrogen or a prodrug moiety; R2is selected from the group consisting of hydrogen, halo, cyano, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -C(O)NR7R8, and CO2R7, wherein halo(C1-3)alkyl is optionally substituted by hydroxyl, -NR7R8, or cyclopropyl; R3is a 5-membered heteroaryl optionally substituted by a prodrug moiety; p is 0, 1, 2, or 3; each R4, R5, R6, and R7is independently -L-Y; each L is a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, -O(CRaRb)n-, -(CRaRb)nO(CRaRb)m-, - SO2-, -SO2(CRaRb)n-, -C(O)O-, -OC(O)-, -C(O)O(CRaRb)n-, -C(O)NH(CRaRb)n-, or - NH(CRaRb)n-, wherein each n is independently 1, 2, or 3; each Raand Rbis independently selected from hydrogen, halo, or C1-4alkyl; each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, hydroxy(C1-6)alkyl, halo(C1-4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, - CO2R10, -COR10, -OSO2R10, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one or two substituents independently selected from halo, amino, C1-4alkyl, C1-4alkoxy, and hydroxy(C1-4)alkyl; or two substituents taken together with the carbon atoms to which they are attached form a ring selected from C5-8cycloalkyl or a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the C5-8cycloalkyl or 5- to 8-membered heterocycloalkyl ring is optionally substituted with one or two substituents independently selected from oxo and C1-4alkyl; R7and R8are independently selected from hydrogen and C1-3alkyl; R9is independently selected from the group consisting of hydrogen, hydroxyl, and C1-4alkyl; and R10is independently selected from hydrogen and C1-6alkyl; or wherein R9and R10taken together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N and O. In an embodiment, R4, R5, R6, and R7are independently selected from hydrogen, halo, cyano, -CO2R10and C1-4alkyl. In an embodiment, R6is hydrogen. In an embodiment, R6and R7are hydrogen. In an embodiment, R4and R5are independently selected from hydrogen, halo, and -CO2R10and R6and R7are hydrogen. In an embodiment, R4, R6and R7are hydrogen. In an embodiment, R4, R5, R6, and R7are hydrogen. In an embodiment, R4, R6, and R7are hydrogen and R5is halo. In an embodiment R4, R6, and R7are hydrogen and R5is fluoro. In an embodiment R4, R6, and R7are hydrogen and R5is -CO2R10. In an embodiment R4, R6, and R7are hydrogen and R5is -CO2Me. In an embodiment R5and R6are hydrogen, R7is F, and R4is C1-4alkyl. In an embodiment R5and R6are hydrogen, R7is F, and R4is methyl. In an embodiment R4, R5, and R6are hydrogen and R7is cyano. In an embodiment, the compound of Formula (I) is selected from the group consisting of: 1-(3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-6- yl)ethan-1-one, 5-(1H-Imidazol-5-yl)-2-methyl-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[2,1- b]oxazole, 7-(1H-imidazol-5-yl)-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- b][1,2,4]triazine, 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydro-8H- imidazo[2,1-c][1,4]oxazine, 5-(1H-imidazol-5-yl)-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-imidazo[1,2- a]imidazole, 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H-pyrrolo[1,2- a]imidazol-6-ol, 6-fluoro-3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine, 2-(3-bromo-1H-1,2,4-triazol-5-yl)-6,8-difluoro-3-(1H-imidazol-5-yl)imidazo[1,2-a]pyridine, (5-(8-fluoro-3-(1H-imidazol-5-yl)-7-methylimidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-1-yl)methyl dihydrogen phosphate, 6-bromo-3-(1H-imidazol-5-yl)-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine, 3-(1H-imidazol-5-yl)-5,7-dimethyl-6-phenyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine, 7-Bromo-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine, 3-(1H-Imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine; 8-Fluoro-3-(1H-imidazol-4-yl)-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine, 3-(1H-Imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine-8- carbonitrile, 6,7-Difluoro-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine, 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H,9H- imidazo[2,1-c][1,4]oxazepine, 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazine, 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-b]pyridazine, 7-chloro-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- c]pyrimidine, 3-(1H-imidazol-4-yl)-6-methoxy-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine, 2-(3-(Difluoromethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-4-yl)imidazo[1,2-a]pyrazine, 6-Ethyl-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine, Methyl 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine-6-carboxylate, 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-7-ol, Methyl 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine-7-carboxylate, 2-(3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-6- yl)-2,2-difluoro-N-methylethan-1-amine, Ethyl 3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-5,6- dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate, and 3-(1H-imidazol-4-yl)-7-(trifluoromethyl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-b]pyridazine, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof. In an embodiment, the compound of Formula (I) is tautomer In an embodiment, the compound of Formula (I) is depicted by one of the following structures, depicting the available tautomers when R3is imidazolyl, R2is CF3: or a pharmaceutically acceptable salt thereof. In an embodiment, the compound of Formula (I) is depicted by one of the following structures, depicting the available tautomers when R3is imidazolyl, R2is CF3: . In an embodiment, the compound of Formula (I) is depicted by one of the following structures, depicting the available tautomers when R3is imidazolyl, R2is CF3: H NNNNNNHNNN . In an embodiment, the compound of Formula (I) is depicted by one of the following structures, depicting the available tautomers when R3is imidazolyl, R2is CF3: F F F H N NNNNN . In an embodiment, the compound of Formula (I) is depicted by one of the following structures, depicting the available tautomers when R3is imidazolyl, R2is CF3: . In an embodiment, the compound of Formula (I) is a prodrug of . ptable salt of said compound or tautomer thereof. In an embodiment, the compound of Formula (I) is salt or tautomer In an embodiment, a compound of Formula (I) is in the form of a free base. In one embodiment, the compound of Formula (I) in the form of a free base is any one of the compounds of Examples 1 to 146. In an embodiment, a compound of Formula (I) is in the form of a pharmaceutically acceptable salt. In one embodiment, the compound of Formula (I) in the form of a pharmaceutically acceptable salt is any one of compounds of Examples 1 to 146. Compounds of Formula (I) or a tautomer thereof may contain an acidic or basic functional group and, thus, a person of skill in the art will appreciate that pharmaceutically acceptable salts of the compounds of Formula (I) may be prepared. Pharmaceutically acceptable salts include, amongst others, those described in Berge, J. Pharm. Sci., 1977, 66, 1-19, or those listed in P H Stahl and C G Wermuth, editors, Handbook of Pharmaceutical Salts; Properties, Selection and Use, Second Edition Stahl / Wermuth: Wiley- VCH / VHCA, 2011 (see http: / / www.wiley.com / WileyCDA / WileyTitle / productCd-3906390519.html). Suitable pharmaceutically acceptable salts can include acid or base addition salts. Such base addition salts can be formed by reaction of a compound of formula (I) (which, for example, contains a carboxylic acid or other acidic functional group) with the appropriate base, optionally in a suitable solvent such as an organic solvent, to give the salt. Such acid addition salts can be formed by reaction of a compound of formula (I) (which, for example contains a basic amine or other basic functional group) with the appropriate acid, optionally in a suitable solvent such as an organic solvent, to give the salt. Salts may be prepared in situ during the final isolation and purification of a compound of formula (I). If a basic compound of formula (I) is isolated as a salt, the corresponding free base form of that compound may be prepared by any suitable method known to the art, including treatment of the salt with an inorganic or organic base. Similarly, if a compound of formula (I) containing a carboxylic acid or other acidic functional group is isolated as a salt, the corresponding free acid form of that compound may be prepared by any suitable method known to the art, including treatment of the salt with an inorganic or organic acid. It will be understood that if a compound of Formula (I) contains two or more basic moieties, the stoichiometry of salt formation may include 1, 2 or more equivalents of acid. Such salts would contain 1, 2 or more acid counterions, for example, a dihydrochloride salt. Stoichiometric and non-stoichiometric forms of a pharmaceutically acceptable salt of a compound of formula (I) are included within the scope of the invention, including sub- stoichiometric salts. Representative pharmaceutically acceptable acid addition salts include, but are not limited to, 4-acetamidobenzoate, acetate, adipate, alginate, ascorbate, aspartate, benzenesulfonate (besylate), benzoate, bisulfate, bitartrate, butyrate, calcium edetate, camphorate, camphorsulfonate (camsylate), caprate (decanoate), caproate (hexanoate), caprylate (octanoate), cinnamate, citrate, cyclamate, digluconate, 2,5-dihydroxybenzoate, disuccinate, dodecylsulfate (estolate), edetate (ethylenediaminetetraacetate), estolate (lauryl sulfate), ethane-1,2-disulfonate (edisylate), ethanesulfonate (esylate), formate, fumarate, galactarate (mucate), gentisate (2,5-dihydroxybenzoate), glucoheptonate (gluceptate), gluconate, glucuronate, glutamate, glutarate, glycerophosphorate, glycolate, hexylresorcinate, hippurate, hydrabamine (N,N'-di(dehydroabietyl)-ethylenediamine), hydrobromide, hydrochloride, hydroiodide, hydroxynaphthoate, isobutyrate, lactate, lactobionate, laurate, malate, maleate, malonate, mandelate, methanesulfonate (mesylate), methylsulfate, mucate, naphthalene-1,5-disulfonate (napadisylate), naphthalene-2- sulfonate (napsylate), nicotinate, nitrate, oleate, palmitate, p-aminobenzenesulfonate, p- aminosalicyclate, pamoate (embonate), pantothenate, pectinate, persulfate, phenylacetate, phenylethylbarbiturate, phosphate, polygalacturonate, propionate, p-toluenesulfonate (tosylate), pyroglutamate, pyruvate, salicylate, sebacate, stearate, subacetate, succinate, sulfamate, sulfate, tannate, tartrate, teoclate (8-chlorotheophyllinate), thiocyanate, triethiodide, undecanoate, undecylenate, and valerate. Representative pharmaceutically acceptable base addition salts include, but are not limited to, aluminium, 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS, tromethamine), arginine, benethamine (N-benzylphenethylamine), benzathine (N,N’-dibenzylethylenediamine), bis- (2-hydroxyethyl)amine, bismuth, calcium, chloroprocaine, choline, clemizole (1-p chlorobenzyl-2-pyrrolildine-1’-ylmethylbenzimidazole), cyclohexylamine, dibenzylethylenediamine, diethylamine, diethyltriamine, dimethylamine, dimethylethanolamine, dopamine, ethanolamine, ethylenediamine, L-histidine, iron, isoquinoline, lepidine, lithium, lysine, magnesium, meglumine (N-methylglucamine), piperazine, piperidine, potassium, procaine, quinine, quinoline, sodium, strontium, t- butylamine, and zinc. The compounds of the invention may exist in tautomeric forms. It is to be understood that any reference to a named compound or a structurally depicted compound is intended to encompass all tautomers of such compound. For example, when R1is hydrogen, the following tautomers exist: . , the following tautomers exist: . (bonded through C), the following tautomers exist: . the invention. An isotopic variation of a compound of the invention, is defined as one in which at least one atom is replaced by an atom having the same atomic number but an atomic mass different from the atomic mass usually found in nature. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine and chlorine such as 2H, 3H, 13C, 14C, 15N, 17O, 18O, 18F and 36Cl, respectively. Certain isotopic variations of a compound of formula (I) or a salt or solvate thereof, for example, those in which a radioactive isotope such as 3H or 14C is incorporated, are useful in drug and / or substrate tissue distribution studies. Tritiated, i.e., 3H, and carbon-14, i.e., 14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with isotopes such as deuterium, i.e., 2H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements and hence may be preferred in some circumstances. Thus, in one embodiment, the present invention includes a compound of the invention, wherein one or more hydrogen atoms attached to carbon atoms are replaced by deuterium. Isotopic variations of a compound of the invention, can generally be prepared by conventional procedures such as by the illustrative methods or by the preparations described in the Examples hereafter using appropriate isotopic variations of suitable reagents. In an embodiment, the present invention includes deuterium. It is to be understood that the disclosed embodiments may be combined with any of the aspects and other embodiments. Statement of Use Therapeutic targeting of the cGAS-STING pathway with small molecule cGAS inhibitors could be beneficial in a broad array of autoinflammatory, autoimmune and immune- mediated diseases. In an embodiment, “treatment” refers to ameliorating or stabilising the specified condition, reducing or eliminating the symptoms of the condition and slowing or eliminating the progression of the condition. Compounds of the invention may be useful in the prevention of a condition in which cGAS or downstream elements of its pathway may play a known or expected role, such as in immune conditions, inflammatory conditions, auto-immune conditions, auto-inflammatory conditions, Type I interferonopathies, allergies, infectious conditions, organ injuries, tissue damage and other cGAS-dependent or related conditions. Compounds of the invention are useful in the treatment of a condition in which cGAS or downstream elements of its pathway may play a known or expected role.Compounds of the invention may therefore be useful in the treatment of a number of immune conditions, inflammatory conditions, auto-immune conditions, auto-inflammatory conditions, Type I interferonopathies, allergies, infectious conditions, organ injuries, tissue damage and other cGAS-dependent or related conditions. Compounds of the invention are useful in the treatment of a cGAS-related disease or disorder. Compounds of the invention are useful in the prevention of a cGAS-related disease or disorder. Compounds of the invention may be useful in the treatment of an autoimmune disease selected from, but not limited to, STING associated vasculitis with onset at infancy (SAVI), Aicardi Goutieres syndrome (AGS), familial chilblain lupus, ataxia telangiectasia (also referred to as Louis-Bar Syndrome), retinal vasculopathy with cerebral leukodystrophy (RVCL), systemic lupus erythematosus (SLE), cutaneous lupus, lupus nephritis (LN), psoriasis, diabetes mellitus including insulin-dependent diabetes mellitus (IDDM), dermatomyositis, human immunodeficiency virus (HIV), AIDS, polymyositis, systemic sclerosis (scleroderma), and Sjogren's syndrome (SS), rheumatoid arthritis (RA), psoriatic arthritis, polyarthritis, myasthenia gravis, polyarteritis nodosa, vasculitis, cutaneous vasculitis, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Henoch- Schonlein purpura, autoimmune hepatitis, primary sclerosing cholangitis, Wegener's granulomatosis, microscopic polyangiitis, Behcet's disease, spondylitis, giant cell arteritis, polymyalgia rheumatic, Raynaud's phenomenon, primary biliary cirrhosis, primary angiitis of the central nervous system microscopic polyangiitis, neuromyelitis optica and mixed connective tissue disease. Compounds of the invention may be useful in the treatment of acute or chronic inflammation of any tissue or organ of the human body including, but not limited to, musculoskeletal inflammation, vascular inflammation, cardiovascular inflammation, neural inflammation, digestive system inflammation, respiratory system inflammation, renal system inflammation, inflammation of the reproductive system, ocular inflammation, periodontal inflammation, and other inflammation, as exemplified below, and the consequent tissue and organ damage. Compounds of the invention may be useful in the treatment of musculoskeletal inflammation (i.e. any inflammatory condition of the musculoskeletal system) including, but not limited to conditions affecting skeletal joints, including joints of the hand, wrist, elbow, shoulder, jaw, spine, neck, hip, knee, ankle, and foot, and conditions affecting tissues connecting muscles to bones such as tendons. Examples of musculoskeletal inflammation which may be treated with compounds of the invention include arthritis (including, for example, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, acute and chronic infectious arthritis, arthritis associated with gout and pseudogout, and juvenile idiopathic arthritis), tendonitis, synovitis, tenosynovitis, bursitis, fibrositis (fibromyalgia), epicondylitis, myositis, and osteitis (including, for example, Paget's disease, osteitis pubis, and osteitis fibrosa cystic). Compounds of the invention may be useful in the treatment of inflammation of the vasculature or lymphatic system including, but not limited to atherosclerosis, arthritis, phlebitis, vasculitis, and lymphangitis. Compounds of the invention may be useful in the treatment of Cardiovascular conditions and cardiomyopathies including, but not limited to heart failure, myocardial infarction, cardiac hypertrophy, cardiac fibrosis, endomyocardial fibrosis, and aortic aneurysm and dissection (AAD). Compounds of the invention may be useful in the treatment of inflammation of the nervous system including, but not limited to encephalitis, sepsis-associated encephalopathy (SAE), cerebral ischemic stroke, traumatic brain injury (TBI), ataxia-telangiectasia, Guillain-Barre syndrome, meningitis, neuromyotonia, narcolepsy, multiple sclerosis, myelitis, CNS vasculitis, and schizophrenia. Compounds of the invention may be useful in the treatment of inflammatory conditions of the digestive system including, but not limited to cholangitis, cholecystitis, enteritis, enterocolitis, gastritis, gastroenteritis, inflammatory bowel disease (such as Crohn's disease and ulcerative colitis), ileitis, proctitis and colorectal cancer. Compounds of the invention may be useful in the treatment of inflammation of the respiratory system including, but not limited to lung inflammation, chronic lung inflammation, cystic fibrosis, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), silicosis, asthma and COVID-19. The compounds of this invention may be used to ameliorate lung inflammation, endothelial and vascular damage, and skin lesions derived from COVID-19 infections. Compounds of the invention may be useful in the treatment of inflammatory conditions and diseases of the liver and kidney including, but not limited to cirrhosis, liver fibrosis, viral hepatitis, non-alcoholic fatty liver disease (NAFLD), steatosis, non-alcoholic steatohepatitis (NASH), alcoholic-related liver disease (ALD), primary hepatocellular cancer (HCC), hepatic ischemia-reperfusion injury (IRI), acute kidney injury (AKI), chronic kidney disease (CKD), and renal fibrosis. Compounds of the invention may be useful in the treatment of metabolic disorders including, but not limited to diabetes melitus, obesity, insulin resistance and glucose intolerance. Compounds of the invention may be useful in the treatment of inflammatory conditions of the reproductive system including, but not limited to, cervicitis, chorioamnionitis, endometritis, epididymitis, omphalitis, oophoritis, orchitis, salpingitis, tubo-ovarian abscess, urethritis, vaginitis, vulvitis, and vulvodynia. Compounds of the invention may be useful in the treatment of ocular inflammation including, but not limited to inflammation of any structure of the eye, including the eye lids. Examples of ocular inflammation which may be treated with the compounds of the invention include blepharitis, blepharochalasis, conjunctivitis, dacryoadenitis, keratitis, fungal keratitis, keratoconjunctivitis sicca (dry eye), scleritis, trichiasis, and uveitis. In addition, other eye related disorders might be treated, including age-related macular degeneration (AMD). Compounds of the invention may be useful in the treatment of inflammatory periodontal disease (also known as gum disease) including, but not limited to gingivitis, odontoblast inflammation, chronic periodontitis, aggressive periodontitis, necrotizing ulcerative gingivitis / periodontitis and combined periodontic-endodontic lesions. Compounds of the invention may be useful in the treatment of autoimmune conditions having an inflammatory component including, but not limited to acute disseminated alopecia universalis, Behcet's disease, Chagas disease, STING associated vasculitis with onset at infancy (SAVI), Aicardi Goutieres syndrome (AGS), chilblain lupus, ataxia telangiectasia (also referred to as Louis-Bar Syndrome), retinal vasculopathy with cerebral leukodystrophy (RCVL), ANCA)-associated vasculitis, chronic fatigue syndrome, dysautonomia, encephalomyelitis, ankylosing spondylitis, aplastic anemia, hidradenitis suppurativa, autoimmune hepatitis, autoimmune oophoritis, celiac disease, Crohn's disease, diabetes mellitus type 1, giant cell arteritis, Goodpasture's syndrome, Grave's disease, Guillain-Barre syndrome, Hashimoto's disease, Henoch-Schonlein purpura, Kawasaki's disease, lupus erythematosus, microscopic colitis, microscopic polyarteritis, mixed connective tissue disease, multiple sclerosis, myasthenia gravis, opsoclonus myoclonus syndrome, optic neuritis, Ord's thyroiditis, pemphigus, polyarteritis nodosa, polymyalgia, rheumatoid arthritis, Reiter's syndrome, Sjogren's syndrome, temporal arteritis, Wegener's granulomatosis, warm autoimmune hemolytic anemia, interstitial cystitis, Lyme disease, morphea, psoriasis, sarcoidosis, scleroderma, ulcerative colitis, and vitiligo. Compounds of the invention may be useful in the treatment of T-cell mediated hypersensitivity diseases having an inflammatory component including, but not limited to contact hypersensitivity, contact dermatitis (including that due to poison ivy), urticaria, skin allergies, respiratory allergies (hay fever, allergic rhinitis) and gluten-sensitive enteropathy (Celiac disease). Compounds of the invention may be useful in the treatment of other inflammatory conditions including, but not limited to, appendicitis, dermatitis, dermatomyositis, endocarditis, fibrositis, gingivitis, glossitis, hepatitis, hidradenitis suppurativa, iritis, laryngitis, mastitis, myocarditis, nephritis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, pneumonitis, prostatitis, pyelonephritis, and stomatitis, transplant rejection (involving organs such as kidney, liver, heart, lung, pancreas (e.g., islet cells), bone marrow, cornea, small bowel, skin allografts, skin homografts, and heart valve xenografts, serum sickness, and graft vs host disease), acute pancreatitis, chronic pancreatitis, acute respiratory syndrome, Sezary's syndrome, congenital adrenal hyperplasia, nonsuppurative thyroiditis, hypercalcemia associated with cancer, pemphigus, bullous dermatitis herpetiformis, severe erythema multiforme, exfoliative dermatitis, seborrheic dermatitis, seasonal or perennial allergic rhinitis, bronchial asthma, contact dermatitis, atopic dermatitis, drug hypersensitivity reactions, allergic conjunctivitis, keratitis, herpes zoster ophthalmicus, iritis and iridocyclitis, chorioretinitis, optic neuritis, symptomatic sarcoidosis, fulminating or disseminated pulmonary tuberculosis chemotherapy, idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults, acquired (autoimmune) hemolytic anemia, leukemia and lymphomas in adults, acute leukemia of childhood, regional enteritis, autoimmune vasculitis, multiple sclerosis, chronic obstructive pulmonary disease, solid organ transplant rejection, sepsis. Compounds of the invention may be useful in the treatment of one or more diseases afflicting humans which are characterized by cellular proliferation in the area of disorders associated with neo-vascularization and / or vascular permeability including blood vessel proliferative disorders including arthritis (rheumatoid arthritis) and restenosis; fibrotic disorders including hepatic cirrhosis and atherosclerosis; mesangial cell proliferative disorders include glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombotic microangiopathy syndromes, proliferative retinopathies, organ transplant rejection and glomerulopathies; and other disorders including psoriasis, diabetes mellitus and chronic wound healing. Compounds of the invention be useful in the treatment of neurodegenerative conditions including, but not limited to, multiple sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Compounds of the invention may be useful in the treatment of inflammatory conditions derived from an infectious disease, which is any disease instigated by or coincident with an infection from a pathogen. Pathogens may be broadly defined as any species or organism that is foreign to a human tissue environment. Common disease-causing pathogens include bacteria (many like TB), viruses (many like HBV, HIV, flu) and parasitic protozoans (like P falciparum that causes malaria). The compounds of this invention may be used to treat infectious diseases derived from bacteria, such as TB infection {Mycobacterium tuberculosis}, Chlamydia, Tularemia infection {Franciseiia tuiarensis}, plasmodium infection or infections from DNA or RNA virus. The compounds of this invention may be used to treat infectious diseases derived from the DNA virus families: Herpesviridae (herpes simplex virus-1, Kaposi's sarcoma-associated virus and Epstein-Barr virus), Papillomaviridae (human papilloma virus), Adenovirus and Hepadnaviridae (Hepatitis B virus). Examples of RNA virus families include Retroviridae (human immunodeficiency virus) Flaviviridae (Dengue virus, Zika virus, Hepatitis C virus), Orthomyxoviridae (influenza), and Coronaviridae (human coronavirus, MERS, SARS and SARS-CoV2 coronavirus). Compounds of the invention may be useful on the amelioration of organ injury or damage sustained as a result of a cGAS mediated disease or disorder, for example, acute kidney injury, liver injury, pulmonary injury, heart injury, etc. Compounds of the invention may be particularly useful in the treatment of systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis, Sjogren’s syndrome, dematomyositis and scleroderma, particularly systemic lupus erythematosus and lupus nephritis. Compounds of the invention may be particularly useful in the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD), acute kidney injury, chronic kidney disease, diabetic kidney disease or injury, myocardial infarction, stroke, heart hypertrophy / heart failure, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD). Aicardi-Goutières syndrome (AGS) is an early onset disease, demonstrating characteristics of both autoinflammatory and autoimmune diseases, that manifests with progressive encephalopathy and chilblain skin lesions, and is biochemically characterized by an increase in type I interferons (Stetson et al. Cell 134(4) 587-598, 2008; Crow et al. Nat Rev Immunol 15(7) 429-440, 2015; Uggenti et al. Annu Rev Immunol 37:247–267, 2019). Many AGS patients show features of systemic autoimmunity such as anti-nuclear and anti-DNA autoantibodies, similar to SLE. More than 75% of AGS patients carry mutations in Trex1 or RnaseH2, resulting in the accumulation of cytoplasmic DNA due to the insufficient DNA clearance (Trex1) or DNA damage-driven micronuclei formation (RnaseH2). Importantly, knocking out these nucleases and / or knocking in inactivating AGS mutations causes in mice lethal autoimmune disease, which can be rescued by cGAS or STING deficiency (Gray et al.2015 J Immunol 195(5) 1939-1943, 2015; Gao et al. PNAS USA 112(42) E5699-E5705, 2015; Pokatayevet et al. J Exp Med 213(3) 329-336, 2016; Mackenzie et al. EMBO J 35(8) 831-844, 2016). In addition to AGS, Trex1 mutations have been linked to familial chilblain lupus (FCL), a cutaneous form of systemic lupus erythematosus, and retinal vasculopathy with cerebral leukodystrophy (RVCL) (Rice et al. J Clin Immunol 35(3) 235-243, 2015). Recently, biallelic mutations in LSM11 and RNU7-1 genes, encoding components of the histone pre-mRNA processing complex, have been identified in genetically uncharacterized AGS patients and linked to excessive cGAS signaling (Uggenti et al. Nat Genet 52(12) 1364–1372, 2020). Direct evidence that activation of STING causes inflammatory disease came from the identification of gain-of-function mutations in the TMEM173 gene encoding STING in patients presenting with early-onset vasculopathy and pulmonary inflammation (Liu et al. N Engl J Med 371(6) 507-518, 2014). The diseases caused by such mutations, now categorized as SAVI (STING associated vasculopathy with onset in infancy), is characterized by recurrent fevers, ulcerative skin lesions, vasculitis and interstitial lung disease. It is thought that SAVI-associated STING mutations lead to spontaneous dimerization and activation of STING in the absence of cGAMP (Ergun et al. Cell, 178(2) 290-301, 2019). COPA Syndrome, named for a defect in the COPa protein that participates in Golgi-to-ER trafficking, has been also linked to aberrant cGAS-STING signaling. It is thought that due to the COPA mutations STING spends a proportionally greater time in the activated state in the Golgi apparatus, resulting in constitutive signaling (Lepelley et al. J Exp Med 217(11) e20200600, 2020; Mukai et al. Nat Commun 12(1) 61, 2021). While all COPA patients present with lung disease, a smaller subset of patients develop arthritis and kidney disease. DNA ceII deficiency has been first described in 2017 in humans. Affected patients demonstrate severe neonatal anemia, membranoproliferative glomerulonephritis, deforming arthropathy and increased levels of anti-dsDNA antibodies (Rodero et al. Nature Communications 8(1) 2176, 2017). While DNAseII is an endosomal nuclease, it is speculated that accumulation of dsDNA in the endo-lysosomes ultimately results in their rupture, exposing DNA to cGAS. DnaseII-deficient mice die during embryonic development owing to severe anemia and if crossed with IFNAR null mice, develop chronic polyarthritis (Kawane et al. Science 292(5521) 1546-1549, 2001; Yoshida et al. Nat Immunol 6(1) 49- 56, 2005). Interestingly, deletion of cGAS or STING completely rescues DnaseII-deficient mice from both, embryonic lethality and chronic arthritis (Gao et al. PNAS USA 112(42) E5699–E5705, 2015). Multiple lines of evidence suggest that the same mechanisms implicated in the pathogenesis of monogenic diseases contribute to the development of complex autoimmune diseases such as SLE. Missense Trex1 mutations have been identified in 0.5- 2% of SLE patients, and lupus-like phenotype has been recapitulated in mice carrying the Trex1 D18N mutation that causes familial chilblain lupus (Namjou et al. Genes and Immunity 12(4) 270-279, 2011; Lee-Kirsch et al. Nat Genet 39(9) 1065-1067, 2007; Barizzone et al. Biomed Res Int 2013:471703, 2013). Similarly, mutations that impair RnaseH2 function have been linked to SLE in addition to AGS (Günther et al. J Clin Invest 125(1) 413–424, 2015). Moreover, elevated cGAMP levels have been reported in 15% of SLE patients, and cGAMP-positive patients presented with higher SLEDAI score (An et al Arthritis Rheumatol 69(4) 800–807, 2017). Based on the presence of interferon signature and overlapping clinical manifestations, diseases including various subtypes of cutaneous lupus erythematosus (CLE), lupus nephritis (LN) and dermatomyositis, are predicted to be driven (at least in part) by the same mechanisms implicated in the pathogenesis of SLE. UV-induced DNA damage may also activate cGAS-STING pathway and contribute to disease pathology (Skopelja-Gardner et al. Sci Rep 10(1) 7908, 2020). Excessive cGAS-STING activation and cGAS-STING-dependent pathogenesis have been implied in several other autoimmune diseases, including rheumatoid arthritis (RA), psoriasis and inflammatory bowel disease (IBD). cGAS deficiency rescues polyarthritis phenotype of DnaseII-KO mice and reduces joint swelling in the K / BxN arthritis mouse model (Gao et al. PNAS USA 112(42) E5699–E5705, 2015; Willemsen et al. Cell Rep 37(6) 109977, 2021). Likewise, STING deficiency attenuates IMQ-induced psoriatic symptoms and skin inflammation (Yu et al. J Invest Dermatol 142(3) 898-906, 2022). In IBD, the cGAS-STING pathway plays both protective and detrimental roles. While elimination of cGAS reduces intestinal inflammation and ameliorates colitis associated with IL-10 deficiency, other studies underscore the beneficial role of cGAS and STING in intestinal homeostasis (Ahn et al. Cell Reports 21(13) 3873-3884, 2017; Canesso et al. Mucosal Immunol 11(3) 820- 834, 2018; Hu et al. PNAS 118(23) e2105747118, 2021). Inflammation is a prominent hallmark of several neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis (ALS), Huntington disease (HD) and Alzheimer disease. In the case of Parkinson’s disease, mutations in the PARKIN and PINK1 genes lead to defective mitophagy, mtDNA leakage into the cytosol and cGAS-STING- dependent cytokine production. Importantly, the motor deficit and neuronal cell loss seen in Parkin mutator mice, can be rescued by STING ablation (Slitter et al. Nature 561(7722) 258- 262, 2018). Recently, cGAS-STING pathway has been implicated in the neuropathological processes associated with ALS and frontotemporal lobar degeneration. In a preclinical model of ALS driven by overexpression of human TDP-43 (A315T) allele, STING ablation dampens neuroinflammation, mitigates rapid disease progression and protects from early death (Yu et al. Cell 183(3) 636–649, 2020). Furthermore, administration of cGAS or STING inhibitors ameliorates the ongoing inflammation, improves motor function and increases survival in the SOD1-ALS mouse model (Tan et al. iScience 25:104404, 2022). Lastly, ALS patients with C9orf72 repeat expansion present with an enhanced type I interferon signature that is driven at least partly by STING activation (McCauley et al. Nature 585(7823) 96-101, 2020). Increased cGAS activity has been also associated with inflammatory responses in HD striatal cells, and activation of microglia with Tau has been linked to the PQBP1-cGAS- STING pathway (Sharma et al. PNAS 117(27) 5989–15999, 2020; Jin et al. Nat Commun 12(1) 6565, 2021). Activation of the cGAS-STING pathway with mtDNA has been proposed as a potential mechanism underlying obesity-induced inflammation and metabolic dysfunction. STING deficiency and / or inhibition prevents (at least partially) diet-induced adipose tissue inflammation, obesity, insulin resistance and glucose intolerance, and reduces senescence of pancreatic b-cells (Mao et al. Arterioscler Thromb Vasc Biol 37(5) 920-929, 2017; Hu et al FASEB J 36(5) e22266, 2022). In addition, excessive cGAS-STING signaling has been implicated in other metabolic diseases such as NAFLD and NASH. Independent labs have demonstrated that STING deficiency decreases severity of hepatic steatosis, inflammation and fibrosis in both methionine / choline-deficient diet (MCD) and high-fat diet (HFD) murine models (Luo et al Gastroenterology 155(6) 1971-1984, 2018; Yu et al. J Clin Invest 129(2) 546-555, 2019; Zhang et a. Front Immunol 13:931176, 2022). Increased cGAS-STING signaling has been demonstrated in acute kidney injury (AKI), chronic kidney (CKD) and other indications associated with fibrosis. Cisplatin induced mtDNA leakage triggers tubular inflammation and acute kidney injury progression, which can be rescued by STING deficiency or treatment with STING inhibitor (Maekawa et al. Cell Rep 29(5) 1261-1273, 2019; Gong et al, Am J Physiol Renal Physiol 320(4) F608-F616, 2021). Chronic kidney disease (CKD), characterized by renal injury, inflammation, and tissue fibrosis, has been associated with compromised mitochondrial integrity and mtDNA release. Moreover, genetic ablation or pharmacological inhibition of STING ameliorates both TFAM-loss-induced and FA-induced kidney inflammation and fibrosis, and improves kidney function in APOL1 transgenic mice expressing G2 risk allele (Chung et al. Cell Metab 30(4) 784-799, 2019; Wu et al. J Clin Invest 131(20) e136329, 2021). Recently, Zhang et al. proposed that cGAS-STING-driven fibrosis is facilitated by a non-canonical cGAS– STING–PERK pathway (Zhang et al. Nat Cell Biol 24(5) 766-782, 2022). Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung scarring. It is believed that the physiopathology relies on repetitive local micro-injuries leading to DNA damage, cell death and fibrosis. In the classical bleomycin-induced murine model of lung fibrosis, contribution of the cGAS-STING pathway to disease pathology is controversial. While Savigny et al. suggest that STING plays a protective role in the bleomycin model by limiting lung fibrosis, Zhang et al. report less severe fibrotic phenotype in STING-deficient mice in comparison to WT mice in response to bleomycin (Savigny et al. Front Immunol 11:588799, 2021; Zhang et al. Nat Cell Biol 24(5) 766-782, 2022). Administration of STING inhibitor also improves intestinal ischemia–reperfusion-mediated acute lung injury as demonstrated by reduced lung injury scores and attenuated fibrosis (Yang et a. Eur J Med Res 27(1) 79, 2022). In addition, cGAS-STING signaling induces lung inflammation in response to cigarette smoke exposure, a leading cause of chronic obstructive pulmonary disease (COPD), and silica particles (Nascimento et al. Sci Rep 9(1) 14848, 2019; Benmerzoug et al. Nat Com 9(1) 5226, 2018). Myocardial infarction (MI) causes ischemic cell death in the heart, releasing debris from dying cells. The released cardiomyocyte DNA is phagocytosed by infiltrating macrophages, leading to cGAS-STING-mediated type I IFN production. Genetic or pharmacological blockade of the cGAS–STING pathway protects against MI-induced adverse ventricular remodeling, improves contractile function and increases survival after myocardial infarction (King et al. Nat Med 23(12) 1481-1487, 2017; Cao at al. Circulation 137(24) 2613-2634, 2018; Lai et al. J Am Heart Assoc 10(15) e020754, 2021; Rech et al. Life Sci 291:120263, 2022). Furthermore, cGAS-STING knockdown blunts pressure overload-induced cardiac hypertrophy and improves cardiac function in the mouse transverse aortic constriction (TAC) model (Hu et al. Am J Physiol Heart circ Physiol 318(6) H1525-H1537, 2020). Activation of the cGAS-STING pathway has been also implicated in the development of atherosclerosis and ischemic stroke brain injury (Pham et al. Eur Heart J 42(42) 4336-4348, 2021; Li et al., EMBO Mol Med 12(4) e11002, 2020). Excessive cGAS-STING signaling contributes to acute and chronic inflammation in multiple tissues, and, in addition to the above mentioned diseases, cGAS-STING pathway has been linked to the pathogenesis of age-related macular degeneration (AMD) (Kerur et al. Nat Med 24(1) 50-61, 2018), acute pancreatitis (Zhao et al. Gastroenterology 154(6): 1822-1835, 2018), acne (Fischer et al. Front Immunol 11:571334, 2020) and sepsis (Hu et al., EBioMedicme 41:497-508, 2019). In the last 5 years, several studies have shown that release of chromatin fragments into the cytosol can activate cGAS–STING pathway and induce senescence (Yang et al. PNAS Sci USA 114(23) E4612-E4620, 2017; Gluck et al. Nat Cell Biol 19(9) 1061-1070, 2017). Senescent cells have a distinctive secretory phenotype (senescence-associated secretory phenotype), which is defined by changes in the expression of proinflammatory cytokines, chemokines, extracellular matrix components, and matrix metalloproteinases (MMPs). The senescence-associated secretory phenotype is thought to contribute to many chronic diseases associated with aging, including atherosclerosis and cardiovascular disease, arthritis, type 2 diabetes, neurodegenerative and other diseases. Inhibition of cGAS can reduce chronic inflammation and provide benefit in many indications associated with elderly patient population. Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the cause of COVID-19 disease. The interaction of SARS-CoV-2 with the host cell has been reported to activate the cGAS-STING pathway through the noncanonical pathway (Neufeldt et al.2022, Commun Biol 5(1) 45, 2022; Di Domizio et al. Nature 603(7899) 145-151, 2022). Fusion of SARS-CoV-2 with the host cell results in cytosolic micronuclei that bind and activate cGAS to induce an interferon response (Liu et al. Sci Signal 5(729) eabg8744, 2022). While activation of the cGAS-STING pathway during a SARS-CoV-2 infection will produce cytokines that can inhibit viral replication, extensive activation will lead to uncontrolled immune responses causative of COVID-19 immunopathology (Di Domizio et al. Nature 603(7899) 145-151, 2022). Pharmacological inhibition of the cGAS-STING pathway is expected to modulate the immune response after infection, which therefore may mitigate the immunopathology associated with disease symptoms. SARS-CoV-2-infected mice that were administered a STING antagonist two-days post-infection demonstrate reduced pathology and decreased levels of Type I IFNs and other cytokines in their lungs (Di Domizio et al. Nature 603(7899) 145-151, 2022). Activation of the cGAS-STING pathway has also been associated with a variety of other viral and bacterial pathogens. Multiple labs have studied the role of the cGAS-STING pathway in cancer. Many cancer cells present with genomic instability, which leads to the formation of micronuclei and cGAS activation. The induced cGAS-STING signaling results in either antitumor or pro- tumorigenic processes, depending on the context. On the one hand, cytokines, such as type I IFN, produced by the activated cGAS-STING pathway boost natural killer (NK) cell responses and prime CD8+ T cells for a more potent tumor surveillance (Marcus et al. Immunity 9(4) 754-763, 2018; Woo et al. Immunity 41(5) 830-842, 2014). On the other hand, activation of the cGAS-STING pathway has been linked to metastasis and immune evasion. It has been proposed that tumor cells with high genomic instability, which is the hallmark of metastatic tumors, utilize the cGAS-STING pathway to facilitate cellular invasion (Bakhoum et al. Nature 553(7689) 467–472, 2018). Furthermore, cGAS and STING shape the immunosuppressive tumor microenvironment by recruiting regulatory T cells and myeloid suppressor cells, as well as upregulating immune checkpoint inhibitors, such as programmed death ligand 1 (PD-L1) (Ding et al. Biochim Biophys Acta 1852(11) 2494-2503, 2015; Liang et al. Nat Commun 8(1) 1736, 2017; Nakamura et al. J Immunother Cancer 9(7) e002852, 2021). In an embodiment, the present invention relates to compounds, compositions containing them, and to their use in the treatment of various disorders, in particular autoimmune, autoinflammatory or immune-mediated conditions, such as systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis, Sjogren’s syndrome, dermatomyositis, scleroderma, amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD), acute kidney injury, chronic kidney disease, diabetic kidney disease or injury, APOL1 nephropathy, focal segmental glomerulosclerosis, membranous nephropathy, idiopathic pulmonary fibrosis, interstitial lung disease, myocardial infarction, stroke, heart hypertrophy / heart failure, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), particularly systemic lupus erythematosus, cutaneous lupus erythematosus and lupus nephritis. In an embodiment, the present invention relates to compounds, compositions containing them, and to their use in the treatment of various disorders, in particular autoimmune, autoinflammatory or immune-mediated conditions, such as systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis, Sjogren’s syndrome, dermatomyositis, scleroderma, amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD), acute kidney injury, chronic kidney disease, diabetic kidney injury, myocardial infarction, stroke, heart hypertrophy / heart failure, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), particularly systemic lupus erythematosus. In an aspect of the invention, there is provided a method of treatment of an autoimmune, autoinflammatory or immune-mediated condition in a human in need thereof comprising administering to said human a therapeutically effective amount of a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof. In a further aspect, there is provided a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof for use in therapy. In a further aspect, there is provided a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof for use in the treatment of an autoimmune, autoinflammatory or immune-mediated condition. In a further aspect, there is provided the use of a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof in the manufacture of a medicament for use in the treatment of an autoimmune, autoinflammatory or immune-mediated condition. In an embodiment, the autoimmune, autoinflammatory or immune-mediated condition is selected from the group consisting of systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis, Sjogren’s syndrome, dematomyositis and scleroderma, particularly systemic lupus erythematosus. In an embodiment, the autoimmune, autoinflammatory or immune-mediated condition is systemic lupus erythematosus (SLE). In an embodiment, the systemic lupus erythematosus is characterised as moderate to severe. In an embodiment, the autoimmune, autoinflammatory or immune-mediated condition is lupus nephritis. In an embodiment, the autoimmune, autoinflammatory or immune-mediated condition is selected from the group consisting of amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD), acute kidney injury, chronic kidney disease, diabetic kidney injury, myocardial infarction, stroke, heart hypertrophy / heart failure, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD). In an embodiment, there is provided a method of treatment of systemic lupus erythematosus in a human in need thereof comprising administering to said human a therapeutically effective amount of a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof. In an embodiment, there is provided a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof for use in the treatment of systemic lupus erythematosus. In an embodiment, the systemic lupus erythematosus is characterised as moderate to severe. Therefore, in an embodiment, there is provided a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof for use in the treatment of moderate to severe systemic lupus erythematosus. In an embodiment, the systemic lupus erythematosus is characterised as active systemic lupus erythematosus. In an embodiment, the systemic lupus erythematosus is active, moderate to severe systemic lupus erythematosus. In an embodiment, there is provided a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof for use in the treatment of lupus nephritis. In an embodiment, there is provided a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof for use in the treatment of lupus nephritis identified via biopsy. In an embodiment, there is provided a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof for use in the treatment of cutaneous lupus erythematosus. In an embodiment, the cutaneous lupus erythematosus is subacute or chronic. In a further embodiment, there is provided the use of a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof in the manufacture of a medicament for use in the treatment of systemic lupus erythematosus. In a further embodiment, there is provided the use of a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof in the manufacture of a medicament for use in the treatment of lupus nephritis. In a further embodiment, there is provided the use of a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof in the manufacture of a medicament for use in the treatment of cutaneous lupus erythematosus. In an embodiment, there is provided a compound having the following structure or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof In an embodiment, there is provided a compound having the following structure or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof In an embodiment, there is provided a compound having the following structure or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof Pharmaceutical Compositions / Routes of Administration / Dosages While it is possible that for use in therapy, compounds of the invention may be administered as the raw chemical, it is common to present the active ingredient as a pharmaceutical composition. In a further aspect, the present invention provides a pharmaceutical composition comprising (a) a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof; and (b) a pharmaceutically acceptable excipient. The excipient(s) must be acceptable in the sense of being compatible with the other ingredients of the composition and not deleterious to the recipient thereof. Pharmaceutical compositions may be adapted for administration by any appropriate route, for example by the oral (including buccal or sublingual), rectal, inhaled, intranasal, topical (including buccal, sublingual or transdermal), ocular (including topical, intraocular, subconjunctival, episcleral, sub-Tenon), parenteral (including subcutaneous, intramuscular, intravenous or intradermal) route. Such compositions may be prepared by any method known in the art of pharmacy, for example by bringing into association the active ingredient with the excipient(s). In one embodiment, the pharmaceutical composition is presented for oral administration, for example as a tablet or capsule. Other suitable compositions for oral administration may be powders or granules; solutions or suspensions in aqueous or non-aqueous liquids; edible foams or whips; or oil-in-water liquid emulsions or water-in-oil liquid emulsions. A compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof may be employed alone or in combination with other therapeutic agents. Combination therapies according to the present invention thus comprise the administration of at least one compound of Formula (I) or pharmaceutically acceptable salt or tautomer thereof, and the use of at least one other therapeutically active agent. A compound of Formula (I) or pharmaceutically acceptable salt or tautomer thereof, and the other therapeutically active agent(s) may be formulated and administered together in a single pharmaceutical composition or may be formulated and administered separately. When formulated and administered separately, administration may occur simultaneously or sequentially in any order. A compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof may be used in combination with one or more other therapeutic agents which may be useful in the treatment of autoimmune, autoinflammatory or immune-mediated conditions. Therefore, in a further aspect of the invention, there is provided a combination of (i) a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof; and (ii) an immune modulatory agent. In an embodiment, the immune modulatory agent is belimumab also known as BENLYSTA. In an embodiment, the present invention provides a pharmaceutical combination comprising a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof together with an immune modulatory agent. In one embodiment, the present invention provides a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof together with an immune modulatory agent for use in combination therapy in the treatment of an autoimmune, autoinflammatory or immune-mediated condition, particularly systemic lupus erythematosus. In one embodiment, the present invention provides a method of treatment of an autoimmune, autoinflammatory or immune-mediated condition, comprising administering a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof together with an immune modulatory agent. In an embodiment, a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof may be used in combination with one or more other therapeutic agents useful in the standard of care for the treatment of systemic lupus erythematosus, such as for example antimalarials, steroids and immunosuppressants. In an embodiment, a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof may be used in the treatment of SLE patients who have failed to respond to standard of care. In an embodiment, a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof may be used in the treatment of patients with SLE receiving standard of care and have failed to respond to at least one immunosuppressant. In an embodiment, a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof may be used in the treatment of patients with active, moderate to severe SLE receiving standard of care and have failed to respond to at least one immunosuppressant. In an embodiment, a compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof may be used in the treatment of patients with having SLE which is not controlled through treatment with standard of care alone. Examples General Synthetic Methods The compounds of this invention may be prepared using synthetic procedures illustrated in the reaction schemes below and knowledge of a skilled organic chemist. The syntheses provided in these schemes are applicable for producing compounds of the invention having a variety of different substituent groups employing appropriate precursors, which are suitably protected if needed, to achieve compatibility with the reactions outlined herein. Subsequent deprotection, where needed, affords compounds of the nature generally disclosed. Suitable protecting groups and the methods for protecting and de-protecting different substituents using such suitable protecting groups are well known to those skilled in the art; examples of which may be found in “Greene’s Protective Groups in Organic Synthesis’ (Peter G. M. Nuts, 5th edition, J. Wiley and Sons, 2014). Intermediates (compounds used in the preparation of the compounds of the invention) may also be present as salts. General Method 1 A suitably protected haloketone triazole compound (A) and cyclic-2-amine (B) are combined in a suitable solvent such as EtOH and heated to provide the resulting fused imidazo-ring system (C). Halogenation of the imidazo-ring with a suitable reagent such as N- bromosuccinimide affords (D), where W is halogen. Catalyst mediated coupling of (D) with suitable reagents such as boronate (E) delivers substituted imidazo compound (F), where - G-Z is R3protected with a suitable protecting group. Removal of the triazole protecting group (Y), and any other potential protecting groups, by any appropriate method, such as acidic hydrolysis affords the desired substituted fused imidazo-ring systems of Formula (IAA). A suitably protected haloketone triazole compound (A) and pyridin-2-amine (B) are combined in a suitable solvent such as EtOH and heated to provide the resulting imidazopyridine (C). Halogenation of the imidazopyridine with a suitable reagent such as N-bromosuccinimide affords (D), where W is halogen. Catalyst mediated coupling of (D) with suitable reagents such as boronate (E) delivers substituted imidazopyridine (F), where -G-Z is R3protected with a suitable protecting group. Removal of the triazole protecting group (Y), and any other potential protecting groups, by any appropriate method, such as acidic hydrolysis affords the desired 1H-triazole of Formula (IFF).

[0002] General Method 3 employs a synthetic strategy of late-stage triazole formation. This synthetic sequence is applicable to form the triazole on cores other than imidazopyridine. Imidazopyridine (W) is formed by reaction of U and V. Amide formation and subsequent halogenation of the imidazopyridine with a suitable reagent such as N-bromosuccinimide affords AA. Catalyst-mediated coupling of AA with a suitable reagent such as boronate E delivers substituted imidazopyridine BB. Two step triazole formation via condensation with a reagent comprising R2(CC) to form the amidine followed by condensation with hydrazine and cyclization to the triazole (DD). Removal of the protecting group Z can be achieved either in this step or with a separate deprotection step to afford 1H-triazole compounds of Formula (IFF).

[0003] Ge ) Triazole (IFF) which can be prepared via one of the described General Methods, is reacted with an appropriate reagent to afford a prodrug of Formula (I) (PM = Prodrug Moiety) which may contain further protecting groups. If protecting groups are present, removal by an appropriate method in Step 6 will complete the synthesis. Prodrug moieties may also be incorporated at an earlier stage in the synthesis. Examples are commercially available from, for example, PharmaTech and Sigma Aldrich. Unless otherwise stated, analytical LCMS run times are 2 min in length. Mass Directed Autopreparative HPLC (MDAP) Mass directed autopreparative HPLC was used for preparation of the compounds of this invention, and the conditions are given below. The UV detection was an averaged signal from wavelength of 210 nm to 350 nm and mass spectra were recorded on a mass spectrometer using alternate-scan positive and negative mode electrospray ionization. MDAP Method A Method A was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 0.1% v / v solution of trifluoroacetic acid in water B = 0.1% v / v solution of trifluoroacetic acid in acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 95 5 Method B was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 0.1% v / v solution of formic acid in water B = 0.1% v / v solution of formic acid in acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 85 15 MDAP Method C Method C was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 0.1% v / v solution of formic acid in water B = 0.1% v / v solution of formic acid in acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 95 5 MDAP Method D Method D was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 0.1% v / v solution of formic acid in water B = 0.1% v / v solution of formic acid in acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 95 5 Method E was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 0.1% v / v solution of trifluoroacetic acid in water B = 0.1% v / v solution of trifluoroacetic acid in acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 85 15 10.5 40 1 99 15 40 1 99 MDAP Method F Method F was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 0.1% v / v solution of formic acid in water B = 0.1% v / v solution of formic acid in acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 70 30 MDAP Method G Method G was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 0.1% v / v solution of formic acid in water B = 0.1% v / v solution of formic acid in acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 50 50 MDAP Method H Method H was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 0.1% v / v solution of trifluoroacetic acid in water B = 0.1% v / v solution of trifluoroacetic acid in acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 70 30 MDAP Method I Method I was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 10 mM ammonium bicarbonate in water adjusted to pH 10 with ammonia B = acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 85 15 MDAP Method J Method J was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 0.1% v / v solution of trifluoroacetic acid in water B = 0.1% v / v solution of trifluoroacetic acid in acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 50 50 MDAP Method K Method K was conducted on a Xselect CSH C18column (typically 150mm x 30mm i.d.5μm packing diameter) at ambient temperature. The solvents employed were: A = 10 mM ammonium bicarbonate in water adjusted to pH 10 with ammonia B = acetonitrile. The gradient employed was: Time (min) Flow rate (mL / min) %A %B 0 40 100 5 Intermediate 1 1-(3-Bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-chloroethanone To a solution of 3,5-dibromo-1H-1,2,4-triazole (200 g, 882 mmol) in AcCN (300 mL) at RT were added DIEA (308 mL, 176 mmol), 1-(chloromethyl)-4-methoxybenzene (143 mL, 1058 mmol) and KI (14.63 g, 88 mmol). After 16 hr, the reaction mixture was diluted with water (200 mL) and extracted with EtOAc (2 X 500 mL). The combined organic layers were washed with water (500 mL) and brine (500 mL), dried over Na2SO4and concentrated. The residue was dissolved in DCM (250 mL) and adsorbed onto silica (100 g), then purified by column chromatography (100-200 mesh silica gel [1 kg]), eluting with 5 - 10 % EtOAc in hexane to yield the title compound (190 g, 531 mmol, 60 % yield) as an off white solid. LCMS: tRET= 1.46 min, [M+H]+= 347.92 O Cl 1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-chloroethanone To 3,5-dibromo-1-(4-methoxybenzyl)-1H-1,2,4-triazole (100 g, 280 mmol) in THF (800 mL) at -40 °C was added isopropylmagnesium lithium chloride (1M in THF) (559 mL, 559 mmol). After 2 hr 2-chloro-N-methoxy-N-methylacetamide (42.3 g, 307 mmol) in THF (200 mL) was added. After 1 hr, the reaction was quenched with sat’d aq NH4Cl (500 mL) and extracted with EtOAc (2 X 1 L). The combined organic extracts were washed with brine (500 mL), dried over Na2SO4and concentrated. The residue was adsorbed onto silica (100 g) and purified by column chromatography (100-200 mesh silica gel [400 g]), eluting with 10 - 20 % EtOAc in hexane to yield the title compound (23.45 g, 66.5 mmol, 24 % yield) as an off white solid.1H NMR (400 MHz, CDCl3) ^ ppm 7.33 - 7.41 (m, 2 H), 6.83 - 6.90 (m, 2 H), 5.66 (s, 2 H), 4.87 (s, 2 H), 3.78 (s, 3 H). LCMS: tRET= 2.46 min, [M+H]+= 345.92 Intermediate 2 N,N-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (I) dimer (3.0 g, 4.53 mmol) and bis(pinacolato)diboron (44.0 g, 173 mmol) in THF (150 mL) was stirred at 45 °C for 20 min, then treated with a solution of 4,4'-di-tert-butyl-2,2'-dipyridyl (1.50 g, 5.59 mmol) in THF (50 mL). After 20 min a solution of N,N-dimethyl-1H-imidazole-1-sulfonamide (20.0 g, 114 mmol) in THF (80 mL) was added, and the temperature was raised to 65 °C. After 2 hr the reaction was concentrated, and the resulting residue was triturated with pentane to yield the title compound (32.2 g, 102 mmol, 89 % yield) as a brown solid.1H NMR (400 MHz, CDCl3) ^ ppm 8.02 (d, J = 1.01 Hz, 1 H), 7.73 (d, J = 1.01 Hz, 1 H), 2.89 (s, 6 H), 1.39 (s, 12 H). LCMS: tRET= 0.26 min, [M+H]+= 220.1 (boronic acid) Intermediate 3 2-Chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethanone Step 1: 3-(Trifluoromethyl)-1H-1,2,4-triazol-5-amine two vessels, hydrazinecarboximidamide, carbonic acid salt (150 g, 1.102 mol) and 2,2,2-trifluoroacetic acid (110 mL, 1.102 mol) were stirred at RT for 30 min. Dean Stark condensers were fitted to both reaction vessels, toluene (1.20 L) was added, and the reactions were heated at 115 °C overnight. The reactions were combined and concentrated, water (1.2 L) was added, and the mixture was extracted with EtOAc (2 X 700 mL). The organic extracts were combined, washed with sat’d aq NaHCO3solution (500 mL) and concentrated to yield the title compound (116 g, 763 mmol, 77 % yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) ^ ppm 12.72 (s, 1 H), 6.47 (s, 2 H). LCMS: tRET= 1.082 min, [M+H]+= 152.9 Step 2: 5-Bromo-3-(trifluoromethyl)-1H-1,2,4-triazole nitrite (118 g, 1.14 mol) and copper(II) bromide (511 g, 2.29 mol) in AcCN (1.40 L) was slowly added 3-(trifluoromethyl)-1H-1,2,4-triazol-5-amine (116 g, 763 mmol). The reaction mixture was stirred at 60 °C for 3 hr, treated with water (2 L) and extracted with EtOAc (2 X 1.5 L). The combined organic extracts were washed with brine (1.5 L), dried over Na2SO4and concentrated. The residue was purified by column chromatography over silica (2 kg), eluting with 3:1 pet ether: EtOAc to yield the title compound (119 g, 551 mmol, 72 % yield) as a yellow oil.1H NMR (400 MHz, DMSO-d6) ^ ppm 15.86 (s, 1 H). LCMS: tRET= 1.437 min, [M+H]+= 215.7, 217.8 Step 3: 5-Bromo-1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazole of 5-bromo-3-(trifluoromethyl)-1H-1,2,4-triazole (119 g, 551 mmol), 1- (chloromethyl)-4-methoxybenzene (104 g, 661 mmol) and K2CO3(152 g, 1.10 mol) in DMF (800 mL) was stirred at RT overnight. The reaction mixture was diluted with water (1 L) and extracted with EtOAc (3 X 700 mL). The combined organic layers were washed with brine (700 mL), dried over Na2SO4and concentrated. The residue was purified by column chromatography over silica gel (1 kg), eluting with 15:1 pet ether: EtOAc to yield the title compound (82 g, 244 mmol, 44 % yield) as a yellow oil.1H NMR (400 MHz, DMSO-d6) ^ ppm 7.28 (d, J = 8.3 Hz, 2 H), 6.96 (d, J = 8.4 Hz, 2 H), 5.46 (s, 2 H), 3.75 (s, 3 H). Step 4: 2-Chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethanone (Intermediate 3) methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazole (40 g, 119 mmol) in THF (500 mL) at -78 °C was added 2.4M n-BuLi (54.5 mL, 131 mmol). After 1 hr, 2-chloro- N-methoxy-N-methylacetamide (19.7 g, 143 mmol) in THF (60 mL) was added, and the reaction was warmed to 0 °C. After another hour, the reaction was treated with 6N HCl and extracted with EtOAc (2 X 500 mL). The combined organic extracts were dried over Na2SO4and concentrated. The residue was purified by column chromatography over silica gel (150 g), eluting with 5:1 pet ether: EtOAc to yield the title compound (19 g, 57 mmol, 48 % yield) as a white solid.1H NMR (400 MHz, DMSO-d6) ^ ppm 7.33 (d, J = 8.5 Hz, 2 H), 6.94 (d, J = 8.6 Hz, 2 H), 5.74 (s, 2 H), 5.19 (s, 2 H), 3.74 (s, 3 H). Intermediate 3, alternate preparation 2-Chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one To a stirred mixture of (4-methoxybenzyl)hydrazine, hydrochloride (50.0 g, 265 mmol) in methanol (500 mL) was added sodium methoxide 25 wt% in methanol (60.0 g, 278 mmol). After stirring the white suspension for 15 minutes methyl 2,2,2-trifluoroacetate (36.0 g, 281 mmol) was added dropwise over 30 minutes. The reaction was stirred for an additional 2 hr. (LCMS showed a new peak 92% (UV) at tRET0.75 min. Weak M+Na+271.2 seen for the acylated PMB hydrazine. PMB hydrazine SM tRET 0.33 min. MS(ES) [M+H]+121.0.) The reaction was treated with formamidine acetate acetic acid salt (30.0 g, 288 mmol), heated to reflux 85 °C, and stirred for 24 hr. (LCMS showed a new peak 47% (UV) at tRET0.95 min with a weak MS(ES) [M+H]+258.2) The reaction was evaporated to dryness, taken up in EtOAc, washed with aq. NaHCO3, dried (Na2SO4), filtered and evaporated to dryness. Purified by silica gel chromatography (Isco RediSep Rf Gold 330g, 0% for 4 minutes to 30% over 2 minutes then to 70% over 15 minutes EtOAc in heptane). The pure fractions were combined and evaporated to dryness to give the product 1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazole (45.4 g) as a yellow oil, which solidified under vacuum to a yellow solid. This material was used without further purification in the next reaction. The reaction was repeated five more times to give a total of 260.5 g product.1H NMR (400 MHz, CDCl3) ^ 8.06 (s, 1H), 7.35-7.30 (m, 2H), 6.97 (d, J=8.9 Hz, 2H), 5.36 (s, 2H), 3.87 (s, 3H). LCMS m / z 258.2 [M+H]+ Step 2: The reaction below was done at half scale two times then combined after purification. To a stirred solution of 1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazole (64.0 g, 249 mmol) in tetrahydrofuran (THF) (400 mL) under nitrogen at -10 °C (ice, NaCl) was added dropwise 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex 1.0 N (400 mL, 400 mmol) over 30 minutes. The reaction was stirred for 30 min then treated with a solution of 2-chloro-N-methoxy-N-methylacetamide (58.0 g, 422 mmol) in tetrahydrofuran (THF) (140 mL). The reaction was stirred for 1 hr then carefully quenched with 1 N aq. HCl (500 mL). (pH ~4) The reaction was extracted with EtOAc (300 mL), washed with brine, dried (Na2SO4), filtered and concentrated under vacuum. Purified by silica gel chromatography (Isco RediSep Rf Gold 330g, 25 to 60% CH2Cl2in heptane; solid was loaded with 30 g Isolute HM-N). The pure fractions were combined and evaporated to dryness to give the product 2-chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)ethan-1-one (53.21 g, 159 mmol, 64.1 % yield) as a white solid.1H NMR (400 MHz, CDCl3) ^ 7.44 (d, J=8.9 Hz, 2H), 6.91 (d, J=8.6 Hz, 2H), 5.78 (s, 2H), 4.97 (s, 2H), 3.83 (s, 3H). Intermediate 4 2-Chloro-1-(3-(difluoromethyl)-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)ethan-1-one To 3,5-dibromo-1H-1,2,4-triazole (20 g, 88 mmol) and K2CO3(24.37 g, 176 mmol) in AcCN (267 mL) was added 1-(chloromethyl)-4-methoxybenzene (13.75 mL, 101 mmol). The reaction was heated to 65 °C for 14 hr, filtered and concentrated. The residue was taken up in EtOAc, washed with water and brine, dried over sodium sulfate and concentrated. The residue was purified by column chromatography over silica gel (330 g column), eluting with 0 – 15 % EtOAc in pet ether to yield the title compound (19.5 g, 52.7 mmol, 60 % yield) as a white solid. LCMS: tRET= 1.107 min, [M+H]+= 347.95. Step 2: 5-Bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazole-3-carbaldehyde 1-(4-methoxybenzyl)-1H-1,2,4-triazole (5 g, 14.4 mmol) in THF (40 mL) at -10 °C was added 1.3 M isopropylmagnesium chloride lithium chloride complex (12.2 mL, 15.9 mmol), dropwise. After 30 min, DMF (2.01 mL, 25.9 mmol) was added dropwise, and the reaction was warmed to RT. After 1 hr, the reaction was cooled to 0 °C, quenched with NH4Cl solution (60 mL) and extracted with EtOAc (3 X 30 mL). The combined organic extracts were washed with brine (60 mL), dried over sodium sulfate and concentrated to yield the title compound (4.1 g, 13.9 mmol, 96 % yield) as a pale yellow oil. LCMS: tRET= 1.510 min, [M+H]+= 296.00. Step 3: 5-Bromo-3-(difluoromethyl)-1-(4-methoxybenzyl)-1H-1,2,4-triazole 1-(4-methoxybenzyl)-1H-1,2,4-triazole-3-carbaldehyde (4.1 g, 13.9 mmol) in DCM (60 mL) at 0 °C was added diethylaminosulfur trifluoride (3.66 mL, 27.7 mmol), dropwise. The reaction was stirred for 10 min, then at RT 10 min, then heated to 50 °C. After 2 hr, the reaction was cooled to 0 °C, quenched with NaHCO3solution to pH = 7~8 and extracted with EtOAc (3 X 40 mL). The combined organic layers were washed with brine (60 mL), dried over Na2SO4and concentrated. The residue was purified by column chromatography over silica gel (80 g), eluting with 3:1 pet ether: EtOAc to yield the title compound (2.4 g, 588 mmol, 42 % yield) as a pale yellow oil.1H NMR (400 MHz, DMSO- d6) ^ ppm 7.28 (d, J = 8.3 Hz, 2 H), 6.96 (d, J = 8.4 Hz, 2 H), 5.46 (s, 2 H), 3.75 (s, 3 H). LCMS: tRET= 1.559 min, [M+H]+= 319.95. Step 4: 2-Chloro-1-(3-(difluoromethyl)-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)ethan-1- one -1-(4-methoxybenzyl)-1H-1,2,4-triazole (50 mg, 0.157 mmol) in THF (2 mL) at -10 °C was added 1.3 M isopropylmagnesium chloride lithium chloride complex (0.242 mL, 0.314 mmol), dropwise. After 30 min, 2-chloro-N-methoxy-N- methylacetamide (25.9 mg, 0.189 mmol) in THF (1 mL) was added, and after 30 more min, the reaction was warmed to RT. After 30 min, the reaction was cooled to 0 °C, quenched with NH4Cl solution (1 mL), filtered and extracted with EtOAc (3 X 5 mL). The combined organic extracts were washed with brine (5 mL), dried over sodium sulfate and concentrated to yield the title compound (30 mg, 0.074 mmol, 47 % yield) as a pale yellow oil.1H NMR (400 MHz, DMSO-d6) ^ ppm 7.61 (t, J = 51.4 Hz), 7.30 (d, J = 8.4 Hz, 2 H), 6.95 (d, J = 8.4 Hz, 2 H), 5.60 (s, 2 H), 5.10 (s, 2 H), 3.75 (s, 3 H). LCMS: tRET= 1.115 min, [M+H+H2O]+= 334.20. Intermediate 4, alternate preparation 2-chloro-1-(3-(difluoromethyl)-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)ethan-1-one To a mixture of (4-methoxybenzyl)hydrazine, hydrochloride (25 g, 133 mmol) and potassium carbonate (37.5 g, 271 mmol) in 2-methyltetrahydrofuran (2-MeTHF) (250 mL) was added 2,2-difluoroacetic anhydride (25 mL, 201 mmol) dropwise over 30 min. The reaction stirred for 30 min then was diluted with EtOAc (300 mL) and water (500 mL). The ethyl acetate phase was removed, washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was taken up in ethanol (250 mL) and treated with formamidine acetate acetic acid salt (20 g, 192 mmol) at 100 °C for 24 hr with acetic acid (75 mL, 1310 mmol) added after 4 hr. The reaction was cooled to rt and was evaporated in vacuo. The residue was taken up in EtOAc, washed with aq. NaHCO3, dried (Na2SO4), filtered and evaporated in vacuo. Purification by silica gel chromatography (Isco RediSep Rf Gold 220g, 20 to 80% EtOAc in heptane) afforded 3-(difluoromethyl)-1-(4-methoxybenzyl)-1H-1,2,4-triazole (26 g, 75 % yield) as a light yellow oil.1H NMR (400 MHz, CHLOROFORM-d) δ 8.06 (s, 1H), 7.28- 7.31 (m, 2H), 6.93-6.99 (m, 2H), 6.75 (t, J=53.7 Hz, 1H), 5.33 (s, 2H), 3.86 (s, 3H). LCMS m / z 240.2 [M+H]+Step 2 To a stirred solution of 3-(difluoromethyl)-1-(4-methoxybenzyl)-1H-1,2,4-triazole (25 g, 105 mmol) in tetrahydrofuran (200 mL) under nitrogen at -10 °C (ice, NaCl) was added dropwise 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex 1.0 N in THF / toluene (180 mL, 180 mmol) over 30 min. The reaction mixture was stirred for 30 min then was treated with a solution of 2-chloro-N-methoxy-N-methylacetamide (25 g, 182 mmol) in tetrahydrofuran (50 mL). The reaction was stirred for 1 hr then carefully quenched with 1N aq. HCl (450 mL) (pH ~4). The reaction was extracted with EtOAc (300 mL), washed (brine), dried (Na2SO4), filtered and concentrated in vacuo. The crude was purified by silica gel chromatography (Isco RediSep Rf Gold 330g, 10 to 50% EtOAc in heptane). The desired fractions were combined and concentrated in vacuo to afford 2-chloro-1-(3-(difluoromethyl)- 1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)ethan-1-one ( 19.6 g, 59.4 % yield) as a white solid.1H NMR (400 MHz, CHLOROFORM-d) δ 7.42 (d, J=8.87 Hz, 2H), 6.90 (d, J=8.87 Hz, 2H), 6.76 (t, J=53.3 Hz, 1H), 5.76 (s, 2H), 4.98 (s, 2H), 3.83 (s, 3H). LCMS m / z 316.0 [M+H]+(weak). Example 1 1-(3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-6- yl)ethan-1-one, trifluoroacetic acid salt O O Step 1 2-chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (1.0 g, 3.00 mmol), 5-iodopyridin-2-amine (1.0 g, 4.55 mmol), and sodium bicarbonate (960 mg, 11.43 mmol) were stirred in acetonitrile (10 mL) at 100 °C for 16 h. The reaction was cooled to room temperature and diluted with DCM (50 mL). The slurry was filtered and the filtered solid rinsed with DCM (50 mL) and EtOAc (50 mL). The filtrate was concentrated in vacuo. The residue had EtOAc (50 mL) added to it. The slurry was mixed and filtered. The filtrate was concentrated in vacuo, taken up in DMSO (15 mL), and purified over flash C18 silica (105 g column), using a gradient of 50-100% ACN:H2O (0.1% NH4OH) over 8 min. The 6-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-a]pyridine was isolated (710 mg, 1.323 mmol, 44% yield) as a light orange solid.1H NMR (400 MHz, DMSO-d6) ^ ppm 9.03 (t, J=1.22 Hz, 1H), 8.61 (s, 1H), 7.62 (dd, J=2.20, 1.22 Hz, 2H), 7.28 - 7.40 (m, 2H), 6.85 - 6.94 (m, 2H), 6.13 (s, 2H), 3.71 (s, 3H). LCMS m / z 500.0 [M+H]+, tret= 1.31 min [TFA]. Step 2 6-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine (420 mg, 0.841 mmol) was stirred in toluene (10 mL) as bis(triphenylphosphine)palladium(II) chloride (60 mg, 0.085 mmol) and tributyl(1- ethoxyvinyl)stannane (500 µL, 1.480 mmol) were added in succession. The reaction was stirred under nitrogen at 100 °C for 24 h. The reaction was then cooled to room temperature. The vessel was placed in an ice bath and 2M aq HCl (5 mL, 850 mL conc HCl diluted with 4.15 mL H2O) was added to the dark solution. The reaction was stirred for 72 h and allowed to warm to room temperature during this time. The reaction mixture was filtered. To the filtrate was added 10% aq NH4F (5 mL). This mixture was stirred at room temperature for 2 h, followed by filtration. The filtrate was washed with brine (1 x 10 mL), separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified over flash silica, 12 g column, using a gradient of 0-20% EtOAc:DCM for 8 min. The 1-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridin-6-yl)ethan-1-one was isolated as a white solid (120 mg).1H NMR (400 MHz, DMSO-d6) δ ppm 9.51 (s, 1H), 8.78 (s, 1H), 7.83 (d, J=0.98 Hz, 2H), 7.36 (m, J=8.80 Hz, 2H), 6.91 (m, J=8.80 Hz, 2H), 6.14 (s, 2H), 3.71 (s, 3H), 2.65 (s, 3H). LCMS m / z 416.1 [M+H]+, tret= 1.15 min [TFA]. Step 3 1-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin- 6-yl)ethan-1-one (120 mg, 0.289 mmol) was stirred in DCM (5 mL) as NBS (65 mg, 0.365 mmol) and TFA (5 µL, 0.065 mmol) were added in succession. The reaction mixture was stirred under nitrogen at room temperature for 1 h and then concentrated in vacuo. The crude material was purified over flash silica, 12 g column, using a gradient of 0-10% EtOAc:DCM over 7 min. The 1-(3-bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-6-yl)ethan-1-one was isolated as a white solid (100 mg).1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (t, J=1.40 Hz, 1H), 7.92 (t, J=1.22 Hz, 2H), 7.35 (d, J=8.80 Hz, 2H), 6.90 (d, J=8.80 Hz, 2H), 6.05 (s, 2H), 3.72 (s, 3H), 2.75 (s, 3H). LCMS m / z 496.0 [M+H]+, tret= 1.25 min [TFA]. Step 4 To a round bottom flask was added 1-(3-bromo-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-6-yl)ethan-1-one (93 mg, 0.188 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole- 1-sulfonamide (Intermediate 2) (75 mg, 0.249 mmol), PdCl2(dppf)-CH2Cl2 adduct (20 mg, 0.024 mmol), and tripotassium phosphate (160 mg, 0.754 mmol). The vessel was placed under nitrogen, and 1,4-dioxane (2mL) and water (0.5 mL) were added. A condenser was attached to the vessel and the reaction was stirred at 100 °C. After 2 h, the reaction mixture was cooled to room temperature and concentrated in vacuo. The crude material was purified over flash silica, 4 g column, using a gradient of 0-10% EtOAc:DCM over 8 min, staying at 10% EtOAc until all product was off the column. The 4-(6-acetyl-2-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-3-yl)-N,N- dimethyl-1H-imidazole-1-sulfonamide was isolated as a white solid (40 mg).1H NMR (400 MHz, DMSO-d6) δ ppm 9.96 (d, J=1.47 Hz, 1H), 8.59 (d, J=1.47 Hz, 1H), 8.46 (d, J=1.47 Hz, 1H), 8.14 - 8.21 (m, 2H), 7.39 (d, J=8.80 Hz, 2H), 6.91 (d, J=8.80 Hz, 2H), 5.96 (s, 2H), 3.72 (s, 3H), 2.88 (s, 6H), 2.66 (s, 3H). LCMS m / z 589.2 [M+H]+, tret= 1.30 min [TFA]. Step 5 4-(6-acetyl-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (36 mg, 0.061 mmol) was stirred in TFA (2.0 mL, 26.0 mmol) at 80 °C for 3 h, then cooled to room temperature and allowed to stir overnight. The volatiles were removed in vacuo. The crude material was taken up in DMSO (1 mL) and purified via reverse phase HPLC, using a gradient of 5-35% ACN:H2O with 0.1%TFA. The TFA salt of the titled compound was isolated as a white solid (15 mg).1H NMR (400 MHz, DMSO-d6) δ ppm 9.87 (br s, 1H) 8.70 (br s, 1H) 8.45 (d, J=0.98 Hz, 1H) 7.91 (dd, J=9.54, 1.71 Hz, 1H) 7.82 (d, J=9.34 Hz, 1H) 2.65 (s, 3H), 2H signals not observed. LCMS m / z 362.1 [M+H]+, tret= 0.47 min [TFA]. Example 2 5-(1H-Imidazol-5-yl)-2-methyl-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[2,1- b]oxazole, trifluoroacetic acid salt

[0004] In each of five equivalent batches, a suspension of 2-chloro-1-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (66 mg, 0.198 mmol) and 5-methyloxazol-2-amine (38.8 mg, 0.396 mmol) in acetonitrile (20 mL) was heated in a microwave reactor for 2 min at 80 °C and then at a temperature between 170 °C and 200 °C for a total of 30-45 min. The five separate reaction mixtures were combined with the reaction mixtures of two smaller scale reaction batches which were prepared under similar reaction conditions (starting from 20 mg / 0.060 mmol and 9.4 mg / 0.028 mmol Intermediate 3) and were concentrated. The residue was purified by silica gel chromatography (ISCO RediSep Rf Gold 24 g SiO2column, eluting with 5-100% EtOAc in heptane) to give 6-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-2-methylimidazo[2,1-b]oxazole (31 mg) as a tan solid, which was used in the next step without further purification.1H NMR (400 MHz, CDCl3) δ ppm 7.72 (s, 1H), 7.48 - 7.42 (m, 2H), 7.12 - 7.08 (m, 1H), 6.90 - 6.84 (m, 2H), 6.00 (s, 2H), 3.81 (s, 3H), 2.46 (d, J=1.5 Hz, 3H). LCMS m / z 378.1 [M+H]+, tret= 1.18 min [TFA]. Step 2 To a solution of 6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-2- methylimidazo[2,1-b]oxazole (26 mg, 0.069 mmol) and N-iodosuccinimide (16 mg, 0.071 mmol) in acetonitrile (2.5 mL) was added a solution of trifluoroacetic acid (0.266 µL, 0.00345 mmol) in acetonitrile (0.1 mL). The reaction mixture was stirred for 1 h at room temperature. The reaction mixture was then combined with the reaction mixture of a separate reaction batch which was prepared under similar reaction conditions (starting from 4.3 mg / 0.011 mmol 6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-2- methylimidazo[2,1-b]oxazole. The combined reaction mixtures were diluted with DCM and washed with aqueous saturated NaHCO3. The organic layer was washed with brine, dried over MgSO4, and concentrated. The residue was purified by silica gel chromatography (ISCO RediSep Rf Gold 12 g SiO2column, eluting with 5-100% EtOAc in heptane) to give 5-iodo-6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-2- methylimidazo[2,1-b]oxazole (25 mg, 0.050 mmol, 62%) as a white solid.1H NMR (400 MHz, CDCl3) δ ppm 7.41 - 7.34 (m, 2H), 7.06 - 7.01 (m, 1H), 6.88 - 6.81 (m, 2H), 5.91 (s, 2H), 3.79 (s, 3H), 2.47 (d, J=1.5 Hz, 3H). LCMS m / z 504.3 [M+H]+, tret= 1.28 min [TFA]. Step 3 To a suspension of 5-iodo-6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)- 2-methylimidazo[2,1-b]oxazole (19.2 mg, 0.038 mmol), N,N-dimethyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (18 mg, 0.059 mmol), and PdCl2(dppf)-CH2Cl2adduct (4.7 mg, 5.7 µmol) in DME (1 mL) was added a 2.0 M aqueous solution of K3PO4(0.048 mL, 0.095 mmol). Nitrogen was bubbled through the reaction mixture. The reaction mixture was heated in a microwave reactor at 100 °C for 45 min. The reaction mixture was combined with the reaction mixture of a separate reaction batch which was prepared under similar reaction conditions (starting from 4.8 mg / 0.0095 mmol 5-iodo-6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-2- methylimidazo[2,1-b]oxazole). The combined reaction mixtures were diluted with DCM and washed with saturated aqueous NH4Cl. The aqueous layer was extracted with DCM. The combined organic layers were dried over MgSO4and concentrated. The residue was purified by silica gel chromatography (ISCO RediSep Rf Gold 12 g SiO2column, eluting with 10-100% EtOAc in heptane) to give 4-(6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)-2-methylimidazo[2,1-b]oxazol-5-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (19.6 mg, 0.036 mmol, 75%) as a pink solid.1H NMR (400 MHz, CDCl3) δ ppm 8.86 (d, J=1.3 Hz, 1H), 7.97 (d, J=1.3 Hz, 1H), 7.91 - 7.88 (m, 1H), 7.47 - 7.40 (m, 2H), 6.88 - 6.82 (m, 2H), 6.06 (s, 2H), 3.79 (s, 3H), 2.97 (s, 6H), 2.47 (d, J=1.3 Hz, 3H). LCMS m / z 551.4 [M+H]+, tret= 1.40 min [TFA]. Step 4 A solution of 4-(6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-2- methylimidazo[2,1-b]oxazol-5-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (18.8 mg, 34.1 µmol) in Trifluoroacetic acid (TFA) (0.7 mL) was heated in a sealed vial at 80 °C for 3 h. The reaction mixture was combined with that of a smaller scale reaction (starting from 0.6 mg / 0.001 mmol 4-(6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-2- methylimidazo[2,1-b]oxazol-5-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide). The combined reaction mixtures were concentrated, and the residue was purified by reverse phase HPLC (MDAP Method E) to give 5-(1H-imidazol-5-yl)-2-methyl-6-(3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[2,1-b]oxazole, trifluoroacetic acid salt (10.3 mg, 23.6 µmol, 67%).1H NMR (400 MHz, DMSO-d6) δ ppm 15.4 (br s, 1H), 13.2 (br s, 1H), 8.46-8.34 (m, 2H), 8.13-8.11 (m, 1H), 2.45 (d, 3H). LCMS m / z 324.0 [M+H]+, tret= 0.53 min [TFA]. Example 3 7-(1H-imidazol-5-yl)-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-b][1,2,4]triazine To a 100 mL round-bottom flask was added 2-chloro-1-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (2.0 g, 5.99 mmol), 1,2,4-triazin-3-amine (1.0 g, 10.41 mmol) and acetonitrile (20 mL). The mixture was refluxed (heated at 90 °C) and stirred for 24 h. The reaction was cooled to room temperature. The reaction was evaporated to dryness under vacuum, basified with aq saturated NaHCO3, extracted with EtOAc, dried (Na2SO4), filtered, and evaporated to dryness under vacuum. The solid, loaded with 10 g Isolute HM-N, was purified by silica gel chromatography (Isco RediSep Rf Gold 80g, 0 to 100% EtOAc in CH2Cl2). The pure fractions were combined and evaporated to dryness under vacuum. The residue was triturated with hexanes, filtered and dried under vacuum to give the product 6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)imidazo[1,2-b][1,2,4]triazine (0.42 g, 1.063 mmol, 17.7% yield) as an orange solid. The reaction was repeated a second time and combined with the above for a total of (0.84 g, 2.24 mmol) product.1H NMR (400 MHz, DMSO-d6) ^ ppm 9.11 (s, 1H), 8.82 (d, J=1.96 Hz, 1H), 8.76 (d, J=1.96 Hz, 1H), 7.35-7.38 (m, 2H), 6.89-6.93 (m, 2H), 6.12 (s, 2H), 3.71 (s, 3H). LCMS m / z 375.9 [M+H]+, tret= 1.06 min [TFA]. Step 2 To a stirred solution of 6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-b][1,2,4]triazine (0.84 g, 2.238 mmol) in acetic acid (20 mL) was added sodium acetate (0.30 g, 3.66 mmol) followed by bromine (120 µL, 2.329 mmol) dropwise. The reaction was stirred for 15 min (formed a thick suspension). The reaction mixture was evaporated to dryness under vacuum, taken up in CHCl3, washed with aq saturated NaHCO3, dried (Na2SO4), filtered and concentrated under vacuum. The residue was purified by silica gel chromatography (Isco RediSep Rf Gold 80g, 0 to 50% EtOAc in CH2Cl2). The pure fractions were combined, evaporated to dryness under vacuum, triturated with hexanes, filtered and dried under vacuum to give the product 7-bromo-6-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-b][1,2,4]triazine (0.77 g, 1.610 mmol, 72.0 % yield) as a light yellow solid.1H NMR (400 MHz, DMSO-d6) ^ ppm 8.95 (d, J=1.96 Hz, 1H), 8.81 (d, J=1.96 Hz, 1H), 7.36 (d, J=8.80 Hz, 2H), 6.87-6.94 (m, 2H), 6.02 (s, 2H), 3.72 (s, 3H). LCMS m / z 454.0, 456.0 [M+H]+, [M+H+2], tret= 1.12 min [TFA]. Step 3 To a 100 mL round-bottom flask was added 7-bromo-6-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-b][1,2,4]triazine (0.77 g, 1.695 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (1.0 g, 3.32 mmol), PdCl2(dppf)-CH2Cl2adduct (0.35 g, 0.429 mmol), potassium phosphate (0.55 g, 2.59 mmol), 1,4-dioxane (20 mL) and water (1.0 mL). The reaction was purged with nitrogen, heated to 100 °C and stirred for 4 h. The reaction mixture was cooled to room temperature and evaporated to dryness under vacuum. The remaining solid was triturated with CH2Cl2, filtered free of insolubles and rinsed with CH2Cl2. The filtrate was loaded directly onto a silca gel column and purified by silica gel chromatography (Isco RediSep Rf Gold 80g, 0 to 80% EtOAc in CH2Cl2). The pure fractions were combined and concentrated under vacuum. Later running fractions that contained some des-bromo starting material were discarded. The residue was triturated with CH2Cl2 / hexanes, filtered, washed with hexane and dried under vacuum to give the product 4-(6-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-b][1,2,4]triazin-7-yl)- N,N-dimethyl-1H-imidazole-1-sulfonamide (0.88 g, 1.524 mmol, 90 % yield) as a yellow solid.1H NMR (400 MHz, DMSO-d6) ^ ppm 8.97 (d, J=1.96 Hz, 1H), 8.84 (d, J=1.96 Hz, 1H), 8.38 (d, J=1.47 Hz, 1H), 8.23 (d, J=1.47 Hz, 1H), 7.21 (d, J=8.80 Hz, 2H), 6.81-6.87 (m, 2H), 5.52 (s, 2H), 3.70 (s, 3H), 2.87 (s, 6H). LCMS m / z 549.1 [M+H]+, tret= 1.06 min [TFA]. Step 4 A solution of 4-(6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-b][1,2,4]triazin-7-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (870 mg, 1.586 mmol) in trifluoroacetic acid (15 mL, 195 mmol) was heated to 70 °C and stirred for 12 h. At this time, the LCMS showed that the reaction was only 63% complete and 33% product still contained the dimethylsulfamoyl group. The reaction was heated at 80oC and stirred for an additional 18 h, at which point the LCMS showed that the reaction was complete. The reaction was cooled to room temperature and evaporated to dryness under vacuum. The residue was adjusted close to pH 6 with aq saturated NaHCO3, treated with 0.2 M sodium hydrogen phosphate buffer (pH 6.3), triturated, filtered, washed with water, filtered, triturated with a small volume of EtOH, filtered, triturated with CH2Cl2, filtered, and dried under vacuum to give the product 7-(1H-imidazol-5-yl)-6-(3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-b][1,2,4]triazine (520 mg, 1.538 mmol, 97 % yield) as an orange solid. Note: the product formed a cloudy suspension in DMSO-d6, so a drop of TFA was added to dissolve for the1H NMR.1H NMR (400 MHz, DMSO-d6w / TFA) ^ ppm 9.33 (s, 1H), 8.96 (s, 1H), 8.90 (s, 1H), 8.41 (s, 1H), 2H signals not observed. LCMS m / z 322.0 [M+H]+, tret= 0.44 min [TFA]. Example 4 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydro-8H- imidazo[2,1-c][1,4]oxazine, Trifluoroacetic acid salt

[0005] To a solution of morpholin-3-one (1 g, 9.89 mmol) in Dichloromethane (DCM) (15 mL) was added Me3OBF4(3.66 g, 24.73 mmol). The reaction was stirred at rt overnight. LCMS analysis showed desired product and consumption of starting material. The mixture was concentrated to remove organic solvents. The crude material was extracted with EtOAc (3 x 15 mL). The combined organics were washed with brine (15 mL), dried over Na2SO4, filtered and concentrated to afford the crude 5-methoxy-3,6-dihydro-2H-1,4-oxazine (400 mg, 3.09 mmol) as a colorless oil. Step 2 To a solution of 5-methoxy-3,6-dihydro-2H-1,4-oxazine (1 g, 8.69 mmol) in Methanol (50 mL) was added NH4Cl (0.929 g, 17.37 mmol). The mixture was stirred at 80 °C for 2 h. LCMS analysis showed desired product and consumption of starting material. The mixture was extracted with EtOAc (30 mL x 3). The combined organics were washed with brine (40 mL), dried over Na2SO4,filtered and concentrated to afford a crude white solid, 5,6-dihydro- 2H-1,4-oxazin-3-amine (1 g, 8.49 mmol). Step 3 To a solution of 5,6-dihydro-2H-1,4-oxazin-3-amine (500 mg, 4.99 mmol) in Acetonitrile (5 mL) was added 2-chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-ethan- 1-one (Intermediate 3) (1833 mg, 5.49 mmol) and Et3N (0.696 mL, 4.99 mmol). The reaction was stirred at 130 °C for 1 h in a microwave reactor. LCMS analysis showed desired product and consumption of starting material. The mixture was cooled to rt and concentrated to remove organic solvents. The crude mixture was extracted with EtOAc (15 mL x 3) and the combined organices were washed with brine (15 mL), dried over NaSO4, filtered, and concentrated to a crude yellow solid. This was combined with crude product from a smaller scale reaction (starting from 20 mg / 0.200 mmol 5,6-dihydro-2H-1,4-oxazin- 3-amine) to afford crude 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)- 5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine (380 mg, 0.892 mmol). LCMS m / z 380.1 [M+H]+, tret= 1.04 min [TFA]. Step 4 To a solution of 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6- dihydro-8H-imidazo[2,1-c][1,4]oxazine (350 mg, 0.923 mmol) in Dichloromethane (DCM) (10 mL) and AcOH (2.000 mL) was added NIS (249 mg, 1.107 mmol). The reaction was stirred at rt for 2 h. LCMS analysis showed desired product and consumption of starting material. The mixture was extracted with EtOAc (13 mL x 3), and the combined organics were washed with aq saturated Na2S2O3(13 mL), brine (14 mL), and then dried over Na2SO4and concentrated to afford crude 3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)-5,6-dihydro-8H-imidazo[2,1- c][1,4]oxazine (270 mg, 0.476 mmol). LCMS m / z 506.0 [M+H]+tret= 1.14 min [TFA]. Step 5 To a solution of 3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6- dihydro-8H-imidazo[2,1- c][1,4]oxazine (240mg, 0.475mml) in 1,4-Dioxane (8 mL) and Water (1.600 mL) was added N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-imidazole-1- sulfonamide (Intermediate 2) (215 mg, 0.713 mmol), Pd(dppf)Cl2CH2Cl2(78 mg, 0.095 mmol) and K3PO4 (202 mg, 0.950 mmol). The reaction mixture was stirred at 110 °C overnight. LCMS analysis indicated desired product and consumption of starting material. The mixture was cooled to rt and concentrated to remove organic solvents. The crude mixture was extracted with EtOAc (15 mL x 3) and the combined organics were washed with brine (15 mL), dried over Na2SO4, filtered and concentrated to afford crude 4- (2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydro-8H- imidazo[2,1-c][1,4]oxazin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (200 mg, 0.333 mmol) as a yellow solid. LCMS m / z 553.2 [M+H]+, tret = 0.68 min (TFA, 1 min run time). Step 6 A solution of 4-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6- dihydro-8H-imidazo[2,1-c][1,4]oxazin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (200 mg, 0.362 mmol) in Trifluoroacetic acid (TFA) (8 mL) was stirred at 75 °C for 2.5 h. LCMS analysis indicated desired product and consumption of starting material. The reaction mixture was concentrated in vacuo, redissolved in DMF (3 mL) and purified by prep HPLC (Sunfire Prep C18 OBD column using an eluent of 10 - 30% ACN:water with 0.05% TFA). The product was collected, concentrated, and lyophilized to give 3-(1H-imidazol-5-yl)-2-(3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydro-8H-imidazo[2,1-c][1,4]oxazine, trifluoroacetic acid salt, as a white solid (63.1 mg, 39.2 % yield)1H NMR (400 MHz, DMSO- d6) ^ ppm 8.88 (s, 1H), 8.07 (s, 1H), 4.90 (s, 2H), 4.15(t, J = 4.4 Hz, 2H), 4.08 (t, J =4.8 Hz, 2H), 2H signals not observed. LCMS m / z 326.1 [M+H]+, tret= 0.69 min [TFA, 3 min run time]. Example 5 5-(1H-imidazol-5-yl)-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-imidazo[1,2- a]imidazole, Trifluoroacetic acid salt Step 1 6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-imidazo[1,2- a]imidazole To a 20 mL microwave vial, 1H-imidazol-2-amine (600 mg, 7.22 mmol), 2-chloro-1-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (2650 mg, 7.94 mmol) and K2CO3(998 mg, 7.22 mmol) were added followed by the addition of Acetonitrile (15 mL). The mixture was heated in a microwave reactor to 130 °C for 1 h. LCMS analysis showed desired product. Silica gel (1.5 g) was added and the reaction mixture was adsorbed onto silica gel and concentrated in vacuo. This was purified on silica gel (80g column, 2:1 PE:EtOAc) and the desired product fractions were pooled and concentrated to afford a yellow solid, 6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)-1H-imidazo[1,2-a]imidazole (500 mg, 1.328 mmol, 18.4 % yield). LCMS m / z 363.1 [M+H]+, tret= 1.17 min [TFA, 3 min run time]. Step 2 To a 100 mL round bottom flask, 6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)-1H-imidazo[1,2-a]imidazole (1.2g, 3.31 mmol) was dissolved in Dichloromethane (DCM) (25 mL). To this solution di-tert-butyl dicarbonate (0.761 mL, 3.31 mmol) and triethylamine (0.460 mL, 3.31 mmol) were added. The mixture was stirred at room temperature overnight and LCMS analysis showed desired product formation. The reaction mixture was adsorbed onto silica gel (2 g) and concentrated in vacuo. This was purified on silica gel (80g column, 3:1 PE:EtOAc) and the desired fractions were pooled and concentrated to afford a white solid, tert-butyl 6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)- 1H-1,2,4-triazol-5-yl)-1H-imidazo[1,2-a]imidazole-1-carboxylate (1.3 g, 2.75 mmol, 83 % yield). LCMS m / z 463.2 [M+H]+, tret= 1.24 min [TFA]. Step 3 To a 100 mL round bottom flask, tert-butyl 6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)-1H-imidazo[1,2-a]imidazole-1-carboxylate (1.2 g, 2.59 mmol) and NIS (1.751 g, 7.78 mmol) were added. Acetonitrile (25 mL) was added. The reaction mixture was stirred at 50 °C for 2 h and LCMS analysis showed desired product formation. The reaction was quenched with saturated aq Na2S2O3(30 mL) and then extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with saturated aq NaCl (50 mL) and then dried over anhydrous Na2SO4, filtered, and concentrated to afford crude tert-butyl 5-iodo-6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-imidazo[1,2- a]imidazole-1-carboxylate (1.3 g, 2.210 mmol) as a yellow solid. LCMS m / z 533.0 [M+H- tBu]+, tret= 2.52 min [TFA, 4 min run time]. Step 4 To a 20 mL microwave vial was added tert-butyl 5-iodo-6-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-imidazo[1,2-a]imidazole-1-carboxylate (300 mg, 0.510 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1- sulfonamide (Intermediate 2) (184 mg, 0.612 mmol), cesium fluoride (155 mg, 1.020 mmol) and 1,1'-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (83 mg, 0.102 mmol). 1,2-Dimethoxyethane (DME) (20 mL) was added to this mixture, which was heated to 100 °C in a microwave reactor under N2for 30 min. LCMS analysis indicated desired product formation. The solvent was removed under reduced pressure to give the crude product. The crude product was dissolved in 20 mL EtOAc and adsorbed onto silica gel (0.6 g) in vacuo. This was then purified on silica gel (40g column, 5:1 PE:EtOAc) and the desired fractions were pooled and concentrated to afford a yellow solid, tert-butyl 5-(1-(N,N-dimethylsulfamoyl)-1H-imidazol-4-yl)-6-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-imidazo[1,2-a]imidazole-1-carboxylate (300 mg, 0.429 mmol, 84 % yield, 91% purity). LCMS m / z 636.3 [M+H]+, tret= 2.09 min [TFA, 3 min run time]. Step 5 To a 100 mL round bottom flask were added tert-butyl 5-(1-(N,N-dimethylsulfamoyl)-1H- imidazol-4-yl)-6-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H- imidazo[1,2-a]imidazole-1-carboxylate (200 mg, 0.315 mmol) and Trifluoroacetic acid (TFA) (10 mL). The reaction mixture was stirred at 80 °C for 5 h. LCMS analysis indicated desired product formation and consumption of starting material. The solution was concentrated in vacuo, dissolved in DMF (2 mL), and purified by prep-HPLC (SunFire C18 OBD column using an eluent of 10 to 35% ACN:water with 0.05% TFA). The product fractions were collected, concentrated, and lyophilized to give the desired product, 5-(1H-imidazol-5-yl)-6- (3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-imidazo[1,2-a]imidazole, Trifluoroacetic acid salt (60 mg, 0.141 mmol, 44.8 % yield).1H NMR (400 MHz, DMSO-d6) δ ppm 12.16 (s, 1H), 8.84 (s, 1H), 8.28 (s, 1H), 7.83 (s, 1H), 7.51 (s, 1H), 2H signals not observed. LCMS m / z 309.0 [M+H]+, tret= 0.78 min [TFA, 3 min run time]. Example 6 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H-pyrrolo[1,2- a]imidazol-6-ol, Trifluoroacetic acid salt Step 1 To a 50 mL flask containing DCM (20 mL), 4-hydroxypyrrolidin-2-one (1.5 g, 14.84 mmol), tert-butylchlorodimethylsilane (2.68 g, 17.80 mmol), 1H-imidazole (2.020 g, 29.7 mmol) and N,N-dimethylpyridin-4-amine (0.200 mL, 1.484 mmol) were added. The reaction was stirred at rt for 4 h. The solution was treated with water (100 mL), extracted with DCM (3 x 40 mL) and the combined organics were washed with brine (3 x 30 mL), dried over Na2SO4, filtered, and concentrated to afford a crude white solid, 4-((tert-butyldimethylsilyl)oxy)pyrrolidin-2- one (3.4 g, 15.79 mmol). Step 2 In a round-bottom flask, 4-((tert-butyldimethylsilyl)oxy)pyrrolidin-2-one (2 g, 9.29 mmol) was dissolved in Dichloromethane (DCM) (10 mL) and trimethyloxonium tetrafluoroborate (4.12 g, 27.9 mmol) was added. The reaction was stirred at rt for 2 h. LCMS analysis showed desired product formation. The mixture was treated with aq saturated NaHCO3 (20 mL) (dropwise at first). The mixture was extracted with DCM (3 x 100 mL) and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated to afford a crude white solid, 3-((tert-butyldimethylsilyl)oxy)-5-methoxy-3,4-dihydro-2H-pyrrole (1.2 g, 5.19 mmol). LCMS m / z 230.2 [M+H]+, tret= 0.64 min [TFA, 1.2 min run time]. Step 3 In a round-bottom flask with methanol (10 mL), 3-((tert-butyldimethylsilyl)oxy)-5-methoxy- 3,4-dihydro-2H-pyrrole (1.2 g, 5.23 mmol) and NH4Cl (0.839 g, 15.69 mmol) were added. The reaction mixture was stirred at 70 °C for 2 h. The mixture was concentrated and DCM (50 mL) was added. The solid was filtered off, rinsing with DCM. The collected crude white solid, 3-((tert-butyldimethylsilyl)oxy)-3,4-dihydro-2H-pyrrol-5-amine (1.2 g, 5.60 mmol), was used in the next step without purification. Step 4 To a microwave vial containing 3-((tert-butyldimethylsilyl)oxy)-3,4-dihydro-2H-pyrrol-5- amine (100 mg, 0.466 mmol) in Acetonitrile (10 mL) was added 2-chloro-1-(1-(4- methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (171 mg, 0.513 mmol) and triethylamine (0.130 mL, 0.933 mmol). The mixture was heated in a microwave reactor at 130 °C for 1 h. LCMS analysis showed desired product formation. The mixture was concentrated in vacuo and the residue was purified by prep TLC (25% EtOAc in Petroleum Ether) and the desired material was isolated to afford a red oil, 6-((tert- butyldimethylsilyl)oxy)-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)- 6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (20 mg, 0.038 mmol, 8.1 % yield). LCMS m / z 494.2 [M+H]+, tret= 1.44 min [formic acid]. Step 5 To a solution of 6-((tert-butyldimethylsilyl)oxy)-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)- 1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (130 mg, 0.263 mmol) in Acetic Acid (5 mL) was added N-iodosuccinimide (71.1 mg, 0.316 mmol). The mixture was stirred at rt for 1 h. LCMS analysis showed desired product formation. The mixture was quenched with aq saturated Na2S2O3(1 mL) and diluted with water (10 mL). The mixture was extracted with EtOAc (3 x 20 mL) and the combined organics were washed with brine (20 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by prep TLC with an eluent of 15% EtOAc in Petroleum ether. The desired material was isolated as a light red solid, 6-((tert-butyldimethylsilyl)oxy)-3-iodo-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H-pyrrolo[1,2- a]imidazole (60 mg, 0.091 mmol, 34.6 % yield). LCMS m / z 620.1 [M+H]+, tret= 1.48 min [formic acid]. Step 6 To a solution of 6-((tert-butyldimethylsilyl)oxy)-3-iodo-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (55 mg, 0.089 mmol) in 1,2-Dimethoxyethane (DME) (3 mL) was added N,N-dimethyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (29.4 mg, 0.098 mmol), cesium fluoride (27.0 mg, 0.178 mmol) and 1,1'- bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (7.25 mg, 8.88 µmol). This mixture was heated to 120 °C under N2for 1 h. LCMS analysis indicated desired product. The reaction was concentrated in vacuo and the residue was purified by prep TLC with an eluent of 40% EtOAc in Petroleum ether. The desired material was isolated as a light yellow solid, 4-(6-((tert-butyldimethylsilyl)oxy)-2-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H-pyrrolo[1,2- a]imidazol3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (38.4 mg, 0.058 mmol, 64.9 % yield). LCMS m / z 667.3 [M+H]+, tret= 1.50 min [formic acid]. Step 7 4-(6-((tert-butyldimethylsilyl)oxy)-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-N,N-dimethyl-1H-imidazole-1- sulfonamide (36 mg, 0.054 mmol) was dissolved in Trifluoroacetic acid (TFA) (1 mL). The solution was stirred and heated to 80 °C for 1 h. LCMS analysis indicated desired product formation. The mixture was concentrated in vacuo and then redissolved in MeCN (0.5 mL) and DMF (0.6 mL). Solids were filtered off and the filtrate was purified by Prep-HPLC (SunFire C18 OBD column using an eluent of 10% to 30% ACN:water w / 0.05% TFA). The product fractions were collected, concentrated, and then lyophilized to give the desired product as a white solid, 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)- 6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-6-ol, Trifluoroacetic acid salt (12.1 mg, 0.028 mmol, 51.0 % yield).1H NMR (400 MHz, Methanol-d4) δ ppm 8.90 (s, 1H), 7.99 (s, 1H), 5.10-5.15 (m, 1H), 4.52-4.57 (dd, J = 11.6, 5.6 Hz, 1H), 4.16-4.19 (d, J = 11.6 Hz, 1H), 3.35-3.49 (m, 1H), 2.89-2.94 (d, J = 17.2 Hz, 1H), 3H signals not observed. LCMS m / z 326.2 [M+H]+, tret= 0.77 min [formic acid, 3 min run time]. Example 7 6-fluoro-3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine 5-fluoropyridin-2-amine (501 mg, 4.47 mmol) and 2-chloro-1-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (1.513 g, 4.53 mmol) were added to a microwave vial and suspended in 2-Methyltetrahydrofuran (2-MeTHF) (19 mL). The mixture was heated to 110 °C for 16 h. The mixture was concentrated and then purified on Silica gel (80 g; 25-40-100% EtOAc / Hep) and the desired fractions were pooled and concentrated to afford 6-fluoro-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-a]pyridine (849 mg, 1.931 mmol, 43.2 % yield). LCMS m / z 392.1 [M+H]+, tret= 1.20 min [NH4HCO3]. Step 2 6-Fluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine (848mg, 2.167 mmol) was dissolved in Acetonitrile (30 mL) followed by the addition of NBS (400 mg, 2.247 mmol) and TFA (.025 mL, 0.324 mmol). The mixture was stirred at rt for 1 h and most of the solvent was removed in vacuo before being added directly onto Silica gel for purification (80 g; 15-40-50-100% EtOAc / Heptane). The desired fractions were pooled and concentrated to afford 3-bromo-6-fluoro-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (951 mg, 2.022 mmol, 93 % yield). LCMS m / z 470.0, 472.0 [M+H]+(Br isotope pattern), tret= 1.31 min [NH4HCO3]. Step 3 3-Bromo-6-fluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine (453 mg, 0.963 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (418 mg, 1.388 mmol), cesium fluoride (611 mg, 4.02 mmol) and Pd(dppf)Cl2 (96 mg, 0.131 mmol) were added to a microwave vial and suspended in 1,2-Dimethoxyethane (DME) (11 mL). The mixture was heated to 135 °C for 80 min in a microwave reactor. The reaction mixture was added directly to a silica gel plug and then purified on Silica gel (80 g; 25-40-55-100% EtOAc / Hep) and the desired fractions were pooled and concentrated to afford, 4-(6-fluoro-2-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-3-yl)-N,N- dimethyl-1H-imidazole-1-sulfonamide (428 mg, 0.758 mmol, 79 % yield). LCMS m / z 565.0 [M+H]+, tret= 1.35 min [NH4HCO3]. Step 4 4-(6-Fluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (234 mg, 0.415 mmol) was dissolved in TFA (6 mL, 0.415 mmol). The solution was stirred at 65 °C for 4.5 h. The reaction was diluted with DCM and concentrated in vacuo (repeat 3x). The residue was dissolved in 1:1 DCM / EtOAc (5 mL) and concentrated (repeat 2x). The residue began to solidify. The solids were suspended with IPA / EtOAc / aq saturated NaHCO3. The solid was filtered and washed with water, IPA, EtOAc / Ether / Heptane to afford 6-fluoro-3-(1H-imidazol- 5-yl)-2-(3-(trifluoromethyl)- 1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (117 mg, 0.333 mmol, 80 % yield).1H NMR (400 MHz, DMSO-d6) ^ ppm 13.56 - 14.50 (m, 2H), 9.63 (br s, 1H), 8.40 (br s, 1H), 7.95 (d, J=0.98 Hz, 1H), 7.72 (dd, J=10.03, 5.62 Hz, 1H), 7.37 - 7.50 (m, 1H). LCMS m / z 338.0 [M+H]+, tret= 0.42 min [NH4HCO3]. Example 8 2-(3-bromo-1H-1,2,4-triazol-5-yl)-6,8-difluoro-3-(1H-imidazol-5-yl)imidazo[1,2-a]pyridine, trifluoroacetic acid salt A mixture of 3,5-difluoropyridin-2-amine (300 mg, 2.306 mmol) and 1-(3-bromo-1-(4- methoxybenzyl)-1H-1,2,4-triazol-5-yl)-2-chloroethan-1-one (Intermediate 1) (954 mg, 2.77 mmol) in Ethanol (20 mL) in a vial was heated to 90 °C and stirred overnight. The mixture was cooled to rt and solid precipitated. The reaction mixture was filtered and the solid was air-dried overnight to yield crude 2-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)- 6,8-difluoroimidazo[1,2-a]pyridine (330 mg. LCMS m / z 420.1 [M+H]+, tret = 1.19 min [TFA]. Step 2 To a mixture of 2-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-6,8- difluoroimidazo[1,2-a]pyridine (330mg, 0.785 mmol) in Dichloromethane (DCM) (10 mL) was added 1-iodopyrrolidine-2,5-dione (265 mg, 1.178 mmol) at rt and the resulting mixture was stirred at 23 °C. After overnight, LCMS showed a major product peak with almost no SM left. The mixture was washed twice with aq saturated Na2CO3. The organics were dried (Na2SO4), filtered and concentrated, giving crude product which was purified using Combiflash Rf200 with a gradient of 100% DCM to 5% MeOH / DCM. The product fractions were collected and concentrated to afford 2-(3-bromo-1-(4-methoxybenzyl)-1H- 1,2,4-triazol-5-yl)-6,8-difluoro-3-iodoimidazo[1,2-a]pyridine (142 mg) as a white solid. LCMS m / z 545.9 [M+H]+, tret= 1.30 min [TFA]. Step 3 A mixture of 2-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-6,8-difluoro-3- iodoimidazo[1,2-a]pyridine (100 mg, 0.183 mmol) , N,N-dimethyl-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (66.2 mg, 0.220 mmol), K3PO4(117 mg, 0.549 mmol) and PdCl2dppf (14.95 mg, 0.018 mmol) in 1,4-Dioxane (3 mL) and Water (1 mL) in a microwave vial was purged with nitrogen. The mixture was then heated to 110 °C for 30 min in a microwave reactor. Analysis by LCMS indicated a major product peak and no remaining SM. The mixture was concentrated with isolute and the residue was purified using Combiflash Rf200 with a gradient of 100% Hexane to 60% 3:1 EA:EtOH. The product fractions were collected and concentrated to afford 4-(2-(3- bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-6,8-difluoroimidazo[1,2-a]pyridin-3-yl)- N,N-dimethyl-1H-imidazole-1-sulfonamide (100 mg) as a yellow solid. LCMS m / z 595.2, 596.1 [M+H]+, tret= 1.34 min [TFA]. Step 4 A mixture of 4-(2-(3-bromo-1-(4-methoxybenzyl)-1H-1,2,4-triazol-5-yl)-6,8- difluoroimidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (100 mg, 0.169 mmol) in TFA (8 mL, 0.169 mmol) was stirred at 65 °C. After overnight, LCMS showed a major product peak with no remaining SM.The mixture was cooled to rt, TFA was removed under reduced pressure, and the residue was purified using reverse phase HPLC (MDAP Method A) to afford 2-(3-bromo-1H-1,2,4-triazol-5-yl)-6,8-difluoro-3-(1H-imidazol- 5-yl)imidazo[1,2-a]pyridine, trifluoroacetic acid salt (15 mg) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 9.49-9.61 (m, 1H), 8.43 (s, 1H), 8.26 (br s, 1H), 7.77 (t, J=2.03 Hz, 1H), 2H signals not observed. LCMS m / z 367.9 [M+H]+, tret= 0.43 min [TFA]. Example 9 (5-(8-fluoro-3-(1H-imidazol-5-yl)-7-methylimidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-1-yl)methyl dihydrogen phosphate hydrogen chloride salt

[0006] A mixture of 3-fluoro-4-methylpyridin-2-amine (810 mg, 6.42 mmol), 2-chloro-1-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (2571 mg, 7.71mmol) in Ethanol (20 mL) in a microwave vial was heated at 90 °C overnight. The mixture was cooled to rt and solid precipitated. The mixture was filtered and the solid was air-dried overnight to yield 8-fluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)-7-methylimidazo[1,2-a]pyridine (1080 mg, 2.66 mmol, 41%) as a white solid. LCMS m / z 406.2 [M+H]+, tret= 1.24 min [TFA]. Step 2 A mixture of 8-fluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-7- methylimidazo[1,2-a]pyridine (2570 mg, 6.34 mmol) in TFA (15 mL, 195 mmol) was stirred at 65 °C overnight. LCMS showed a new major peak and no SM left. The mixture was then cooled to rt and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-10% MeOH in DCM) to yield 8-fluoro-7-methyl-2-(3-(trifluoromethyl)- 1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (1660 mg, 5.82 mmol, 92%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.66 (d, J=2.79 Hz, 1H), 8.40 (d, J=6.84 Hz, 1H), 6.95 (t, J=6.72 Hz, 1H), 2.26 - 2.39 (m, 3H), 1H signal not observed. Step 3 To a mixture of 8-fluoro-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine (1660 mg, 5.82 mmol) in Dichloromethane (DCM) (40 mL) was added NIS (1440 mg, 6.40 mmol) at rt and the resulting mixture was stirred at 40 °C overnight. LCMS showed a major peak and little SM left. To the reaction mixture was added 3 mL of aq saturated Na2CO3. The mixture was concentrated and the residue purified by silica gel chromatography (0-5% MeOH in DCM) to yield 8-fluoro-3-iodo-7-methyl-2-(3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (2000 mg, 4.86 mmol, 84%) as a yellow solid. LCMS m / z 412.0 [M+H]+, tret= 1.01 min [TFA]. Step 4 A mixture of 8-fluoro-3-iodo-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine (2000 mg, 4.86 mmol), di-tert-butyl (chloromethyl) phosphate (2517 mg, 9.73 mmol), potassium carbonate (2017 mg, 14.59 mmol) and sodium iodide (72.9 mg, 0.486 mmol) in N,N-Dimethylformamide (DMF) (25 mL) in a round-bottom flask was stirred at 50 °C overnight. Analysis by LCMS indicated no remaining SM. To the reaction mixture were added water and EA. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organics were concentrated and purified by silica gel chromatography (0-70% Ethyl Acatate in Hexane) to yield di-tert-butyl ((5-(8-fluoro-3-iodo-7-methylimidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-1H-1,2,4-triazol- 1-yl)methyl) phosphate (1290 mg, 2.04 mmol, 42%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.34 (d, J=7.10 Hz, 1H), 7.14 (s, 1H), 6.63 (d, J=11.15 Hz, 2H), 2.38 (d, J=2.28 Hz, 3H), 1.24 - 1.32 (m, 18H). LCMS m / z 634.2 [M+H]+, tret= 1.32 min [TFA]. Step 5 A mixtureof di-tert-butyl ((5-(8-fluoro-3-iodo-7-methylimidazo[1,2-a]pyridin-2-yl)-3- (trifluoromethyl)-1H-1,2,4-triazol-1-yl)methyl) phosphate (1290 mg, 2.037 mmol), N,N- dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (736 mg, 2.444 mmol), PdCl2dppf (166 mg, 0.204 mmol) and CsF (774 mg, 5.09 mmol) in 1,2-Dimethoxyethane (DME) (10 mL) in a microwave vial was purged with nitrogen. The reaction mixture was then heated at 115 °C for 30 min using a microwave. The reaction mixture was concentrated and the residue purified by silica gel chromatography (0-10% MeOH in DCM) to yield di-tert-butyl ((5-(3-(1-(N,N- dimethylsulfamoyl)-1H-imidazol-4-yl)-8-fluoro-7-methylimidazo[1,2-a]pyridin-2-yl)-3- (trifluoromethyl)-1H-1,2,4-triazol-1-yl)methyl) phosphate (1300 mg,1.91 mmol, 94%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.98 (d, J=7.35 Hz, 1H), 8.54 (d, J=1.27 Hz, 1H), 8.44 (d, J=1.52 Hz, 1H), 7.09 (s, 1H), 6.61 (d, J=11.66 Hz, 2H), 2.84 - 2.90 (m, 6H), 2.39 (d, J=2.03 Hz, 3H), 1.24 (s, 18H). LCMS m / z 681.3 [M+H]+, tret= 1.35 min [TFA]. Step 6 A mixture of di-tert-butyl ((5-(3-(1-(N,N-dimethylsulfamoyl)-1H-imidazol-4-yl)-8-fluoro-7- methylimidazo[1,2-a]pyridin-2-yl)-3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)methyl) phosphate (1300 mg, 1.910 mmol), and 4N HCl in Dioxane (20 mL, 80 mmol) in Dichloromethane (DCM) (20 mL) in a round-bottom flask was stirred at rt overnight. LCMS showed a major product peak and no remaining SM. The reaction mixture was concentrated. MeOH (10 mL) was added to dissolve the residue, then diethyl ether (30 mL) was added slowly until the mixture became cloudy. The final mixture was allowed to sit at rt and solid precipitated. The mixture was filtered and the solid was air-dried overnight to yield (5-(8-fluoro-3-(1H-imidazol-5-yl)-7-methylimidazo[1,2-a]pyridin-2-yl)-3- (trifluoromethyl)-1H-1,2,4-triazol-1-yl)methyl dihydrogen phosphate hydrochloride salt (520 mg, 0.99 mmol, 52%) as an off-white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.90 (d, J=7.10 Hz, 1H), 8.37 (s, 1H), 8.08 (d, J=1.27 Hz, 1H), 7.05 (t, J=6.84 Hz, 1H), 6.42 (d, J=11.41 Hz, 2H), 2.34 - 2.41 (m, 3H), 3H signals not observed. LCMS m / z 462.2 [M+H]+, tret= 0.50 min [TFA]. Example 10 6-bromo-3-(1H-imidazol-5-yl)-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine, 2 trifluoroacetic acid salt A mixture of 5-bromo-4-methylpyridin-2-amine (1g, 5.35 mmol), 2-chloro-1-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (1.784 g, 5.35 mmol),and sodium bicarbonate (0.494 g, 5.88 mmol) in Ethanol (30 mL) was heated to 85 °C and stirred overnight. The reaction mixture was cooled to 0°C, the precipitate was filtered off, and the solid was washed with cold EtOH (2x), water (2x), and was dried to afford 6-bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)-7-methylimidazo[1,2-a]pyridine (1.328g,2.85 mmol, 53.3% yield) as an off-white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (s, 1H), 8.56 (s, 1H), 7.80 (s,1H), 7.30-7.40 (m, 2H), 6.84-6.94 (m, 2H), 6.12 (s, 2H), 3.72 (s, 3H), 2.44 (s, 3H). LCMS m / z 466.12, 468.10 [M+H]+; tret= 1.39 min [NH4HCO3]. Step 2 A solution of 6-bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-7- methylimidazo[1,2-a]pyridine (1.322 g, 2.84 mmol), NIS (0.829 g, 3.69 mmol), and TFA (10.92 µl, 0.142 mmol) in Dichloromethane (DCM) (25mL) was stirred at room temperature over the weekend. The mixture was washed with water (2x), 10% aq Na2SO3(2x), water (2x), brine (1x), dried over sodium sulfate and concentrated to afford 6-bromo-3-iodo-2-(1- (4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-7-methylimidazo[1,2- a]pyridine (1.579 g, 2.67 mmol, 94 % yield) as a pale yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.64 (s, 1H), 7.86 (s, 1H), 7.26-7.38 (m, 2H), 6.85-6.95 (m, 2H), 5.99 (s, 2H), 3.72 (s, 3H), 2.49 (s, 3H). LCMS m / z 592.06, 594.04 [M+H]+; tret= 1.51 min [NH4HCO3]. Step 3 A mixture of 6-bromo-3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)-7-methylimidazo[1,2-a]pyridine (0.666 g, 1.125 mmol), N,N-dimethyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (0.423 g, 1.406 mmol), PdCl2(dppf) (0.123 g, 0.169 mmol), and CsF (0.342 g, 2.249 mmol) in 1,2- Dimethoxyethane (DME) (10.5 mL) was heated in a microwave reactor at 110 °C for 75 min. The mixture was filtered and the filtrate was concentrated. The off-white solid was washed with AcN, DCM, and concentrated to afford 206 mg of 4-(6-bromo-2-(1-(4-methoxybenzyl)- 3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-7-methylimidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl- 1H-imidazole-1-sulfonamide as an off-white solid. The solid that was filtered off the reaction mixture was then washed with water (3x) and dried to afford 257 mg more of 4-(6-bromo-2- (1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-7-methylimidazo[1,2- a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide. A third batch of product was separated (filtered) from the filtrate upon some evaporation. The combined batches afforded 778 mg of product (quantitative).1H NMR (400 MHz, DMSO-d6) δ ppm 9.56 (s, 1H), 8.53 (d, J=0.98 Hz, 1H), 8.42 (d, J=0.98 Hz, 1H), 7.90 (s, 1H), 7.33-7.44 (m, 2H), 6.80-6.95 (m, 2H), 5.96 (s, 2H), 3.72 (s, 3H), 2.87 (s, 6H), 2.49 (s, 3H). LCMS m / z 639.14, 641.12 [M+H]+; tret= 1.52 min [NH4HCO3]. Step 4 A solution of 4-(6-bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)- 7-methylimidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (17 mg, 0.027 mmol) in Trifluoroacetic acid (TFA) (4 mL) was heated and stirred at 75 °C overnight. The TFA was evaporated and the residue purified with reverse phase HPLC (MDAP Method E) to afford 6-bromo-3-(1H-imidazol-5-yl)-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-a]pyridine, 2 trifluoroacetic acid salt (12 mg, 0.019 mmol, 70.5 % yield) as a white lyophile.1H NMR (400 MHz, DMSO-d6) δ ppm 9.33 (br s, 1H), 8.80 (br s, 1H), 8.34 (d, J=0.98 Hz, 1H), 7.79 (d, J=0.98 Hz, 1H), 2.50 (br s, 3H), 2H signals not observed. LCMS m / z 411.94, 413.94 [M+H]+; tret= 0.56 min [TFA]. Example 11 3-(1H-imidazol-5-yl)-5,7-dimethyl-6-phenyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine,1.5 Trifluoroacetic acid salt A mixture of 5-bromo-4,6-dimethylpyridin-2-amine (931 mg, 4.63 mmol), 2-chloro-1-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (2318 mg, 6.95 mmol), and sodium bicarbonate (661 mg, 7.87 mmol) in Ethanol (30 mL) was heated to 85 °C and stirred overnight. The reaction mixture was cooled to 0 °C, the precipitate was filtered off, and the solid was washed with cold EtOH (2x), water (2x), and dried to afford 6-bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)- 5,7-dimethylimidazo[1,2-a]pyridine (940 mg, 1.957 mmol, 42.3 % yield) as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.64 (s, 1H), 7.72 (s, 1H), 7.30-7.39 (m, 2H), 6.85- 6.94 (m, 2H), 6.15 (s, 2H), 3.71 (s, 3H), 2.88 (s, 3H), 2.48 (s, 3H). LCMS m / z 466.12, 468.10 [M+H]+; tret= 1.47 min [NH4HCO3]. Step 2 A mixture of 6-bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,7- dimethylimidazo[1,2-a]pyridine (938 mg, 1.953 mmol), NIS (571 mg, 2.54 mmol), and TFA (7.52 µL, 0.098 mmol) in Dichloromethane (DCM) (20 mL) was stirred at room temperature overnight. The temperature was increased to 40 °C, and the reaction mixture was stirred for 6 h. The reaction was still not complete, therefore more NIS (114mg, 0.51 mmol) was added and the reaction mixture was stirred overnight at 40 °C. TFA (20 µL) was added and the stirring continued for 1 day. The dark brown mixture was then washed with water (1x), 10% aq Na2SO3(2x), water (2x), brine (1x), dried over sodium sulfate, and was concentrated. The residue was purified on silica gel (40 g Isco RediSep Rf Gold column, eluting with 0- 30% (EtOAC / EtOH 3 / 1) in heptane) to afford 6-bromo-3-iodo-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,7-dimethylimidazo[1,2-a]pyridine (996 mg, 1.643 mmol, 84 % yield) as a yellow solid. LCMS m / z 606.01, 608.08 [M+H]+; tret= 1.44 min [TFA]. Step 3 A mixture of 6-bromo-3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)-5,7-dimethylimidazo[1,2-a]pyridine (50 mg, 0.082 mmol), N,N-dimethyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (37.3 mg, 0.124 mmol), PdCl2(dppf) (9.05 mg, 0.012 mmol), CsF (25.06 mg, 0.165 mmol), and DME (1.5 mL) was heated at 130 °C for 1.5 h. The reaction mixture contained ~41% desired product by LCMS. Four additional 50 mg scale reactions were run, varying the temperature (110 – 150 °C) and base (K3PO4) with similar results (reaction not to completion). All five reaction mixtures were combined and used in the next step directly. Step 4 To the combined reaction mixtures 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (168 mg, 0.823 mmol), cesium carbonate (402 mg, 1.235 mmol), and PdCl2(dppf) (45.2 mg, 0.062 mmol) was added. The reaction mixture was heated in a microwave reactor at 120 °C for 1.5 h. The mixture was filtered through Celite and was concentrated. The residue was partitioned between water and EtOAc, and the organic layer was washed with brine (1x) and then evaporated. The residue was purified with reverse phase HPLC (MDAP Method J) to afford 4-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,7- dimethyl-6-phenylimidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (75 mg, 0.115 mmol, 28.0 % yield). LCMS m / z 651.0 [M+H]+; tret= 1.36 min [TFA]. Step 5 A solution of 4-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,7- dimethyl-6-phenylimidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (75 mg, 0.115 mmol) in Trifluoroacetic acid (TFA) (4 mL) was heated and stirred at 75 °C overnight. The TFA was evaporated and the residue purified with reverse phase HPLC (MDAP Method E) to afford 3-(1H-imidazol-5-yl)-5,7-dimethyl-6-phenyl-2-(3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine, 1.5 Trifluoroacetic acid salt (29 mg, 0.049 mmol, 42.3 % yield) as a white lyophile.1H NMR (DMSO-d6) δ ppm 9.21 (s, 1H), 7.96 (d, J=1.0 Hz, 1H), 7.70 (s,1H), 7.44-7.56 (m, 3H), 7.24-7.28 (m, 2H), 2.09 (s, 3H), 1.99 (s, 3H), 2H signals not observed. LCMS m / z 424.3 [M+H]+; tret= 0.66 min [TFA]. Example 12 7-Bromo-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine A mixture of 4-bromopyridin-2-amine (10 g, 57.8 mmol), ethyl 4-bromo-3-oxobutanoate (14.50 g, 69.4 mmol) and sodium carbonate (6.13 g, 57.8 mmol) in ethanol (100 mL) was refluxed at 85 °C for 16 h. The reaction was cooled to room temperature and solvent was removed under reduced pressure. Purification of the residue by column chromatography on silica gel (2:1 to 2:3 petroleum ether / ethyl acetate) afforded ethyl 7-bromoimidazo[1,2- a]pyridine-2-carboxylate (11 g, 70.7%) as a light yellow solid.1H NMR (400 MHz, DMSO- d6) δ ppm 8.58 (s, 1H), 8.53 (d, J = 8.0 Hz, 1H), 7.98 (s, 1H), 7.19 (dd, J = 8.0, 1.6 Hz, 1H), 4.32 (q, J = 6.8 Hz, 2H), 1.32 (t, J = 7.2 Hz, 3H). LCMS m / z 270.8 [M+H]+, tret= 1.34 min [formic acid, 2.5 min run time]. Step 2 A sealed tube was charged with a mixture of ethyl 7-bromoimidazo[1,2-a]pyridine-2- carboxylate (10 g, 37.2 mmol) and 7 M ammonia in methanol (220 mL, 1540 mmol) and heated at 65 °C for 18 h. The solvent was removed in vacuo to afford 7-bromoimidazo[1,2- a]pyridine-2-carboxamide (9 g, 81%) as a brown solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.55 (d, J = 7.2Hz, 1H), 8.37 (s, 1H), 7.90 (d, J = 0.8 Hz, 1H), 7.73 (s, 1H), 7.47 (s, 1H), 7.16 (dd, J = 7.4, 1.8Hz, 1H). LCMS m / z 239.8, 241.8 [M+H]+, tret= 1.16 min [formic acid, 2.5 min run time]. Step 3 A solution of 7-bromoimidazo[1,2-a]pyridine-2-carboxamide (9 g, 30.0 mmol) in pyridine (180 mL) was cooled to -20 °C and neat 2,2,2-trifluoroacetic anhydride (15.75 g, 75.0 mmol) was added dropwise. After complete addition, the reaction was allowed to warm to rt and stirred for 1 h. The reaction mixture was diluted with EtOAc and washed with aqueous 1.0 M aq NaOH. The aqueous layer was further extracted with EtOAc (3 x 300mL) and the combined organics dried over MgSO4. Removal of the solvent in vacuo afforded 7- bromoimidazo[1,2-a]pyridine-2-carbonitrile (7.5 g, 96%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.80 (s, 1H), 8.58 (d, J = 7.2 Hz, 1H), 8.05 (s, 1H), 7.27 (dd, J = 7.4, 1.4 Hz, 1H). LCMS m / z 222.1 [M+H]+, tret= 1.38 min [formic acid, 2.5 min run time]. Step 4 To a solution of 7-bromoimidazo[1,2-a]pyridine-2-carbonitrile (13 g, 58.5 mmol) in methanol (200 mL) at room temperature was added hydrazine hydrate (117 g, 2342 mmol). The reaction was stirred at room temperature for 18 h then the resulting suspension was filtered. The collected solids were washed with EtOAc then the filtrate was concentrated under reduced pressure. The previously collected solids were combined with the concentrate then dried under vacuum to afford 7-bromoimidazo[1,2-a]pyridine-2-carboximidhydrazide (12 g, 81%) as a beige solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.50 (d, J = 7.2 Hz, 1H), 8.07 (s, 1H), 7.83 (s, 1H), 7.08 (dd, J = 7.2, 1.8 Hz, 1H), 5.58 (s, 2H), 5.13 (s, 2H). LCMS m / z 253.8 [M+H]+, tret= 1.01 min [formic acid, 2.5 min run time]. Step 5 To a solution of 7-bromoimidazo[1,2-a]pyridine-2-carboximidhydrazide (12 g, 47.2 mmol) in THF (250 mL) was added 2,2,2-trifluoroacetic anhydride (24.80 g, 118 mmol) dropwise at room temperature. After complete addition, the reaction was heated at 90 °C for 18 h. The reaction mixture was then cooled to room temperature and the solvent was removed under reduced pressure to yield a residue that was washed with DCM (3 X 200 mL) to afford 7- bromo-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (12 g, 77%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 15.63 (s, 1H), 8.65 (s, 1H), 8.62 (d, J = 7.2 Hz, 1H), 8.00 (s, 1H), 7.24 (dd, J = 7.2, 1.6 Hz, 1H). LCMS m / z 331.7, 333.7 [M+H]+, tret= 1.45 min [formic acid, 2.5 min run time]. Step 6 A three-necked round-bottom flask equipped with a magnetic stir bar, thermocouple, nitrogen bleed, and cooling ice bath was charged with a solution of 7-bromo-2-(3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (12 g, 36.1 mmol) in acetonitrile (220 mL). To the stirring solution at 0 °C was added N-iodosuccinimide (9.76 g, 43.4 mmol) portion-wise. The resulting yellow suspension was allowed to warm to room temperature and stirred for 18 h. The precipitate was gathered by filtration, washed with acetonitrile (3 x 80 mL), and purified by column chromatography on silica gel (2:1 to 3:4 petroleum ether / ethyl acetate) to afford 7-bromo-3-iodo-2-(3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-a]pyridine (10 g, 60.4%) as a white solid.1H NMR (400 MHz, DMSO- d6) δ ppm 15.67 (s, 1H), 8.46 (d, J = 7.6 Hz, 1H), 8.04 (s, 1H), 7.31 (dd, J = 7.2, 1.6 Hz, 1H). LCMS m / z 457.5, 459.5 [M+H]+, tret= 1.59 min [formic acid, 2.5 min run time]. Step 7 A mixture of 7-bromo-3-iodo-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine (3 g, 6.55 mmol), (1H-pyrazol-4-yl)boronic acid (1.099 g, 9.83 mmol), PdCl2(PPh3)2(1.839 g, 2.62 mmol) and K2CO3(2.72 g, 19.65 mmol) in 1,4-dioxane (50 mL) and water (5 mL) was stirred at 110 °C under Nitrogen for 24 h. The reaction mixture was cooled to rt and concentrated under reduced pressure to yield a residue that was purified by column chromatography on silica gel (20:1 to 0:100 petroleum ether / ethyl acetate) to give a crude solid that was further purified by prep-HPLC to afford 7-bromo-3-(1H-pyrazol- 4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (30 mg 1.2%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 15.50 (s, 1H), 8.39 (d, J = 7.6 Hz, 1H), 8.21 (s, 2H), 8.02 (s, 1H), 7.18 (dd, J = 7.2, 1.6 Hz, 1H), 1H signal not observed. LCMS m / z 398.1, 400.0 [M+H]+, tret= 0.82 min [formic acid]. Example 13 3-(1H-Imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine

[0007] To a mixture of pyridin-2-amine (203 mg, 2.158 mmol) and 2-chloro-1-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (600 mg, 1.798 mmol) in 1-butanol (10 mL) was added sodium bicarbonate (166 mg, 1.978 mmol). The reaction mixture was heated at 80 °C for 18 h and then cooled to room temperature. The reaction mixture was diluted with water and extracted with EtOAc. The combined extracts were evaporated to a residue that was suspended in a mixture of MeOH / water (1:4 v / v) to give a suspension that was filtered. The collected solids were rinsed well with water and dried under suction to afford 2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (500 mg, 74.5%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.73 (s, 1H), 8.64 (d, J = 6.84 Hz, 1H), 7.76 (d, J = 9.12 Hz, 1H), 7.42 (ddd, J = 9.06, 6.91, 1.01 Hz, 1H), 7.36 (d, J = 8.62 Hz, 2H), 7.04- 7.13 (m, 1H), 6.90 (d, J = 8.62 Hz, 2H), 6.16 (s, 2H), 3.71 (s, 3H). LCMS m / z 374.1 [M+H]+, tret= 1.09 min [TFA]. Step 2 To a solution of 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine (500 mg, 1.339 mmol) in DCM (20 mL) at 35 °C was added N- iodosuccinimide (542 mg, 2.411 mmol). Stirring was continued at the same temperature for 12 h then the reaction was diluted with saturated aq NaHCO3and extracted with DCM. The organic extracts were evaporated to a residue that was purified by silica gel chromatography (0-35% EtOAc / hexanes) to afford 3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (530 mg, 75%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.54 (d, J = 6.5 Hz, 1H), 7.80 (d, J = 8.9 Hz, 1H), 7.52 (ddd, J = 9.1, 6.8, 1.3 Hz, 1H), 7.36-7.28 (m, 2H), 7.22 (td, J = 6.8, 1.3 Hz, 1H), 6.92-6.87 (m, 2H), 6.03 (s, 2H), 3.71 (s, 3H). LCMS m / z 500.1 [M+H]+, tret= 1.29 min [TFA]. Step 3 A microwave reaction vial with stir bar was charged with a suspension of 3-iodo-2-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (520 mg, 1.042 mmol) and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- imidazole-1-sulfonamide (Intermediate 2) (408 mg, 1.354 mmol) in DME (10 mL). To the mixture were added Pd(dppf)Cl2-CH2Cl2adduct (85 mg, 0.104 mmol) and CsF (316 mg, 2.083 mmol). The vial was sealed with an aluminum crimp cap then heated with stirring at 110 °C for 35 min. The reaction mixture was filtered through celite which was rinsed with MeOH. The filtrate was evaporated to a brown residue that was triturated with MeOH / Et2O (1:8 v / v) to afford crude 4-(2-(1-(4-Methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (700 mg) as a tan solid, which was used without purification.1H NMR (400 MHz, DMSO-d6) δ ppm 9.17 (d, J = 7.4 Hz, 1H), 8.51 (s, 1H), 8.34 (s, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.54 (br. d, J = 16.0 Hz, 1H), 7.38 (d, J = 8.6 Hz, 2H), 7.18 (t, J = 6.5 Hz, 1H), 6.90 (d, J = 8.6 Hz, 2H), 5.97 (s, 2H), 3.72 (s, 3H), 2.86 (s, 6H). LCMS m / z 547.2 [M+H]+, tret= 1.28 min [TFA]. Step 4 A microwave reaction vial with stir bar was charged with a suspension of 4-(2-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-3-yl)-N,N- dimethyl-1H-imidazole-1-sulfonamide (700 mg, 1.281 mmol) in TFA (20 mL). The vial was sealed with an aluminum crimp cap then heated with stirring at 72 °C for 3 days. The reaction mixture was cooled to rt and evaporated under reduced pressure to an oil that was evaporated twice from DCM. The resulting residue was purified by reverse phase HPLC (MDAP Method B). The fractions of interest were combined, made neutral with ammonium hydroxide, and evaporated under reduced pressure to afford 3-(1H-imidazol-4-yl)-2-(3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (150 mg, 35.6%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 15.73-15.33 (br s, 1H), 12.85-12.47 (br s, 1H), 9.64 (d, J = 6.3 Hz, 1H), 8.39 (s, 1H), 8.01 (d, J = 1.3 Hz, 1H), 7.71 (d, J = 9.1 Hz, 1H), 7.45 (ddd, J = 9.1, 6.6, 1.3 Hz, 1H), 7.09 (td, J = 6.8, 1.3 Hz, 1H). LCMS m / z 320.1 [M+H]+, tret = 0.49 min [formic acid]. Example 14 8-Fluoro-3-(1H-imidazol-4-yl)-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine trifluoroacetic acid salt To a mixture of 3-fluoro-4-methylpyridin-2-amine (431 mg, 3.42 mmol) and 2-chloro-1-(1- (4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (950 mg, 2.85 mmol) in 1-butanol (10 mL) was added sodium bicarbonate (263 mg, 3.13 mmol). The reaction mixture was heated with stirring at 85 °C for 18 h. The resulting suspension was cooled and filtered, and the collected solids were rinsed with a mixture of MeOH and water (1:1 v / v). The solids were triturated from MeOH / EtOAc (8:1 v / v) to afford 8-fluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-7- methylimidazo[1,2-a]pyridine (270 mg, 22.2%) as a white solid.1H NMR (400 MHz, DMSO- d6) δ ppm 8.75 (d, J = 2.8 Hz, 1H), 8.41 (d, J = 6.8 Hz, 1H), 7.38 (d, J = 8.9 Hz, 2H), 6.99 (t, J = 6.6 Hz, 1H), 6.91 (d, J = 8.9 Hz, 2H), 6.12 (s, 2H), 3.71 (s, 3H), 2.35 (d, J = 2.3 Hz, 3H). LCMS m / z 406.2 [M+H]+, tret= 1.28 min [TFA]. Step 2 To a solution of 8-fluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-7- methylimidazo[1,2-a]pyridine (270 mg, 0.666 mmol) in DCM (10 mL) was added N- iodosuccinimide (225 mg, 0.999 mmol). The reaction mixture was heated with stirring at 30 °C for 18 h. The solvent was evaporated and the resulting yellow residue was triturated with MeOH / water (1:1 v / v) to afford 8-fluoro-3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)- 1H-1,2,4-triazol-5-yl)-7-methylimidazo[1,2-a]pyridine (300 mg, 81%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.33 (d, J = 6.8 Hz, 1H), 7.39 – 7.32 (m, 2H), 7.14 (t, J = 6.7 Hz, 1H), 6.92 – 6.88 (m, 2H), 5.99 (s, 2H), 3.71 (s, 3H), 2.39 (d, J = 2.3 Hz, 3H). LCMS m / z 532.3 [M+H]+, tret= 1.38 min [TFA]. Step 3 To a solution of 8-fluoro-3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol- 5-yl)-7-methylimidazo[1,2-a]pyridine (580 mg, 1.092 mmol) and N,N-dimethyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (395 mg, 1.310 mmol) in DME (20 mL) were added Pd(dppf)Cl2-CH2Cl2adduct (89 mg, 0.109 mmol) and CsF (332 mg, 2.184 mmol). The reaction mixture was heated at 110 °C for 45 min and then cooled and filtered. The solids were washed with MeOH and dried under suction to afford 4-(8-fluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)-7-methylimidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (313 mg) as a white solid, which was used without purification.1H NMR (400 MHz, DMSO-d6) δ ppm 8.98 (br. d, J = 7.1 Hz, 1H), 8.52 (s, 1H), 8.38 (s, 1H), 7.43 (br. d, J = 8.6 Hz, 2H), 7.09 (br. t, J = 6.7 Hz, 1H), 6.91 (br. d, J = 8.1 Hz, 2H), 5.93 (s, 2H), 3.72 (s, 3H), 2.86 (s, 6H), 2.40 (br s, 3H). LCMS m / z 579.3 [M+H]+, tret= 1.40 min [TFA]. Step 4 A solution of 4-(8-fluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-7- methylimidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (313 mg, 0.541 mmol) in TFA (5 mL) was heated at 70 °C for 18 h. The reaction was evaporated under reduced pressure to a residue that was purified by reverse phase HPLC (MDAP Method E). The fractions of interest were combined and concentrated under reduced pressure to afford 8-fluoro-3-(1H-imidazol-4-yl)-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-a]pyridine trifluoroacetic acid salt (30 mg, 11.3%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 15.89 (br s, 1H), 12.66 (br s, 1H), 9.42 (br d, J = 7.1 Hz, 1H), 8.42 (s, 1H), 8.01 (d, J = 1.3 Hz, 1H), 7.41 – 7.22 (m, 1H), 6.99 (t, J = 7.0 Hz, 1H), 2.37 (d, J = 2.3 Hz, 3H). LCMS m / z 352.0 [M+H]+, tret= 0.59 min [formic acid]. Example 15 3-(1H-Imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine-8-carbonitrile

[0008] A solution of 3-(trifluoromethyl)-1H-1,2,4-triazol-5-amine (100 g, 658 mmol) in acetic acid (320 mL) was stirred at 5 °C and then treated with hydrochloric acid (80 mL, 960 mmol). To this was added dropwise a solution of sodium nitrite (54.4 g, 789 mmol) in water (320 mL) and the reaction mixture was stirred for 20 min. The resulting diazonium salt solution was added dropwise to a stirring solution of copper(II) bromide (294 g, 1315 mmol) in water (1.0 L) chilled to 0 °C, maintaining the internal temperature below 5 °C. The reaction mixture was then allowed to warm to room temperature with stirring over 2 h. The reaction mixture was diluted with water and extracted with ethyl acetate (3x). The organic extracts were washed with water (2x) and brine, dried (Mg2SO4), and evaporated to a wet oil that was azeotroped from ethanol to afford 5-bromo-3-(trifluoromethyl)-1H-1,2,4-triazole (118.5 g, 83%) as a crude oil. LCMS m / z 215.9, 217.9 [M+H]+, tret= 0.68 min [TFA]. Step 2 To a vigorously stirring suspension of potassium carbonate (151 g, 1093 mmol) and 5- bromo-3-(trifluoromethyl)-1H-1,2,4-triazole (118 g, 546 mmol) in 2-butanone (500 mL) at 55 °C was added a solution of chloromethyl methyl ether (49.8 mL, 656 mmol) in butanone (150 mL) over 10 min. The reaction mixture was stirred at the same temperature for 1 h then was cooled, filtered, and evaporated under reduced pressure to afford crude 5-bromo- 1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazole (95 g, 66.9%) as a clear oil. The mixture of isomers was used without purification.1H NMR (400 MHz, CDCl3) δ ppm 3.47 - 3.54 (m, 3H) 5.52 - 5.63 (m, 2H). LCMS m / z 260.1, 262.1 [M+H]+, tret= 0.86 min [TFA]. Step 3 To a stirred solution of 5-bromo-1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazole (208 g, 800 mmol) in 2-methyltetrahydrofuran (1600 mL) under nitrogen at -10 °C was added dropwise isopropylmagnesium chloride lithium chloride complex in THF (1.3M, 800 mL, 1040 mmol) over 30 min. The dark mixture was stirred at -10 °C for 30 min than was treated with a solution of 2-chloro-N-methoxy-N-methylacetamide (143 g,1040 mmol) in 2- methyltetrahydrofuran (800mL), keeping the internal temperature below -5 °C. The reaction mixture was allowed to warm to ambient temperature over 30 min, then was quenched with dilute ammonium chloride solution (1000 mL). The mixture was separated, and the aqueous solution was extracted twice with EtOAc. The combined organic extracts were washed with water and brine, dried (Mg2SO4) and concentrated under vacuum. Purification by flash chromatography on silica gel (10% EtOAc in heptane) afforded 2-chloro-1-(1- (methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (92.2 g, 44.7%).1H NMR (400 MHz, CDCl3) δ ppm 5.93 (s, 2H), 4.99 (s, 2H), 3.50 (s, 3H). LCMS m / z 515.4, 517.2 [2M+H]+, tret= 0.82 min [NH4HCO3]. Step 4 A suspension of 3-bromopyridin-2-amine (15 g, 87 mmol), sodium bicarbonate (5 g, 59.5 mmol), and 2-chloro-1-(1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1- one (20.0 g, 78 mmol) in 1-butanol (200 mL) was stirred at 90 °C for 1 h, then at 60 °C for 18 h. The reaction mixture was filtered hot to remove the sodium bicarbonate solid and concentrated. The residue was taken up into dichloromethane and adsorbed onto silica gel. Purification by flash chromatography on silica gel (0-15% EtOAc in DCM) gave 8-bromo-2- (1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (11.0 g, 37.7%).1H NMR (400 MHz, CDCl3) δ ppm 8.44 (s, 1H), 8.21 (dd, J = 6.6, 1.0 Hz, 1H), 7.60 (dd, J = 7.4, 1.0 Hz, 1H), 6.84 (t, J = 6.9 Hz, 1H), 6.37 (s, 2H), 3.58 (s, 3H). LCMS m / z 376.0, 378.0 [M+H]+, tret= 1.04 min [formic acid]. Step 5 A mixture of 8-bromo-2-(1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine (10.6 g, 28.2 mmol) and N-iodosuccinimide (7.61 g, 33.8 mmol) in chloroform (200 mL) was stirred at 75 °C for 24 h. The reaction was not yet complete, so additional N-iodosuccinimide was added and the reaction was heated until completion. The reaction mixture was cooled, diluted with chloroform, and washed with water. The phases were separated, and the aqueous phase was extracted with chloroform. The combined organics were washed with 15% aq sodium thiosulfate solution, dried (Mg2SO4), and evaporated under reduced pressure. The resulting solid was slurried from diethyl ether, collected, washed with diethyl ether and hexanes, and dried to give 8-bromo-3-iodo-2-(1- (methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (12.0 g, 85%).1H NMR (400 MHz, CDCl3) δ ppm 8.35 (dd, J = 6.8, 1.0 Hz, 1H), 7.69 (dd, J = 7.4, 1.0 Hz, 1H), 6.98 (t, J = 7.1 Hz, 1H), 6.33 (s, 2H), 3.55 (s, 3H). LCMS m / z 501.9, 504.0 [M+H]+, tret= 1.21 min [formic acid]. Step 6 A mixture of 8-bromo-3-iodo-2-(1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine (12 g , 23.9 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (12.48 g, 41.4 mmol), potassium phosphate tribasic (7.44 g, 35.1 mmol) and Pd(dppf)Cl2(1.399 g, 1.912 mmol) in 1,4-dioxane (200 mL) was flushed with nitrogen and heated at 120 °C for 24 h. The reaction mixture was cooled, filtered, and evaporated to a residue that was purified by flash chromatography on silica gel (15-45% ethyl acetate in heptane) to afford 4-(8-bromo-2-(1- (methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-3-yl)-N,N- dimethyl-1H-imidazole-1-sulfonamide (7.1 g, 54.1%).1H NMR (400 MHz, CDCl3) δ ppm 9.34 (dd, J = 7.1, 1.0 Hz, 1H), 8.61 (d, J = 1.3 Hz, 1H), 8.10 (d, J = 1.3 Hz, 1H), 7.67 (dd, J = 7.4, 1.0 Hz, 1H), 6.88 (t, J = 7.1 Hz, 1H), 6.38 (s, 2H), 3.56 (s, 3H), 3.03 (s, 6H). LCMS m / z 549.2, 551.2 [M+H]+, tret= 1.25 min [TFA]. Step 7 A mixture of 4-(8-bromo-2-(1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (820 mg, 1.493 mmol), tris(dibenzylideneacetone)dipalladium(0) (137 mg, 0.149 mmol), 1,1'- bis(diphenylphosphino)ferrocene (83 mg, 0.149 mmol), and zinc cyanide (175 mg, 1.493 mmol) in DMF (12 mL) was flushed with nitrogen and heated at 120 °C for 24 h. The reaction mixture was cooled, diluted with water and extracted with DCM. The organic extracts were filtered through Celite and evaporated to a residue that was purified by flash chromatography on silica gel (40 g column using an eluent of 0-50% ethyl acetate in heptane) to give 4-(8-cyano-2-(1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (356 mg, 48.1%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm 9.47 (dd, J = 7.2, 1.1 Hz, 1H), 8.56 (d, J = 1.3 Hz, 1H), 8.49 (d, J = 1.3 Hz, 1H), 8.27 (dd, J = 7.1, 1.0 Hz, 1H), 7.32 (t, J = 7.1 Hz, 1H), 6.13 (s, 2H), 3.42 (s, 3H), 2.89 (s, 6H). LCMS m / z 496.1 [M+H]+, tret= 1.14 min [formic acid]. Step 8 A mixture of 4-(8-cyano-2-(1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (45 mg, 0.091 mmol) and 3M HCl in CPME (5.0 mL, 15.00 mmol) was stirred at 60 °C for 18 h. The reaction mixture was evaporated under reduced pressure and the resulting residue was purified by reverse phase HPLC (0-99% acetonitrile in water w / 0.1% formic acid) to afford 3-(1H- imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine-8- carbonitrile (8 mg, 25.3%).1H NMR (400 MHz, DMSO-d6) δ ppm 15.61 (br s, 1H), 12.78 (br s, 1H), 9.93 (br d, J = 7.4 Hz, 1H), 8.42 (s, 1H), 8.18 (dd, J = 7.1, 1.0 Hz, 1H), 8.04 (d, J = 1.0 Hz, 1H), 7.25 (t, J = 7.2 Hz, 1H). LCMS m / z 345.1 [M+H]+, tret= 0.54 min [formic acid]. Example 16 6,7-Difluoro-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine A microwave reaction vial with stir bar was charged with a mixture of 4,5-difluoropyridin-2- amine (300 mg, 2.306 mmol) and 2-chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (923 mg, 2.77 mmol) in propionitrile (3 mL). The reaction mixture was sealed with an aluminum crimp cap then subjected to microwave irradiation with heating at 175 °C for 2 h. The reaction mixture was diluted with EtOAc, washed with saturated aq NaHCO3solution and brine, then evaporated under reduced pressure. The resulting residue was purified by flash chromatography on silica gel (0-40% ethyl acetate in heptane) to give 6,7-difluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (555 mg, 58.8%).1H NMR (400 MHz, CDCl3) δ ppm 8.30 – 8.25 (m, 1H), 8.25 – 8.21 (m, 1H), 7.49 – 7.46 (m, 1H), 7.45 – 7.39 (m, 2H), 6.86 (d, J = 7.7 Hz, 2H), 6.12 (s, 2H), 3.79 (s, 3H). LCMS m / z 410.1 [M+H]+, tret= 1.20 min [TFA]. Step 2 A mixture of 6,7-difluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine (547 mg, 1.336 mmol) and N-iodosuccinimide (361 mg, 1.604 mmol) in chloroform (10mL) was stirred at 50 °C for 18 h. The reaction mixture was washed with aq sodium thiosulfate solution, then the aqueous phase was extracted with chloroform. The combined organic extracts were evaporated to a residue that was purified by flash chromatography on silica gel (0-60% ethyl acetate in heptane) to give 6,7-difluoro-3-iodo- 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (421 mg, 58.9%).1H NMR (400 MHz, CDCl3) δ ppm 8.40 (dd, J = 7.1, 5.1 Hz, 1H), 7.51 (dd, J = 9.5, 7.1 Hz, 1H), 7.38 – 7.34 (m, 2H), 6.86 – 6.82 (m, 2H), 6.03 (s, 2H), 3.79 (s, 3H). LCMS m / z 536.1 [M+H]+, tret= 1.33 min [TFA]. Step 3 A microwave reaction vial with stir bar was charged with a suspension of 6,7-difluoro-3- iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (410 mg, 0.766 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- imidazole-1-sulfonamide (Intermediate 2) (346 mg, 1.149 mmol), cesium fluoride (233 mg, 1.532 mmol), and Pd(dppf)Cl2(84 mg, 0.115 mmol) in DME (10 mL). The vessel was sealed with an aluminum crimp cap then subjected to microwave irradiation at 120 °C for 2 h. The reaction mixture was filtered through celite then evaporated to a residue that was purified by flash chromatography on silica gel (0-50% ethyl acetate in heptane) to give 4-(6,7- difluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (140 mg, 31.4%).1H NMR (400 MHz, CDCl3) δ ppm 9.61 (dd, J = 7.2, 6.0 Hz, 1H), 8.58 (d, J = 1.5 Hz, 1H), 8.07 (d, J = 1.5 Hz, 1H), 7.48 (dd, J = 9.5, 7.6 Hz, 1H), 7.39 – 7.34 (m, 2H), 6.83 (d, J = 7.7 Hz, 2H), 6.08 (s, 2H), 3.78 (s, 3H), 2.98 (s, 6H). LCMS m / z 583.1 [M+H]+, tret= 1.39 min [TFA]. Step 4 A mixture of 4-(6,7-difluoro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (135 mg, 0.232mmol) in TFA (5 mL) was heated at 70 °C for 4 h. The reaction was evaporated to a residue that was purified by reverse phase HPLC (5-75% acetonitrile-water / 0.1% TFA). The fractions of interest were combined, neutralized with dilute ammonium hydroxide, and evaporated under reduced pressure to give 6,7-difluoro-3-(1H-imidazol-4-yl)-2-(3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (10 mg, 11.8%).1H NMR (400 MHz, DMSO-d6) δ ppm 15.63 (br s, 1H), 13.14 (br s, 1H), 9.84 (br s, 1H), 8.44 (s, 1H), 8.35 (br s, 1H), 7.92 (dd, J = 10.8, 7.3 Hz, 1H). LCMS m / z 356.0 [M+H]+, tret= 0.56 min [formic acid]. Example 17 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H,9H- imidazo[2,1-c][1,4]oxazepine, 2.7 Trifluoroacetic acid salt

[0009] A solution of 3-aminopropan-1-ol (20 g, 266 mmol) and K2CO3(110 g, 799 mmol) in tetrahydrofuran (THF) (150 mL) and water (30.0 mL) was cooled to 0 °C. 2-Chloroacetyl chloride (23.30 mL, 293 mmol) was added dropwise and the mixture was allowed to gradually warm to rt with stirring overnight. LCMS analysis indicated desired production formation. The reaction mixture was slightly concentrated to remove organic solvents. The crude mixture was extracted with a solution of 10 / 1 DCM / MeOH (6 x 15 mL) and the combined organics were washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated to afford a colorless oil, 2-chloro-N-(3-hydroxypropyl)acetamide (20 g, 124 mmol, 46.6 % yield).1H NMR (400 MHz, CDCl3) δ ppm 7.28 – 7.16 (m, 1H), 4.05 (s, 2H), 3.68 (t, J = 5.6 Hz, 2H), 3.46 (q, J = 6.2 Hz, 2H), 1.81 – 1.69 (m, 2H), 1H signal not observed. LCMS m / z 152.0,154.0 [M+H]+, tret= 0.27 min [TFA]. Step 2 To a solution of 2-chloro-N-(3-hydroxypropyl)acetamide (20 g, 132 mmol) in tetrahydrofuran (THF) (40 mL) was added a mixture of KOtBu (44.4 g, 396 mmol) in HOBut (20.00 mL). The reaction was stirred at rt for 6 h; LCMS analysis indicated desired production formation. The mixture was concentrated to dryness. The residue was adsorbed onto silica gel (~25 g) and purified by flash column chromatography (100 g column) using 10 / 1 DCM / MeOH as the eluent. The desired fractions were pooled and concentrated to afford 1,4-oxazepan-3-one (20 g, 113 mmol, 86 % yield). LCMS m / z 116.3 [M+H]+, tret= 0.31 min [NH4HCO3]. Step 3 To a 500 mL flask was added 1,4-oxazepan-3-one (3 g, 26.1 mmol), P2S5(8.69 g, 39.1 mmol), and toluene (100 mL). The reaction mixture was stirred at 90 °C for 5 h; LCMS analysis indicated desired product formation. The reaction mixture was quenched with aq NaHCO3solution (100 mL), filtered, and the filter cake was washed by DCM (3 x 100 mL). The biphasic filtrate was separated and the organic phase was washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated. This residue was adsorbed onto silica gel (~6 g) and then purified by flash column chromatography (80 g) using 20:1 DCM:MeOH as the eluent. The desired fractions were pooled and concentrated to afford impure 1,4- oxazepane-3-thione (700 mg, 2.170 mmol) as a yellow solid. LCMS m / z 132.1 [M+H]+, tret= 0.56 min [formic acid, 3 min run time]. Step 4 To a 20 mL flask was added 1,4-oxazepane-3-thione (800 mg, 6.10 mmol) and ammonia (17.4 mL, 122 mmol, 7N in MeOH), and the reaction mixture was stirred at 25 °C for 17 h. LCMS analysis showed desired product formation. The mixture was concentrated.in vacuo. The residue was suspended in MeOH (10 mL), the solids were filtered off, and the filtrate was purified using reverse phase HPLC (C18 column, 0 – 5% MeCN / water). The desired fractions were combined and concentrated to afford an impure yellow oil, 2,5,6,7-tetrahydro- 1,4-oxazepin-3-amine (190 mg). Step 5 To a 10 mL microwave vial was added 2,5,6,7-tetrahydro-1,4-oxazepin-3-amine (100 mg, 0.876 mmol), 2-chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)ethan-1-one (Intermediate 3) (292 mg, 0.876 mmol), TEA (0.122 mL, 0.876 mmol), and acetonitrile (4 mL). The reaction mixture was stirred at 130 °C for 1 h in a microwave reactor. LCMS analysis indicated desired product formation. The reaction mixture was concentrated in vacuo and the residue was purified by prep TLC (1:1 PE:EA) to obtain impure 2-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H,9Himidazo[2,1- c][1,4]oxazepine (40 mg) as a brown solid. LCMS m / z 394.1 [M+H]+, tret= 1.59 min [formic acid, 3 min run time]. Step 6 To a 5 mL flask was added 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)-6,7-dihydro-5H,9H-imidazo[2,1-c][1,4]oxazepine (20 mg, 0.051 mmol), Acetic Acid (1 mL), and NIS (11.4mg, 1.0 eq). The reaction mixture was stirred at 30 °C for 1 h and LCMS analysis indicated mostly starting material remained. Additional NIS (11.4 mg, 1.0 eq) was added and the mixture was stirred for 17 h. LCMS analysis still showed some unreacted starting material. Additional NIS (11.4 mg, 1.0 eq) was added and the mixture was stirred for 1 h. LCMS analysis showed consumption of starting material and desired product formation. The reaction mixture was concentrated in vacuo. This residue was purified by prep TLC (1:1 PE:EA) to afford impure 3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)- 1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H,9H-imidazo[2,1- c][1,4]oxazepine (10 mg) as a yellow oil. LCMS m / z 520.1 [M+H]+, tret= 0.83 min [TFA, 1.8 min run time]. Step 7 To a 10 mL microwave vial was added 3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)- 1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H,9H-imidazo[2,1-c][1,4]oxazepine (20 mg, 0.039 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1- sulfonamide (Intermediate 2) (13.92 mg, 0.046 mmol), cesium fluoride (11.70 mg, 0.077 mmol), and Pd(dppf)Cl2.DCM (6.29 mg, 7.70 µmol). DME (1.0 mL) was added and the reaction mixture was purged with nitrogen and then heated in a microwave reactor at 100 °C for 15 min. LCMS analysis indicated desired product formation. The reaction mixture was concentrated in vacuo. The residue was dissolved in MeOH (1 mL) and purified by prep TLC (20:1 DCM:MeOH) to obtain impure 4-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)-6,7-dihydro-5H,9Himidazo[2,1-c][1,4]oxazepin-3-yl)-N,N-dimethyl-1H- imidazole-1-sulfonamide (10 mg) as a yellow oil. LCMS m / z 567.1 [M+H]+, tret = 1.05 min [formic acid, 2 min run time]. Step 8 To an 8 mL flask was added 4-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol- 5-yl)-6,7-dihydro-5H,9H-imidazo[2,1-c][1,4]oxazepin-3-yl)-N,N-dimethyl-1Himidazole-1- sulfonamide (10 mg, 0.018 mmol) and Trifluoroacetic acid (TFA) (1 mL). The reaction mixture was stirred at 80 °C for 2 h. LCMS analysis indicated desired product formation. The reaction mixture was concentrated in vacuo. The residue was dissolved in DMF (1 mL), purified by reverse phase HPLC (XBridge Shield RP18 OBD Column using an eluent of 5% - 40% ACN in water with 0.05% TFA). The desired fractions were pooled and concentrated to afford 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro- 5H,9H-imidazo[2,1-c][1,4]oxazepine, 2.7 Trifluoroacetic acid salt (1.4 mg) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.50 (s, 1H), 7.90 (s, 1H), 4.76 (s, 2H), 4.35 (m, 2H), 4.01 (m, 2H), 1.90 (m, 2H), 2H signals not observed. LCMS m / z 340.1 [M+H]+, tret= 0.67 min [TFA, 3 min run time]. Example 18 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazine Pyrazin-2-amine (200 mg, 2.103 mmol) and 2-chloro-1-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (842 mg, 2.52 mmol) were mixed in MeTHF (10 mL). The reaction mixture was stirred at 100 °C for 16 h. This reaction was repeated on the same scale once more. The combined reaction mixtures were partitioned between saturated aq NaHCO3and DCM. The organic layer was washed with brine, dried over MgSO4and concentrated to a brown residue. The residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 5% - 50% (3:1 EtOAc / EtOH with 1% NEt3) / Hexane). Collected fractions containing the product were combined and concentrated to give impure 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyrazine as a brown solid (340 mg). LCMS m / z 375.2 [M+H]+, tret= 1.13 min [TFA]. Step 2 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazine (340 mg, 0.908 mmol) was dissolved in DCE (10 mL), and then NBS (323 mg, 1.816 mmol) was added, followed by 3 drops of TFA. The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was partitioned between 1:1 saturated aq Na2S2O3 / NaHCO3and DCM. The organic layer was washed with brine, dried over MgSO4and concentrated to a brown residue. The residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 10% - 50% (3:1 EtOAc / EtOH) / Hexane). The fractions containing the product were combined and concentrated to give impure 3-bromo-2-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazine as an orange solid (250 mg). LCMS m / z 453.1 / 455.0 [M+H]+, tret= 1.00 min [TFA]. Step 3 3-Bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine (120 mg, 0.265 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (159 mg, 0.530 mmol), PdCl2(dppf)- CH2Cl2adduct (21.62 mg, 0.026 mmol), and cesium fluoride (80 mg, 0.530 mmol) were mixed in DME (10 mL). The reaction vial was sealed and heated in an Biotage microwave reactor at 110 °C for 30 min. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated and the residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 10% - 80% (3:1 EtOAc / EtOH with 1% NEt3) / Hexane). Collected fractions containing the product were combined and concentrated to give impure 4-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazin-3- yl)-N,N-dimethyl-1H-imidazole-1- sulfonamide as a yellow solid (134 mg). LCMS m / z 548.3 [M+H]+, tret= 1.19 min [TFA]. Step 4 4-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazin-3- yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (133.8 mg, 0.244 mmol) was dissolved in 2 mL of TFA. The reaction mixture was stirred at 90 °C for 2 h. The reaction mixture was concentrated and the brown residue was purified by reverse phase HPLC (MDAP Method D). The clean fractions were combined and concentrated to give 3-(1H-imidazol-4-yl)-2-(3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazine as a yellow solid (70 mg, 89% yield).1H NMR (400 MHz, CD3OD) δ ppm 9.23 (d, J=4.82 Hz, 1H), 9.15 (d, J=1.52 Hz, 1H), 8.38 (d, J=1.01 Hz, 1H), 8.09 (s, 1H), 8.00 (d, J=4.82 Hz, 1H), 2H signals not observed. LCMS m / z 321.2 [M+H]+, tret= 0.39 min [TFA]. Example 19 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-b]pyridazine A mixture of 2-chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)ethan-1-one (Intermediate 3) (2 g, 5.99 mmol), pyridazin-3-amine (1.140 g, 11.99 mmol) and TEA (1.671 mL, 11.99 mmol) was stirred at 80 °C for 16 h in acetonitrile (200 mL). The reaction mixture was cooled to room temperature and concentrated onto celite. The celite material was dry loaded for purification by silica gel chromatography (0% - 40% 3:1 EtOAc / EtOH in DCM). The desired fractions were combined and concentrated in vacuo. The final material was dried under high vacuum to afford 2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-b]pyridazine (334 mg, 14% yield) as an orange oil.1H NMR (400 MHz, DMSO-d6) δ ppm 9.03 (s, 1H), 8.69 (dd, 1H, J=1.5, 4.4 Hz), 8.3-8.4 (m, 1H), 7.4-7.5 (m, 1H), 7.3-7.4 (m, 2H), 6.9-6.9 (m, 2H), 6.14 (s, 2H), 3.72 (s, 3H). LCMS m / z 375.1 [M+H]+, tret= 1.10 min [TFA]. Step 2 A mixture of 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- b]pyridazine (293 mg, 0.783 mmol) and NBS (142 mg, 0.798 mmol) in acetonitrile (16 mL) was stirred at room temperature for 16 h. The reaction solvent was removed and contents were concentrated onto celite for purification using silica gel chromatography (0% - 20 % 3:1 EtOAc / EtOH in DCM). The desired fractions were combined and concentrated. The unclean fractions were combined and concentrated onto 4:1 celite:silica and subjected to purification again (0-50% 3:1 EtOAc:EtOH in Heptanes). The desired fractions from both runs were combined and concentrated to afford impure 3-bromo-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-b]pyridazine (450 mg) as a pink-white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.8-8.8 (m, 1H), 8.38 (dd, 1H, J=1.5, 9.3 Hz), 7.51 (dd, 1H, J=4.4, 9.3 Hz), 7.3-7.4 (m, 2H), 6.9-6.9 (m, 2H), 6.0-6.0 (m, 2H), 3.71 (s, 3H). LCMS m / z 453.0, 455.0 [M+H]+, tret= 1.16 min [TFA]. Step 3 A mixture of 3-bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-b]pyridazine (450 mg, 0.993 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (314 mg, 1.043 mmol), potassium phosphate tribasic (632 mg, 2.98 mmol), and PdCl2(dppf)-CH2Cl2adduct (81 mg, 0.099 mmol) was sparged with argon for 5 min in 1,4-Dioxane (12 mL) and Water (4.80 mL). The reaction mixture was kept under argon and heated to 101 °C with stirring for 16 h. The reaction mixture was partitioned between DCM (100 mL) and water (10 mL). The organic layer was separated and concentrated onto celite for purification by flash column chromatography (0% - 60% (3:1 EtOAc / EtOH) in DCM). The desired fractions were combind and concentrated to afford 4-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-b]pyridazin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (324 mg, 57% yield) as a tan foam.1H NMR (400 MHz, CD2Cl2) δ ppm 8.61 (dd, 1H, J=1.5, 4.4 Hz), 8.27 (d, 1H, J=1.0 Hz), 8.1-8.2 (m, 1H), 7.99 (d, 1H, J=1.5 Hz), 7.2-7.3 (m, 3H), 6.8-6.8 (m, 2H), 5.68 (s, 2H), 3.78 (s, 3H), 2.96 (s, 6H). LCMS m / z 548.1 [M+H]+, tret= 1.11 min [TFA]. Step 4 4-(2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-b]pyridazin- 3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (324 mg, 0.592 mmol) was dissolved in Trifluoroacetic acid (TFA) (12 mL) and stirred at 80 °C for 16 h. The reaction solvent was removed in vacuo and the remaining material was adsorbed onto celite for purification by column chromatography (C18Aq 100 g column using an eluent of 5% - 100% CH3CN / water with 1% NH4OH). The desired fractions were combined and concentrated. The material was dried under high vacuum to afford 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-b]pyridazine (150 mg, 76 % yield) as a granular yellow powder.1H NMR (400 MHz, DMSO-d6) δ ppm 8.79 (br dd, 1H, J=1.7, 4.2 Hz), 8.35 (s, 1H), 8.2-8.3 (m, 2H), 7.40 (dd, 1H, J=4.4, 8.8 Hz), 2H signals not observed. LCMS m / z 321.1 [M+H]+, tret= 0.51 min [TFA]. Example 20 7-chloro-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- c]pyrimidine 2-Chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (500 mg, 1.498 mmol) and 6-bromopyrimidin-4-amine (521 mg, 3.00 mmol) were mixed in 10 mL CH3CN. The reaction vial was sealed and heated in a Biotage microwave reactor at 150 °C for 1 h. This reaction was repeated on 500 mg scale once more and the two reactions were combined. The black reaction mixture was concentrated and the residue was partitioned between saturated aq NaHCO3and DCM. The organic layer was washed with brine, dried over MgSO4and concentrated to a brown residue.The residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 20% - 80% (3:1 EtOAc / EtOH) / Hexane). Collected fractions containing the product were combined and concentrated to give a mixture of 7-chloro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)imidazo[1,2-c]pyrimidine and 7-bromo-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-c]pyrimidine as a brown solid (466 mg). LCMS m / z 409.1, 411.1 [M+H]+, tret= 1.26 min [formic acid]. Step 2 7-Chloro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- c]pyrimidine (230 mg, 0.563 mmol) was dissolved in DCM (20 mL) and NBS (150 mg, 0.844 mmol) was added. The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was partitioned between 1:1 saturated aq Na2S2O3 / NaHCO3and DCM. The organic layer was washed with brine, dried over MgSO4and concentrated to a yellow residue. The residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 20% - 50% (3:1 EtOAc / EtOH) / Hexane). Collected fractions containing the product were combined and concentrated to give a mixture of 3-bromo-7-chloro-2-(1-(4-methoxybenzyl)- 3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-c]pyrimidine and the corresponding dibromide as a yellow solid (143 mg). LCMS m / z 487.2, 489.1 [M+H]+, tret= 1.26 min [TFA]. Step 3 3-Bromo-7-chloro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-c]pyrimidine (143.1 mg, 0.293 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (133 mg, 0.440 mmol), PdCl2(dppf)-CH2Cl2adduct (23.96 mg, 0.029 mmol), and cesium fluoride (89 mg, 0.587 mmol) were mixed in DME (10 mL). The reaction vial was sealed and heated in a Biotage microwave reactor at 100 °C for 10 min. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated and the residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 10% - 80% (3:1 EtOAc / EtOH with 1% NEt3) / Hexane). Collected fractions containing the product were combined and concentrated to give impure 4-(7-chloro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-c]pyrimidin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide as a yellow solid (25 mg). LCMS m / z 582.3, 584.1 [M+H]+, tret= 1.37 min [TFA]. Step 4 4-(7-Chloro-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- c]pyrimidin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (25 mg, 0.042 mmol) was dissolved in 2 mL of TFA. The reaction mixture was stirred at 90 °C for 5 h. The mixture was concentrated and the residue was purified by reverse phase HPLC (MDAP Method D) to give 7-chloro-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-c]pyrimidine (11 mg, 74% yield).1H NMR (400 MHz, CD3OD) δ ppm 9.13 (s, 1H), 8.15 (s, 1H), 8.00 (d, J = 1.3 Hz, 1H), 7.75 (d, J = 1.0 Hz, 1H), 2H signals not observed. LCMS m / z 355.2 [M+H]+, tret= 0.44 min [TFA]. Example 21 3-(1H-imidazol-4-yl)-6-methoxy-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine (5- methoxypyrazin-2-amine), the title product was produced as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm 9.32 (br s, 1H), 9.03 (d, J=1.22 Hz, 1H), 8.56 (s, 1H), 8.07 (d, J=1.22 Hz, 1H), 3.95 (s, 3H), 2H signals not observed. LCMS m / z 351.1 [M+H]+, tret= 0.46 min [TFA]. Example 22 2-(3-(Difluoromethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-4-yl)imidazo[1,2-a]pyrazine, Trifluoroacetic acid salt Following the methods of Example 18 except using (2-chloro-1-(3-(difluoromethyl)-1-(4- methoxybenzyl)-1H-1,2,4-triazol-5-yl)ethan-1-one) (Intermediate 4), the title product was produced as a yellow solid.1H NMR (400 MHz, CD3OD) δ ppm 9.27 (d, J=1.22 Hz, 1H), 9.15 (d, J=0.98 Hz, 1H), 8.67 (dd, J=4.77, 1.35 Hz, 1H), 8.31 (d, J=1.22 Hz, 1H), 8.13 (d, J=4.65 Hz, 1H), 6.75 - 7.16 (m, 1H), 2H signals not observed. LCMS m / z 303.2 [M+H]+, tret= 0.33 min [NH4HCO3]. Example 23 6-Ethyl-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine ethylpyrazin-2-amine), the title product was produced as a white solid.1H NMR (400 MHz, CD3OD) δ ppm 9.08 (d, J=1.47 Hz, 1H), 9.01 (s, 1H), 8.33 (s, 1H), 8.03 (d, J=0.98 Hz, 1H), 2.88 (q, J=7.58 Hz, 2H), 1.39 (t, J=7.58 Hz, 3H), 2H signals not observed. LCMS m / z 349.0 [M+H]+, tret= 0.74 min [TFA]. Example 24 Methyl 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine-6-carboxylate

[0010] (methyl 5-aminopyrazine-2-carboxylate), the title product was produced as a yellow solid. 1H NMR (400 MHz, CD3OD) δ ppm 10.57 (s, 1H), 9.23 (d, J=1.22 Hz, 1H), 8.69 (s, 1H), 8.11 (d, J=0.98 Hz, 1H), 3.94 (s, 3H), 2H signals not observed. LCMS m / z 379.1 [M+H]+, tret= 0.54 min [formic acid]. Example 25 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-7-ol 4-(Benzyloxy)pyridin-2-amine (720 mg, 3.60 mmol) and 2-chloro-1-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (800 mg, 2.397 mmol) were mixed in CH3CN (10 mL). The reaction mixture was stirred at 100 °C for 16 h. The rxn mixture was cooled to room temperature and concentrated to a residue. The residue was partitioned between saturated aq NaHCO3and DCM. The organic layer was washed with brine, dried over MgSO4and concentrated to yield impure 7-(benzyloxy)-2-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (1.15 g) as a white solid. LCMS m / z 480.3 [M+H]+, tret= 1.35 min [formic acid]. Step 2 7-(Benzyloxy)-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine (1.15 g, 2.396 mmol) was dissolved in DCM (0.5 mL), and then NBS (640 mg, 3.59 mmol) was added. The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was partitioned between 1:1 saturated aq Na2S2O3 / sat.NaHCO3and DCM. The organic layer was washed with brine, dried over MgSO4and concentrated to a brown residue.The residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 5% - 50% (3:1 EtOAc / EtOH) / Hexane). Collected fractions containing the product were combined and concentrated to give 7-(benzyloxy)-3-bromo-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine as a yellow solid (555 mg, 41% yield).1H NMR (400 MHz, CDCl3) δ ppm 8.09 (d, J=7.58 Hz, 1H), 7.37 - 7.55 (m, 7H), 7.03 (d, J=2.20 Hz, 1H), 6.79 - 6.90 (m, 3H), 6.09 (s, 2H), 5.19 (s, 2H), 3.79 (s, 3H). LCMS m / z 557.8, 559.8 [M+H]+, tret= 1.45 min [TFA]. Step 3 7-(Benzyloxy)-3-bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine (250 mg, 0.448 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl1,3,2- dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (270 mg, 0.895 mmol), cesium fluoride (204 mg, 1.343 mmol) and PdCl2(dppf) (32.8 mg, 0.045 mmol) were mixed in DME (10 mL). The reaction vial was sealed and heated in a Biotage microwave reactor at 110 °C for 30 min. The reaction mixture was cooled to room temperature and then filtered. The filtrate was concentrated to a brown residue. The residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 20% - 80% EtOAc / Hexane). Collected fractions containing the product were combined and concentrated to give 4-(7-(benzyloxy)- 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-3-yl)- N,N-dimethyl-1H-imidazole-1-sulfonamide as a white solid (213.3 mg, 73% yield).1H NMR (400 MHz, CDCl3) ^ ppm 9.17 (d, J=7.83 Hz, 1H), 8.49 (d, J=1.22 Hz, 1H), 8.07 (d, J=1.22 Hz, 1H), 7.35 - 7.56 (m, 7H), 7.06 (d, J=2.45 Hz, 1H), 6.84 - 6.87 (m, 2H), 6.78 (dd, J=7.82, 2.45 Hz, 1H), 6.14 (s, 2H), 5.21 (s, 2H), 3.79 (s, 3H), 2.98 (s, 6H). LCMS m / z 653.0 [M+H]+, tret= 1.36 min [TFA]. Step 4 4-(7-(Benzyloxy)-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (213.3 mg, 0.327 mmol) was dissolved in trifluoroacetic acid (2 mL, 26.0 mmol). The reaction mixture was stirred at 90 °C for 3 h. The reaction mixture was concentrated and the brown residue was purified by reverse phase HPLC (MDAP Method F). The clean fractions after HPLC were combined and concentrated to give 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-a]pyridin-7-ol as a white solid (37 mg, 34% yield).1H NMR (400 MHz, DMSO-d6) ^ ppm 15.67 – 14.58 (m, 1H), 13.55 – 12.31 (m, 1H), 11.00 – 10.23 (m, 1H), 9.38 (br d, J = 7.8 Hz, 1H), 8.33 (d, J = 1.0 Hz, 1H), 8.06 (s, 1H), 6.81 (d, J = 2.0 Hz, 1H), 6.75 (dd, J = 7.8, 2.4 Hz, 1H). LCMS m / z 336.0 [M+H]+, tret= 0.38 min [TFA]. Example 26 Methyl 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine-7-carboxylate A mixture of methyl 2-aminoisonicotinate (16.0 g, 105 mmol), sodium bicarbonate (7.83 g, 93 mmol) and 2-chloro-1-(1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)ethan-1-one (24.0 g, 93 mmol) in 1-butanol (250 mL) was stirred at 90 °C for 4 h. The reaction mixture was cooled to room temperature and the precipitate was collected by filtration. The solid was then washed with ethanol, water, ethanol and hexane. The mother liquors were evaporated and purified by flash column chromatography (0%-30% EtOAc / Hexane). Collected fractions containing the product were combined and concentrated to give methyl 2-(1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine-7-carboxylate (18.3g, 55% yield).1H NMR (400 MHz, CDCl3) δ ppm 8.53 – 8.42 (m, 2H), 8.26 (dd, J = 7.1, 1.0 Hz, 1H), 7.55 (dd, J = 7.1, 1.5 Hz, 1H), 6.30 (s, 2H), 4.03 (s, 3H), 3.56 (s, 3H). LCMS m / z 356.1 [M+H]+, tret= 1.01 min [TFA]. Step 2 Methyl 2-(1-(methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine-7-carboxylate (29.6 g, 83 mmol) and NIS (22.49 g, 100 mmol) in chloroform (800 mL) was stirred at 50 °C for 24 h. Another amount of NIS was added (3.2 g) and the reaction mixture was stirred at 75 °C for 16 h. The reaction mixture was evaporated and the residue was purified twice by flash column chromatography (330 g RediSep column and then 220 g RediSep column, each using an eluent of 0% - 60% EtOAc / Heptane). Collected fractions containing the product were combined and concentrated to give methyl 3-iodo-2-(1- (methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine-7- carboxylate (33.5 g, 84% yield).1H NMR (400 MHz, DMSO-d6) δ ppm 8.64 (dd, J = 7.4, 0.8 Hz, 1H), 8.29 (d, J = 1.0 Hz, 1H), 7.57 (dd, J = 7.2, 1.6 Hz, 1H), 6.16 (s, 2H), 3.94 (s, 3H), 2.57 (s, 3H). LCMS m / z 482.1 [M+H]+, tret= 1.17 min [TFA]. Step 3 A 1L round bottom flask was charged with methyl 3-iodo-2-(1-(methoxymethyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine-7-carboxylate (10.0 g, 20.78 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole-1- sulfonamide (Intermediate 2) (18.78 g, 62.3 mmol), potassium phosphate tribasic (6.62 g, 31.2 mmol) and PdCl2(dppf) (2.281 g, 3.12 mmol) in 1,4-Dioxane (300 mL). The flask was well flushed with nitrogen and stirred under reflux (bath at 120 °C) in a dry nitrogen atmosphere for 16 h. The mixture was cooled to room temperature and evaporated. Addition of ethyl acetate gave a thick precipitate that was collected by filtration. The solid was washed with ethyl acetate and hexane. The crude material was purified by flash column chromatography (330 g RediSep column using an eluent of 0% - 10% EtOAc / dichloromethane). Collected fractions containing the product were combined and concentrated to give methyl 3-(1-(N,N-dimethylsulfamoyl)-1H-imidazol-4-yl)-2-(1- (methoxymethyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine-7- carboxylate (10 g, 91% yield).1H NMR (400 MHz, DMSO-d6) δ ppm 9.30 (dd, J = 7.4, 1.0 Hz, 1H), 8.56 (d, J = 1.3 Hz, 1H), 8.48 (d, J = 1.3 Hz, 1H), 8.36 (dd, J = 1.6, 0.9 Hz, 1H), 7.57 (dd, J = 7.4, 1.8 Hz, 1H), 6.13 (s, 2H), 3.95 (s, 3H), 3.37 (s, 3H), 2.89 (s, 6H). LCMS m / z 529.3 [M+H]+, tret= 1.18 min [TFA]. Step 4 Methyl 3-(1-(N,N-dimethylsulfamoyl)-1H-imidazol-4-yl)-2-(1-(methoxymethyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine-7-carboxylate (9.2 g, 17.41 mmol) in a 1L Erlenmeyer flask was dissolved in chloroform (100 mL), and then treated with 4 M HCl in dioxane (60 mL, 240 mmol). The mixture was stirred at 40 °C for 3 h. Methanol was added during the reaction to improve solubility and allow for better deprotection. The mixture was evaporated and the residue was taken up in water. The aqueous solution was extracted with diethyl ether twice, followed by ethyl acetate extraction. The combined organic solution was washed with 1M aq HCl twice. The combined aqueous solution was carefully basified with solid NaHCO3and adjusted to pH=6.0 with 0.2M ammonium citrate buffer. The precipitate was collected by filtration, and then washed with water, acetonitrile and hexanes and dried to give methyl 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-a]pyridine-7-carboxylate (4.5 g, 68% yield).1H NMR (400 MHz, DMSO-d6) δ ppm 15.72 (br s, 1H), 12.72 (br s, 1H), 9.86 – 9.65 (m, 1H), 8.47 (br s, 1H), 8.29 – 8.19 (m, 1H), 8.05 (s, 1H), 7.51 (dd, J = 7.4, 1.8 Hz, 1H), 3.94 (s, 3H). LCMS m / z 378.1 [M+H]+, tret= 0.57 min [TFA]. Example 27 2-(3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-6- yl)-2,2-difluoro-N-methylethan-1-amine

[0011] To 5-iodopyridin-2-amine (20.10 g, 91 mmol) in dichloromethane (DCM) (500 mL) at 0 °C was added Boc-anhydride (25.5 mL, 110 mmol) and then DMAP (1.116 g, 9.14 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 18 h. LCMS analysis indicated mono and bis Boc products. The reaction mixture was concentrated and the residue purified by flash column chromatography (330 g RediSep column using an eluent of 0 to 30% EtOAc in hexanes). A broad peak of mono and bis Boc product was isolated. To the isolated, concentrated mixture was added MeOH (200 mL) and K2CO3(5 g). The mixture was then stirred for 1 h at 65 °C. The reaction mixture was allowed to cool to room temperature and the solid was isolated by filtration and washed with water to give a first batch of desired product. The filtrate was concentrated, diluted with water, and extracted with EtOAc (2 x 50 mL). The organic extracts were combined and washed with brine, dried over MgSO4, filtered, and concentrated by reduced pressure to give a solid. The solid was washed with 1:1 DCM:Hexane to afford a second batch of desired product. The two batches of solid were then combined to afford tert-butyl (5-iodopyridin-2-yl)carbamate (22.83 g, 71.3 mmol, 78 % yield) as a white solid.1H NMR (400 MHz, DMSO-d6): δ ppm 9.93 (s, 1H), 8.44 (dd, J=2.45, 0.73 Hz, 1H), 8.04 (dd, J=8.80, 2.45 Hz, 1H), 7.68 (dd, J=8.80, 0.73 Hz, 1H), 1.47 (s, 9H). LCMS m / z 321.0 [M+H]+, tret= 1.04 min [TFA]. Step 2 To a 20 mL microwave vial were added tert-butyl (5-iodopyridin-2-yl)carbamate (1.00 g, 3.12 mmol), ethyl 2-bromo-2,2-difluoroacetate (0.561 mL, 4.37 mmol), Copper powder (0.993 g, 15.6 mmol) and dimethyl sulfoxide (DMSO) (15 mL). the mixture was then capped and heated in a microwave reactor for 3.5 h at 85 °C. The above conditions were repeated 13 more times. When all 14 reactions were completed, they were all combined and diluted with 200 mL of water and 300 mL of EtOAc. The mixture was filtered through filter paper and the filtrate was extracted with EtOAc (2 x 100mL). The organic extracts were combined, washed with brine, dried over MgSO4, filtered, and concentrated by reduced pressure. The residue was purified by flash column chromatograhy (330 g RediSep column using an eluent of 0 to 20% EtOAc in Hexanes) to isolate the starting tert-butyl (5-iodopyridin-2- yl)carbamate (1.67 g, 5.22 mmol, 11.93 % yield) and the desired product ethyl 2-(6-((tert- butoxycarbonyl)amino)pyridin-3-yl)-2,2-difluoroacetate (7.50 g, 23.71mmol, 54.2 % yield). LCMS m / z 317.1 [M+H]+, tret= 1.10 min [TFA]. Step 3 To ethyl 2-(6-((tert-butoxycarbonyl)amino)pyridin-3-yl)-2,2-difluoroacetate (7.50 g, 23.71 mmol) in methanol (200 mL), sodium borohydride (1.166 g, 30.8 mmol) was added. The reaction mixture slowly turned clear and bubbled. After 1 h, analysis by LCMS indicated only product was present. The reaction mixture was then partly concentrated and diluted with water (200 mL). A solid precipitate formed which was isolated by filtration and placed under vacuum overnight to afford tert-butyl (5-(1,1-difluoro-2-hydroxyethyl)pyridin-2- yl)carbamate (5.48 g, 19.98 mmol, 84 % yield) as a white solid.1H NMR (400 MHz, DMSO- d6) δ ppm 10.04 (s, 1H), 8.36-8.41 (m, 1H), 7.85-7.92 (m, 2H), 5.62-5.67 (m, 1H), 3.87 (td, J=13.82, 6.11 Hz, 2H), 1.45-1.52 (m, 9H). LCMS m / z 275.1 [M+H]+, tret= 0.69 min [TFA]. Step 4 To tert-butyl (5-(1,1-difluoro-2-hydroxyethyl)pyridin-2-yl)carbamate (5.48 g, 19.98 mmol) in dichloromethane (DCM) (50 mL) was added TFA (12.31 mL, 160 mmol) and the reaction mixture was stirred for 3 h. Analysis by LCMS indicated no remaining starting material. The reaction mixture was concentrated to a clear oil. The oil was dissolved in DCM (150 mL) and imidazole (6.80 g, 100 mmol) and then TBDMS-Cl (3.91 g, 26.0 mmol) were added. A precipitate formed. After 1 h, analysis by LCMS indicated only desired product was present. The reaction mixture was diluted with water (150 mL) and extracted with EtOAc (3 x 50 mL). The organic extracts were combined, washed with brine, dried over MgSO4, filtered, and concentrated by reduced pressure. Purification of the residue by flash column chromatography (220 g RediSep column using an eluent of 0 to 40% EtOAc in Hexanes) afforded 5-(2-((tert-butyldimethylsilyl)oxy)-1,1-difluoroethyl)pyridin-2-amine (4.10 g, 14.22 mmol, 71.1 % yield) as a clear oil.1H NMR (400 MHz, DMSO-d6) δ ppm 8.03 (dd, J=2.45, 0.98 Hz, 1H), 7.45 (dd, J=8.80, 2.45 Hz, 1H), 6.47 (d, J=8.80 Hz, 1H), 6.31 (s, 2H), 3.99 (t, J=13.20 Hz, 2H), 0.82 (s, 9H), 0.01 (s, 6H). LCMS m / z 289.2 [M+H]+, tret= 0.84 min [TFA]. Step 5 To 5-(2-((tert-butyldimethylsilyl)oxy)-1,1-difluoroethyl)pyridin-2-amine (4.10 g, 14.22 mmol, 1.00 equiv) in acetonitrile (150 mL) were added 2-chloro-1-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (6.17 g, 18.48 mmol) and sodium bicarbonate (1.672 g, 19.90 mmol). The reaction mixture was heated at 85 °C for 4 h. Analysis by LCMS indicated starting material remained. An additional 0.2 equivalents of 2-chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)ethan-1-one (Intermediate 3) were added and the reaction mixture was stirred at 85 °C for another 4 h. Analysis by LCMS indicated only a small amount of the aniline starting material remained. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (3 x 100 mL). The organic extracts were combined, washed with brine, dried over MgSO4, filtered, and concentrated by reduced pressure. Purification of the residue by flash column chromatography (330 g RediSep column using an eluent of 0 to 15% EtOAc in Hexanes) yielded the 6-(2-((tert-butyldimethylsilyl)oxy)-1,1-difluoroethyl)-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (6.52 g, 11.49 mmol, 81% yield) as a slightly yellow oil which solidified upon sitting.1H NMR (400 MHz, DMSO-d6) δ ppm 8.97 (s, 1H), 8.80 (s, 1H), 7.89 (d, J=9.29 Hz, 1H), 7.53 (dd, J=9.54, 1.71 Hz, 1H), 7.32-7.38 (m, 2H), 6.86-6.93 (m, 2H), 6.14 (s, 2H), 4.18 (t, J=13.20 Hz, 2H), 3.71 (s, 3H), 0.80 (s, 9H), 0.02 (s, 6H). LCMS m / z 568.4 [M+H]+, tret= 1.58 min [TFA]. Step 6 To 6-(2-((tert-butyldimethylsilyl)oxy)-1,1-difluoroethyl)-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (6.52 g, 11.49 mmol) in acetonitrile (150 mL) was added NBS (2.147 g, 12.06 mmol) in portions and the reaction mixture was stirred for 0.5 h. Analysis by LCMS indicated only product present. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (3 x 100 mL). The organic extracts were combined, washed with brine, dried over MgSO4, filtered, and concentrated by reduced pressure. Purification of the residue by flash column chromatography (220 g RediSep column using an eluent of 0 to 15% EtOAc in Hexanes) afforded the 3-bromo-6- (2-((tert-butyldimethylsilyl)oxy)-1,1-difluoroethyl)-2-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (6.55 g, 10.13 mmol, 88 % yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.54 (s, 1H), 8.00 (d, J=9.78 Hz, 1H), 7.64-7.69 (m, 1H), 7.30-7.38 (m, 2H), 6.87-6.93 (m, 2H), 6.05 (s, 2H), 4.24 (t, J=12.96 Hz, 2H), 3.72 (s, 3H), 0.81 (s, 9H), 0.03 (s, 6H). LCMS m / z 648.1 [M+H]+, tret= 1.73 min [TFA]. Step 7 To 3-bromo-6-(2-((tert-butyldimethylsilyl)oxy)-1,1-difluoroethyl)-2-(1-(4-methoxybenzyl)-3 (trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine (498 mg, 0.770 mmol) in 1,4- dioxane (6 mL) were sequentially added N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-imidazole-1-sulfonamide (Intermediate 2) (278 mg, 0.924 mmol), tripotassium phosphate (490 mg, 2.311 mmol), PdCl2(dppf)-CH2Cl2adduct (62.9 mg, 0.077 mmol) and water (3.00 mL). The reaction mixture was then capped and heated at 80 °C. After 1 min, everything went into solution. The reaction was heated overnight. Analysis by LCMS indicated no remaining starting material, the presence of desired product, and about 20% of deprotected product. The reaction mixture was diluted with water (15 mL) and extracted with EtOAc (3 x 10mL). The organic extracts were combined, washed with brine, dried over MgSO4, filtered, and concentrated by reduced pressure. Tetrahydrofuran (THF) (3 mL) and 1M TBAF in THF (0.770 mL, 0.770 mmol) were added and the reaction was stirred for 1 h at room temperature. Analysis by LCMS indicated only the presence of deprotected product. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (4 x 5 mL). The organic extracts were combined, washed with brine, dried over MgSO4, filtered, and concentrated by reduced pressure. The residue was purified by flash column chromatography (24 g RediSep column eluting with 0 to 60% EtOAc in Hexanes) to afford the 4-(6-(1,1-difluoro-2-hydroxyethyl)-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (399 mg, 0.637 mmol, 83 % yield) as a pale yellow oil that foamed to a solid under high vacuum.1H NMR (400 MHz, DMSO-d6) δ ppm 9.52 (s, 1H), 8.57 (d, J=1.47 Hz, 1H), 8.43 (d, J = 1.47 Hz, 1H), 7.94-7.99 (m, 1H), 7.61-7.66 (m, 1H), 7.36-7.40 (m, 2H), 6.88-6.94 (m, 2H), 5.97 (s, 2H), 5.73-5.79 (m, 1H), 3.92-4.02 (m, 2H), 3.72 (s, 3H), 2.87 (s, 6H). LCMS m / z 627.1 [M+H]+, tret= 0.77 min [TFA]. Step 8 To 4-(6-(1,1-difluoro-2-hydroxyethyl)-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (257 mg, 0.410 mmol) in dichloromethane (DCM) (3 mL) was added sequentially pyridine (0.166 mL, 2.051 mmol) and trifluoromethanesulfonic anhydride (0.076 mL, 0.451 mmol). The reaction mixture was stirred for 15 min at room temperature. Analysis by LCMS indicated only desired intermediate. The reaction mixture was concentrated and diluted with tetrahydrofuran (THF) (3.00 mL) and methanamine (2.051 mL of 2M in THF, 4.10 mmol) and then transferred to a 20 mL microwave vial for heating at 85 °C for 1 h. Analysis by LCMS indicated only desired product. The reaction mixture was concentrated by reduced pressure and the residue purified by reverse phase HPLC (MDAP Method H). The fractions with the desired product were combined and lyophilized to afford 4-(6-(1,1-difluoro-2- (methylamino)ethyl)-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide, Trifluoroacetic acid salt (217mg, 0.288 mmol, 70.2 % yield) as a white solid. LCMS m / z 640.4 [M+H]+, tret= 0.93 min [TFA]. Step 9 To 4-(6-(1,1-difluoro-2-(methylamino)ethyl)-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H- 1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-3-yl)-N,N-dimethyl-1H-imidazole-1-sulfonamide (217mg, 0.339 mmol) in a 5 mL microwave vial was added TFA (4 mL, 51.9 mmol). The vial was capped and heated at 80 °C for 0.5 h. Analysis by LCMS indicated only the product was present. The reaction mixture was then concentrated by reduced pressure, diluted with DMSO (1 mL), and purified by reverse phase HPLC (MDAP Method K). The fractions with the desired product were combined and lypophilized overnight to afford 2-(3-(1H-imidazol- 4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridin-6-yl)-2,2-difluoro-N- methylethan-1-amine (60.0 mg, 0.146 mmol, 42.9 % yield) as a white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 10.02 (br s, 1H), 8.47 (s, 1H), 8.05 (d, J=1.0 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.54 (dd, J=9.5, 1.7 Hz, 1H), 3.22-3.30 (m, 2H), 2.32 (s, 3H), 3H signals not observed. LCMS m / z 413.0 [M+H]+, tret= 0.39 min [TFA]. Example 28 Ethyl 3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-5,6- dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate

[0012] Pyrazin-2-amine (0.855 g, 8.99 mmol) and and 2-chloro-1-(1-(4-methoxybenzyl)-3- (trifluoromethyl)-1H-1,2,4-triazol-5-yl)ethan-1-one (Intermediate 3) (1.5 g, 4.50 mmol) were mixed in CH3CN (100 mL) and the mixture was stirred at 90 °C for 16 h. The reaction mixture was then cooled to room temperature and the solvent was removed via rotovap. The brown residue was purified by Isco Combiflash (120 g RediSep column using an eluent of 10% - 50% (3:1 EtOAc / EtOH) / Hexane). Collected fractions containing the product were combined and concentrated to give 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyrazine as a yellow solid (267mg, 16% yield).1H NMR (400 MHz, DMSO- d6) δ ppm 9.30 (d, J=0.76 Hz, 1H), 8.87 (s, 1H), 8.68 (dd, J=4.69, 1.65 Hz, 1H), 8.06 (d, J=4.56 Hz, 1H), 7.37 (d, J=8.87 Hz, 2H), 6.91 (d, J=8.87 Hz, 2H), 6.14 (s, 2H), 3.72 (s, 3H). LCMS m / z 375.1 [M+H]+, tret= 1.07 min [TFA]. Step 2 2-(1-(4-Methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazine (200 mg, 0.534 mmol) was dissovled in 5 mL MeOH. Pd-C (10 wt%, 56.9 mg, 0.053 mmol) was added to the reaction under a nitrogen flow. A hydrogen balloon was put on top of the reaction flask. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was filtered and the filtrate was concentrated to afford crude 2-(1-(4- methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6,7,8-tetrahydroimidazo[1,2- a]pyrazine as a brown oil (233 mg, 97% yield). LCMS m / z 379.2 [M+H]+, tret= 0.72 min [TFA]. Step 3 2-(1-(4-Methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6,7,8- tetrahydroimidazo[1,2-a]pyrazine (233 mg, 0.616 mmol) was dissovled in DCM (5 mL), and then ethyl chloroformate (0.089 mL, 0.924 mmol) was added. The reaction mixture was stirred at room temperature for 1 h, and LCMS analysis indicated the reaction had proceeded ~80%. The reaction mixture was stirred another 5 h; no further progression by LCMS. Triethylamine (0.258 mL, 1.847 mmol) and additional ethyl chloroformate (0.089 mL, 0.924 mmol) was added and the reaction mixture was stirred at rt for 16 h, but no further conversion occurred. The reaction mixture was partitioned between saturated aq NaHCO3and DCM. The organic layer was washed with brine, dried over MgSO4, and concentrated to a brown residue.The residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 20% - 80% EtOAc / Hexanes). Collected fractions containing the product were combined and concentrated to give ethyl 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)- 1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate as a colorless oil (164 mg, 59% yield).1H NMR (400 MHz, CDCl3) δ ppm 7.62 (s, 1H), 7.37 (d, J=8.62 Hz, 2H), 6.84 (d, J=8.62 Hz, 2H), 5.97 (s, 2H), 4.82 (s, 2H), 4.25 (q, J=7.10 Hz, 2H), 4.08 (d, J=5.32 Hz, 2H), 3.96 (d, J=4.82 Hz, 2H), 3.78 (s, 3H), 1.34 (t, J=7.10 Hz, 3H). LCMS m / z 451.1 [M+H]+, tret= 1.15 min [TFA]. Step 4 Ethyl 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6- dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate (164 mg, 0.364 mmol) was dissovled in DMF (5 mL), and then NIS (246 mg, 1.092 mmol) was added. The reaction mixture was stirred 90 °C for 16 h. The brown reaction mixture was concentrated and the residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 20% - 80% EtOAc / Hexanes). Collected fractions containing the product were combined and concentrated to give ethyl 3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate as a colorless oil (146 mg, 70% yield).1H NMR (400 MHz, CDCl3) δ ppm 7.32 (d, J=8.62 Hz, 2H), 6.85 (d, J=8.62 Hz, 2H), 5.88 (s, 2H), 4.84 (s, 2H), 4.26 (q, J=7.10 Hz, 2H), 4.00 (s, 4H), 3.79 (s, 3H), 1.35 (t, J=7.10 Hz, 3H). LCMS m / z 577.1 [M+H]+, tret= 1.25 min [TFA]. Step 5 Ethyl 3-iodo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6- dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate (146 mg, 0.253 mmol), 1-(tetrahydro-2H- pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (78 mg, 0.279 mmol), and K3PO4(108 mg, 0.507 mmol) were mixed in 1,4-dioxane (6.00 mL) and water (2 mL). Nitrogen was bubbled into the reaction mixture for 5 min, and then PdCl2dppf (20.69 mg, 0.025 mmol) was added. The reaction vial was sealed and heated in a Biotage microwave reactor at 100 °C for 15 min. The reaction mixture was cooled to room temperature and partitioned between H2O and DCM. The organic layer was washed with brine, dried over MgSO4, and concentrated to a brown residue. The residue was purified by Isco Combiflash (40 g RediSep column using an eluent of 10% - 80% (3:1 EtOAc / EtOH) / Hexanes). Collected fractions containing the product were combined and concentrated to give ethyl 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)- 3-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)- carboxylate as a light brown solid (91 mg, 60% yield). LCMS m / z 601.3 [M+H]+, tret= 1.21 min [TFA]. Step 6 Ethyl 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-3-(1-(tetrahydro-2H- pyran-2-yl)-1H-pyrazol-4-yl)-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate (30 mg, 0.050 mmol) was dissolved in TFA (2 mL). The reaction mixture was stirred at 65 °C for 16 h. The black reaction mixture was concentrated and the black residue was was purified by reverse phase HPLC (XSELECT CSH C18 column using an eluent of 30% - 85% CH3CN / H2O with 0.1% formic acid). The clean fractions after HPLC were combined and concentrated to give ethyl 3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)- 5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate as a white solid (13 mg, 65% yield).1H NMR (400 MHz, DMSO-d6) δ ppm 15.13 – 14.72 (m, 1H), 13.39 – 13.03 (m, 1H), 8.29 (s, 1H), 7.97 (d, J = 1.5 Hz, 1H), 4.73 (br s, 2H), 4.16 – 4.11 (m, 2H), 4.06 (br t, J = 5.3 Hz, 2H), 3.86 (br d, J = 4.8 Hz, 2H), 1.25 (t, J = 7.1 Hz, 3H). LCMS m / z 397.2 [M+H]+, tret= 0.67 min [TFA]. Example 29 3-(1H-imidazol-4-yl)-7-(trifluoromethyl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-b]pyridazine

[0013] Steps 1-3 To a solution of 5-(trifluoromethyl)pyridazin-3-amine (250 mg, 1.53 mmol) in acetonitrile (16 mL) was added 2-chloro-1-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)ethan-1-one (Intermediate 3) (767 mg, 2.30 mmol). The reaction mixture was heated in a microwave reactor at 175 °C for 4 h. The reaction mixture was concentrated, and the residue was purified by silica gel chromatography, eluting with 0-100% ethyl acetate in heptane, to give 2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-7- (trifluoromethyl)imidazo[1,2-b]pyridazine (440 mg). This material was dissolved in acetonitrile (10 mL), and NBS (266 mg, 1.49 mmol) was added. The reaction mixture was heated at 70 °C for 3 h. The reaction mixture was concentrated. The residue was taken up in ethyl acetate, and the organic phase was washed with H2O (x4), dried over Na2SO4, and concentrated. The residue was taken up in DCM, insolubles were removed by filtration, and the filtrate was directly purified by silica gel chromatography, eluting with 0-50% ethyl acetate in heptane to give 3-bromo-2-(1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-1,2,4- triazol-5-yl)-7-(trifluoromethyl)imidazo[1,2-b]pyridazine (440 mg). This material (410 mg of the isolated 440 mg) and N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- imidazole-1-sulfonamide (Intermediate 2) (421 mg, 1.40 mmol) were dissolved in 1,4- dioxane (16 mL). K3PO4(342 mg, 1.61 mmol), PdCl2(dppf)-CH2Cl2(128 mg, 0.157 mmol), and water (4 mL) were added. Nitrogen was bubbled through the mixture. The reaction mixture was heated in a microwave reactor at 115 °C for 1.75 h. The volatiles were removed. The residue was taken up in ethyl acetate and filtered through Celite. The filtrate was washed with water and dried over Na2SO4. The crude material was purified by silica gel chromatography, eluting with 0-100% ethyl acetate in heptane. The isolated material (300 mg) was dissolved in TFA (4 mL) and heated in a sealed vessel at 75 °C overnight. The reaction mixture was concentrated. The residue was taken up in methanol, and the pH was adjusted using 7N ammonia in methanol. The volatiles were removed. The residue was taken up in DMSO, filtered, and purified by reverse phase chromatography (MDAP Method I) to give 3-(1H-imidazol-4-yl)-7-(trifluoromethyl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-b]pyridazine (8.3 mg).1H NMR (400 MHz, DMSO-d6) δ ppm 9.20 (d, J = 2.4 Hz, 1H), 8.96 (s, 1H), 8.42 (s, 1H), 8.37 (s, 1H), 2H signals not observed. LCMS m / z 389.3 [M+H]+, tret= 0.63 min [TFA]. The following examples were also prepared using analogous methods to those described above and in accordance with the General Methods.

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F mrmrmr [ [ 0T[ N F FF- - - - - - -24,- , - -3-4,-el-3-4 -H2 2 3l 1[cit ,2-7- 1( ,1[ l (o(- (- -4,- 2,21,(-2,2, irtH-1[2-)1-1[i1n-yo )l htz ec ,1-3- en -2o-26-2-)2,2,eaa H nidi-)lza -n)lyly 1-1[Ho1z l-ey-H ozobyh -6di or1-aruryety-di at-4ht H oz)a ldyini41- a hz-l)ldr tiace-)mioutl of(pmly)l lfiasm-]a4- m 3a ly loi) u -lb)le 1om)-)a ldeinidtmiae )lroyz yahtmi-8o -e )l- ro5 y-- ro l4-T,di r -b ) -ly 2,xoz yba - ly zay yd 5hmiir- -7 di xo te )l ymy- p] dimy- enulo loeca -3 -15[orai lo-yn mhm-p]o5-l ami o 5-liz fi zaizni(- -lzcmi- z id i-teo 5-la rooz - roozar d(- rta -diza2l oz ad H air irH1 yx rooulH iurl y 3 ryai 1t- y (i o ulzfati1( fai p (4,myhi( pfai(rt-3irt(rt]a-22,i-p] trtmi1 H) -34,]ad-ht irt rt1 a el( my (-22,e (1 7,3m 637 8 9 0 113131314141]A]] ]A]A F T[05A73A F T F [T[3.F.F 80T[ 0T[ 1433 - - 4 3- - - - 3- , -(-4-(-4-N-5-l- ot2 -l-- 2, ,-23,21,2-,2,2,-1[ )l1-1[-2,l2 o-,)l2,21,ore z- -1[ ou niair4a-4-nl -,s lioz2- a)l eyni(- H o-zy-H oz 2 -1y-H ozlfimt-o 2 endi z di-r5me 2) 1ae4- 1a -)l- 4- 1ada-4, za,1 iz caad y-la- diy -)dini l-)diynx loy al-)di-21-2,d[ai p]o1-romz oz ly-7hoz ly ,i2n 1ozirt cit mibza n lhhhtt iee )l arahmy- ypd]itmime )l -ty ni ea odi htmie)l-y)l a -miy htH- ad] e -- i4,cH2i,rt-ahtcoirm-dir ro mm- -el 1-H1m2, ao 1(-1[ 4, edm)l or5-l a -o 5-lyui-o 5-l7- yo(-i)l 1[r 3 o2,or yyoo Hru oop] lfiHroo nihtm7-y ]o bu (-za1lzfira1(-oH -ulzaad1( ulza dieor )llfi3( diHulfti(rt3(f-irtir-t3(firtirt rymb- y rT - 2mi1-id 2( -2( p] 3a(-)6l)yly243 45 614141 4141 Biological Data Recombinant human CGAS Production. Human cGAS (157-522) was purified from E. coli (BL21(DE3)*) expressing an amino- terminal His-MBP-tev tag by Ni-IDA affinity chromatography in lysis buffer ((20 mM HEPES, pH 7.5, 400mM NaCl, 10% glycerol, 30mM Imidazole, 1mM PMSF, 1mM TCEP, 100mM Arginine, 100mM Glutamic Acid, and protease inhibitors (Roche complete EDTA-free)) and eluted step-wise using 50 and 500mM imidazole in wash buffer (20 mM HEPES, pH 7.5, 400mM NaCl, 10% glycerol, 1mM TCEP). The eluted protein was further purified by size exclusion chromatography using Superdex 75 equilibrated in 20mM HEPES, pH 7.5, 400mM NaCl, 1mM TCEP, 1mM PMSF. RapidFire 300 Mass Spectrometric (RF-MS 300) Assay. Compounds were resuspended in 10mM stock concentration using DMSO and tested to determine their IC50 values against human CGAS (157-522) using a RapidFire Mass spectrometry assay. Compounds were serially diluted 2, 3, or 4-fold in neat DMSO to generate 11-point dose response curves and then 250nL compound or DMSO solution was transferred to Greiner 384-well V-bottom assay plates (Catalog # 781280) using an Echo acoustic dispenser (Labcyte). A solution of 150 µM ATP, 150 µM GTP, 20 µM pppGpA (GTP-2’5’-AMP, custom synthesis from ChemGenes), and 10 µg / mL sheared salmon sperm DNA (Sigma, Catalog # D1626) in assay buffer (20mM Trizma, pH 7.5, 10mM magnesium chloride, 0.3mM CHAPS, and 0.01% (w / v) bovine serum albumin) was added to columns 1-17, 19-24 of the plate at 12.5 µL / well using a Combi liquid handler (ThermoFisher). A 12.5 µL / well low control solution containing 150 µM ATP, 150 µM GTP, 20 µM pppGpA in assay buffer was added to column 18 using the Combi. A 12.5 µL / well solution of 10-100 nM human CGAS (157-522) in assay buffer was then added to all wells of the plate using the Combi. Plates were centrifuged to mix the solutions and then incubated for 1-2 hr at room temperature. Reactions were quenched by added 50 µL / well of 0.5% (v / v) trifluoroacetic acid (TFA) in mass spectrometry grade deionized water containing 5 µM cyclic-di-UMP (ci- di-UMP; Invivogen Catalog # tlrl-cdu) as the internal standard (IS). Plates were centrifuged for 1 min and then quenched reactions were analyzed using a RF-MS 300 system operating in a Multiple Reaction Monitoring (MRM) detection mode. Samples (10 µL injection volume) were passed over a silica C18 / type C solid phase extraction (SPE) cartridge for analyte (2’3’-cyclic guanosine monophosphate adenosine monophosphate (2’3’-cGAMP), product of biochemical reaction) / pppGpA / c-di-UMP IS adsorption. Adsorbed samples were desalted for 3000 ms using a 100 % water eluent A / desalting solution. Afterwards, desalted samples were eluted using a 0.5 % TFA in 20 % / 80 % acetonitrile / water eluent B / elution solution directly into either a Sciex 4000, 5000 or 5500 triple quadrupole mass spectrometer (QQQ-MS) for MRM analyte / IS detection. QQQ- MS detection conditions were as follow: scan type: MRM; curtain (CUR) gas: 30 psi; nebulizer (GS1) gas: 50 psi; drying (GS2) gas: 60 psi; collisionally activated dissociation (CAD) gas: 12 relative setting; precursor ion (Q1) masses: 2’3’-cGAMP: m / z 675.1 Da / pppGpA: m / z 853.0 Da / c-di-UMP: m / z 613.1 Da; fragment ion (Q3) masses: 2’3’- cGAMP: m / z 524.1 Da / pppGpA: m / z 702.0 Da / c-di-UMP: 307.1 Da; declustering potentials (DPs): 2’3’-cGAMP: +81 V / pppGpA: +85 V / c-di-UMP: +85 V; entrance potential: +10 V (all analytes); collision energies (CEs): 2’3’-cGAMP: +33 V / pppGpA: +36 V / c-di-UMP: +35 V; collision cell exit potential (CXP): +10 V (all analytes); interface heater (Sciex 4000 / 5000 only): on; Q1 resolution: unit (all analyte); Q3 resolution: unit (all analytes). The area under the curve (AUC) for all analytes was obtained using the RapidFire Integrator software application to calculate AUC-2’3’-cGAMP / AUC-c-di-UMP intensity ratio. Percent product formation was calculated by comparison to column 6 (high control) / column 18 (low control) responses. The % product inhibition was calculated as follows: % inhibition = 100 x [(sample – average low control) / (average high control – average low control)]Curve fitting was performed using the equation ^^ ൌ ^^ ^ ^^^ି^^ ವ൩,where A is the minimum response, B is the C is the log10 * XC50, D is the slope factor, and x is the log10 compound concentration [M] in ABASE XE. CGAS Whole Blood Cytokine Release Assay Blood collection: Blood was collected in a tube containing 10% Sodium Heparin (5ml / 45ml blood final). Protocol for CGAS Whole Blood Cytokine Release Assay: Compounds serial diluted at 1:3 were provided at 150nL per well, in a 384 well polypropylene microplate (cat. 781280; Greiner Bio-One, Frickenhausen, Germany).5μL of PBS / 20% Null BacMam was dispensed to all wells except for column 18 on a Multidrop Combi (Thermo Scientific, Waltham, MA). 5uL of PBS was dispensed into column 18. The Bravo (Agilent, Santa Clara, CA) was used to transfer 45uL of donor derived blood into the compound plates. The Bravo protocol mixed the blood and compound / PBS 5 times. The plates were incubated at 37 °C, 5% CO2, for 6 hours. At the 6 hour mark the plates were removed and centrifuged for 10 minutes at 3000 RPM. 3uL of supernatant was transferred from the plate to a 384 well NBS microplate (cat. 4513; Corning Life Sciences, Corning, NY). These plates were sealed with adhesive foil and stored in a -80 freezer until ready for analysis. For cytokine detection, Human IP-10 BD cytometric bead array (CBA) beads (BD Biosciences, Franklin Lakes, NJ) were used. Capture bead solution was prepared by performing a 1:50 dilution of the IP-10 capture bead stock solution in BD diluent for serum / plasma (cat.51-9003991 BD Biosciences, Franklin Lakes, NJ).2 μL of this solution was added per well to the assay microplates which were then sealed with adhesive foil and incubated at room temperature for 2 h in the dark. Detection reagent was further prepared by performing a 1:50 dilution of the detection reagent stock solution. 2 μL of detection reagent was added per well and microplates were sealed with adhesive foil and incubated at room temperature in the dark for 1 h. After the 1 h incubation 3 uL of BD CBA wash buffer was added per well of the microplates. Data were acquired on an iQue Screener flow cytometer. The iQue used fluorescence detection to quantify the inhibition of IP-10 present in the sample wells. A sip time of 1 second per sample was used. The blue laser with excitation of 488 nm and emission filters 585 / 40 nm were used to capture the mean and median of IP-10 with the detector in logarithmic mode (FL2-H). All data analysis was carried out in IDBS ActivityBase XE. Percent inhibition is determined using the formula 100-(100(U-C2) / (C1-C2)), where U is the unknown value, C1 is the average high control response of the mixture in DMSO only, and C2 is the average of minimum response of column 18 no BacMam stimulation control. Curve fitting was performed using the equation ^^ ൌ ^^ ^ ^^^ି^^ ವ൩,where A is the minimum response, B is the maximum C is the log10* XC50, D is the slope factor, and x is the log10compound concentration [M] in ABASE XE. The biological data from the RF-MS 300 assay and the whole blood (hWB) cytokine release assay for the compounds are shown in Table 2 below. Example RF-MS hWB Example RF-MS hWB Example RF-MS hWB Example RF-MS hWB Example RF-MS hWB Example RF-MS hWB Example RF-MS hWB Example RF-MS hWB

Claims

CLAIMS 1. A compound of Formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof, wherein 1R is hydrogen or a R2is selected from the group consisting of hydrogen, halo, cyano, nitro, C1-3alkyl, halo(C1-3)alkyl, halo(C1-3)alkoxy, -S(O)R7, -SO2R7, -C(O)NR7R8, -NR7C(O)R8, and -CO2R7, wherein C1-3alkyl, halo(C1-3)alkyl, and halo(C1-3)alkoxy is optionally substituted by hydroxyl, -NR7R8, or C3-4cycloalkyl; R3is a 5- or 6-membered heteroaryl optionally substituted by C1-3alkyl, -C(O)R8, or a prodrug moiety; ring A is a 5- or 6-membered heteroaryl or 5- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S; p is 0, 1, 2, or 3; each X is independently selected from oxo and L-Y; each L is independently selected from a bond, -(CRaRb)n-, -O-, -(CRaRb)nO-, -O(CRaRb)n-, -(CRaRb)nO(CRaRb)m-, -SO2-, -SO2(CRaRb)n-, -C(O)O-, -OC(O)-, - C(O)O(CRaRb)n-, -(CRaRb)nC(O)O-, -C(O)NH(CRaRb)n-, -NRaC(O)(CRaRb)n-, or - NH(CRaRb)n-, wherein each n or m is independently selected from 1, 2, or 3; each Raand Rbis independently selected from hydrogen, halo, or C1-4alkyl; each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7cycloalkenyl, C2-4alkenyl, C2-6alkynyl, thio(C1-4)alkyl, hydroxy(C1-6)alkyl, cyano(C1-4)alkyl, halo(C1-4)alkyl, halo(C2-4)alkenyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, - C(O)SR10, -CO2R10, -C(O)R10, -CHCHC(O)OR10, -OSO2R10, -S(O)R10, - N(R10)SO2R10, -P(O)(Ph)OR10, -P(O)(OR10)2, -P(S)(Ph)OR10, phenyl, 5- or 6- membered heteroaryl, and 3- to 7-membered heterocycloalkyl ring containing one, two, or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, phenyl, heteroaryl, and heterocycloalkyl groups areoptionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; or two X substituents taken together with the carbon atoms to which they are attached form a ring selected from phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8- membered heteroaryl, or a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the phenyl, C5-8cycloalkyl, C5-8cycloalkenyl, 5- to 8-membered heteroaryl, or 5- to 8-membered heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, C1-4alkyl, oxo, -C(O)R10, -SO2R10, -C1-3alkylene- NR9R10, and -C1-3alkylene-OR10; R7and R8are independently selected from hydrogen and C1-3alkyl; R9is independently selected from the group consisting of hydrogen, hydroxy, C1-4alkyl, -C(O)C1-4alkyl, and halo(C1-4)alkyl; and R10is independently selected from hydrogen and C1-6alkyl; or wherein R9and R10taken together with the nitrogen atom to which they are attached form a 5- to 8-membered heterocycloalkyl ring containing one or two heteroatoms independently selected from N, O, and S, wherein the heterocycloalkyl ring is optionally substituted with one, two, or three substituents independently selected from halo, amino, hydroxyl, -C(O)R10, oxo, C1-4alkyl, C1-4alkoxy, halo(C1-4)alkyl, and hydroxy(C1-4)alkyl; with the proviso that the compound of Formula I is not a compound of Formula (II), wherein R1, R2, R3, X and p arewith Formula (I).

2. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according Claim 1, wherein ring A is selected from. g ypny one of the preceding claims.

3. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to Claim 1 or Claim 2, wherein the compound of Formula (I) is a compound of Formula (ID) .

4. A compound or aacceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein each Raand Rbis independently selected from hydrogen and fluoro.

5. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein each prodrug moiety is independently selected from the group consisting of -CH(Rc)O-P(O)(ORd)(ORe), -CH(Rc)O-C(O)-C1-6alkylene-O-P(O)(ORd)(ORe), - CH(Rc)O-C(O)-C1-6alkylene-P(O)(ORd)(ORe), -CH(Rc)O-C(O)-C1-6alkylene-CO2H, - CH(Rc)O-C(O)Rd, -CH(Rc)O-C(O)ORd, -CH(Rc)O-C(O)O-C1-6alkylene-CO2H, - CH(Rc)O-C(O)-C1-6alkylene-NRdRe, -CH(Rc)O-C(O)O-C1-6alkylene-NRdRe, - C(O)Rd, -CH(Rc)O-C(O)-C1-6alkylene-heterocycloalkyl, -CH(Rc)O-C(O)-C1-6alkylene-heterocycloalkyl and -CRdRe-O-(C(O)-NRd-heteroarylene-CH2O-C(O)- CH2-NRdRe; wherein Rcis independently selected from hydrogen and methyl; Rdand Reare each independently hydrogen or C1-6alkyl;each heterocycloalkyl is 4- to 6-membered and contains one or two heteroatoms independently selected from N, O, and S; and each heteroarylene is 5- or 6-membered and contains one or two heteroatoms independently selected from N, O, and S.

6. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein each prodrug moiety is independently selected from7. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein each prodrug moiety is . 8.or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein R3is a 5-membered heteroaryl.

9. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein R3is a 5-membered nitrogen containing heteroaryl.

10. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein R3is imidazolyl or pyrazolyl.

11. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein R1is a prodrug moiety and R3is imidazolyl.

12. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of claims 1 or 2, wherein R1is hydrogen and R3is imidazolyl.

13. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein R2is selected from the group consisting of hydrogen, bromo, cyano, - C(O)NH2, -CF2CH2NH2, -CF2CH2CH2NH2, -CHFCH2NH2, -CF2CH2NHCH3, - CF2CH2OH, -CH2F, -CHF2, -CF3, -CF2CF3, -CF2CH3, -CF2CH(OH)CH3, - CF2CH(NH2)CH3, -CF2CHF2, -OCHF2, -S(O)CH3, -C(O)OCH2CH3, -CClF2, -CH3, and -CF2-cyclopropyl.

14. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein R2is selected from the group consisting of Br, -CHF2, and -CF3.

15. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein R2is -CF3.

16. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein each L is a bond, -(CRaRb)n-, -O-, -(CRaRb)nO, -O(CRaRb)n-, - (CRaRb)nO(CRaRb)m-, -SO2-, -SO2CH2-, -C(O)O-, -OC(O)-, -C(O)O(CRaRb)n-, - C(O)NH(CRaRb)n-, or -NH(CRaRb)n- and each Y is independently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-7cycloalkyl, C5-7 cycloalkenyl, C2-4 alkenyl, C2-6 alkynyl, hydroxy(C1-6)alkyl, halo(C1- 4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10-CO2R10, -COR10, -OSO2R10, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two or three heteroatoms independently selected from N, O, and S, wherein the C3-7cycloalkyl, C5-7cycloalkenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one, two or three substituents independently selected from halo, amino, C1-4alkyl, C1-4alkoxy, and hydroxy(C1-4)alkyl.

17. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein each L is a bond.

18. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to claim 17, wherein each Y isindependently selected from the group consisting of hydrogen, halo, hydroxyl, cyano, C1-4alkyl, C1-4alkoxy, C3-6cycloalkyl, cyclohexenyl, C2-4alkenyl, C2-6alkynyl, hydroxy(C1-6)alkyl, halo(C1-4)alkyl, hydroxy(C2-6)alkynyl, -NR9R10, -C(O)NR9R10, - CO2R10, -C(O)R10, -SO2R10, -OSO2R10, -SO2NR9R10, phenyl, 5- or 6-membered heteroaryl, and 4- to 6-membered heterocycloalkyl ring containing one, two or three heteroatoms independently selected from N, O, and S, wherein the C3-6cycloalkyl, cyclohexenyl, heteroaryl, and heterocycloalkyl groups are optionally substituted with one C1-3alkyl.

19. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein X is independently selected from oxo and L-Y.

20. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein each Y is independently selected from hydrogen, halo, hydroxyl, cyano, C1-3alkyl, -CO2R10, -COR10, halo(C1-3)alkyl, C1-3alkoxy, and phenyl.

21. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein Y is independently selected from hydrogen, fluoro, cyano, methyl, and - CO2Me.

22. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof according to any one of the preceding claims, wherein p is 1.

23. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof selected from the group consisting of: 1-(3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridin-6-yl)ethan-1-one, 5-(1H-Imidazol-5-yl)-2-methyl-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[2,1-b]oxazole, 7-(1H-imidazol-5-yl)-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- b][1,2,4]triazine, 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydro-8H- imidazo[2,1-c][1,4]oxazine,5-(1H-imidazol-5-yl)-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-1H-imidazo[1,2- a]imidazole, 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H- pyrrolo[1,2-a]imidazol-6-ol, 6-fluoro-3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2- a]pyridine, 2-(3-bromo-1H-1,2,4-triazol-5-yl)-6,8-difluoro-3-(1H-imidazol-5-yl)imidazo[1,2- a]pyridine, (5-(8-fluoro-3-(1H-imidazol-5-yl)-7-methylimidazo[1,2-a]pyridin-2-yl)-3- (trifluoromethyl)-1H-1,2,4-triazol-1-yl)methyl dihydrogen phosphate, 6-bromo-3-(1H-imidazol-5-yl)-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine, 3-(1H-imidazol-5-yl)-5,7-dimethyl-6-phenyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine, 7-Bromo-3-(1H-pyrazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine, 3-(1H-Imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine; 8-Fluoro-3-(1H-imidazol-4-yl)-7-methyl-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine, 3-(1H-Imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine-8-carbonitrile, 6,7-Difluoro-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyridine, 3-(1H-imidazol-5-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)-6,7-dihydro-5H,9H- imidazo[2,1-c][1,4]oxazepine, 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine, 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- b]pyridazine,7-chloro-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-c]pyrimidine, 3-(1H-imidazol-4-yl)-6-methoxy-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-a]pyrazine, 2-(3-(Difluoromethyl)-1H-1,2,4-triazol-5-yl)-3-(1H-imidazol-4-yl)imidazo[1,2- a]pyrazine, 6-Ethyl-3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine, Methyl 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyrazine-6-carboxylate, 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridin-7-ol, Methyl 3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridine-7-carboxylate, 2-(3-(1H-imidazol-4-yl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2- a]pyridin-6-yl)-2,2-difluoro-N-methylethan-1-amine, Ethyl 3-(1H-pyrazol-4-yl)-2-(5-(trifluoromethyl)-1H-1,2,4-triazol-3-yl)-5,6- dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate, and 3-(1H-imidazol-4-yl)-7-(trifluoromethyl)-2-(3-(trifluoromethyl)-1H-1,2,4-triazol-5- yl)imidazo[1,2-b]pyridazine, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof.

24. A compound according to claim 1, which is ,or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof.

25. A compound according to any one of claims 1 to 24.

26. A pharmaceutical composition comprising (a) a compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof as defined in any one of claims 1 to 25; and (b) a pharmaceutically acceptable excipient.

27. A method of treatment of an autoimmune, autoinflammatory or immune-mediated condition in a human in need thereof comprising administering to said human a therapeutically effective amount of a compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof as defined in any one of claims 1 to 25.

28. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof as defined in any one of claims 1 to 25 for use in therapy.

29. A compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof as defined in any one of claims 1 to 25, for use in the treatment of an autoimmune, autoinflammatory or immune-mediated condition.

30. Use of a compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof as defined in any one of claims 1 to 25 in the manufacture of a medicament for use in the treatment of autoimmune, autoinflammatory or immune-mediated condition.

31. The method of treatment, compound for use or use according to any one of claims 27, 29 or 30, wherein the condition is selected from the group consisting of systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), lupus nephritis, Sjogren’s syndrome, dematomyositis, scleroderma, amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD), acute kidney injury, chronic kidney disease, diabetic kidney injury, myocardial infarction, stroke, heart hypertrophy / heart failure, nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD).

32. The method, compound for use or use according to claim 31, wherein the condition is systemic lupus erythematosus or lupus nephritis.

33. A combination of (i) a compound or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer thereof as defined in any one of claims 1 to 25; and (ii) an immune modulatory agent.

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