Substituted Bicyclic Heteroaryl Compounds

Abstract

Substituted Bicyclic Heteroaryl Compounds Formula (I) Disclosed are compounds of the formula TIFF2022550203000320.tif26153, N-oxides thereof, or salts thereof, where X, Y, A, G, R1, and R5 are defined herein. Also disclosed are methods of using the compounds as inhibitors of signaling through Toll-like receptors 7, 8, or 9, and pharmaceutical compositions containing the compounds. These compounds are useful for treating inflammatory and autoimmune diseases.

Description

[Technical Field]

[0001] (Related Applications) This application claims priority to U.S. Provisional Application No. 62 / 908,840, filed October 1, 2019, which is incorporated herein by reference in its entirety. [Background technology]

[0002] The present invention generally relates to substituted bicyclic heteroaryl compounds that are effective as inhibitors of signaling through Toll-like receptors 7, 8, or 9 (TLR7, TLR8, TLR9), or combinations thereof. The present invention provides substituted bicyclic heteroaryl compounds, compositions containing such compounds, and methods of using them. The present invention also relates to pharmaceutical compositions containing at least one compound described herein that are effective in treating conditions involving TLR modulation (e.g., inflammatory and autoimmune diseases), and methods of inhibiting TLR activity in mammals.

[0003] Members of the Toll / IL-1 receptor family are important regulators of inflammation and host resistance. The Toll-like receptor family recognizes molecular patterns derived from infectious organisms (e.g., bacteria, fungi, parasites, and viruses) (reviewed in Kawai, T. et al., Nature Immunol., 11:373-384 (2010)). Ligand binding to the receptor induces dimerization and recruitment of adaptor molecules to a conserved cytoplasmic motif in the receptor called the Toll / IL-1 receptor (TIR) ​​domain. With the exception of TLR3, all TLRs recruit the adaptor molecule, MyD88. The IL-1 receptor family also contains a cytoplasmic TIR motif and recruits MyD88 upon ligand binding (reviewed in Sims, JE et al., Nature Rev. Immunol., 10:89-102 (2010)).

[0004] Toll-like receptors (TLRs) are a family of transmembrane innate immune receptors conserved throughout evolution and involved in the first line of defense. As pattern-recognition receptors, TLRs are activated by pathogen-associated molecular patterns (PAMPs) to defend against foreign molecules or by damage-associated molecular patterns (DAMPs) to protect against damaged tissue. A total of 13 TLR family members have been identified, with 10 identified in humans, located on the cell surface or in endosomal compartments. TLR7 / 8 / 9, a group located in endosomes, recognize single-stranded RNA (TLR7 and TLR8) or unmethylated single-stranded DNA containing cytosine-phosphate-guanine (CpG) motifs (TLR9).

[0005] Activation of TLR7 / 8 / 9 can initiate various inflammatory responses (cytokine production, B cell activation and IgG production, type I interferon response). In autoimmune disorders, persistent abnormal activation of TLR7 / 8 / 9 leads to exacerbation of the pathology. TLR7 overexpression mice showed exacerbation of autoimmune disease, whereas TLR7 knockout mice in a lupus model mouse (MRL / lpr) were found to be protective against the disease. Dual knockout of TLR7 and 9 was shown to further enhance protection.

[0006] Since numerous conditions can be ameliorated by treatments involving modulation of cytokines, IFN production, and B cell activity, it is clear that novel compounds capable of modulating TLR7 and / or TLR8 and / or TLR9, and methods of using those compounds, may offer substantial therapeutic benefit to a wide range of patients. Summary of the Invention

[0007] The present invention relates to novel substituted bicyclic heteroaryls that have been found to be effective inhibitors of TLR7 / 8 / 9-mediated signaling. These compounds provide effective pharmaceutical agents with desirable stability, bioavailability, therapeutic index, and toxicity values ​​important for their druggability.

[0008] The present invention provides compounds of formula (I), or stereoisomers, N-oxides, tautomers, pharmaceutically acceptable salts, solvates or prodrugs thereof, which are effective as inhibitors of signaling through Toll-like receptors 7, 8, or 9, and which are effective in the treatment of proliferative, allergic, autoimmune and inflammatory diseases.

[0009] The present invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier and at least one compound of the present invention, or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate, or prodrug thereof.

[0010] The present invention also provides a method for inhibiting Toll-like receptor 7, 8, or 9, comprising administering to a patient in need of such treatment a therapeutically effective amount of at least one compound of the present invention, or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate, or prodrug thereof.

[0011] The present invention also provides methods for treating proliferative, metabolic, allergic, autoimmune and inflammatory diseases, comprising administering to a patient in need of such treatment a therapeutically effective amount of at least one compound of the present invention, or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate, or prodrug thereof.

[0012] The present invention also provides a method for treating a disease or disorder associated with Toll-like receptor 7, 8, or 9 activity, comprising administering to a mammal in need thereof at least one of a compound of formula (I), or a salt, solvate, or prodrug thereof.

[0013] The present invention also provides methods and intermediates for synthesizing compounds of formula (I), including salts, solvates, and prodrugs thereof.

[0014] The present invention also provides at least one compound of formula (I), or a salt, solvate, or prodrug thereof, for use in therapy.

[0015] The present invention also provides the use of at least one of the compounds of formula (I), or salts, solvates, and prodrugs thereof, for the manufacture of a medicament for the treatment or prevention of conditions associated with Toll-like receptors 7, 8, or 9 (e.g., allergic, autoimmune, inflammatory, and proliferative diseases).

[0016] Compounds of formula (I) and compositions comprising compounds of formula (I) can be used to treat, prevent, or ameliorate a variety of conditions associated with Toll-like receptors 7, 8, or 9. Pharmaceutical compositions comprising these compounds are effective in treating, preventing, or delaying the progression of diseases or disorders in a variety of therapeutic areas, such as allergic diseases, autoimmune diseases, inflammatory diseases, and proliferative diseases.

[0017] These and other features of the present invention are set forth in the broader disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0018] A first aspect of the present invention provides a compound having at least one formula (I): [ka] [In the formula, X is N and Y is S; or X is S and Y is N or CH; R1 is H, F, Cl, -CN, C 1-4 Alkyl, C 1-3 Fluoroalkyl, -OCH3, or -S(O)2(C 1-3 alkyl); G is (i) [ka] (ii) [ka] (iii) [ka] (iv) [ka] [ka] [ka] [ka] or a 9-membered heterocycle selected from (v) [ka] [ka] [ka] is a 10-membered heterocycle selected from: Each R2 is independently a halogen, -CN, -OH, -NO2, C 1-4 Alkyl, C 1-2 Fluoroalkyl, C 1-2 Cyanoalkyl, C 1-3 Hydroxyalkyl, C 1-3 Aminoalkyl, -O(CH2) 1-2 OH, -(CH2) 0-4 O(C 1-4 alkyl), C 1-3 Fluoroalkoxy, -(CH2) 1-4 O(C 1-3 alkyl), -O(CH2) 1-2 OC(O)(C 1-3 alkyl), -O(CH2) 1-2 NR x R x , -C(O)O(C 1-3 alkyl), -(CH2) 0-2 C(O)NRy R y , -C(O)NR x (C 1-5 hydroxyalkyl), -C(O)NR x (C 2-6 Alkoxyalkyl), -C(O)NR x (C 3-6 cycloalkyl), -NR y R y , -NR y (C 1-3 Fluoroalkyl), -NR y (C 1-4 hydroxyalkyl), -NR x CH2(phenyl), -NR x S(O)2(C 3-6 cycloalkyl), -NR x C(O)(C 1-3 alkyl), -NR x CH2(C 3-6 cycloalkyl), -(CH2) 0-2 S(O)2(C 1-3 alkyl), -(CH2) 0-2 (C 3-6 cycloalkyl), -(CH2) 0-2 (phenyl), morpholinyl, dioxothiomorpholinyl, dimethylpyrazolyl, methylpiperidinyl, methylpiperazinyl, amino-oxadiazolyl, imidazolyl, pyrimidinyl, triazolyl, or —C(O)(thiazolyl); R 2a is C 1-6 Alkyl, C 1-3 Fluoroalkyl, C 1-6 Hydroxyalkyl, C 1-3 Aminoalkyl, -(CH2) 0-4 O(C 1-3 alkyl), C 3-6 Cycloalkyl, -(CH2) 1-3 C(O)NR y R y , -CH2(C 3-6 cycloalkyl), -CH2(phenyl), tetrahydrofuranyl, tetrahydropyranyl, or phenyl; Each R 2b are independently H, halogen, -CN, -NRx R x , C 1-6 Alkyl, C 1-3 Fluoroalkyl, C 1-3 Hydroxyalkyl, C 1-3 Fluoroalkoxy, -(CH2) 0-2 O(C 1-3 alkyl), -(CH2) 0-3 C(O)NR x R x , -(CH2) 1-3 (C 3-6 cycloalkyl), -C(O)O(C 1-3 alkyl), -C(O)NR x (C 1-3 alkyl), -CR x =CR x R x , or -CR x =CH(C 3-6 cycloalkyl); R 2c is R 2a or R 2b and; R 2d is R 2a or R 2b where R 2c and R 2d One of them is R 2a and R 2c and the other of R2 is R 2b and; A is, (i) H, -NR y R y , or -CH2NHCH2C(O)NR x R x ; (ii)-CR x R x R3, -CR x R x NR x R3, -CR x R x NR x CH2R3, -C(O)NR x R3, -C(O)NR x R4, -C(O)R3, or -NR x C(O)R3; or (iii) R3; R3 is (I C 3-5 cycloalkyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolidinonyl, piperidinyl, piperazinyl, piperazinonyl, morpholinyl, dioxidethiomorpholinyl, oxazepanyl, diazaspiro[3.3]heptanyl, dioxidethiazaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, or oxazaspiro[3.5]nonanyl, each of which has 0 to 2 R 3a and 0 to 2 R 3b is replaced by; (ii) cyclohexyl (such a group is -NR y R y , -NR x (C 1-6 hydroxyalkyl), -NR x (CR x R x ) 1-2 O(C 1-3 alkyl), -NR x (C 1-6 Hydroxy-fluoroalkyl), -NR x CH2C(O)NR x R x , -NR x (CH2) 1-2 S(O)2(C 1-3 alkyl), -NR x C(O)(C 1-3 alkyl), -NR x C(O)CH2NR x R x , -NR x C(O)CH2NR x R y , -NR x (CH2) 1-2 C(O)NR x R x , -NR x (CH2) 1-2 NR x R x , -NR x S(O)2(C 1-3 alkyl), -S(O)2(C 1-3 alkyl), -NR x(cyanocyclopropyl), -NR x (azetidinyl), -NR x (oxetanyl), -NR x (methyloxetanyl), -NR x (ethyloxetanyl), -NR x (isopropyloxetanyl), -NR x (tetrahydropyranyl), -NR x (bicyclo[1.1.1]pentyl), -NR x (CH2(methyloxetanyl)), -NR x (tetrahydrothiophenyl dioxide), -NR x CH2 (hydroxymethylcyclopropyl), -NR x CH2(methylsulfonylcyclopropyl), -NR x CH2 (methylcyclobutyl), -NR x or substituted with HCH2C(O)(morpholinyl), azetidinyl, fluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, pyrrolidinyl, piperazinonyl, morpholinyl, dioxothiomorpholinyl, oxazepanyl, bicyclo[1.1.1]pentanyl, azaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, dioxidethiazaspiro[3.3]heptanyl, oxazabicyclo[3.2.1]octanyl, oxazaspiro[3.5]nonanyl, or diazaspiro[4.4]nonanyl; or (iii) diazaspiro[3.3]heptanyl (such groups are C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(CH2) 1-3 S(O)2(C 1-6 alkyl), oxetanyl, or -CH2 (tetrahydropyranyl); Each R 3a are independently F, Cl, and C 1-6 Alkyl, C 1-6 Cyanoalkyl, C 1-6 Fluoroalkyl, C 1-6 Hydroxyalkyl, -(CH2)1-3 O(C 1-3 alkyl), -C(O)(C 1-6 alkyl), -CH2C(O)NR y R y , -NR y R y , -NR x (C 1-4 hydroxyalkyl), -C(O)(CH2) 1-3 NR y R y , -C(O)(C 1-6 alkyl), -(CH2) 0-2 S(O)2(C 1-3 alkyl), -(CH2) 1-2 NR x S(O)2(C 1-3 alkyl), -NR x CH2C(O)NR y R y , -NR x (CH2) 1-3 S(O)2(C 1-3 alkyl), -NR x (C 3-6 cycloalkyl), -NR x (oxetanyl), -CH2(methyltriazolyl), C 3-6 Cycloalkyl, oxetanyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, -CH2(C 3-6 Cycloalkyl), -CH2 (oxetanyl), -CH2 (methyloxetanyl), -CH2 (tetrahydropyranyl), -NR x (C 3-6 cycloalkyl), -NR x (oxetanyl), -NR x (methyloxetanyl), -NR x CH2 (methyloxetanyl), or -C(O) (dioxidetetrahydrothiopyranyl); Each R 3b is -CH3; R4 is H, C 1-2 Fluoroalkyl, -(CR x R x ) 1-2 NR y R y , or -(CRx R x ) 1-3 R3; R5 is H, C 1-3 Alkyl, or C 1-3 is a fluoroalkyl; Each R x are independently H or -CH3; Each R y are independently H or C 1-6 is alkyl; and p is 0, 1, or 2] or an N-oxide or salt thereof.

[0019] One embodiment provides a compound of formula (I), an N-oxide, or a salt thereof, wherein X is N and Y is S. The compound of this embodiment has the formula (II): [ka] It has the following structure.

[0020] One embodiment provides a compound of formula (I), an N-oxide, or a salt thereof, wherein X is S and Y is N. The compound of this embodiment has the formula (III): [ka] It has the following structure.

[0021] One embodiment provides a compound of formula (I), an N-oxide, or a salt thereof, wherein X is S and Y is CH. The compound of this embodiment has the formula (IV): [ka] It has the following structure.

[0022] In one embodiment, the compound of formula R1 is H, -CH3, -CH2CH3, -CH(CH3)2, -CF3, -OCH3, or -S(O)2(C 1-2 alkyl); G, (i) [ka] (ii) [ka] (iii) [ka] (iv) [ka] [ka] [ka] or a 9-membered heterocycle selected from (v) [ka] [ka] is a 10-membered heterocycle selected from: Each R2 is independently F, Cl, -CN, -OH, or C 1-3 Alkyl, C 1-2 Fluoroalkyl, C 1-2 Cyanoalkyl, C 1-3 Hydroxyalkyl, C 1-2 Aminoalkyl, -(CH2) 0-2 O(C 1-3 alkyl), C 3-6 Cycloalkyl, -NR x R x , -(CH2) 0-2 C(O)NR x R x , -(CH2) 0-2 S(O)2(C 1-3 alkyl), -CH2(C 3-6 cycloalkyl), -CH2(phenyl), phenyl, pyrimidinyl, or triazolyl; R 2a But C 1-4 Alkyl, C 1-2 Fluoroalkyl, C 1-4 Hydroxyalkyl, -(CH2) 1-3 OCH3, C 3-6 Cycloalkyl, -CHC(O)NR x R x , -CH2(C 3-6 cycloalkyl), -CH2(phenyl), tetrahydrofuranyl, or phenyl; Each R 2b are independently H, F, Cl, -CN, -NR x R x , C 1-6 Alkyl, C 1-2 Fluoroalkyl, C 1-3 Hydroxyalkyl, -(CH2) 0-2 O(C 1-2 alkyl), -(CH2) 0-2 C(O)NR x R x , -(CH2) 1-3 (cyclopropyl), -C(O)O(C 1-2 alkyl), or -C(O)NR x (C 1-3 alkyl); A, (i) -CH2NHCH2C(O)NR x R x ; (ii)-CR x R x R3, -CH2NR x R3, -CH2NR x CH2R3, -C(O)NR x R3, -C(O)NR x R4, -C(O)R3, or -NR x C(O)R3; or (iii) R3; and R3, (i) azetidinyl, oxetanyl, cyclopropyl, pyrrolidinyl, pyrrolidinonyl, piperidinyl, piperazinyl, piperazinonyl, morpholinyl, dioxidethiomorpholinyl, oxazepanyl, diazaspiro[3.3]heptanyl, dioxidethiazaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, or oxazaspiro[3.5]nonanyl, each of which has 0 to 1 R 3a and 0 to 2 R 3b is replaced by; (ii) cyclohexyl (such a group is -NR y R y , -NR x (C 1-4 hydroxyalkyl), -NR x (CR x R x ) 1-2 O(C 1-2 alkyl), -NR x (C 1-6 Hydroxy-fluoroalkyl), -NR x CH2C(O)NR x R x , -NR x (CH2) 1-2 S(O)2(C 1-2 alkyl), -NR x C(O)(C 1-2 alkyl), -NR x C(O)CH2NR x R x , -NR x C(O)CH2NR x R y , -NR x (CH2) 1-2 C(O)NR x R x , -NR x (CH2) 1-2 NR x R x , -NR x S(O)2(C 1-2 alkyl), -S(O)2(C 1-2 alkyl), -NR x (cyanocyclopropyl), -NR x (azetidinyl), -NR x (oxetanyl), -NRx (methyloxetanyl), -NR x (ethyloxetanyl), -NR x (isopropyloxetanyl), -NR x (tetrahydropyranyl), -NR x (bicyclo[1.1.1]pentyl), -NR x (CH2(methyloxetanyl)), -NR x (tetrahydrothiophenyl dioxide), -NR x CH2 (hydroxymethylcyclopropyl), -NR x CH2(methylsulfonylcyclopropyl), -NR x CH2 (methylcyclobutyl), -NR x or substituted with HCH2C(O)(morpholinyl), azetidinyl, fluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, pyrrolidinyl, piperazinonyl, morpholinyl, dioxothiomorpholinyl, oxazepanyl, bicyclo[1.1.1]pentanyl, azaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, dioxidethiazaspiro[3.3]heptanyl, oxazabicyclo[3.2.1]octanyl, oxazaspiro[3.5]nonanyl, or diazaspiro[4.4]nonanyl; or (iii) diazaspiro[3.3]heptanyl (such groups are C 1-4 Alkyl, C 1-4 Hydroxyalkyl, -(CH2) 1-2 S(O)2(C 1-3 alkyl), oxetanyl, or -CH2 (tetrahydropyranyl); Each R 3a However, F, Cl, and C are independently 1-5 Alkyl, C 1-3 Cyanoalkyl, C 1-3 Fluoroalkyl, C 1-4 Hydroxyalkyl, -(CH2) 1-2 O(C 1-2 alkyl), -C(O)(C 1-3 alkyl), -CH2C(O)NRx R x , -NR y R y , -NH(C 1-4 hydroxyalkyl), -C(O)(CH2) 1-3 NR x R x , -C(O)(C 1-3 alkyl), -(CH2) 0-2 S(O)2(C 1-2 alkyl), -(CH2) 1-2 NR x S(O)2(C 1-2 alkyl), -NR x CH2C(O)NR y R y , -NR x CH2CH2S(O)2(C 1-2 alkyl), -NR x (C 3-6 cycloalkyl), -NR x (oxetanyl), -CH2(methyltriazolyl), cyclobutyl, oxetanyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, -CH2(C 3-4 Cycloalkyl), -CH2 (oxetanyl), -CH2 (methyloxetanyl), -CH2 (tetrahydropyranyl), -NR x (cyclobutyl), -NR x (oxetanyl), -NR x (methyloxetanyl), -NR x CH2 (methyloxetanyl), or -C(O) (dioxidetetrahydrothiopyranyl); Each R 3b is -CH3; and R5 is H, -CH3, -CH2CH3, -CF3, -CH2CHF2, or -CH2CF3; Provided is a compound of formula (I), an N-oxide, or a salt thereof: Included in this embodiment are compounds where X is N and Y is S. Also included in this embodiment are compounds where X is S and Y is N. Additionally included in this embodiment are compounds where X is S and Y is CH.

[0023] In one embodiment, the compound of formula R1 is independently -CH3, -CH2CH3, or -CH(CH3)2; G, [ka] and; each R2 is independently -CN, -CH3, or -OCH3; A, (i) -CH2NHCH2C(O)NH2; (ii)-CH2R3, -CH2NHR3, -CH2NHCH2R3, -C(O)NHR3, -C(O)NR x R4, or -C(O)R3; or (iii) cyclohexyl, piperidinyl, piperazinyl, methylpiperazinyl, dimethylpiperazinyl, or diazaspiro[3.3]heptanyl, each of which has 0 to 1 R 3a is replaced by; R3 is azetidinyl, oxetanyl, cyclopropyl, cyclobutyl, pyrrolidinyl, pyrrolidinonyl, piperidinyl, piperazinyl, piperazinonyl, morpholinyl, dioxidethiomorpholinyl, oxazepanyl, diazaspiro[3.3]heptanyl, dioxidethiazaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, or oxazaspiro[3.5]nonanyl, each of which may contain 0 to 1 R 3a and 0 to 2 R 3b is replaced by; R 3a is F, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH2C(CH3)3, -CH2CH(CH2CH3)2, -CH2CF3, -CH2CN, -CH2C(CH3)2OH, -CH2CH2OCH3, -CH2CH2S(O)2CH3, -CH2C(O)NR x R x, -OCH3, -C(O)CH3, -C(O)CH2N(CH3)2, -NH2, -NH(CH3), -NH(CH(CH3)2), -NH(CH2C(CH3)3), -NH(CH2C(CH3)2OH), -NH(CH2CHFC(CH3)2OH), -NH(CH2C( CH3)2OCH3), -N(CH3)(CH2CH3), -N(CH3)(CH(CH3)2), -N(CH3)CH2CH(CH3)2, -N(CH3)CH2C(O)N(CH3)2, -N(CH3)CH2CH2S(O)2CH3, -NHC(O)CH2N(CH3) 2, -NHC(O)CH2N(CH3)(CH2CH3), -NHC(O)CH2NH(CH2CH(CH3)2), -NHCH2C(O)NH2, -NHCH2C(O)NH(CH3), -NHCH2C(O)N(CH3)2, -NHCH2CH2NH(CH3), -NHS(O)2CH3, -S(O)2CH3, -CH2(cyclopropyl), -CH2(methyloxetanyl), -CH2(tetrahydropyranyl), -C(O)(dioxidetetrahydrothiopyranyl), -NH(cyanocyclopropyl), -NH(cyclobutyl), -NH(methyl) -cyclobutyl), -NH(oxetanyl), -NH(methyloxetanyl), -NH(ethyloxetanyl), -NH(isopropylpiperidinyl), -NH(tetrahydropyranyl), -NH(bicyclo[1.1.1]pentyl), -NHCH2(methyloxetanyl), -NH(dioxidetetrahydrothiophenyl), -NHCH2(hydroxymethylcyclopropyl), -NHCH2(methylsulfonylcyclopropyl), -NHCH2(methylcyclobutyl), -NHCH2C(O)(morpholinyl), cyclobutyl, azetidinyl, fluoro Oloazetidinyl, difluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, oxetanyl, pyrrolidinyl, acetamidopyrrolidinyl, piperazinonyl, tetrahydropyranyl, morpholinyl, dioxothiomorpholinyl, oxazepanyl, bicyclo[1.1.1]pentanyl, azaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, dioxidothiazaspiro[3.3]heptanyl, oxazabicyclo[3.2.1]octanyl, oxazaspiro[3.5]nonanyl, or diazaspiro[4.4]nonanyl;. Each R 3b is -CH3; R4 is H, -CH2CHF2, -CH2CF3, -CH2CH2N(CH3)2, -CH2R3, -CH2CR x R x R3, or -(CH2)3R3; R5 is H or -CH2CF3; and p is 0, 1, or 2; Provided is a compound of formula (I), an N-oxide, or a salt thereof: Included in this embodiment are compounds where X is N and Y is S. Also included in this embodiment are compounds where X is S and Y is N. Additionally included in this embodiment are compounds where X is S and Y is CH.

[0024] In one embodiment, A is 0 to 1 R 3a The compound of this embodiment is a compound of formula (I), an N-oxide, or a salt thereof, wherein the compound is cyclohexyl substituted with [ka] It has the following structure. Included in this embodiment are compounds where X is N and Y is S. Also included in this embodiment are compounds where X is S and Y is N. Additionally included in this embodiment are compounds where X is S and Y is CH.

[0025] In one embodiment, A is 0 to 1 R 3a The compound of this embodiment is a compound of formula (I), an N-oxide, or a salt thereof, wherein the compound is cyclohexyl substituted with [ka] It has the following structure. In this embodiment, G is [ka] Also included in this embodiment are compounds in which R 3a is F, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH2C(CH3)3, -CH2CH(CH2CH3)2, -CH2CF3, -CH2CN, -CH2C(CH3)2OH, -CH2CH2OCH3, -CH2CH2S(O)2CH3, -CH2C(O)NR x R x, -OCH3, -C(O)CH3, -C(O)CH2N(CH3)2, -NH2, -NH(CH3), -NH(CH(CH3)2), -NH(CH2C(CH3)3), -NH(CH2C(CH3)2OH), -NH(CH2CHFC(CH3)2OH), -NH(CH2C( CH3)2OCH3), -N(CH3)(CH2CH3), -N(CH3)(CH(CH3)2), -N(CH3)CH2CH(CH3)2, -N(CH3)CH2C(O)N(CH3)2, -N(CH3)CH2CH2S(O)2CH3, -NHC(O)CH2N(CH3) 2, -NHC(O)CH2N(CH3)(CH2CH3), -NHC(O)CH2NH(CH2CH(CH3)2), -NHCH2C(O)NH2, -NHCH2C(O)NH(CH3), -NHCH2C(O)N(CH3)2, -NHCH2CH2NH(CH3), -NHS(O)2CH3, -S(O)2CH3, -CH2(cyclopropyl), -CH2(methyloxetanyl), -CH2(tetrahydropyranyl), -C(O)(dioxidetetrahydrothiopyranyl), -NH(cyanocyclopropyl), -NH(cyclobutyl), -NH(methyl) -cyclobutyl), -NH(oxetanyl), -NH(methyloxetanyl), -NH(ethyloxetanyl), -NH(isopropylpiperidinyl), -NH(tetrahydropyranyl), -NH(bicyclo[1.1.1]pentyl), -NHCH2(methyloxetanyl), -NH(dioxidetetrahydrothiophenyl), -NHCH2(hydroxymethylcyclopropyl), -NHCH2(methylsulfonylcyclopropyl), -NHCH2(methylcyclobutyl), -NHCH2C(O)(morpholinyl), cyclobutyl, azetidinyl, fluoro Oloazetidinyl, difluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, oxetanyl, pyrrolidinyl, acetamidopyrrolidinyl, piperazinonyl, tetrahydropyranyl, morpholinyl, dioxothiomorpholinyl, oxazepanyl, bicyclo[1.1.1]pentanyl, azaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, dioxidothiazaspiro[3.3]heptanyl, oxazabicyclo[3.2.Also included are compounds in which the aryl group is oxazaspiro[3.5]nonanyl, oxazaspiro[3.5]nonanyl, or diazaspiro[4.4]nonanyl.

[0026] In one embodiment, A is 0 to 1 R 3a The compound of this embodiment is 1-piperidinyl substituted with [ka] Included in this embodiment are compounds where X is N and Y is S. Also included in this embodiment are compounds where X is S and Y is N. Additionally included in this embodiment are compounds where X is S and Y is CH.

[0027] In one embodiment, A is 0 to 1 R 3a The compound of this embodiment is 1-piperidinyl substituted with [ka] It has the following structure.

[0028] In this embodiment, G is [ka] Also included in this embodiment are compounds in which R 3a is F, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH2C(CH3)3, -CH2CH(CH2CH3)2, -CH2CF3, -CH2CN, -CH2C(CH3)2OH, -CH2CH2OCH3, -CH2CH2S(O)2CH3, -CH2C(O)NR x R x, -OCH3, -C(O)CH3, -C(O)CH2N(CH3)2, -NH2, -NH(CH3), -NH(CH(CH3)2), -NH(CH2C(CH3)3), -NH(CH2C(CH3)2OH), -NH(CH2CHFC(CH3)2OH), -NH(CH2C( CH3)2OCH3), -N(CH3)(CH2CH3), -N(CH3)(CH(CH3)2), -N(CH3)CH2CH(CH3)2, -N(CH3)CH2C(O)N(CH3)2, -N(CH3)CH2CH2S(O)2CH3, -NHC(O)CH2N(CH3) 2, -NHC(O)CH2N(CH3)(CH2CH3), -NHC(O)CH2NH(CH2CH(CH3)2), -NHCH2C(O)NH2, -NHCH2C(O)NH(CH3), -NHCH2C(O)N(CH3)2, -NHCH2CH2NH(CH3), -NHS(O)2CH3, -S(O)2CH3, -CH2(cyclopropyl), -CH2(methyloxetanyl), -CH2(tetrahydropyranyl), -C(O)(dioxidetetrahydrothiopyranyl), -NH(cyanocyclopropyl), -NH(cyclobutyl), -NH(methyl) -cyclobutyl), -NH(oxetanyl), -NH(methyloxetanyl), -NH(ethyloxetanyl), -NH(isopropylpiperidinyl), -NH(tetrahydropyranyl), -NH(bicyclo[1.1.1]pentyl), -NHCH2(methyloxetanyl), -NH(dioxidetetrahydrothiophenyl), -NHCH2(hydroxymethylcyclopropyl), -NHCH2(methylsulfonylcyclopropyl), -NHCH2(methylcyclobutyl), -NHCH2C(O)(morpholinyl), cyclobutyl, azetidinyl, fluoro Oloazetidinyl, difluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, oxetanyl, pyrrolidinyl, acetamidopyrrolidinyl, piperazinonyl, tetrahydropyranyl, morpholinyl, dioxothiomorpholinyl, oxazepanyl, bicyclo[1.1.1]pentanyl, azaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, dioxidothiazaspiro[3.3]heptanyl, oxazabicyclo[3.2.Also included are compounds in which the aryl group is oxazaspiro[3.5]nonanyl, oxazaspiro[3.5]nonanyl, or diazaspiro[4.4]nonanyl.

[0029] In one embodiment, A is 0 to 1 R 3a The compound of this embodiment is 4-piperidinyl substituted with [ka] It has the following structure. Included in this embodiment are compounds where X is N and Y is S. Also included in this embodiment are compounds where X is S and Y is N. Additionally included in this embodiment are compounds where X is S and Y is CH.

[0030] In one embodiment, A is 0 to 1 R 3a The compound of this embodiment is 4-piperidinyl substituted with [ka] It has the following structure. In this embodiment, G is [ka] The compounds include compounds in which: In this embodiment, R 3a is -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH2C(CH3)3, -CH2CH(CH2CH3)2, -CH2CF3, -CH2CN, -CH2C(CH3)2OH, -CH2CH2OCH3, -CH2CH2S(O)2CH3, -CH2C(O)NR x R x, -C(O)CH3, -C(O)CH2N(CH3)2, -S(O)2CH3, -CH2(cyclopropyl), -CH2(methyloxetanyl), -CH2(tetrahydropyranyl), -C(O)(dioxidetetrahydrothiopyranyl), cyclobutyl, azetidinyl, fluoroazetidinyl, difluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, oxetanyl, pyrrolidinyl, acetamidopyrrolidinyl, tetrahydropyranyl, oxazepanyl, or bicyclo[1.1.1]pentanyl.

[0031] In one embodiment, A is 0 to 1 R 3a and 0 to 2 R 3b The compound of this embodiment is a compound of formula (I), an N-oxide, or a salt thereof, which is piperazinyl substituted with [ka] It has the following structure. Included in this embodiment are compounds where X is N and Y is S. Also included in this embodiment are compounds where X is S and Y is N. Additionally included in this embodiment are compounds where X is S and Y is CH.

[0032] In one embodiment, A is 0 to 1 R 3a and 0 to 2 R 3b The compound of this embodiment is a compound of formula (I), an N-oxide, or a salt thereof, which is piperazinyl substituted with [ka] It has the following structure. In this embodiment, G is [ka] Also included in this embodiment are compounds in which R 3ais -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH2C(CH3)3, -CH2CH(CH2CH3)2, -CH2CF3, -CH2CN, -CH2C(CH3)2OH, -CH2CH2OCH3, -CH2CH2S(O)2CH3, -CH2C(O)NR x R x , -C(O)CH3, -C(O)CH2N(CH3)2, -S(O)2CH3, -CH2(cyclopropyl), -CH2(methyloxetanyl), -CH2(tetrahydropyranyl), -C(O)(dioxidetetrahydrothiopyranyl), cyclobutyl, azetidinyl, fluoroazetidinyl, difluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, oxetanyl, pyrrolidinyl, acetamidopyrrolidinyl, tetrahydropyranyl, oxazepanyl, or bicyclo[1.1.1]pentanyl.

[0033] In one embodiment, A is 0 to 1 R 3a The compound of this embodiment is a diazaspiro[3.3]heptanyl substituted with [ka] It has the following structure. In this embodiment, G is [ka] The compounds include compounds in which: Also included in this embodiment is R 3a is -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH(CH3)2, -CH2C(CH3)3, -CH2CH(CH2CH3)2, -CH2CF3, -CH2CN, -CH2C(CH3)2OH, -CH2CH2OCH3, -CH2CH2S(O)2CH3, -CH2C(O)NR x R x, -C(O)CH3, -C(O)CH2N(CH3)2, -S(O)2CH3, -CH2(cyclopropyl), -CH2(methyloxetanyl), -CH2(tetrahydropyranyl), -C(O)(dioxidetetrahydrothiopyranyl), cyclobutyl, azetidinyl, fluoroazetidinyl, difluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, oxetanyl, pyrrolidinyl, acetamidopyrrolidinyl, tetrahydropyranyl, oxazepanyl, or bicyclo[1.1.1]pentanyl.

[0034] In some embodiments, the compound is a compound of the formula y R y , or -CH2NHCH2C(O)NR x R x

[0023] This embodiment includes compounds where A is H. This embodiment also includes compounds where A is -NR y R y Also included within this embodiment are compounds in which A is -CHNHCHC(O)NR x R x Also included are compounds in which:

[0035] An embodiment provides a compound of formula (I), an N-oxide, or a salt thereof, wherein A is -CH2R3, -CH2NHR3, or -CH2NHCH2R3. This embodiment includes compounds in which G is [ka] Also included within this embodiment are compounds where R3 is isopropylpiperidinyl, dioxidethiazaspiro[3.3]heptanyl, oxazaspiro[3.5]nonanyl, methylsulfonylcyclopropyl, piperazinonyl, morpholinyl, oxazaspiro[3.3]heptanyl, or diazaspiro[3.3]heptanyl.

[0036] In one embodiment, A is —C(O)NHR 3 or —C(O)NR x R4. In this embodiment, G is [ka] Also included in this embodiment are compounds wherein R3 is dimethylaminocyclohexyl, pyrrolidinyl, pyrrolidinonyl, morpholinyl, methylpiperidinyl, morpholinyl, or methylsulfonylcyclopropyl; and R4 is H, —CH2CHF2, —CH2CF3, —CH2CH2N(CH3)2, —CH2R3, —CH2CR x R x Also included are compounds where R3, or -(CH2)3R3.

[0037] One embodiment provides a compound of formula (I), an N-oxide, or a salt thereof, wherein A is -C(O)R3. This embodiment includes compounds in which G is [ka] Also included within this embodiment are compounds where R3 is azetidinyl, fluoroazetidinyl, dimethylaminoazetidinyl, dioxidethiomorpholinyl, morpholinyl, oxazepanyl, oxetanyl, piperazinonyl, acetylpiperazinyl, isopropylpiperazinyl, methylsulfonylpiperazinyl, dimethylaminopiperidinyl, or pyrrolidinyl.

[0038] In some embodiments, A is cyclohexyl, piperidinyl, piperazinyl, methylpiperazinyl, dimethylpiperazinyl, or diazaspiro[3.3]heptanyl, each of which may contain 0 to 1 R 3a The present invention provides a compound of formula (I), an N-oxide, or a salt thereof, substituted with:

[0039] In one embodiment, the compound of formula G, (i) [ka] (ii) [ka] (iii) [ka] (iv) [ka] [ka] [ka] or a 9-membered heterocycle selected from (v) [ka] [ka] The present invention provides a compound of formula (I), an N-oxide, or a salt thereof, wherein R is a 10-membered heterocycle selected from: In this embodiment, G is [ka] Also included in this embodiment are compounds in which G is [ka] Also included are compounds in which:

[0040] In some embodiments, each R2 is independently selected from F, Cl, —CN, —OH, C 1-3 Alkyl, C 1-2 Fluoroalkyl, C 1-2 Cyanoalkyl, C 1-3 Hydroxyalkyl, C 1-2 Aminoalkyl, -(CH2) 0-2 O(C 1-3 alkyl), C3-6 Cycloalkyl, -NR x R x , -(CH2) 0-2 C(O)NR x R x , -(CH2) 0-2 S(O)2(C 1-3 alkyl), -CH2(C 3-6

[0023] Provided is a compound of formula (I), an N-oxide, or a salt thereof, wherein R is independently -CN, -CH, or -OCH.

[0041] An embodiment provides a compound of Formula (I), an N-oxide, or a salt thereof, wherein R5 is H, -CH3, -CH2CH3, -CF3, -CH2CHF2, or -CH2CF3. This embodiment includes compounds where R5 is H or -CH2CF3.

[0042] In some embodiments, R1 is H, -CH3, -CH2CH3, -CH(CH3)2, -CF3, -OCH3, or -S(O)2(C 1-2 The present invention provides a compound of formula (I), an N-oxide, or a salt thereof, wherein R is independently —CH, —CHCH, or —CH(CH). This embodiment includes compounds where R is —CH(CH). This embodiment also includes compounds where R is —CH(CH).

[0043] In some embodiments, R1 is H, -CH3, -CH2CH3, -CH(CH3)2, -CF3, -OCH3, or -S(O)2(C 1-2 alkyl); each R2 is independently F, Cl, —CN, —OH, C 1-3 Alkyl, C 1-2 Fluoroalkyl, C 1-2 Cyanoalkyl, C 1-3 Hydroxyalkyl, C 1-2 Aminoalkyl, -(CH2) 0-2 O(C 1-3 alkyl), C 3-6Cycloalkyl, -NR x R x , -(CH2) 0-2 C(O)NR x R x , -(CH2) 0-2 S(O)2(C 1-3 alkyl), -CH2(C 3-6 and R5 is H, -CH3, -CH2CH3, -CF3, -CH2CHF2, or -CH2CF3, an N-oxide, or a salt thereof.

[0044] One embodiment provides a compound of formula (I), an N-oxide, or a salt thereof, wherein R1 is independently -CH3, -CH2CH3, or -CH(CH3)2; each R2 is independently -CN, -CH3, or -OCH3; R5 is H or -CH2CF3; and p is 0, 1, or 2.

[0045] In some embodiments, the compound is 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (1); 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (2); 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (3); 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (4); 5-(6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (5); 2-(dimethylamino)-1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (6); 2-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (7); 2-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N-methylacetamide (8); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-(2,2,2-trifluoroethyl)-2-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (9); 6-Isopropyl-2-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (10);6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (11); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (12); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-neopentylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (13); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (14); 1-(4-(6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol (15); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (16); 2-(4-(6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (17); 1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol (18); 2-(dimethylamino)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (19);6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (20); 6-Isopropyl-2-(1-isopropylpiperidin-4-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (21); 6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (22); 6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (23); 2-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (24); 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(1-isopropylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (25); 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (26); 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (27); 2-(dimethylamino)-1-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (28); 1-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol (29);2-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (30); 2-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)acetamide (31); 2-(dimethylamino)-1-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (32); 6-Isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (33); 6-Isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (34); 6-Isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (35); 6-Isopropyl-2-(1-isopropylpiperidin-4-yl)-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazole (36); 5-(6-Isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (37); 5-(6-Isopropyl-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (38); 5-(2-(1-(dimethylglycyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (39);2-(4-(5-(8-cyanoquinolin-5-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (40); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (41); 5-(6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (42); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (43); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-isopropylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (44); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(methylsulfonyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (45); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (46); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (47); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (48);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-methylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (49); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-ethylpiperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (50); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-propylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (51); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-isobutylpiperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (52); 2-(1-(cyclopropylmethyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (53); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(2-ethylbutyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (54); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (55); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N-methylacetamide (56); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (57);2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)acetamide (58); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (59); 5-(6-isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (60); 5-(6-Isopropyl-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (61); 2-(4-(6-Isopropyl-5-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (62); The compound of formula (I), its N-oxide, or salt is 2-(4-(6-isopropyl-5-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N-methylacetamide (63); or 2-(4-(6-isopropyl-5-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)acetamide (64).

[0046] In some embodiments, the compound is N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (65-66); (1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)azetidin-3,3-diyl)dimethanol (67); 6-(4-(6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (68-69); N-(4-(6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-methyloxetan-3-amine (70-71); N-ethyl-4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (72-73); 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (74-75); 2-(4-(azetidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)- N-Isopropyl-4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-amine (78-79);4-(4-(6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)thiomorpholine 1,1-dioxide (82-83); 1-((4-(6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (84-85); 4-(6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(2-methoxy-2-methylpropyl)cyclohexan-1-amine (86-87); N-Isopropyl-4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (88-89); (R)-3-Fluoro-4-((4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylbutan-2-ol (90-91); 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl-1-amine (92-93); 3-Ethyl-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (94-95); 6-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide (96-97);6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-(pyrrolidin-1-yl)cyclohexyl)-4H-pyrrolo[3,2-d]thiazole (98-99); (R)-N-(1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)pyrrolidin-3-yl)acetamide (100-101); 4-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-1,4-oxazepane (102-103); (1R,5S)-8-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-oxa-8-azabicyclo[3.2.1]octane (104-105); 1-((4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)cyclopropane-1-carbonitrile (106-107); 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(1-methylcyclobutyl)cyclohexan-1-amine (108-109); 2-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-7-oxa-2-azaspiro[3.5]nonane (110-111); 7-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-7-azaspiro[3.5]nonane (112-113);2-(4-(2,7-diazaspiro[4.4]nonan-2-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (114-115); N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-azaspiro[3.3]heptan-6-amine (116-117); 1-(4-(6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-(trifluoromethyl)azetidin-3-ol (118-119); 4-(4-(6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (120-121); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-4H-pyrrolo[3,2-d]thiazole (122-123); N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-N-methyloxetan-3-amine (124-125); 2-(Dimethylamino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (126); N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)methanesulfonamide (127);trans 2-(ethyl(methyl)amino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (128); 2-(isobutylamino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (129); N-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (130-131); N-ethyl-4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (132); 4-(6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine (134-135); 6-(4-(6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (136-137); N-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)bicyclo[1.1.1]pentan-1-amine (138-139); 1-((4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (140-141);(1-(((4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)methyl)cyclopropyl)methanol (142-143); N-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-methyloxetan-3-amine (144-145); 4-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-1,4-oxazepane (146-147); 4-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (148-149); 6-Isopropyl-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (150-151); N-(4-(6-Isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (152-153); 6-Isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-(pyrrolidin-1-yl)cyclohexyl)-4H-pyrrolo[3,2-d]thiazole (154-155); 1-((4-(6-Isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (156-157);N-isopropyl-4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (158-159); N-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (160-161); 2-((4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide (162-163); 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methyl-N-(2-(methylsulfonyl)ethyl)cyclohexan-1-amine (164-165); 1-Isopropyl-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperidin-4-amine (166-167); N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)bicyclo[1.1.1]pentan-1-amine (168-169); N1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-N2-methylethane-1,2-diamine (170-171); 4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine (172-173);N-ethyl-4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (174-175); N-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)bicyclo[1.1.1]pentan-1-amine (176-177); N-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (178-179); 6-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (180-181); 1-((4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (182-183); N-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (184-185); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(2-methylpropan-2-ol); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-4H-pyrrolo[3,2-d]thiazole (188-189); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-ethyl-N-methylcyclohexan-1-amine (190-191); 6-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (192-193); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isopropylcyclohexan-1-amine (194-195); 1-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (196-197); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-neopentylcyclohexan-1-amine (198-199); N-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (200-201); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((1-methylcyclobutyl)methyl)cyclohexan-1-amine (202-203);2-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-N,N-dimethylacetamide (204-205); 2-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-1-morpholinoethan-1-one (206-207); 2-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-N-methylacetamide (208-209); 2-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)acetamide (210-211); 4-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)morpholine (212-213); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexan-1-amine (214-215); 2-(4-(azetidin-1-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (216-217); 2-(4-(3,3-difluoroazetidin-1-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (218-219);4-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (220-221); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isopropyl-N-methylcyclohexan-1-amine (222-223); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)azetidin-3-ol (224-225); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-(3-fluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (226-227); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isobutyl-N-methylcyclohexan-1-amine (228-229); 3-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)tetrahydrothiophene 1,1-dioxide (230-232); 6-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide (233-234); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-(trifluoromethyl)azetidin-3-ol (235-236);7-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-7-azaspiro[3.5]nonane (237-238); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-7-oxa-2-azaspiro[3.5]nonane (239-240); 5-(6-Isopropyl-2-(4-(oxetan-3-ylamino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (241-242); 5-(6-Isopropyl-2-(4-((2-methoxy-2-methylpropyl)amino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (243-244); 5-(2-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (245-246); 5-(2-(4-(ethyl(methyl)amino)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (247-248); 5-(6-Isopropyl-2-(4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (249-250); 5-(2-(4-((2-hydroxy-2-methylpropyl)amino)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (251-252); 5-(6-Isopropyl-2-(4-(isopropylamino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (253-254);5-(2-(4-(azetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (255-256); 5-(6-isopropyl-2-(4-(((1-(methylsulfonyl)cyclopropyl)methyl)amino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (257-258); 4-(4-(6-Isopropyl-5-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (259-260); 5-(6-Isopropyl-2-(4-(isopropyl(methyl)amino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (261-262); 5-(2-(4-(3-hydroxyazetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (263-264); 5-(2-(4-(3-fluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (265-266); 5-(2-(4-(3-hydroxy-3-(trifluoromethyl)azetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (267-268); 6-(4-(6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (269-270); N-(4-(6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (271-272);Provided is a compound of formula (I), an N-oxide thereof, or a salt thereof, which is N-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (273); or 4-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (275-276).

[0047] In some embodiments, the compound is 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (278); 5-(6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (279); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one (280); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-2-methylpropan-2-ol (281); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (282); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-N,N-dimethylacetamide (283); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-N-methylacetamide (284); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)acetamide (285); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (286);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (287); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-isopropylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (288); 5-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-((3-methyloxetan-3-yl)methyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (289); (R)-5-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole·HCl (308); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-((2S,5R)-2,5-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (309); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (310); (R)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (311); (R)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide (312); (R)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)acetamide (313);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (314); (R)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (315); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (316); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (317); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (318); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(2,4-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (319); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-ethyl-2-methylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (320); (R)-2-(4-(cyclopropylmethyl)-2-methylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (321);(R)-2-(4-cyclobutyl-2-methylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (322); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(1-isopropylpiperidin-4-yl)-2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (323); (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol (325); (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(methylamino)ethan-1-one (326); (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(dimethylamino)ethan-1-one (327); 2-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (328); 2-((2S,5R)-2,5-dimethyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (329); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-((2S,5R)-4-isopropyl-2,5-dimethylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (330);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-((2S,5R)-4-ethyl-2,5-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (331); 2-((2S,5R)-4-(cyclopropylmethyl)-2,5-dimethylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (332); 2-((2S,5R)-4-Cyclobutyl-2,5-dimethylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (333); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-((2S,5R)-4-isopropyl-2,5-dimethylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (334); 2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-N,N-dimethylacetamide (335); 2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-N-methylacetamide (336); 2-((2S,5R)-2,5-dimethyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (337); 2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)acetamide (338);1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-methylpropan-2-ol (339); 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-(methylamino)ethan-1-one (340); 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-(dimethylamino)ethan-1-one (341); (S)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (342); (S)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide (343); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (344); (S)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol (345);(S)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(dimethylamino)ethan-1-one (346); (S)-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)(1,1-dioxidetetrahydro-2H-thiopyran-4-yl)methanone (347); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (348); (S)-2-(4-cyclobutyl-2-methylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (349); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (350); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-isopropyl-2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (351); (S)-2-(4-(cyclopropylmethyl)-2-methylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (352); (R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (353);(R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide (354); (R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)acetamide (355); (R)-6-Isopropyl-2-(2-methyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (356); (R)-6-Isopropyl-2-(4-(2-methoxyethyl)-2-methylpiperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (357); (R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)acetonitrile (358); (R)-1-(4-(6-isopropyl; Propyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol (359); (R)-2-(dimethylamino)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)ethan-1-one (360); (R)-2-(4-Isobutyl-2-methylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (361); (R)-2-(4-Cyclobutyl-2-methylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (362); (R)-6-Isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (363); (R)-6-Isopropyl-2-(2-methyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (364); (R)-2-(4-(cyclopropylmethyl)-2-methylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (365); (R)-6-isopropyl-2-(4-isopropyl-2-methylpiperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (366);or (R)-2-(2,4-dimethylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (367), its N-oxide, or salt.

[0048] In some embodiments, the compound is 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(3-methyloxetan-3-yl)piperidin-4-amine (290); 1-((1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-4-yl)amino)-2-methylpropan-2-ol (291); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isopropyl-N-methylpiperidin-4-amine (292); N-cyclobutyl-1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-4-amine (293); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(2-methoxy-2-methylpropyl)piperidin-4-amine (294); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((3-methyloxetan-3-yl)methyl)piperidin-4-amine (295); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(oxetan-3-yl)piperidin-4-amine (296); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isopropylpiperidin-4-amine (297);The compound of formula (I), its N-oxide, or salt is 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-ethyl-N-methylpiperidin-4-amine (298); or 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-4-amine (299).

[0049] In some embodiments, the compound is 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-isobutyl-2,6-diazaspiro[3.3]heptan-2-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (300); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(6-((tetrahydro-2H-pyran-4-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (301); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (302); 1-(6-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-methylpropan-2-ol (303); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(6-(2-(methylsulfonyl)ethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (304); 5-(6-isopropyl-2-(6-(2-(methylsulfonyl)ethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (305); 5-(6-isopropyl-2-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (306); or 5-(6-isopropyl-2-(6-((tetrahydro-2H-pyran-4-yl)methyl)-2,6-diazaspiro[3.The compound of formula (I), its N-oxide, or salt, is (307), wherein the compound is (3,3,4-trimethylpyridin-2(1H)-one, N-oxide, or salt thereof.

[0050] In some embodiments, the compound is 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-(dimethylamino)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (368-369); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(2-(pyrrolidin-1-yl)ethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (370); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(3-(2-oxopyrrolidin-1-yl)propyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (371); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(2-(dimethylamino)ethyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (372); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(2-methyl-2-morpholinopropyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (374); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(2-(1-methylpiperidin-4-yl)ethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (381); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(2-(dimethylamino)ethyl)-6-isopropyl-N-methyl-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (382); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(morpholin-2-ylmethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (386); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(2-(pyrrolidin-1-yl)ethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (387);N-(2-(dimethylamino)ethyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (388); N-(2,2-difluoroethyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (389); 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(2,2,2-trifluoroethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (390); 6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (391); The compound of formula (I), its N-oxide, or salt is 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (399); or N-(2-(dimethylamino)ethyl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (400).

[0051] In some embodiments, the compound is (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(1,1-dioxidethiomorpholino)methanone (373); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-carbonyl)piperazin-1-yl)ethan-1-one (375); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(4-(dimethylamino)piperidin-1-yl)methanone (376); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(pyrrolidin-1-yl)methanone (377); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-carbonyl)piperazin-2-one (378); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(3-fluoroazetidin-1-yl)methanone (379); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(4-isopropylpiperazin-1-yl)methanone (380); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(3-(dimethylamino)azetidin-1-yl)methanone (383); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(4-(methylsulfonyl)piperazin-1-yl)methanone (384);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (385); 4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carbonyl)piperazin-2-one (392); (6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)(pyrrolidin-1-yl)methanone (393); (6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)(1,4-oxazepan-4-yl)methanone (394); (4-(dimethylamino)piperidin-1-yl)(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)methanone (395); (6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)(3-methoxyazetidin-1-yl)methanone (396); The compound of formula (I), its N-oxide, or salt is 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(oxetan-3-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (397); or (6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)(morpholino)methanone (398).

[0052] In some embodiments, the compound is N-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-1-isopropylpiperidin-4-amine (401); 2-(((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)amino)acetamide (402); 6-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide (403); 2-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-7-oxa-2-azaspiro[3.5]nonane (404); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)methanamine (405); 4-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)piperazin-2-one (406); 4-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)morpholine (407); 6-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-2-oxa-6-azaspiro[3.3]heptane (408); or 2-((2,6-diazaspiro[3.The compound of formula (I), its N-oxide, or salt thereof, is provided, which is (3)heptan-2-yl)methyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (409).

[0053] In one embodiment, the compound is 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[2,3-d]thiazole (410); Provided is a compound of formula (I), an N-oxide thereof, or a salt thereof, which is 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[2,3-d]thiazole (411); or 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[2,3-d]thiazole (412).

[0054] One embodiment provides a compound of Formula (I), an N-oxide, or a salt thereof, wherein the compound is 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-thieno[3,2-b]pyrrole (413).

[0055] The present invention may be embodied in other specific forms without departing from its spirit or essential characteristics. The present invention includes any and all combinations of the aspects and / or embodiments of the present invention described herein. It is understood that any and all embodiments of the present invention may be combined with any and all other embodiments to describe additional embodiments. It is also understood that each individual element of an embodiment is meant to be combined with any and all other elements from any embodiment to describe additional embodiments.

[0056] (definition) The features and advantages of the present invention may be more readily understood by those skilled in the art upon reading the following detailed description. It is understood that, for clarity, certain features of the invention that are described before or after the context of separate embodiments may also be combined to form a single embodiment. Conversely, various features of the invention that are, for brevity, described in the context of a single embodiment may also be combined to form subcombinations thereof. The embodiments identified herein as exemplary or preferred are intended to be illustrative, not limiting.

[0057] Unless otherwise stated herein, references made in the singular include the plural, for example, "a" and "an" can refer to either "one" or "one or more."

[0058] As used herein, the phrase "compound" refers to at least one compound. For example, a compound of formula (I) includes one compound of formula (I) and two or more compounds of formula (I).

[0059] Unless otherwise specified, any heteroatom with unsatisfied valences is assumed to include enough hydrogen atoms to satisfy the valences.

[0060] The definitions set forth herein take precedence over definitions set forth in any patents, patent applications, and / or published patent applications incorporated herein by reference.

[0061] Listed below are definitions of various terms used to describe this invention. These definitions apply to the terms as they are used throughout the specification (unless otherwise limited in specific instances) either individually or as part of a larger group.

[0062] Throughout the specification, groups and substituents may be chosen by one skilled in the art to provide stable moieties and compounds.

[0063] According to the practice used in the art, [ka] is used in structural formulas herein to represent the bond that is the point of attachment of a moiety or substituent to the core or backbone structure.

[0064] The terms "halo" and "halogen" as used herein refer to F, Cl, Br, and I.

[0065] The term "cyano" refers to the group --CN.

[0066] The term "amino" refers to the group --NH.sub.2.

[0067] The term "oxo" refers to the group =O.

[0068] As used herein, the term "alkyl" refers to both branched and straight-chain saturated aliphatic hydrocarbon groups containing, for example, 1 to 12 carbon atoms, 1 to 6 carbon atoms, and 1 to 4 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and i-propyl), butyl (e.g., n-butyl, i-butyl, sec-butyl, and t-butyl), and pentyl (e.g., n-pentyl, isopentyl, neopentyl), n-hexyl, 2-methylpentyl, 2-ethylbutyl, 3-methylpentyl, and 4-methylpentyl. When a number appears as a subscript after the symbol "C," the subscript more specifically qualifies the number of carbon atoms that a particular group may contain. For example, "C 1-6 "Alkyl" means straight and branched chain alkyl groups having from 1 to 6 carbon atoms.

[0069] As used herein, the term "fluoroalkyl" refers to both branched and straight-chain saturated aliphatic hydrocarbon groups substituted with one or more fluorine atoms. For example, "C 1-4"Fluoroalkyl" is meant to include C, C, C, and C alkyl groups that are substituted with one or more fluorine atoms. Representative examples of fluoroalkyl groups include, but are not limited to, -CF and -CHCF.

[0070] The term "cyanoalkyl" includes both branched and straight-chain saturated alkyl groups that are substituted with one or more cyano groups. For example, "cyanoalkyl" includes -CHCN, -CHCHCN, and -C 1-4 Cyanoalkyl is included.

[0071] The term "aminoalkyl" includes both branched and straight-chain saturated alkyl groups substituted with one or more amino groups. For example, "aminoalkyl" includes -CH2NH2, -CH2CH2NH2, and -C 1-4 Aminoalkyl is included.

[0072] The term "hydroxyalkyl" includes both branched and straight-chain saturated alkyl groups that are substituted with one or more hydroxyl groups. For example, "hydroxyalkyl" includes -CHOH, -CHCHOH, and -C 1-4 Contains hydroxyalkyl.

[0073] The term "hydroxy-fluoroalkyl" includes both branched and straight-chain saturated alkyl groups substituted with one or more hydroxyl groups and one or more fluorine atoms. For example, "hydroxy-fluoroalkyl" includes -CHFCHOH, -CHCHFC(CH)OH, and -CHFCHOH. 1-4 Hydroxy-fluoroalkyl is included.

[0074] As used herein, the term "cycloalkyl" refers to a group derived from a non-aromatic monocyclic or polycyclic hydrocarbon molecule by removing one hydrogen atom from a saturated ring carbon atom. Representative examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclopentyl, and cyclohexyl. When a number appears as a subscript after the symbol "C," the subscript more specifically defines the number of carbon atoms that a particular cycloalkyl group may contain. For example, "C3-C6 cycloalkyl" refers to a cycloalkyl group having from 3 to 6 carbon atoms.

[0075] The term "alkoxy," as used herein, refers to an alkyl group attached to the parent molecular moiety through an oxygen atom, for example, a methoxy group (-OCH). 1-3 "Alkoxy" means an alkoxy group having 1 to 3 carbon atoms.

[0076] The term "alkoxyalkyl," as used herein, refers to an alkoxy group that is connected through its oxygen atom to an alkyl group, which in turn is connected to the parent molecular moiety, such as a methoxymethyl group (-CH2OCH3). For example, "C 2-4 "Alkoxyalkyl" means an alkoxyalkyl group having 2 to 4 carbon atoms, for example, -CH2OCH3, -CH2CH2OCH3, -CH2OCH2CH3, and -CH2CH2OCH2CH3.

[0077] As used herein, the phrase "pharmaceutically acceptable" refers to compounds, substances, compositions, and / or dosage forms that are, within the scope of ordinary medical judgment, suitable for use in contact with the tissues of human beings and animals without undue toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0078] The compound of formula (I) may be provided as an amorphous solid or a crystalline solid. Lyophilization may be used to provide the compound of formula (I) as an amorphous solid.

[0079] Additionally, solvates (e.g., hydrates) of the compounds of formula (I) are also considered to be within the scope of the present invention. The term "solvate" refers to a physical association of a compound of formula (I) with one or more organic or inorganic solvent molecules. This physical association includes hydrogen bonding. In some cases, it is possible to isolate the solvate, for example, when one or more solvent molecules are incorporated into the crystal lattice of a crystalline solid. "Solvate" includes both solution-phase and isolable solvates. Exemplary solvates include hydrates, ethanolates, methanolates, isopropanolates, acetonitrile solvates, and ethyl acetate solvates. Methods of solvation are known in the art.

[0080] Various forms of prodrugs are known in the art: a) The Practice of Medicinal Chemistry, Camille G. Wermuth et al., Ch 31, (Academic Press, 1996); b) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985); c) A Textbook of Drug Design and Development, P. Krogsgaard-Larson and H. Bundgaard, eds. Ch 5, pgs 113 -191 (Harwood Academic Publishers, 1991); and d) Hydrolysis in Drug and Prodrug Metabolism, Bernard Testa and Joachim M. Mayer, (Wiley-VCH, 2003) is described in.

[0081] Additionally, the compound of formula (I) may be isolated and purified after its preparation to obtain a composition containing the compound of formula (I) in an amount of 99% by weight or greater ("substantially pure"), which is then used or formulated as described herein. Such "substantially pure" compounds of formula (I) are also considered herein to be part of the present invention.

[0082] By "stable compound" and "stable structure" is intended a compound that is sufficiently robust that it will not decompose upon isolation to a useful degree of purity from a reaction mixture, nor upon formulation into an efficacious therapeutic agent. The present invention embodies stable compounds.

[0083] A "therapeutically effective amount" is intended to include an amount of a compound of the invention alone, or in combination with the claimed compounds, or in combination with other active ingredients, that is effective to act as an inhibitor of TLR7 / 8 / 9 or to treat or prevent autoimmune and / or inflammatory diseases (e.g., SLE, IBD, multiple sclerosis (MS), and Sjogren's syndrome, and rheumatoid arthritis).

[0084] As used herein, the term "treating" or "treatment" covers the treatment of a condition in a mammal, particularly a human, and includes (a) preventing the mammal from acquiring the condition, particularly where the mammal is susceptible to the condition but has not yet been diagnosed as having the condition; (b) inhibiting the condition, i.e., arresting the progression of the condition; and / or (c) alleviating the condition, i.e., causing regression of the condition.

[0085] Compounds of the present invention are intended to include all isotopes of atoms present in the compounds of the present invention. Isotopes include atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include deuterium (D) and tritium (T). Isotopes of carbon include 13 C and 14C. Isotopically labeled compounds of the invention can generally be prepared by conventional techniques known to those skilled in the art, or by analogous methods described therein, substituting the appropriate isotopically labeled reagent for the non-labeled reagent used elsewhere. For example, methyl (-CH3) also includes deuterated methyl groups such as -CD3.

[0086] (usefulness) The human immune system has evolved to protect the body from microorganisms, viruses, and parasites that can cause infection, disease, or death. Complex control mechanisms ensure that various cellular components of the immune system target foreign substances or organisms without causing permanent or significant damage to the individual. Although the initiating events are not fully understood at present, in autoimmune disease states, the immune system directs its inflammatory response toward target organs in the affected individual. Various autoimmune diseases are generally characterized by the primary or initial target organ or tissue affected, such as the joints in rheumatoid arthritis, the thyroid gland in Hashimoto's thyroiditis, the central nervous system in multiple sclerosis, the pancreas in type 1 diabetes, and the intestines in inflammatory bowel disease.

[0087] The compounds of the present invention inhibit signaling through Toll-like receptors 7 or 8 or 9 (TLR7, TLR8, TLR9) or combinations thereof. Accordingly, the compounds of formula (I) are useful for treating conditions associated with the inhibition of signaling through one or more of TLR7, TLR8, or TLR9. Such conditions include diseases associated with the TLR7, TLR8, or TLR9 receptors in which cytokine levels are regulated as a result of intracellular signaling.

[0088] As used herein, the term "treating" or "treatment" encompasses the treatment of a condition in a mammal, particularly a human, and includes (a) preventing or delaying the mammal from acquiring the condition, particularly where the mammal is susceptible to the condition but has not yet been diagnosed as having the condition; (b) inhibiting the condition, i.e., arresting the progression of the condition; and / or (c) achieving complete or partial alleviation of the symptoms or condition, and / or palliating, ameliorating, alleviating, or curing the disease or disorder and / or its symptoms.

[0089] In view of the activity of the compounds of the present invention as selective inhibitors of TLR7, TLR8, or TLR9, the compounds of formula (I) are effective in treating diseases associated with TLR7, TLR8, or TLR9 family receptors, including, but not limited to, inflammatory diseases (e.g., Crohn's disease, ulcerative colitis, asthma, graft-versus-host disease, allograft rejection, chronic obstructive pulmonary disease), autoimmune diseases (e.g., Graves' disease, rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, cutaneous lupus, psoriasis), autoinflammatory diseases (e.g., cryopyrin-associated periodic fever syndromes (CAPS), TNF-associated periodic syndromes (TRAPS), familial Mediterranean fever (FMF), adult Still's disease, systemic juvenile idiopathic arthritis, gout, gouty arthritis), metabolic diseases (e.g., type 2 diabetes, atherosclerosis, myocardial infarction), and bone destructive diseases. These include diseases (e.g., bone resorption diseases, osteoarthritis, osteoporosis, multiple myeloma-related bone disease), proliferative diseases (e.g., acute myeloid leukemia, chronic myeloid leukemia), angiogenic diseases (e.g., solid tumors, intraocular neovascular diseases, and neovascular diseases including infantile hemangiomas), infectious diseases (e.g., sepsis, septic shock, and Shigellosis), neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, traumatic cerebral ischemia or traumatic neurodegenerative diseases), neoplastic diseases, and viral diseases (e.g., metastatic melanoma, Kaposi's sarcoma, multiple myeloma, and HIV infection and CMV retinitis, AIDS).

[0090] In particular, specific conditions or diseases that may be treated with the compounds of the present invention include, but are not limited to, pancreatitis (acute or chronic), asthma, allergies, adult respiratory distress syndrome, chronic obstructive pulmonary disease, glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, chronic thyroiditis, Graves' disease, autoimmune gastritis, diabetes, autoimmune hemolytic anemia, autoimmune neutropenia, thrombocytopenia, atopic dermatitis, chronic active pneumonia, myasthenia gravis, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, and rheumatoid arthritis. Ulcerative colitis, Crohn's disease, psoriasis, graft-versus-host disease, endotoxin-induced inflammatory reactions, tuberculosis, atherosclerosis, muscle degeneration, cachexia, psoriatic arthritis, Reiter's syndrome, gout, traumatic arthritis, rubella-related arthritis, acute synovitis, pancreatic beta-cell disease; diseases characterized by massive neutrophil infiltration; rheumatoid spondylitis, gouty arthritis and other arthritic conditions, cerebral malaria, chronic pulmonary inflammatory diseases, silicosis, pulmonary sarcoidosis, bone resorption disorders, allograft rejection, infection-related Fever and myalgia, cachexia following infection, keloid formation, scar tissue formation, ulcerative colitis, fever, influenza, osteoporosis, osteoarthritis, acute myeloid leukemia, chronic myeloid leukemia, metastatic melanoma, Kaposi's sarcoma, multiple myeloma, sepsis, septic shock, and bacillary dysentery; Alzheimer's disease, Parkinson's disease, traumatic cerebral ischemia or traumatic neurodegenerative diseases; angiogenic diseases (e.g., solid tumors, intraocular neovascular disease, and childhood hemangioma); viral diseases (e.g., acute Hepatitis (including hepatitis A, hepatitis B, and hepatitis C) infection, HIV infection and CMV retinitis, AIDS (ARC or malignant tumors), and herpes; stroke, myocardial ischemia, ischemia in stroke heart attack, organ hypoxia, vascular hyperplasia, cardiac and renal reperfusion injury, thrombosis, cardiac hypertrophy, thrombin-induced platelet aggregation, endotoxemia and / or toxic shock syndrome, conditions associated with prostaglandin endoperoxidase synthase 2, and pemphigus vulgaris. This embodiment includes a method of treating a condition selected from lupus (e.g., lupus nephritis and systemic lupus erythematosus (SLE)), Crohn's disease, ulcerative colitis, allograft rejection, rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis, and pemphigus vulgaris).Also included are methods of treating a condition selected from ischemia-reperfusion injury (e.g., cerebral ischemia-reperfusion injury due to stroke and cardiac ischemia-reperfusion injury due to myocardial infarction).Further included are methods of treating wherein the condition is multiple myeloma.

[0091] In certain embodiments, compounds of Formula (I) are effective in treating cancer (e.g., Waldenstrom's macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), cutaneous diffuse large B-cell lymphoma, and primary CNS lymphoma).

[0092] Additionally, the TLR7, TLR8, or TLR9 inhibitors of the present invention inhibit the expression of inducible inflammatory proteins (e.g., prostaglandin endoperoxide synthase-2 (PGHS-2), cyclooxygenase-2 (COX-2), IL-1, IL-6, IL-18, also known as chemokines). Accordingly, additional TLR7 / 8 / 9-associated conditions include edema, analgesia, fever, and pain (e.g., neuromuscular pain, headache, cancer pain, dental pain, and arthritis pain). The compounds of the present invention may also be used to treat animal viral infections, such as lentiviral infections (e.g., but not limited to, equine infectious anemia virus) or retroviral infections (e.g., feline immunodeficiency virus, bovine immunodeficiency virus, and canine immunodeficiency virus).

[0093] The present invention provides methods for treating such conditions, comprising administering to a patient in need thereof a therapeutically effective amount of at least one compound of formula (I) or a salt thereof. "Therapeutically effective amount" is intended to encompass an amount of a compound of the invention that is effective, when administered alone or in combination, to inhibit autoimmune or chronic inflammatory disease.

[0094] Methods for treating TLR7-, TLR8-, or TLR9-associated conditions may include administering the compounds of formula (I) alone or in combination with each other and / or other suitable therapeutic agents effective in treating such conditions. Accordingly, "therapeutically effective amount" is also intended to encompass the amount of the claimed combination of compounds that is effective to inhibit TLR7-, TLR8-, or TLR9 and / or treat a disease associated with TLR7-, TLR8-, or TLR9.

[0095] Representative examples of other therapeutic agents include corticosteroids, rolipram, calphostin, cytokine suppressive anti-inflammatory drugs (CSAIDs), interleukin-10, glucocorticoids, salicylates, nitric oxide, and other immunosuppressants; nuclear transport inhibitors (e.g., deoxyspergualin (DSG)), nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., ibuprofen, celecoxib, and rofecoxib), steroids (e.g., prednisone or dexamethasone), antivirals (e.g., abacavir), antiproliferative agents (e.g., methotrexate, leflunomide, FK506), and others. (tacrolimus, PROGRAF®), antimalarials (e.g., hydroxychloroquine), cytotoxic drugs (e.g., azathioprine and cyclophosphamide), TNF-α inhibitors (e.g., tenidap, anti-TNF antibodies or soluble TNF receptors, and rapamycin (sirolimus or RAPAMUNE®)), or derivatives thereof.

[0096] When used in combination with the compounds of the present invention, the other therapeutic agents described above may be used, for example, in amounts as set forth in the Pharmaceutical and Medical Devices Manual (PDR) or as otherwise specifically determined by one of ordinary skill in the art. In the methods of the present invention, the other therapeutic agents may be administered before, simultaneously with, or after the administration of the compounds of the present invention. The present invention also provides pharmaceutical compositions capable of treating TLR7 / 8 / 9 receptor-related conditions (e.g., IL-1 family receptor-mediated diseases described above).

[0097] The compositions of the present invention may include and be formulated with other therapeutic agents described above according to techniques known to those skilled in the art of pharmaceutical formulation, using, for example, conventional solid or liquid vehicles or diluents, as well as pharmaceutical excipients (e.g., additives, binders, preservatives, stabilizers, flavoring agents, etc.) of a type appropriate to the desired method of administration.

[0098] Accordingly, the present invention further includes compositions comprising one or more compounds of formula (I) and a pharmaceutically acceptable carrier.

[0099] A "pharmaceutically acceptable carrier" refers to a medium generally accepted in the art for delivering biologically active agents to animals, particularly mammals. Pharmaceutically acceptable carriers are formulated according to many factors well within the expertise of those skilled in the art. These factors include, but are not limited to, the type and nature of the active agent being formulated, the patient to whom the composition containing the active agent will be administered, the intended route of administration of the composition, and the targeted therapeutic index. Pharmaceutically acceptable carriers include both aqueous and non-aqueous liquid media, as well as a variety of solid and semi-solid dosage forms. Such carriers can contain many different components and additives in addition to the active agent; such additional components are included in the formulation for various reasons, such as stabilization of the active agent, binders, and the like, as known to those skilled in the art. Descriptions of suitable pharmaceutically acceptable carriers and factors to consider when selecting them can be found in a variety of readily available texts, such as Remington's Pharmaceutical Sciences, 17th Edition (1985), the entire contents of which are incorporated herein by reference.

[0100] The compounds according to formula (I) may be administered by any means appropriate to the condition to be treated, which may depend on the need for site-specific treatment or the amount of compound of formula (I) to be delivered.

[0101] The present invention also encompasses a class of pharmaceutical compositions comprising a compound of Formula (I) and one or more nontoxic, pharmaceutically acceptable carriers and / or diluents and / or adjuvants (collectively referred to herein as "carriers"), and optionally other active ingredients. The compound of Formula (I) may be administered by any appropriate route, preferably in the form of a pharmaceutical composition adapted for such a route, and in a dosage effective for the intended treatment. The compounds and compositions of the present invention may be administered, for example, orally, transmucosally, or parenterally, including intravascularly, intravenously, intraperitoneally, subcutaneously, intramuscularly, and intrasternally, in dosage unit formulations containing conventional pharmaceutically acceptable carriers, adjuvants, and vehicles. For example, pharmaceutical carriers may include mixtures of mannitol or lactose and microcrystalline cellulose. The mixture may also include additional ingredients, such as lubricants (e.g., magnesium stearate) and disintegrants (e.g., crospovidone). The carrier mixture may be filled into gelatin capsules or compressed into tablets. The pharmaceutical composition may be administered, for example, in oral dosage form or as an infusion.

[0102] For oral administration, the pharmaceutical composition may be in the form of, for example, a tablet, capsule, liquid capsule, suspension, or liquid. The pharmaceutical composition is preferably formulated in a dosage unit form containing a specific amount of active ingredient. For example, the pharmaceutical composition may be provided as a tablet or capsule containing an amount of active ingredient ranging from about 0.1 to 1000 mg, preferably from about 0.25 to 250 mg, more preferably from about 0.5 to 100 mg. The appropriate daily dose for administration to humans or other mammals may vary greatly depending on the patient's condition and other factors, but can be determined using conventional methods.

[0103] Any of the pharmaceutical compositions discussed herein can be orally delivered, for example, via any acceptable and suitable oral formulation. Typical examples of oral formulations include, but are not limited to, tablets, troches, lozenges, aqueous and oily suspensions, dispersible powders or granules, emulsions, hard and soft capsules, liquid capsules, syrups, and elixirs. Pharmaceutical compositions for oral administration can be prepared according to any method known in the art for preparing pharmaceutical compositions for oral administration. To provide a pharmaceutically easy-to-take formulation, the pharmaceutical compositions described in the present invention can include at least one substance selected from sweeteners, flavoring agents, coloring agents, demulcents, antioxidants, and preservatives.

[0104] Tablets can be prepared, for example, by mixing at least one compound of formula (I) with at least one non-toxic, pharmaceutically acceptable additive suitable for tablet manufacture. Typical additives include, but are not limited to, inert diluents (e.g., calcium carbonate, sodium carbonate, lactose, calcium phosphate, and sodium phosphate), granulating and disintegrating agents (e.g., microcrystalline cellulose, croscarmellose sodium, corn starch, and alginic acid), binders (e.g., starch, gelatin, polyvinylpyrrolidone, and gum arabic), and lubricants (e.g., magnesium stearate, stearic acid, and talc). Furthermore, tablets can be uncoated or coated by known techniques to mask the unpleasant taste of unpleasant drugs or to delay the disintegration and absorption of active ingredients in the gastrointestinal tract, thereby prolonging the effect of the active ingredients. Typical examples of water-soluble taste-masking materials include, but are not limited to, hydroxypropylmethylcellulose and hydroxypropylcellulose. Exemplary time delay materials include, but are not limited to, ethyl cellulose and cellulose acetate butyrate.

[0105] Hard gelatin capsules may be prepared, for example, by mixing at least one compound of formula (I) with at least one inert solid diluent (eg, calcium carbonate, calcium phosphate, and kaolin).

[0106] Soft gelatin capsules can be prepared, for example, by mixing at least one compound of formula (I) with at least one water-soluble carrier (e.g., polyethylene glycol) and at least one oil medium (e.g., peanut oil, liquid paraffin, and olive oil).

[0107] Aqueous suspensions can be prepared, for example, by mixing at least one compound of formula (I) with at least one additive suitable for preparing aqueous suspensions. Typical examples of additives suitable for preparing aqueous suspensions include, but are not limited to, suspending agents (e.g., sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, alginic acid, polyvinylpyrrolidone, tragacanth gum, and gum arabic), dispersing or wetting agents (e.g., naturally occurring phosphatides (e.g., lecithin), condensation products of alkylene oxides and fatty acids (e.g., polyoxyethylene stearate), condensation products of ethylene oxide and long-chain aliphatic alcohols (e.g., heptadecaethyleneoxycetanol), condensation products of ethylene oxide and fatty acids and and partial esters derived from hexitols (e.g., polyoxyethylene sorbitol monooleate), and condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides (e.g., polyethylene sorbitan monooleate). The aqueous suspension may also contain at least one preservative (e.g., ethyl p-hydroxybenzoate and n-propyl p-hydroxybenzoate), at least one coloring agent, at least one flavoring agent, and / or at least one sweetening agent (e.g., but not limited to, sucrose, saccharin, and aspartame).

[0108] Oily suspensions can be prepared, for example, by suspending at least one compound of formula (I) in either vegetable oil (e.g., peanut oil, olive oil, sesame oil, and coconut oil) or mineral oil (e.g., liquid paraffin). Oily suspensions can also contain at least one thickening agent (e.g., beeswax, hard paraffin, and cetyl alcohol). To provide oily suspensions that are easy to drink, at least one sweetener and / or at least one flavoring agent as described above can be added to the oily suspension. Oily suspensions can also contain at least one preservative (for example, but not limited to, antioxidants (e.g., butylhydroxyanisole and α-tocopherol)).

[0109] Dispersible powders and granules can be prepared, for example, by mixing at least one compound of formula (I) with at least one dispersant and / or wetting agent, at least one suspending agent, and / or at least one preservative. Suitable dispersants, wetting agents, and suspending agents have already been described above. Typical examples of preservatives include, but are not limited to, antioxidants (e.g., ascorbic acid). Furthermore, dispersible powders and granules can also contain at least one excipient (e.g., but not limited to, sweeteners, flavoring agents, and coloring agents).

[0110] The emulsion of at least one compound of formula (I) can be prepared, for example, as an oil-in-water emulsion. The oil phase of the emulsion containing the compound of formula (I) can be composed of known ingredients in a known manner. The oil phase can be provided by, but is not limited to, vegetable oils (e.g., olive oil and peanut oil), mineral oils (e.g., liquid paraffin), and mixtures thereof. The oil phase can include only an emulsifier, or a mixture of at least one emulsifier and a fat or oil, or both a fat and an oil. Suitable emulsifiers include, but are not limited to, naturally occurring phosphatides (e.g., soybean lecithin), esters or partial esters derived from fatty acids and hexitol anhydrides (e.g., sorbitan monooleate), and condensation products of partial esters with ethylene oxide (e.g., polyoxyethylene sorbitan monooleate). Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier, which acts as a stabilizer. It is also preferred to include both an oil and a fat. Together, the emulsifier, with or without a stabilizer, makes up the so-called emulsifying wax, which, together with the oil and fat, forms the oily dispersed phase of the cream formulation, making up the so-called emulsifying ointment base. The emulsion may also contain sweeteners, flavoring agents, preservatives, and / or antioxidants. Suitable emulsifiers and emulsion stabilizers for use in the formulations of the present invention include Tween 60, Span 80, cetostearyl alcohol, myristyl alcohol, glyceryl monostearate, sodium lauryl sulfate, glyceryl distearate, alone or in combination with wax; or other materials known in the art.

[0111] The compound of formula (I) can also be delivered, for example, intravenously, subcutaneously, and / or intramuscularly via any pharmaceutically acceptable and suitable injection form. Typical examples of injection forms include, but are not limited to, sterile aqueous solutions containing acceptable vehicles and solvents (e.g., water, Ringer's solution, and isotonic sodium chloride solution), sterile oil-in-water microemulsions, and aqueous or oily suspensions.

[0112] Preparations for parenteral administration may be in the form of aqueous or non-aqueous isotonic sterile injection solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules by using one or more of the carriers or diluents described for use in oral preparations, or by using other suitable dispersing or wetting agents and suspending agents. The compound may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride solution, tragacanth gum, and / or various buffer solutions. Other adjuvants and administration methods are well known and widely known in the pharmaceutical field. The active ingredient may also be administered by injection in a composition with a suitable carrier (e.g., saline, dextrose, or water), or cyclodextrins (i.e., Captisol), solubilizing cosolvents (i.e., propylene glycol), or solubilizing micelles (i.e., Tween 80).

[0113] Alternatively, a sterile injectable preparation may be a sterile injectable solution or suspension in a non-toxic, parenterally acceptable diluent or solvent (e.g., a solution in 1,3-butanediol). Among the acceptable vehicles and solvents that may be used, water, Ringer's solution, and isotonic sodium chloride solution are used. Furthermore, sterile, fixed oils are conventionally used as solvents or suspending media. For this purpose, any sterile, fixed oil may be used, including synthetic monoglycerides or diglycerides. Furthermore, fatty acids such as oleic acid are used in injectable preparations.

[0114] Sterile injectable oil-in-water microemulsions can be prepared, for example, by: 1) dissolving at least one compound of formula (I) in an oil phase (e.g., a mixture of soybean oil and lecithin), 2) combining the formula (I) containing oil phase with a mixture of water and glycerol, and 3) treating the combination to form a microemulsion.

[0115] Sterile aqueous suspensions or sterile oily suspensions can be prepared according to methods known to those skilled in the art. For example, sterile aqueous solutions or sterile aqueous suspensions can be prepared using non-toxic, parenterally acceptable diluents or solvents (e.g., 1,3-butanediol), and sterile oily suspensions can be prepared using non-toxic, acceptable solvents or suspension media (e.g., sterile fixed oils (e.g., synthetic monoglycerides or diglycerides), and fatty acids (e.g., oleic acid)).

[0116] Pharmaceutically acceptable carriers, adjuvants, and vehicles that may be used in the pharmaceutical compositions of the present invention include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifying drug delivery systems (SEDDS) (e.g., d-alpha-tocopherol polyethylene glycol 1000 succinate), surfactants used in pharmaceutical dosage forms (e.g., Tween, polyethoxylated castor oil (e.g., CREMOPHOR surfactants (BASF), or other similar polymeric delivery matrices), serum proteins (e.g., human serum albumin), buffer substances (e.g., phosphate, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids), water, salts, or electrolytes (e.g., protamines, PEG-100, PEG-1000), and the like. Examples of suitable carriers include cellulose acetate, cellulose acetate sulphate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinylpyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. Cyclodextrins (e.g., α-, β-, and γ-cyclodextrin, or chemically modified derivatives (e.g., hydroxyalkyl cyclodextrins, including 2- and 3-hydroxypropyl cyclodextrin, or other solubilizing derivatives) may also be advantageously used to enhance delivery of compounds of the formulae described herein.

[0117] The pharmaceutically active compounds of the present invention can be processed according to conventional pharmaceutical methods to prepare medicaments for administration to patients (e.g., humans and other mammals). The pharmaceutical compositions may be subjected to conventional pharmaceutical operations (e.g., sterilization) and / or may contain conventional adjuvants (e.g., preservatives, stabilizers, wetting agents, emulsifiers, buffers, etc.). Tablets and pills may additionally be prepared with enteric coatings. Such compositions may also contain adjuvants (e.g., wetting agents, sweeteners, flavoring agents, and fragrances).

[0118] The amount of compound and dosage regimen administered to treat a condition using the compounds and / or compositions of the present invention depend on various factors (e.g., age, weight, sex, the patient's condition, the type of disease, the severity of the disease, the route and frequency of administration, and the specific compound used). Therefore, dosage regimens may vary widely but can be routinely determined using standard methods. A daily dose of about 0.001 to 100 mg / kg body weight, preferably about 0.0025 to about 50 mg / kg body weight, and most preferably about 0.005 to 10 mg / kg body weight, may be appropriate. The daily dose may be administered one to four times daily. Other dosage regimens include weekly and biday cycles.

[0119] For therapeutic purposes, the active compound of the present invention is usually combined with one or more adjuvants suitable for the intended route of administration.When administered orally, the compound can be mixed with lactose, sucrose, starch powder, cellulose ester of alkanoic acid, cellulose alkyl ester, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphate and sulfate, gelatin, gum arabic, sodium alginate, polyvinylpyrrolidone, and / or polyvinyl alcohol, and then be tableted or encapsulated for convenient administration.Such capsules or tablets can also contain controlled-release formulations, and can also be provided by dispersing the active compound in hydroxypropylmethylcellulose.

[0120] The pharmaceutical compositions of the present invention include at least one compound of formula (I) and additives selected from any pharmaceutically acceptable carriers, adjuvants, and vehicles, as appropriate. Another composition of the present invention includes a compound of formula (I) described herein, or a prodrug thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

[0121] The present invention also encompasses articles of manufacture. As used herein, the term "article of manufacture" is intended to include, but is not limited to, kits and packages. An article of manufacture of the present invention includes (a) a first container, (b) a pharmaceutical composition contained within the first container (wherein the composition contains a first therapeutic agent, the first therapeutic agent comprising a compound of the present invention or a pharmaceutically acceptable salt form thereof), and (c) a package insert stating that the pharmaceutical composition can be used to treat an inflammatory disease and / or an autoimmune disease, as defined above. In other embodiments, the package insert states that the pharmaceutical composition can be used in combination with a second therapeutic agent (as defined above) to treat an inflammatory disease and / or an autoimmune disease. The article of manufacture may further include (d) a second container (wherein components (a) and (b) are contained within the second container and component (c) is located within or outside the second container). "Located in the first and second containers" means that each container holds the item within its area.

[0122] A primary container is a container used to hold a pharmaceutical composition. This container may be for manufacturing, storage, distribution, and / or individual / bulk sales. Primary container is intended to encompass bottles, jars, vials, flasks, syringes, tubes (e.g., for cream formulations), or any other container used in manufacturing, holding, storing, or distributing a pharmaceutical formulation.

[0123] The second container is for holding the first container and, optionally, the package insert. Examples of the second container include, but are not limited to, boxes (e.g., cardboard or plastic), wooden boxes, corrugated boxes, bags (e.g., paper or plastic bags), pouches, and cloth bags. The package insert can be physically attached to the first container by tape, glue, staples, or other methods, or can be present in the second container without being physically attached to the first container. Alternatively, the package insert is located on the outside of the second container. When located on the outside of the second container, the package insert is preferably physically attached by tape, glue, staples, or other methods. Alternatively, the package insert can be in close proximity to or in contact with the outside of the second container without being physically attached.

[0124] A package insert is a label, tag, marker, etc. that lists information related to the pharmaceutical composition placed in the first container. The information listed is usually determined by a regulatory agency (e.g., the U.S. Food and Drug Administration) that governs the region in which the product will be sold. In some embodiments, the package insert specifically lists indications for which the pharmaceutical composition is approved. The package insert may be made of any material that allows a person to read the information contained therein or thereon. For example, the package insert is a printable material (e.g., paper, plastic, cardboard, foil, adhesive paper or plastic, etc.) on which the desired information is formed (e.g., printed or affixed).

[0125] (Manufacturing method) The compounds of the present invention can be prepared by many methods known to those skilled in the art of organic synthesis. The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of organic synthetic chemistry, or using analogous synthetic methods appreciated by those skilled in the art. Preferred methods include, but are not limited to, the methods described below. All references cited herein are incorporated by reference.

[0126] The compounds of the present invention may be prepared using the reactions and techniques described in this section. The reactions are carried out in solvents appropriate to the reagents and materials used and are suitable for the transformations being effected. It is also understood that in the description of the synthetic methods set forth below, all proposed reaction conditions (including solvent selection, reaction atmosphere, reaction temperature, experimental time, and work-up method) have been selected to be standard conditions for the reactions, and should be readily recognized by those skilled in the art. Those skilled in the art of organic synthesis will understand that functional groups present on various portions of the molecule must be compatible with the proposed reagents and reactions. Such limitations on substituents compatible with the reaction conditions will be readily apparent to those skilled in the art, and alternative methods must be used. The reactions may sometimes require the determination to alter the order of synthetic steps or to select a different course of action for certain reactions in order to obtain the desired compounds of the present invention. It is also recognized that another important consideration in planning any synthetic route in this field is the judicious selection of protecting groups used to protect reactive functional groups present in the desired compounds of the present invention. For the experienced experimenter, an authoritative reference describing many protecting group alternatives is Protective Groups In Organic Synthesis by Greene and Wuts (Fourth Edition, Wiley & Sons, 2007).

[0127] (Example) The preparation of compounds of formula (I), and intermediates used in the preparation of compounds of formula (I), may be prepared using the processes described in the Examples below, and processes related thereto. The methods and conditions used in these Examples, and the actual compounds prepared in these Examples, are not intended to be limiting, but rather to illustrate how compounds of formula (I) may be prepared. The starting materials and reagents used in these Examples, if not prepared by the processes described herein, are generally either commercially available or reported in the chemical literature, or may be prepared by using processes described in the chemical literature. [Table 1]

[0128] Analytical and preparative HPLC conditions: Method A (SCP): Column: XBridge BEH XP C18 (50x2.1) mm, 2.5 μm; Mobile phase A: 5:95 acetonitrile:10 mM ammonium acetate in water; Mobile phase B: 95:5 acetonitrile:10 mM ammonium acetate in water; Temperature: 50 °C; Gradient: 0-100% B over 3 min; Flow rate: 1.11 mL / min; Detection: UV (220 nm) Method B (SCP): Column: XBridge BEH XP C18 (50x2.1) mm, 2.5 μm: A: 95% water: 5% acetonitrile; 0.1% TFA; B: 5% water: 95% acetonitrile; 0.1% TFA; Temperature: 50 °C; Gradient: 0–100% B over 3 min; Flow rate: 1.11 mL / min; Detection: UV (220 nm) (C): Kinetex XB-C18 (75x3mm) 2.6µ; Solvent A: 10mM ammonium formate in water:acetonitrile (98:2); Mobile phase B: 10mM ammonium formate in water:acetonitrile (2:98); Temperature: 50°C; Gradient: 0-100% B over 5 min; Flow rate: 1.1mL / min; Detection: UV (220nm) (D): Column: Ascentis Express C18 (50x2.1) mm, 2.7 μm; Mobile phase A: 5:95 acetonitrile:water (containing 10 mM NH4OAc); Mobile phase B: 95:5 acetonitrile:water (containing 10 mM NH4OAc); Temperature: 50 °C; Gradient: 0–100% B over 3 min; Flow rate: 1.1 mL / min (E) Waters Acquity SDS; Mobile phase: A: Water, B: ACN; 5%–95% B in 1 min; Gradient range: 50%–98% B (0–0.5 min), 98% B (0.5–1 min), 98%–2% B (1–1.1 min); Elution time: 1.2 min; Flow rate: 0.7 mL / min; Analysis time: 1.7 min; Detection: Detector 1: UV (220 nm); Detector 2: MS (ES) + ) (F)Acquity UPLC BEH C18(3.0x50mm) 1.7μm; Buffer: 5mM ammonium acetate; Mobile phase A: Buffer: ACN(95:5); Mobile phase B: Buffer: ACN(5:95)Method: %B: 0 min~20%: 1.1 min~90%:1.7 min~90%; Elution time: 2.25 min; Flow rate: 0.7mL / min; Detection: Detector 1: UV(220nm); Detector 2: MS(ES + ) (G) Column: Luna 3.0 C18(2) 100Å LC column (20x4.0mm); Mercury MS™; Mobile phase A: 0.1% TFA / Milli-Q water; Mobile phase B: 0.1% TFA / ACN; Flow rate: 1.5mL / min (H): Column: Ascentis Express C18 (50x2.1) mm, 2.7 μm; Mobile phase A: 5:95 acetonitrile:water (containing 0.1% TFA); Mobile phase B: 95:5 acetonitrile:water (containing 0.1% TFA); Temperature: 50°C; Gradient: 0–100% B over 3 min; Flow rate: 1.1 mL / min (I) Preparative LCMS: Waters XBridge C18, 19x150mm, particle size: 5µm; Mobile phase A: 10mM ammonium acetate; Mobile phase B: methanol; Gradient: 10-45% B over 20min, followed by 100% B for 5min; Flow rate: 20mL / min

[0129] Example 1 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole [ka]

[0130] Intermediate 1A: 2-Bromothiazole-5-carboxylic acid [ka] To a solution of methyl 2-bromothiazole-5-carboxylate (100 g, 450 mmol) in methanol (1500 mL) was added 10% NaOH (300 mL, 450 mmol) at 0 °C and stirred at the same temperature for 3 h. The reaction was concentrated under reduced pressure to remove the solvent, and the solid was dissolved in water (200 mL) and acidified with cold HCl (1.5 N) to a pH of 4 to 5. The resulting precipitate was filtered and dried to give 2-bromothiazole-5-carboxylic acid (81 g, 389 mmol, 86% yield) as a white solid product. LCMS retention time: 0.35 min [C]; MS (E - ) m / z: 208.0(M+2H)

[0131] Intermediate 1B: tert-butyl (2-bromothiazol-5-yl)carbamate [ka] To a solution of 2-bromothiazole-5-carboxylic acid (81 g, 389 mmol) in t-BuOH (1000 mL) was added TEA (65.1 mL, 467 mmol), followed by the dropwise addition of diphenylphosphoryl azide (111 mL, 506 mmol) at room temperature, and the resulting solution was heated at 80° C. for 12 hours. The reaction was concentrated under reduced pressure, diluted with water (500 mL), brine (300 mL), and extracted with ethyl acetate (3×500 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude product. The resulting crude product was purified by combiflash (120 g silica column) and the compound was eluted with 15% EtOAc / petroleum ether. The fractions were collected and concentrated to give tert-butyl (2-bromothiazol-5-yl)carbamate (52 g, 186 mmol, 47.8% yield) as an off-white solid. LCMS retention time 1.57 min[G];MS(E-)m / z: 281.1(M+2H)

[0132] Intermediate 1C: tert-butyl 4-(5-((tert-butoxycarbonyl)amino)thiazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate [ka] To a solution of tert-butyl (2-bromothiazol-4-yl)carbamate (15 g, 53.7 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (19.94 g, 64.5 mmol) in dioxane (300 mL) and water (34 mL) was added potassium phosphate tribasic (34.2 g, 161 mmol), and the solution was degassed with N for 10 min. PdCl(dppf)-CHCl adduct (4.39 g, 5.37 mmol) was then added, degassed for an additional 5 min, and the mixture was heated at 90 °C for 12 h. The reaction mixture was diluted with ethyl acetate (250 mL), washed with water (2 × 200 mL), brine (100 mL), dried over sodium sulfate, and concentrated to give the crude product. The resulting crude material was purified by combiflash (120 g silica column) and the compound was eluted with 45% EtOAc / petroleum ether. The fractions were collected and concentrated to give tert-butyl 4-(4-((tert-butoxycarbonyl)amino)thiazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (19 g, 49.3 mmol, 92% yield) as a pale yellow solid. LCMS retention time 3.38 min [C]; MS (E - ) m / z: 382.1(M+H)

[0133] Intermediate 1D: tert-butyl 4-(5-((tert-butoxycarbonyl)amino)thiazol-2-yl)piperidine-1-carboxylate [ka] A solution of tert-butyl 4-(4-((tert-butoxycarbonyl)amino)thiazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (19 g, 49.8 mmol) and EtOAc (500 mL) was purged with nitrogen (N), then Pd / C (9.54 g, 8.96 mmol) was added and the reaction was purged with N three times. Hydrogen gas was introduced into the mixture via a balloon and then stirred at room temperature for 8 hours. The suspension was filtered through Celite, and the filtrate was collected and concentrated to give tert-butyl 4-(4-((tert-butoxycarbonyl)amino)thiazol-2-yl)piperidine-1-carboxylate (18 g, 46.0 mmol, 92% yield) as a pale yellow solid. LCMS retention time 3.24 min [C]; MS (E - ) m / z: 384.1 (M+H)

[0134] Intermediate 1E: tert-butyl 4-(5-((tert-butoxycarbonyl)amino)-4-iodothiazol-2-yl)piperidine-1-carboxylate [ka] To a solution of tert-butyl 4-(5-((tert-butoxycarbonyl)amino)thiazol-2-yl)piperidine-1-carboxylate (17 g, 44.3 mmol) in acetonitrile (700 mL) was added NIS (9.97 g, 44.3 mmol) in acetonitrile (250 mL) dropwise at 0° C. The resulting solution was stirred at the same temperature for 10 minutes. The reaction was quenched with aqueous sodium thiosulfate (200 mL) and extracted with EtOAc (3×200 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give the crude product. The resulting crude product was purified by combiflash (120 g silica column) and the compound was eluted with 16% EtOAc / petroleum ether. The fractions were collected and concentrated to give tert-butyl 4-(5-((tert-butoxycarbonyl)amino)-4-iodothiazol-2-yl)piperidine-1-carboxylate (17 g, 33.0 mmol, 74.5% yield) as a pale yellow solid. LCMS retention time 3.40 min [C]; MS (E -) m / z: 510.1(M+H)

[0135] Intermediate 1F: tert-butyl 4-(5-((tert-butoxycarbonyl)(3-methylbut-2-en-1-yl)amino)-4-iodothiazol-2-yl)piperidine-1-carboxylate [ka] To a solution of tert-butyl 4-(5-((tert-butoxycarbonyl)amino)-4-iodothiazol-2-yl)piperidine-1-carboxylate (17 g, 33.4 mmol) in DMF (250 mL) was added NaH (1.335 g, 33.4 mmol) at 0° C. and stirred at the same temperature for 10 minutes. Then 1-bromo-3-methylbut-2-ene (4.27 mL, 36.7 mmol) was added dropwise and stirred at the same temperature for 10 minutes. The reaction was quenched with ice water (250 mL) and extracted with EtOAc (3×250 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give tert-butyl 4-(5-((tert-butoxycarbonyl)(3-methylbut-2-en-1-yl)amino)-4-iodothiazol-2-yl)piperidine-1-carboxylate (17.2 g, 28.3 mmol, 85% yield) as a pale yellow oil. LCMS retention time 4.13 min [C]; MS (E - ) m / z: 578.1(M+H)

[0136] Intermediate 1G: tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 4-(5-((tert-butoxycarbonyl)(3-methylbut-2-en-1-yl)amino)-4-iodothiazol-2-yl)piperidine-1-carboxylate (3.0 g, 5.19 mmol) and potassium carbonate (1.077 g, 7.79 mmol) in DMF (90 mL) was added tetrabutylammonium bromide (1.675 g, 5.19 mmol). The mixture was degassed for 10 min, Pd(OAc)2 (0.035 g, 0.156 mmol) was added, degassed for an additional 5 min, and the resulting reaction mixture was heated at 100 °C for 12 h. The reaction mixture was filtered through Celite, washed with EtOAc (100 mL), and the filtrate was concentrated to give the crude product. The resulting crude product was purified by combiflash (40 g silica column) and the compound was eluted with 18% to 45% EtOAc / petroleum ether. The fractions were collected and concentrated to give tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (510 mg, 0.245 mmol, 27.71% yield) as a pale yellow solid. LCMS retention time 4.29 min [C]; MS (E - ) m / z: 450.1(M+2)

[0137] Intermediate 1H: tert-butyl 5-bromo-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 4-(6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidine-1-carboxylate (480 mg, 1.373 mmol) in DCE (10 mL) was added dropwise NBS (269 mg, 1.511 mmol) dissolved in DCE (10 mL) at 0 °C. The solution was stirred at room temperature for 15 minutes, and the reaction was quenched with water (50 mL) and extracted with ethyl acetate (3 × 50 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give the crude product. The resulting crude product was purified by combiflash (24 g silica column) and the compound was eluted with 8% EtOAc / petroleum ether. The fractions were collected and concentrated to give tert-butyl 4-(5-bromo-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidine-1-carboxylate (100 mg, 0.233 mmol, 17.00% yield) as a white solid. LCMS retention time 4.29 min [C]; MS (E - ) m / z: 528.1(M+H)

[0138] Intermediate 1I: tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 5-bromo-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (150 mg, 0.284 mmol), 8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (94 mg, 0.341 mmol) in dioxane (5 mL) and water (0.556 mL) was added potassium phosphate tribasic (148 mg, 0.851 mmol). The solution was degassed with N for 10 minutes, and PdCl(dppf)-CHCl adduct (11.59 mg, 0.014 mmol) was added. The solution was degassed again for 5 minutes and heated at 85 °C for 3 hours. The reaction mixture was diluted with EtOAc (200 mL), washed with water (2×100 mL), brine (50 mL), dried over sodium sulfate, and concentrated to give the crude product. The crude product was purified by combiflash (24 g silica column) and the compound was eluted with 48% EtOAc / petroleum ether. The fractions were collected and concentrated to give tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (130 mg, 0.302 mmol, 76% yield) as a brown solid. LCMS retention time 1.43 min [C]; MS (E - ) m / z: 597.1(M+H)

[0139] Example 1: 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole To a solution of tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (95 mg, 0.159 mmol) in DCM (1 mL) was added hydrochloric acid in dioxane (1 mL, 32.9 mmol) and the solution was stirred at room temperature for 30 minutes. The reaction was concentrated under reduced pressure to remove volatiles, washed with diethyl ether (2×5 mL), the ether layer was decanted, and the solid was dried to give 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (62 mg, 0.156 mmol, 98% yield) as a yellow solid. LCMS retention time 0.93 min [A]; MS (E - ) m / z: 397.1(M+H); 1 H NMR (400MHz, DMSO-d6)δ 11.63(s, 1H), 8.48(s, 2H), 7.11(d, J=1.2Hz, 1H), 4.09-3.98(m, 3H), 3.23-3.19(m, 2H), 2.92-2.84(m, 3H), 2.13(d, J=10.0Hz, 2H), 1.90(s, 1H), 1.88-1.73(m, 2H), 1.43(d, J=6.8Hz, 6H)

[0140] The following examples were prepared according to the general procedures described in Example 1. [Table 2]

[0141] Example 6 2-(Dimethylamino)-1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one [ka] To a solution of 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (16 mg, 0.040 mmol) and dimethylglycine (4.99 mg, 0.048 mmol) in DMF (2 mL) was added TEA (0.011 mL, 0.081 mmol) followed by HATU (16.88 mg, 0.044 mmol) and stirred at 25 °C for 3 h. The reaction was diluted with water (5 mL) and extracted with EtOAc (3 × 10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(dimethylamino)-1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (4.4 mg, 9.14 μmol, 22.64% yield) as a pale yellow solid. LCMS retention time 1.14 min [A]; MS (E - ) m / z: 482.2(M+H); 1 H NMR (400MHz, DMSO-d6) δ 11.62(s, 1H), 8.55-8.37(m, 2H), 7.10(s, 1H), 4.39 (d,J=13.0Hz, 1H), 4.10-3.98(m, 3H), 3.36-3.27(m, 4H), 3.21-3.13(m, 3H), 2.88-2.78 (m,1H), 2.31(s, 4H), 2.07(d, J=15.4Hz, 3H), 1.73(d, J=10.3Hz, 1H), 1.64-1.50(m, 1H), 1.42(d, J=6.8Hz, 6H)

[0142] Example 7 2-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide [ka] To a solution of 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (16 mg, 0.040 mmol) and 2-chloro-N,N-dimethylacetamide (7.07 μL, 0.069 mmol) in DMF (2 mL) was added TEA (0.017 mL, 0.121 mmol) and stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (9.5 mg, 0.019 mmol, 46.3% yield) as a pale yellow solid. LCMS retention time 1.29 min [A]; MS (E - ) m / z: 482.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.60(s, 1H), 8.53-8.39(m, 2H), 7.10(s, 1H), 4.11-4.02(m, 2H), 3.21-3.10(m, 3H), 3.06-2.97(m, 3H), 2.92(d, J=11.0Hz, 2H), 2.82(s, 3H), 2.23(t, J=10.6Hz, 2H), 2.10-1.99(m, 2H), 1.90(s, 2H), 1.83-1.67(m, 2H), 1.42(d, J=6.8Hz, 6H)

[0143] The following examples were prepared according to the general procedures described in Example 7. [Table 3]

[0144] Example 10 6-Isopropyl-2-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (18 mg, 0.045 mmol) in MeOH (2 mL) was added TEA (0.013 mL, 0.091 mmol), propan-2-one (5.80 mg, 0.050 mmol), followed by acetic acid (0.260 μL, 4.54 μmol) dropwise at 0° C. The solution was stirred at room temperature for 12 hours, and then sodium cyanoborohydride (5.71 mg, 0.091 mmol) was added at 0° C. and stirred for 2 hours at room temperature. The reaction mixture was concentrated, and the resulting residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated. The resulting crude sample was purified by preparative LCMS (Method I). After preparative LCMS purification, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 6-isopropyl-2-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (4.14 mg, 0.09 mmol, 20.3% yield) as a pale yellow solid. LCMS retention time 1.15 min [A]; MS (E - ) m / z: 439.2 (M+H); 1H NMR (400MHz, DMSO-d6)δ 11.68(s, 1H), 8.48(s, 2H), 7.18-7.05(m, 1H), 4.06(s, 2H),3.58-3.46(m, 3H), 3.25-3.08(m, 2H), 2.93 (dd, J=12.7, 6.6Hz, 2H), 2.31(br. s., 2H), 2.13-2.00(m, 2H), 1.44(d, J=6.8Hz, 2H), 1.28(d, J=6.6Hz, 5H), 1.16(t, J=7.2Hz, 6H)

[0145] The following examples were prepared according to the general procedures described in Example 10. [Table 4]

[0146] Example 15 1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol [ka] To a solution of 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (18 mg, 0.045 mmol) and 1-chloro-2-methylpropan-2-ol (4.93 mg, 0.045 mmol) in DMF (2 mL) was added potassium carbonate (18.82 mg, 0.136 mmol) and heated at 85° C. for 12 h. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol (5.4 mg, 0.012 mmol, 25.4% yield) as a pale yellow solid. LCMS 1.37 min [A]; MS (E - ) m / z: 469.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.66(s, 1H), 8.46(d, J=1.5Hz, 2H), 7.09(s, 1H), 5.30(br.s., 2H), 4.05(s, 3H), 3.24-3.14(m, 4H), 3.11(br. s., 3H), 2.23(br. s., 4H), 1.43(d, J=6.8Hz,6H), 1.26(s, 6H)

[0147] Example 16 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (16 mg, 0.040 mmol) and 1-chloro-2-(methylsulfonyl)ethane (9.78 mg, 0.069 mmol) in DMF (1 mL) was added DIPEA (0.017 mL, 0.121 mmol) and heated at 85° C. for 12 h. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (7.7 mg, 0.015 mmol, 38% yield) as a pale yellow solid. LCMS 1.35 min [A]; MS (E - ) m / z: 503.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.60(s, 1H), 8.46(s, 2H), 7.11(s, 1H), 4.05(s, 3H), 3.31 (d,J=6.1Hz, 2H), 3.22-3.13(m, 1H), 3.09-2.91(m, 6H), 2.75(br. s., 2H), 2.17(br. s., 2H), 2.07(d, J=8.3Hz, 2H), 1.82-1.65(m, 2H), 1.43(d, J=6.8Hz, 6H)

[0148] Example 17 2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide [ka] To a solution of 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (16 mg, 0.042 mmol) in DMF (2 mL) was added TEA (0.018 mL, 0.126 mmol) followed by 2-chloro-N,N-dimethylacetamide (7.36 μL, 0.071 mmol) at room temperature and stirred at the same temperature for 12 hours. The reaction mixture was diluted with water (5 mL) and extracted with ethyl acetate (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (4.1 mg, 8.37 μmol, 19.89% yield) as a pale yellow solid. LCMS 1.33 min [A]; MS(E-) m / z: 466.2 (M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.62(s, 1H), 8.71(s, 1H), 8.50(s, 1H), 7.55(s, 1H), 4.26(s, 3H), 3.18-3.08(m, 4H), 2.99-2.85(m, 5H), 2.61(s, 3H), 2.29(br. s., 3H), 2.23-2.12(m, 2H), 1.42(d, J=6.6Hz, 6H)

[0149] Example 18 1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol [ka] To a solution of 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (18 mg, 0.047 mmol) in DMF (2 mL) was added potassium carbonate (19.61 mg, 0.142 mmol) followed by 1-chloro-2-methylpropan-2-ol (5.14 mg, 0.047 mmol) dropwise, and the resulting pale yellow solution was heated at 85° C. for 6 h. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol (2.6 mg, 5.51 μmol, 11.66% yield) as a pale yellow solid. LCMS 1.41 min [A]; MS (E - ) m / z: 453.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.69-11.54(m, 1H), 8.73(s, 1H), 8.51(s, 1H), 7.55(s, 1H),5.24(br. s., 1H), 3.72(d, J=10.5Hz, 2H), 3.22(br. s., 2H), 3.17(s, 3H), 3.12(br. s., 3H), 2.93(dd, J=12.1, 7.0Hz, 2H), 2.62(s, 3H), 2.24(br. s., 3H), 2.19(s, 3H), 1.42(d, J=6.8Hz, 6H)

[0150] Example 19 2-(Dimethylamino)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one [ka] To a solution of 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (16 mg, 0.042 mmol) and dimethylglycine (5.20 mg, 0.050 mmol) in DMF (2 mL) was added TEA (0.012 mL, 0.084 mmol) followed by HATU (17.59 mg, 0.046 mmol) and stirred at room temperature for 3 hours. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (3 x 10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(dimethylamino)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (1 mg, 2.083 μmol, 4.95% yield) as a pale yellow solid. LCMS retention time 1.19 min [A]; MS (E - ) m / z: 466.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.58(br. s., 1H), 8.71(s, 1H), 8.50(s, 1H), 7.55(s, 1H), 4.39(d, J=13.0Hz, 1H), 4.12(d, J=13.7Hz, 1H), 3.14-3.06(m, 6H), 2.84-2.71(m, 2H), 2.61 (s,3H), 2.19(s, 4H), 2.15-2.02(m, 2H), 1.80-1.63(m, 2H), 1.41(d, J=6.8Hz, 6H)

[0151] Example 20 6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (10 mg, 0.026 mmol) in MeOH (2 mL) was added TEA (7.33 μL, 0.053 mmol), oxetan-3-one (2.083 mg, 0.029 mmol), followed by acetic acid (0.150 μL, 2.63 μmol) dropwise at 0° C. and stirred at room temperature for 12 hours. Sodium cyanoborohydride (3.30 mg, 0.053 mmol) was then added at 0° C. and stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I) to give 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (1 mg, 2.268 μmol, 8.63% yield) as a pale yellow solid. LCMS retention time 1.43 min [A]; MS (E - ) m / z: 437.2 (M+H); 1 H NMR(400MHz, DMSO-d6)δ 8.71(s, 1H), 8.50(s, 2H), 7.55(s, 1H), 4.55(t, J=6.5Hz, 2H),4.48-4.40(m, 2H), 3.16-3.10(m, 2H), 3.04(d, J=2.9Hz, 2H), 2.76(s, 2H), 2.78(s, 1H), 2.61(s, 2H), 2.12-2.02(m, 2H), 1.98-1.86(m, 1H), 1.84-1.70(m, 2H), 1.41(d, J=6.6Hz, 6H)

[0152] The following examples were prepared according to the general procedures described in Example 20. [Table 5]

[0153] Example 24 2-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide [ka] To a solution of 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (20 mg, 0.056 mmol) in DMF (2 mL) was added TEA (0.024 mL, 0.169 mmol) and 2-chloro-N,N-dimethylacetamide (9.88 μL, 0.096 mmol) at room temperature and stirred at the same temperature for 3 hours. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude sample obtained was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (5.4 mg, 0.012 mmol, 21.12% yield) as a pale yellow solid. LCMS retention time 1.50 min [A]; MS (E - ) m / z: 440.2(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.57(s, 1H), 7.08(s, 2H), 3.27(d, J=6.8Hz, 2H), 3.18(br.s, 1H), 2.49-2.36(m, 7H), 2.12-1.98(m, 4H), 1.92(s, 4H), 1.42(d, J=6.8Hz, 6H), 1.15(s, 6H)

[0154] Example 25 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(1-isopropylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (20 mg, 0.056 mmol) in MeOH (2 mL) was added TEA (0.016 mL, 0.113 mmol), propan-2-one (3.60 mg, 0.062 mmol), followed by acetic acid (0.323 μL, 5.64 μmol) dropwise at 0° C. and stirred at room temperature for 12 hours. Sodium cyanoborohydride (7.09 mg, 0.113 mmol) was then added at 0° C. and stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with ethyl acetate (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(1-isopropylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (10.6 mg, 0.027 mmol, 47.4% yield) as a pale yellow solid. LCMS retention time 1.38 min [A]; MS (E - ) m / z: 397.2(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.57(s, 1H), 7.72(d, J=9.8Hz, 1H), 7.43-7.32(m, 1H), 4.06(s, 2H),3.58-3.46(m, 3H), 3.25-3.08(m, 2H), 2.93 (dd, J=12.7, 6.6Hz, 2H), 2.31(br. s., 2H), 2.13-2.00(m, 3H), 1.44(d, J=6.8Hz, 4H), 1.28(d, J=6.6Hz, 5H), 1.16(t, J=7.2Hz, 6H)

[0155] The following examples were prepared according to the general procedures described in Example 25. [Table 6]

[0156] Example 28 2-(Dimethylamino)-1-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one [ka] To a solution of 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (20 mg, 0.056 mmol) and dimethylglycine (6.98 mg, 0.068 mmol) in DMF (2 mL) was added TEA (0.016 mL, 0.113 mmol) followed by HATU (23.60 mg, 0.062 mmol) and stirred at room temperature for 3 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(dimethylamino)-1-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (7.9 mg, 0.018 mmol, 31.9% yield) as a pale yellow solid. LCMS retention time 1.36 min [A]; MS (E - ) m / z: 440.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.57(s, 1H), 7.72(d, J=9.8Hz, 1H), 7.43-7.32(m, 1H), 4.43(d, J=13.7Hz, 1H), 4.39-4.24(m, 2H), 3.72(br. s., 1H), 3.25(br. s., 1H), 3.18(s, 1H), 2.94(t, J=11.7Hz, 1H), 2.83(s, 6H), 2.65(s, 6H), 2.22-2.09(m, 2H), 1.83(d, J=9.5Hz, 1H), 1.64(d, J=8.6Hz, 1H), 1.46(d, J=6.8Hz, 6H)

[0157] Example 29 1-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol [ka] To a solution of 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (20 mg, 0.056 mmol) in DMF (2 mL) was added potassium carbonate (23.39 mg, 0.169 mmol), followed by 1-chloro-2-methylpropan-2-ol (6.12 mg, 0.056 mmol), and the resulting pale yellow solution was heated at 80 °C for 6 h. The reaction was diluted with water (5 mL) and extracted with EtOAc (3 x 10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 1-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol (2.8 mg, 6.56 μmol, 11.63% yield) as a pale yellow solid. LCMS 1.61 min [A]; MS (E - ) m / z: 427.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.57(s, 1H),,7.72(d, J=9.8Hz, 1H), 7.43-7.32(m, 1H), 5.24(br. s., 1H), 3.72(d, J=10.5Hz, 2H), 3.22(br. s., 3H), 3.17(s, 3H), 3.12(br. s., 4H), 2.93(dd, J=12.1, 7.0Hz, 2H), 2.62(s, 3H), 2.24(br. s., 3H), 2.19(s, 3H), 1.42(d, J=6.8Hz, 6H)

[0158] Example 30 2-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide [ka] To a solution of 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (35 mg, 0.092 mmol) in DMF (2 mL) was added TEA (0.013 mL, 0.092 mmol) and 2-chloro-N,N-dimethylacetamide (45 mg, 0.370 mmol) at room temperature and stirred at the same temperature for 3 hours. The reaction mixture was diluted with water (5 mL) and extracted with ethyl acetate (3 x 10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude sample obtained was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (7.0 mg, 0.014 mmol, 14.95% yield) as a pale yellow solid. LCMS retention time 1.56 min [A]; MS (E - ) m / z: 465.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.16(s, 1H), 8.34 (dd, J=4.5, 1.6Hz, 1H), 7.99 (dd, J=7.8,1.5Hz, 1H), 7.60(s, 1H), 7.17 (dd, J=7.9, 4.5Hz, 1H), 3.91(d, J=4.6Hz, 3H), 3.22(br. s., 2H),3.11-2.99(m, 3H), 2.95(br. s., 2H), 2.90(s, 1H), 2.87-2.78(m, 2H), 2.26(br. s., 2H), 2.07 (d,J=15.2Hz, 3H), 1.87-1.64(m, 3H), 1.38(d, J=6.8Hz, 6H)

[0159] The following examples were prepared according to the general procedures described in Example 30. [Table 7]

[0160] Example 32 2-(Dimethylamino)-1-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one [ka] To a solution of 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (35 mg, 0.092 mmol) and dimethylglycine (45 mg, 0.436 mmol) in DMF (2 mL) was added TEA (0.013 mL, 0.092 mmol) followed by HATU (35.1 mg, 0.092 mmol) and stirred at room temperature for 3 hours. The reaction was diluted with water (5 mL) and extracted with ethyl acetate (3 x 10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(dimethylamino)-1-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (12 mg, 0.024 mmol, 26.2% yield) as a pale yellow solid. LCMS retention time 1.44 min [A]; MS (E - ) m / z: 465.2(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.17(s, 1H), 8.34 (dd, J=4.6, 1.5Hz, 1H), 7.99 (dd, J=7.8,1.5Hz, 1H), 7.60(s, 1H), 7.18 (dd, J=8.1, 4.6Hz, 1H), 4.41(d, J=12.7Hz, 1H), 4.13(d, J=13.7Hz, 1H), 3.93-3.86(m, 4H), 3.22-3.04(m, 3H), 2.79(t, J=11.6Hz, 1H), 2.26-2.15(m, 2H), 2.14-1.99(m, 3H), 1.92(s, 2H), 1.81-1.66(m, 2H), 1.66-1.47(m, 2H), 1.38(d, J=6.8Hz, 6H)

[0161] Example 33 6-Isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (25 mg, 0.066 mmol) and 1-chloro-2-(methylsulfonyl)ethane (9.39 mg, 0.066 mmol) in DMF (1 mL) was added TEA (0.018 mL, 0.132 mmol). The solution was heated at 90° C. for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (4.4 mg, 8.82 μmol, 13.40% yield) as a pale yellow solid. LCMS 1.63 min [A]; MS (E - ) m / z: 486.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.16(s, 1H), 8.33 (dd, J=4.6, 1.5Hz, 1H), 7.99 (dd, J=7.9,1.6Hz, 1H), 7.60(s, 1H), 7.17 (dd, J=7.9, 4.5Hz, 1H), 3.91(d, J=4.9Hz, 4H), 3.33(br. s., 2H),3.12-2.88(m, 6H), 2.75(br. s., 2H), 2.16(br. s., 2H), 2.07(d, J=7.6Hz, 2H), 1.75(d, J=9.5Hz,2H), 1.38(d, J=6.8Hz, 6H)

[0162] Example 34 6-Isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (25 mg, 0.066 mmol) in MeOH (2 mL) was added TEA (0.018 mL, 0.132 mmol) and oxetan-3-one (5.22 mg, 0.072 mmol), followed by acetic acid (0.377 μL, 6.59 μmol) dropwise at 0° C. and stirred at room temperature for 12 hours. Sodium cyanoborohydride (8.28 mg, 0.132 mmol) was then added at 0° C. and stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole as a pale yellow solid. LCMS retention time 1.65 min [A]; MS (E - ) m / z: 436.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.15(s, 1H), 8.34 (dd, J=4.6, 1.5Hz, 1H), 7.99 (dd, J=7.8,1.5Hz, 1H), 7.69-7.46(m, 2H), 7.18 (dd, J=7.9, 4.5Hz, 1H), 4.56(t, J=6.5Hz, 2H), 4.46(t, J=6.1Hz, 2H), 3.99-3.86(m, 2H), 3.42(d, J=4.9Hz, 1H), 3.18(d, J=5.1Hz, 1H), 3.12-2.93(m, 2H), 2.79(d, J=10.3Hz, 2H), 2.07(d, J=8.1Hz, 2H), 1.94(t, J=11.0Hz, 2H), 1.86-1.70(m, 2H), 1.38(d, J=7.1Hz, 6H)

[0163] The following examples were prepared according to the general procedures described in Example 34. [Table 8]

[0164] Example 37 5-(6-Isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile [ka] To a solution of 5-(6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (25 mg, 0.062 mmol) in MeOH (2 mL) was added oxetan-3-one (4.49 mg, 0.062 mmol), TEA (8.68 μL, 0.062 mmol), followed by acetic acid (0.356 μL, 6.23 μmol) dropwise at 0° C. and stirred at room temperature for 12 hours. Sodium cyanoborohydride (7.83 mg, 0.125 mmol) was then added at 0° C. and stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(6-isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (9.1 mg, 0.020 mmol, 31.4% yield) as a pale yellow solid. LCMS retention time 1.74 min [A]; MS (E - ) m / z: 458.2(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.70(s, 1H), 9.13 (dd, J=4.2, 1.7Hz, 1H), 8.45(d, J=7.6Hz,1H), 8.40 (dd, J=8.6, 1.7Hz, 1H), 7.75 (dd, J=8.7, 4.3Hz, 1H), 7.72(d, J=7.6Hz, 1H), 4.57(t, J=6.5Hz, 2H), 4.47(t, J=6.1Hz, 2H), 3.91(s, 2H), 3.44(br. s., 1H), 2.90-2.71(m, 2H), 2.10(d, J=12.2Hz, 2H), 1.97(br. s., 2H), 1.88-1.69(m, 2H), 1.34(d, J=6.8Hz, 6H)

[0165] The following examples were prepared according to the general procedures described in Example 37. [Table 9]

[0166] Example 39 5-(2-(1-(dimethylglycyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile [ka] To a solution of 5-(6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (20 mg, 0.050 mmol) and dimethylglycine (5.14 mg, 0.050 mmol) in DMF (2 mL) was added TEA (0.014 mL, 0.100 mmol) followed by HATU (18.94 mg, 0.050 mmol) and stirred at room temperature for 3 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(2-(1-(dimethylglycyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (10.5 mg, 0.020 mmol, 40.2% yield) as a pale yellow solid. LCMS retention time 1.50 min [A]; MS (E - ) m / z: 487.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.71(s, 1H), 9.13 (dd, J=4.2, 1.5Hz, 1H), 8.49-8.42 (m,1H), 8.39 (dd, J=8.7, 1.6Hz, 1H), 7.83-7.64(m, 2H), 4.43(d, J=12.2Hz, 1H), 4.15(d, J=12.2Hz, 1H), 3.91(s, 1H), 3.24-3.08(m, 3H), 2.96-2.86(m, 1H), 2.84-2.70(m, 2H), 2.30-2.17(m, 6H), 2.16-2.04(m, 2H), 1.92(s, 1H), 1.34 (d, J=6.8Hz, 6H)

[0167] Example 40 2-(4-(5-(8-cyanoquinolin-5-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide [ka] To a solution of 5-(6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (20 mg, 0.050 mmol) in DMF (2 mL) was added TEA (0.014 mL, 0.100 mmol) followed by 2-chloro-N,N-dimethylacetamide (6.06 mg, 0.050 mmol) dropwise and stirred at room temperature for 3 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(4-(5-(8-cyanoquinolin-5-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (7.2 mg, 0.015 mmol, 29.7% yield) as a pale yellow solid. LCMS retention time 1.64 min [A]; MS (E - ) m / z: 487.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.70(s, 1H), 9.13(d, J=4.2Hz, 1H), 8.45(d, J=7.3Hz, 1H),8.40(d, J=8.6Hz, 1H), 7.80-7.65(m, 1H), 3.04(s, 6H), 2.85(br. s., 4H), 2.79-2.73(m, 2H), 2.09(br. s., 4H), 1.83(br. s., 2H), 1.34(d, J=6.8Hz, 6H)

[0168] Example 41 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole [ka]

[0169] Intermediate 41A: tert-butyl 4-(5-((tert-butoxycarbonyl)amino)-4-((7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)ethynyl)thiazol-2-yl)piperidine-1-carboxylate [ka] To a solution of tert-butyl 4-(5-((tert-butoxycarbonyl)amino)-4-iodothiazol-2-yl)piperidine-1-carboxylate (2 g, 3.93 mmol) in toluene (40 mL) and diisopropylamine (10 mL) in a sealed tube, copper(I) iodide (0.075 g, 0.393 mmol) and triphenylphosphine (0.103 g, 0.393 mmol) were added while purging with argon. Bis(triphenylphosphine)palladium(II) dichloride (0.138 g, 0.196 mmol) was added, and the mixture was stirred for 5 minutes. 6-ethynyl-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (1.008 g, 5.89 mmol) was added, and the mixture was heated at 45° C. for 3 hours. The reaction was diluted with DCM, filtered through Celite, washed with water and brine, dried over Na2SO4, concentrated, and purified on silica gel (eluting solvent: 60% EtOAc / petroleum ether) to give tert-butyl 4-(5-((tert-butoxycarbonyl)amino)-4-((7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)ethynyl)thiazol-2-yl)piperidine-1-carboxylate as a pale yellow solid. LCMS retention time 2.07 min [F]; MS (E - ) m / z: 553.5(M+H)

[0170] Intermediate 41B: tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a stirred solution of tert-butyl 4-(5-((tert-butoxycarbonyl)amino)-4-((7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)ethynyl)thiazol-2-yl)piperidine-1-carboxylate (1.9 g, 3.44 mmol) in toluene (40 mL) in a sealed tube was added silver acetate (0.574 g, 3.44 mmol) and stirred at 100° C. for 30 minutes. The reaction mixture was filtered through Celite, concentrated, and purified on a silica column (40 g, elution solvent: 0-70% EtOAc / petroleum ether) to give tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.8 g, 3.26 mmol, 95% yield) as an off-white solid. LCMS retention time 2.12 min [F]; MS (E - ) m / z: 553.6(M+H)

[0171] Intermediate 41C: tert-butyl 6-bromo-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.5 g, 2.71 mmol) in DMF (30 mL) was added a solution of NBS (0.725 g, 4.07 mmol) in DMF (5 mL) at 0° C. and then stirred at room temperature overnight. Next, water (40 mL) was added to the reaction mixture and stirred for 20 minutes at room temperature. The resulting solid was collected by filtration and then dried under vacuum to give tert-butyl 6-bromo-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.4 g, 2.217 mmol, 82% yield) as an off-white solid. LCMS retention time 1.16 min [F]; MS (E - ) m / z: 633.4(M+2H)

[0172] Intermediate 41D: tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(prop-1-en-2-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 6-bromo-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.5 g, 2.375 mmol) and 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (1.596 g, 9.50 mmol) in 1,4-dioxane (30 mL) and water (3 mL) was added potassium phosphate tripotassium (1.512 g, 7.12 mmol) and then purged with nitrogen for 5 minutes. PdCl(dppf)-CHCl adduct (0.194 g, 0.237 mmol) was added and the reaction was purged for an additional 2 minutes. The reaction mixture was heated at 90° C. in a sealed tube for 4 hours. The reaction mixture was filtered through Celite, concentrated, and purified on silica gel (eluent: 50% EtOAc / petroleum ether) to give tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(prop-1-en-2-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.3 g, 2.193 mmol, 92% yield). LCMS retention time 1.4 minutes [F]; MS (E - ) m / z: 593.4(M+H)

[0173] Intermediate 41E: tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] tert-Butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(prop-1-en-2-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.3 g, 2.193 mmol) was added to ethyl acetate (30 mL). The flask was purged with N2, and Pd—C (0.233 g, 2.193 mmol) was added. After purging with nitrogen gas, hydrogen gas was introduced using a balloon and the mixture was stirred at ambient temperature for 4 hours. The flask was evacuated and backfilled with N2. The resulting suspension was filtered, and the filtrate was concentrated to give the crude product. The resulting crude product was purified on silica gel (eluent: 50% EtOAc / petroleum ether) to give tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (0.95 g, 1.597 mmol, 72.8% yield). LCMS retention time 1.57 min [F]; MS (E - ) m / z: 595.5(M+H)

[0174] Example 41: 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole To a stirred solution of tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (0.45 g, 0.757 mmol) in DCM (5 mL) was added TFA (2.91 mL, 37.8 mmol) at 0° C., and the reaction mixture was then stirred at room temperature for 16 hours. The reaction was concentrated, and to the resulting residue was added MTBE (12 mL) and stirred at room temperature for 5 minutes. The resulting solid was collected by filtration to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (0.28 g, 0.710 mmol, 94% yield) as a light brown solid. LCMS retention time 1.127 min [A]; MS(E-) m / z: 395.2 (M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.37-11.30(m, 1H), 8.72(s, 1H), 8.45(s, 1H), 3.20-3.00(m, 4H), 2.75-2.63(m, 3H), 2.58(s, 3H), 2.18(s, 3H), 2.06-1.98(m, 2H), 1.74-1.63(m, 2H), 1.31(d, J=6.8Hz, 6H)

[0175] The following intermediates were prepared according to the general method described in Intermediate 41. [Table 10]

[0176] Example 43 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (20 mg, 0.051 mmol) and oxetan-3-one (18.27 mg, 0.253 mmol) in methanol (2 mL) was added AcOH (0.290 μL, 5.07 μmol) and stirred at room temperature overnight. Sodium cyanoborohydride (6.37 mg, 0.101 mmol) was then added to the reaction at 0° C. and stirred at room temperature for 2 hours. The reaction was diluted with water (2 ml) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (12.1 mg, 0.026 mmol, 52.1% yield). LCMS retention time 1.443 min [A]; MS(E-) m / z: 451.3 (M+H); 1 H NMR (400MHz, DMSO-d6)δ 11.31(s, 1H), 8.72(s, 1H), 8.45(s, 1H), 4.65-4.51(m, 2H), 4.46(t, J=6.2Hz, 2H), 3.91(s, 2H), 3.44(br. s., 1H), 3.05(br. s., 1H), 2.78(br. s., 2H), 2.74-2.65(m, 1H), 2.64-2.53(m, 3H), 2.19(s, 3H), 2.14-2.04(m, 2H), 1.94.(d, J=17.9Hz, 2H), 1.85-1.71(m, 2H), 1.31(d, J=6.8Hz, 6H)

[0177] The following examples were prepared according to the general procedures described in Example 43. [Table 11] TIFF0007629007000100.tif128141

[0178] Example 55 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a mixture of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (20 mg, 0.051 mmol) and 1-chloro-2-(methylsulfonyl)ethane (7.23 mg, 0.051 mmol) in THF (1.5 mL) and DMF (0.5 mL) was added TEA (7.07 μL, 0.051 mmol) and stirred overnight at room temperature. The reaction mixture was diluted with water (2 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (7.4 mg, 0.015 mmol, 29.2% yield). LCMS retention time 0.974 min [B]; MS (E - ) m / z: 501.3(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.31(s, 1H), 8.72(s, 1H), 8.45(s, 1H), 3.06(s, 4H), 3.01(br. s., 2H), 2.82-2.63(m, 4H), 2.58(s, 3H), 2.18(s, 6H), 2.11-1.99(m, 2H), 1.76(d, J=11.5Hz, 2H), 1.31(d, J=6.8Hz, 6H)

[0179] The following examples were prepared according to the general procedures described in Example 55. [Table 12]

[0180] Example 59 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (25 mg, 0.063 mmol) in DCM, TEA (26.5 μL, 0.190 mmol) and acetyl chloride (24.87 mg, 0.317 mmol) were added at 0° C. and then stirred at room temperature for 2 h. The reaction mixture was diluted with water (10 mL) and extracted with DCM (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude sample obtained was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (15.5 mg, 0.035 mmol, 54.5% yield). LCMS retention time 1.387 min [A]; MS (E - ) m / z: 437.2 (M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.32(s, 1H), 8.72(s, 1H), 8.45(s, 1H), 4.44(d, J=12.7Hz, 1H), 3.99-3.89(m, 1H), 3.27-3.17(m, 1H), 2.90(s, 1H), 2.80-2.62(m, 5H), 2.58(s, 3H), 2.19(s, 3H), 2.15-1.95(m, 2H), 1.74 (dd, J=12.3, 3.5Hz, 1H), 1.57 (dd, J=12.3, 3.8Hz, 1H), 1.31(d, J=6.8Hz, 6H)

[0181] Example 60 5-(6-Isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one [ka] To a solution of 5-(6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (40 mg, 0.104 mmol) and oxetan-3-one (37.5 mg, 0.520 mmol) in methanol (2 mL) was added AcOH (0.595 μL, 10.40 μmol) and stirred at room temperature overnight. Sodium cyanoborohydride (13.07 mg, 0.208 mmol) was added to the reaction at 0° C. and stirred at room temperature for 2 hours. The reaction was diluted with water (2 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(6-isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (17 mg, 0.037 mmol, 35.9% yield) as a white solid. LCMS retention time 1.925 min [C]; MS (E - ) m / z: 441.2 (M+H); 1 H NMR (400MHz, DMSO-d6) δ 11.05(s, 1H) 7.53(s, 1H) 4.52-4.58(m, 2H) 4.45(t, J=6.02Hz, 2H) 3.46(s, 3H) 3.40-3.44(m, 1H) 3.37(s, 1H) 2.95-3.05(m, 2H) 2.66-2.81(m, 3H) 2.54-2.63(m, 1H) 2.31-2.36(m, 2H) 2.04(s, 3H) 1.88-1.98(m, 2H) 1.70-1.83(m, 2H) 1.29(d, J=7.03Hz, 6H)

[0182] Example 61 5-(6-Isopropyl-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one [ka] To a mixture of 5-(6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (40 mg, 0.104 mmol) and 1-chloro-2-(methylsulfonyl)ethane (14.83 mg, 0.104 mmol) in THF (1.5 mL) and DMF (0.5 mL) was added TEA (0.014 mL, 0.104 mmol) and stirred overnight at room temperature. The reaction mixture was diluted with water (2 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude sample obtained was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(6-isopropyl-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (16 mg, 0.032 mmol, 30.5% yield). LCMS retention time 1.949 min [C]; MS (E - ) m / z: 491.2 (M+H); 1 H NMR(400MHz, DMSO-d6)δ ppm 11.06(s, 1H) 7.53(s, 1H) 3.46(s, 3H) 3.05(s, 3H) 2.98(d, J=11.55Hz, 3H) 2.63-2.79(m, 5H) 2.10-2.34(m, 3H) 2.04(s, 5H) 1.65-1.82(m, 4H) 1.29(d, J=7.03Hz, 6H)

[0183] The following examples were prepared according to the general procedures described in Example 61. [Table 13]

[0184] Examples 65 and 66 N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine [ka]

[0185] Intermediate 65A: tert-butyl (2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)thiazol-5-yl)carbamate [ka] To a solution of tert-butyl (2-bromothiazol-5-yl)carbamate (70 g, 251 mmol) and 4,4,5,5-tetramethyl-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (100 g, 376 mmol) in dioxane (1500 mL) was added potassium phosphate tribasic (160 g, 752 mmol) dissolved in water (375 mL). The reaction mixture was pre-degassed with argon for 20 minutes, and then PdCl(dppf)-CHCl adduct (20.48 g, 25.08 mmol) was added. The reaction mixture was degassed again for 5 minutes, and the mixture was stirred at 80 °C for 12 hours. The reaction mixture was diluted with EtOAc (3000 mL), placed in a separatory funnel, washed with water (2×1500 mL), brine (1500 mL), dried over sodium sulfate, and concentrated to give the crude product. The crude product was purified by silica gel chromatography (eluting with 30% ethyl acetate / hexanes), and the collected fractions were concentrated to give tert-butyl (2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)thiazol-5-yl)carbamate (75 g, 84% yield) as a yellow solid. LCMS retention time 2.44 min [C]; MS (E - ) m / z: 339.2 (M+H)

[0186] Intermediate 65B: tert-butyl (2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate [ka] A solution of tert-butyl (2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)thiazol-5-yl)carbamate (75 g, 222 mmol) in MeOH (1000 mL) and ethyl acetate (1000 mL) was added to a flask, which was purged with N, and Pd / C (23.58 g, 222 mmol) was added. After purging with N three times, H gas was introduced via a balloon and the mixture was stirred at ambient temperature for 12 hours. The flask was evacuated and backfilled with N. The resulting suspension was filtered, and the filtrate was concentrated to give the crude product. The crude sample was purified by silica gel chromatography (eluent: 30% EtOAc / petroleum ether), and the collected fractions were concentrated to give tert-butyl (2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate (70 g, 88% yield) as a pale white solid. LCMS retention time: 2.36 min [C], MS (E - ) m / z: 341(M+H)

[0187] Intermediate 65C: tert-butyl (4-iodo-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate [ka] To a solution of tert-butyl (2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate (50 g, 147 mmol) in acetonitrile (2000 mL) was added dropwise NIS (36.3 g, 162 mmol) dissolved in acetonitrile (2000 mL) and stirred for 30 minutes at 0° C. The reaction was diluted with ethyl acetate (2000 mL), washed with water (1500 mL), saturated NaCl (1500 mL), and finally dried over sodium sulfate and concentrated at 45° C. to give the crude product. The crude product was purified by silica gel chromatography (eluent: 30% EtOAc / petroleum ether), and the collected fractions were concentrated to give tert-butyl (4-iodo-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate (45 g, 66% yield) as a yellow solid. LCMS retention time 3.05 min [C]; MS(E-) m / z: 467.2 (M+H).

[0188] Intermediate 65D: tert-butyl (4-iodo-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)(3-methylbut-2-en-1-yl)carbamate [ka] To a solution of tert-butyl (4-iodo-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate (30 g, 64.3 mmol) in DMF (100 mL) was slowly added NaH (5.15 g, 129 mmol) portionwise, followed by dropwise addition of 1-bromo-3-methylbut-2-ene (18.44 mL, 96 mmol) at 0 °C and stirring at the same temperature for 20 min. The reaction was quenched with ice-cold water, diluted with EtOAc (1000 mL), placed in a separatory funnel, washed with brine (1000 mL), dried over sodium sulfate, and concentrated to give the crude product. The crude material was purified by silica gel chromatography (eluent: 30% EtOAc / petroleum ether), and the collected fractions were concentrated to give tert-butyl (4-iodo-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate (28 g, 81% yield) as a white solid. LCMS retention time 2.5 min [C]; MS (E - ) m / z: 535.2(M+H)

[0189] Intermediate 65E: tert-butyl 6-isopropyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl (4-iodo-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)(3-methylbut-2-en-1-yl)carbamate (28 g, 52.4 mmol) in DMF (600 mL) was added potassium carbonate (14.48 g, 105 mmol) and tetrabutylammonium bromide (50.7 g, 157 mmol), degassed with argon for 10 minutes, added PdOAc (1.176 g, 5.24 mmol), and heated at 90 °C for 12 hours. The reaction was diluted with EtOAc and filtered through Celite. The combined organic extracts were concentrated to give the crude product. The crude product was purified by silica gel chromatography (eluent: 10% EtOAc / petroleum ether), and the collected fractions were concentrated to give tert-butyl 6-isopropyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (9.5 g, 40% yield) as a pale yellow solid. LCMS retention time: 2.5 min [C]; MS (E - ) m / z: 535.2(M+H)

[0190] Intermediate 65F: tert-butyl 5-bromo-6-isopropyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 6-isopropyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (9.5 g, 23.37 mmol) in DCE (100 mL) was added NBS (3.74 g, 21.03 mmol) in DCE (100 mL) dropwise at 0 °C and stirred at the same temperature for 20 min. The reaction was quenched with saturated sodium sulfite (50 mL), diluted with DCM (500 mL), placed in a separatory funnel, washed with brine (500 mL), dried over sodium sulfate, and concentrated to give the crude product. The crude product was purified by silica gel chromatography (eluent: 30% EtOAc / petroleum ether), and the collected fractions were concentrated to give tert-butyl 5-bromo-6-isopropyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (6.2 g, 54% yield) as a pale yellow solid. LCMS retention time 2.3 min [C]; MS (E - ) m / z: 485.2(M+H)

[0191] Intermediate 65G: tert-butyl 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 5-bromo-6-isopropyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (5.5 g, 11.33 mmol) in dioxane (150 mL) and water (20 mL) was added potassium phosphate tribasic (7.21 g, 34.0 mmol) and 8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (6.23 g, 22.66 mmol). The reaction was degassed with argon for 10 minutes, and then PdCl(dppf)-CHCl adduct (0.925 g, 1.133 mmol) was added and heated at 75 °C for 4 hours. The reaction mixture was diluted with EtOAc (3000 mL), placed in a separatory funnel, washed with water (2×500 mL), brine (500 mL), dried over sodium sulfate, and concentrated to give the crude product. The crude product was purified by silica gel chromatography (eluting solvent: 40% EtOAc / petroleum ether), and the collected fractions were concentrated to give tert-butyl (2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)thiazol-5-yl)carbamate (3.7 g, 60% yield) as a yellow solid. LCMS retention time 3.58 min [C]; MS (E - ) m / z: 554.2(M+H)

[0192] Intermediate 65H: 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one [ka] To a solution of tert-butyl 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (3.5 g, 6.32 mmol) in DCM (55 mL) was added TFA (55 mL) and stirred at ambient temperature for 12 hours. The reaction was concentrated under reduced pressure, and the resulting residue was triturated with n-hexane to give 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (2.5 g, 92%) as a pale yellow solid. LCMS retention time 2.82 min[C];MS(E - ) m / z: 410.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.63(s, 1H), 8.57-8.38(m, 2H), 7.13(d, J=1.0Hz, 1H),4.07(s, 3H), 3.64-3.51(m, 1H), 3.25-3.14(m, 1H), 2.65-2.53(m, 2H), 2.44-2.28(m, 4H), 2.12-1.93(m, 2H), 1.45(d, J=6.8Hz, 6H)

[0193] The following intermediates were prepared following the general procedure described in Intermediate 65H. [Table 14]

[0194] Examples 65 and 66: N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine To a solution of 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (2.6 g, 6.35 mmol) in THF (20 mL) and DMF (20.00 mL) was added acetic acid (0.363 mL, 6.35 mmol) and oxetan-3-amine (9.28 g, 127 mmol) and stirred at ambient temperature for 12 hours. The reaction mixture was concentrated to remove DMF and THF, and the resulting residue was added to dry methanol (Aldrich, 30 mL) and cooled to −78 °C under a nitrogen atmosphere. NaBHCN (1.995 g, 31.7 mmol) was added in one portion. The reaction was continued at −78 °C for 3 hours and then warmed to 0 °C over 1 hour. The reaction was quenched with ice-cold water (10 mL), and the reaction mixture was concentrated. The resulting residue was extracted with 10% methanol / DCM (100 mL x 2). The organic layer was concentrated, and the resulting crude product was purified by preparative LCMS (Method I). The fractions corresponding to peak 1 (isomer 1) and peak 2 (isomer 2) were collected and concentrated. This was further triturated with absolute ethanol (100 mL x 2), and the resulting white solid was added to deionized water (150 mL) and lyophilized for 2 days. NMR showed residual ethanol. The lyophilized compound was again dissolved in deionized water (150 mL) and lyophilized for another 2 days. Example 65 (Isomer 1): LCMS retention time 1.62 min [C]; MS (E - ) m / z: 467.3(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.58(s, 1H), 8.56-8.37(m, 2H), 7.10(s, 1H), 4.64(t, J=6.6Hz, 2H), 4.33(t, J=6.4Hz, 2H), 4.05(s, 3H), 3.98(t, J=6.7Hz, 1H), 3.23-3.12(m, 1H), 2.99-2.89(m, 1H), 2.43(t, J=11.0Hz, 1H), 2.17-2.04(m, 2H), 1.85(d, J=10.5Hz, 2H), 1.59-1.46(m, 2H), 1.42(d, J=6.6Hz, 6H), 1.28-1.10(m, 2H) Example 66 (isomeric form 2): LCMS retention time 2.82 minutes [C]; MS (E - )m / z: 467.3(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.60(s, 1H), 8.56-8.38(m, 2H), 7.12(s, 1H), 4.63(t, J=6.6Hz, 2H), 4.35(t, J=6.4Hz, 2H), 4.17(d, J=4.9Hz, 1H), 4.06(s, 3H), 3.98-3.85(m, 1H), 3.26-3.06(m, 1H), 2.09-1.95(m, 2H), 1.80(br. s., 2H), 1.65-1.54(m, 3H), 1.49(d, J=7.8Hz, 1H), 1.44(d, J=6.8Hz, 6H), 1.24(s, 2H)

[0195] The following Examples 65 and 66 describe the general manufacturing method.

Table 15

Table 17

Table 18

[0196] Example 126 2-(Dimethylamino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide [ka] To 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-amine (20 mg, 0.049 mmol) in DMF (5 mL) was added dimethylglycine (5.02 mg, 0.049 mmol), TEA (6.79 μL, 0.049 mmol), and HATU (18.52 mg, 0.049 mmol). The reaction mixture was stirred at ambient temperature for 12 hours, then quenched with ice-cold water (1 mL) and concentrated under reduced pressure. The resulting residue was extracted with 10% methanol / DCM (5 mL×2). The organic layer was concentrated, and the resulting crude product was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(dimethylamino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (4.6 mg, 18% yield) as a pale white solid. LCMS retention time 1.42 min [C]; MS (E -) m / z: 496.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.62(s, 1H), 8.55-8.38(m, 2H), 7.75-7.63(m, 1H), 7.12(d, J=1.2Hz, 1H), 4.06(s, 3H), 3.75-3.62(m, 1H), 3.24-3.13(m, 1H), 3.06-2.89(m, 3H), 2.33-2.23(m, 6H), 2.20-2.12(m, 2H), 1.97-1.83(m, 2H), 1.71-1.54(m, 2H), 1.44(d, J=6.8Hz, 6H)

[0197] Example 127 N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)methanesulfonamide [ka] To 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-amine (20 mg, 0.049 mmol) in DCM (5 mL) was added TEA (6.79 μL, 0.049 mmol) and methanesulfonyl chloride (5.58 mg, 0.049 mmol) and stirred at ambient temperature for 12 hours. The reaction was quenched with ice-cold water (1 mL) and the reaction mixture was concentrated. The resulting residue was extracted with 10% methanol / DCM (5 mL×2). The organic layer was concentrated and the resulting crude product was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)methanesulfonamide (3.6 mg, 15% yield) as a pale white solid. LCMS retention time 1.42 min [C]; MS (E -) m / z: 489.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.61(s, 1H), 8.52-8.44(m, 2H), 7.12(d, J=1.2Hz, 1H), 7.08(d, J=7.3Hz, 1H), 4.06(s, 3H), 3.27-3.13(m, 2H), 2.94(s, 4H), 2.20-2.10(m, 2H), 2.07-1.96(m, 2H), 1.71-1.57(m, 2H), 1.43(d, J=6.8Hz, 7H)

[0198] Example 128 trans 2-(ethyl(methyl)amino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide [ka]

[0199] Intermediate 128A: chloro-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide [ka] To a mixture of trans 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-amine (100 mg, 0.244 mmol) in DCM (5 mL) was added TEA (0.068 mL, 0.487 mmol) and 2-chloroacetyl chloride (27.5 mg, 0.244 mmol) and stirred at ambient temperature for 12 hours. The reaction was diluted with DCM, washed with water, and concentrated to give 2-chloro-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (80 mg, 0.164 mmol, 68%) as a colorless liquid. LCMS retention time 1.26 min [C]; MS (E - ) m / z: 488.1(M+H)

[0200] Example 128: To 2-chloro-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (10 mg, 0.021 mmol) in DCM (5 mL) was added TEA (5.72 μL, 0.041 mmol), N-methylethanamine (3.64 mg, 0.062 mmol), and stirred at ambient temperature for 12 hours. The reaction was quenched with ice-cold water (1 mL), and the reaction mixture was concentrated. The resulting residue was extracted with 10% methanol / DCM (5 mL×2). The organic layer was concentrated, and the resulting crude product was purified by preparative LCMS (Method I). After purification by preparative LCMS, the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give trans 2-(ethyl(methyl)amino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (6.3 mg, 60% yield) as a pale white solid. LCMS retention time 1.58 min [C]; MS (E - ) m / z: 510.1(M+H);1 H NMR(400MHz, DMSO-d6)δ 11.62(s, 1H), 8.55-8.41(m, 2H), 7.75-7.54(m, 1H), 7.12(d, J=1.2Hz, 1H), 4.06(s, 3H), 3.75-3.62(m, 1H), 3.18(td, J=6.9, 13.6Hz, 1H), 3.09-2.92(m, 3H), 2.29(s, 3H), 2.19-2.10(m, 2H), 1.97-1.81(m, 3H), 1.69-1.54(m, 2H), 1.44(d, J=6.8Hz, 6H), 1.04(t, J=7.1Hz, 3H)

[0201] The following examples were prepared according to the general procedures described in Example 128. [Table 23]

[0202] Examples 130 and 131 N-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine [ka] N-(4-(6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine was prepared as described in Examples 65 and 66 using 4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (0.1 g, 0.254 mmol) as the starting intermediate. Example 130 (Isomer 1): After purification by preparative LCMS, fractions containing Isomer 1 were collected and concentrated to dryness to give an off-white solid (0.0016, 1.4% yield). LCMS retention time 1.42 min [C]; MS (E - ) m / z: 451.3(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.56(s, 1H), 8.69(s, 1H), 8.49(s, 1H), 7.54(s, 1H), 4.75(t, J=7.2Hz, 2H), 4.56(t, J=6.6Hz, 2H), 3.19-3.07(m, 4H), 2.61(s, 3H), 2.17(d, J=12.2Hz, 2H), 1.98(br. s., 2H), 1.59(d, J=12.5Hz, 2H), 1.40(d, J=6.8Hz, 8H) Example 131 (Isomer 2): After purification by preparative LCMS, fractions containing Isomer 2 were collected and concentrated to dryness to give an off-white solid (0.0074 6.4% yield). LCMS retention time 1.58 min [C]; MS (E - ) m / z: 451.3(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.55(s, 1H), 8.70(s, 1H), 8.49(s, 1H), 7.56(s, 1H), 4.63(t, J=6.6Hz, 2H), 4.35(t, J=6.2Hz, 2H), 3.99-3.92(m, 1H), 3.22-3.06(m, 3H), 2.68(d, J=2.2Hz, 1H), 2.61(s, 3H), 2.07-1.97(m, 2H), 1.77(d, J=13.4Hz, 2H), 1.65-1.48(m, 4H), 1.42(d, J=6.8Hz, 6H)

[0203] The following examples were prepared according to the general procedures described in Examples 130 and 131. [Table 24] [Table 25]

[0204] Examples 144 and 145 N-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-methyloxetan-3-amine [ka]

[0205] Intermediate 144A: tert-butyl (4-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)ethynyl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate [ka] To a solution of tert-butyl (4-iodo-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate (4.0 g, 8.58 mmol) in toluene (50 mL) and DIPEA (10.00 mL), triphenylphosphine (0.225 g, 0.858 mmol) and copper(I) iodide (0.163 g, 0.858 mmol) were added and the mixture was degassed with argon for 10 minutes. Next, 6-ethynyl-7-methyl-[1,2,4]triazolo[1,5-a]pyridine (1.753 g, 11.15 mmol) was added, followed by bis(triphenylphosphine)palladium(II) dichloride (0.33 g, 0.429 mmol), and the mixture was degassed again for 5 minutes. The resulting reaction mixture was heated at 45 °C for 3 hours. The reaction mixture was filtered, washed with ethyl acetate (100 mL), and the filtrate was concentrated to give the crude product. The crude product was purified by combiflash (40 g silica column, elution solvent: 60% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl (4-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)ethynyl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate (2.0 g, 4.04 mmol, 47.0% yield) was recovered as a pale yellow solid. LCMS retention time 3.01 min [E]; MS (E - ) m / z: 496.2(M+H)

[0206] Intermediate 144B: tert-butyl 5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl (4-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)ethynyl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)thiazol-5-yl)carbamate (3.5 g, 7.06 mmol) in toluene (50 mL) was added silver acetate (1.179 g, 7.06 mmol). The resulting solution was heated at 100° C. for 45 minutes. The reaction was filtered through Celite, washed with EtOAc (10 mL), and the filtrate was concentrated to give tert-butyl 5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (2.0 g, 4.04 mmol, 57.1% yield) as a pale yellow solid. LCMS retention time 2.91 min [E]; MS (E - ) m / z: 496.2.1(M+H)

[0207] Intermediate 144C: ​​tert-butyl 6-bromo-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (2.0 g, 4.04 mmol) in DMF (50 mL) was added NBS (0.790 g, 4.44 mmol) in DMF (20 mL) dropwise at 0° C. and stirred at room temperature for 12 hours. The reaction was quenched with ice water (70 mL), stirred for 10 min, and the resulting precipitate was filtered and dried to give tert-butyl 6-bromo-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.6 g, 2.79 mmol, 69.0% yield) as a pale yellow solid. LCMS retention time 3.24 min [E]; MS (E - ) m / z: 576.2(M+2H)

[0208] Intermediate 144D: tert-butyl 5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(prop-1-en-2-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 6-bromo-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.6 g, 2.79 mmol) in dioxane (15 mL) and water (1.667 mL) was added potassium phosphate tribasic (0.970 g, 5.57 mmol). The solution was degassed for 10 min, and PdCl(dppf)-CHCl adduct (0.227 g, 0.279 mmol) was added and degassed again for 5 min. Subsequently, 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (2.63 mL, 13.93 mmol) was added and heated to 70° C. for 4 hours. The reaction was concentrated, diluted with water (100 mL), and extracted with DCM (3×100 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was purified by combiflash (40 g silica column, elution solvent: 80% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl 5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(prop-1-en-2-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.1 g, 2.054 mmol, 73.7% yield) was recovered as a pale yellow solid. LCMS retention time 3.59 min [E]; MS (E - ) m / z: 536.2(M+H)

[0209] Intermediate 144E: tert-butyl 6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] A solution of tert-butyl 5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(prop-1-en-2-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.1 g, 2.054 mmol) in methanol (75 mL) and DCM (25 mL) was purged with nitrogen gas, and Pd / C (0.874 g, 4.11 mmol) was added. The system was evacuated, purged with hydrogen gas, and stirred under a hydrogen atmosphere for 24 hours. The reaction was filtered through Celite. The Celite was rinsed with additional methanol and the filtrate was concentrated to dryness to give tert-butyl 6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate as a white solid (0.85 g, 92%). LCMS retention time 2.22 min [F]; MS (E - ) m / z: 538.2(M+H)

[0210] Intermediate 144F: 4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one [ka] To a solution of tert-butyl 6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.1 g, 2.046 mmol) in DCM (20 mL) was added TFA (10 mL, 130 mmol) dropwise and stirred at room temperature for 12 h. The reaction was diluted with DCM (20 mL) and washed with 10% NaHCO (20 mL). The reaction was concentrated, azeotroped with DCM and petroleum ether (3x20 mL), and dried under vacuum to give 4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (0.8 g, 2.033 mmol, 99% yield) as a yellow solid. LCMS retention time 1.34 min [F]; MS (E - ) m / z: 394.2(M+H)

[0211] The following intermediates were prepared in a similar manner to intermediates 144 and 145. [Table 26]

[0212] Examples 144 and 145: N-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-methyloxetan-3-amine To a solution of 4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (75 mg, 0.191 mmol) in THF (5 mL) and DMF (5 mL), 3-methyloxetan-3-amine (16.60 mg, 0.191 mmol) was added dropwise, followed by TEA (0.027 mL, 0.191 mmol), and the resulting pale yellow solution was stirred at room temperature for 12 hours under a nitrogen atmosphere. Sodium cyanoborohydride (23.95 mg, 0.381 mmol) was then added at 0°C, and stirring was continued at room temperature for 2 hours. The reaction was concentrated to remove volatiles, and the crude was diluted with DCM (30 mL) and washed with water (25 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude product was purified by preparative LCMS (Method I). After purification by preparative LCMS, fractions containing isomers 1 and 2 were collected and dried using a centrifugal evaporator (Genevac) to give isomers 1 and 2, respectively. Example 144 (Isomer 1) was obtained as a pale yellow solid (23 mg, 0.048 mmol, 24.93% yield). LCMS retention time 1.38 min [A]; MS (E - ) m / z: 465.3; 1 H NMR(400MHz, DMSO-d6)δ 11.32(s, 1H) 8.84(s, 1H) 8.49(s, 1H) 7.80(s, 1H) 4.41(d, J=5.38Hz, 2H) 4.21(d, J=5.62Hz, 2H) 2.91-2.98(m, 1H) 2.68-2.77(m, 2H) 2.57-2.65(m, 2H) 2.28(s, 3H) 2.06-2.15(m, 2H) 1.73-1.81(m, 2H) 1.58 (qd, J=12.76, 2.81Hz, 2H) 1.44(s, 3H) 1.31(d, J=6.85Hz, 6H) Example 145 (Isomer 2) was obtained as a pale yellow solid. LCMS retention time 1.58 min [A]; MS (E - ) m / z: 465.3; 1H NMR(400MHz, DMSO-d6)δ 11.31-11.38(m, 1H) 8.86(s, 1H) 8.49(s, 1H) 7.81(s, 1H) 4.42(d, J=5.62Hz, 2H) 4.18(d, J=5.62Hz, 2H) 3.13-3.18(m, 1H) 2.79-2.86(m, 1H) 2.71-2.78(m, 1H) 2.29(s, 3H) 2.03-2.14(m, 2H) 1.78-1.88(m, 2H) 1.54-1.64(m, 2H) 1.49(br d, J=3.18Hz, 2H) 1.42(s, 3H) 1.33(d, J=6.85Hz, 6H)

[0213] The following examples were prepared according to the general procedures described in Examples 144 and 145. [Table 27] [Table 28] [Table 29]

[0214] Examples 162 and 163 2-((4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide [ka]

[0215] Intermediate 162A: 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine [ka] To a solution of 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (200 mg, 0.488 mmol) in THF (5 mL) and DMF (5 mL), methanamine in THF (4.88 mL, 9.77 mmol) was added dropwise, followed by acetic acid (2.80 μL, 0.049 mmol). The resulting pale yellow solution was stirred at room temperature under a nitrogen atmosphere for 12 hours. Sodium cyanoborohydride (61.4 mg, 0.977 mmol) was then added at 0° C., and stirring was continued at room temperature for 2 hours. The reaction was concentrated to remove volatiles, the crude was diluted with DCM (30 mL), washed with water (25 mL), and the extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (250 mg, 0.353 mmol, 72.3% yield) as a yellow solid. LCMS retention time 1.6 min [C]; MS (E - ) m / z: 425.3

[0216] Examples 162 and 163: 2-((4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide To a solution of 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (70 mg, 0.165 mmol) in THF (2 mL) and DMF (1 mL) was added TEA (0.046 mL, 0.330 mmol) followed by 2-chloro-N,N-dimethylacetamide (20.04 mg, 0.165 mmol) and stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product obtained was purified by preparative LCMS (Method I). After purification by preparative LCMS, fractions containing isomers 1 and 2 were collected and dried using a centrifugal evaporator (Genevac) to give isomers 1 and 2, respectively. Example 162 (Isomer 1) was obtained as a pale yellow solid (19.8 mg, 0.036 mmol, 22.01% yield). LCMS retention time 1.30 min [A]; MS (E - ) m / z: 510.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.62(s, 1H), 8.57-8.43(m, 2H), 7.12(s, 1H), 4.12-3.99(m, 3H), 3.24-3.14(m, 2H), 3.01(s, 5H), 2.92-2.77(m, 5H), 2.74 (s,2H), 2.22(br. s., 3H), 1.92(s, 1H), 1.60(br. s., 3H), 1.44(d, J=6.8Hz, 6H) Example 163 (Isomer 2) was obtained as a pale yellow solid (4.1 mg, 7.32 μmol, 4.44% yield). LCMS retention time 1.44 min [A]; MS (E - ) m / z: 510.2(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.61(s, 1H), 8.55-8.42(m, 2H), 7.14(d, J=1.2Hz, 1H),4.07(s, 3H), 3.28(br. s., 1H), 3.25-3.15(m, 2H), 3.09-2.93(m, 3H), 2.82(s, 3H), 2.55 (s,2H), 2.30-2.16(m, 3H), 2.16-2.03(m, 2H), 1.81(d, J=9.0Hz, 3H), 1.64(br. s., 2H), 1.52-1.37(m, 6H)

[0217] The following examples were prepared according to the general procedures described in Examples 162 and 163. [Table 30]

[0218] The following examples were prepared according to the general procedures described in Intermediates 144 and 145. [Table 31] [Table 32]

[0219] Examples 172 and 173 4-(6-Isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine [ka] To a solution of 4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (75 mg, 0.191 mmol) in THF (3 mL) and DMF (2 mL) was added (3-methyloxetan-3-yl)methanamine (19.33 mg, 0.191 mmol) followed by acetic acid (1.094 μL, 0.019 mmol) dropwise at 0° C., and the resulting pale yellow solution was stirred at room temperature for 12 hours under a nitrogen atmosphere. Sodium cyanoborohydride (24.01 mg, 0.382 mmol) was then added at 0° C., and stirring was continued at room temperature for 2 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude product was purified by preparative LCMS (Method I). After purification by preparative LCMS, fractions containing isomers 1 and 2 were collected and dried using a centrifugal evaporator (Genevac). Example 172 (Isomer 1) was obtained as a pale yellow solid (2.7 mg, 5.42 μmol, 2.84% yield). LCMS retention time 1.48 min [A]; MS (E - ) m / z: 478.3(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.16(s, 1H), 8.39-8.28(m, 1H), 8.00-7.97(m, 1H), 7.60(s, 1H), 7.18 (dd, J=8.1, 4.6Hz, 1H), 4.43(d, J=6.4Hz, 2H), 4.28(d, J=6.4Hz,2H), 3.91(d, J=3.4Hz, 4H), 3.23(br. s., 3H), 3.13-3.00(m, 3H), 2.23(br. s., 3H), 1.69-1.46(m, 4H), 1.43-1.32(m, 6H) Example 173 (Isomer 2) was obtained as a pale yellow solid (3.0 mg, 5.69 μmol, 2.98% yield). LCMS retention time 1.53 min [A]; MS (E - ) m / z: 478.3(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.17(s, 1H), 8.34(d, J=4.4Hz, 1H), 7.98(d, J=7.8Hz, 1H),7.60(s, 2H), 7.18 (dd, J=7.7, 4.5Hz, 1H), 4.38(d, J=6.1Hz, 2H), 4.28-4.13 (m,2H), 3.96-3.86(m, 3H), 3.18-3.02(m, 2H), 2.90(s, 1H), 2.74(s, 1H), 2.28(br. s., 2H), 2.08(br. s., 1H), 2.02(s, 1H), 1.92(s, 2H), 1.89-1.79(m, 2H), 1.74(d, J=12.0Hz, 2H), 1.40 (d,J=6.8Hz, 6H)

[0220] The following examples were prepared according to the general procedures described in Examples 172 and 173. [Table 33] [Table 34]

[0221] Examples 184 and 185 N-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine [ka] To a mixture of 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (50 mg, 0.123 mmol) and oxetan-3-amine (90 mg, 1.227 mmol) in DMF (1 mL) and THF (1 mL) was added AcOH (7.02 μL, 0.123 mmol) at 0° C. and stirred overnight at room temperature. Sodium cyanoborohydride (15.42 mg, 0.245 mmol) was added to the reaction mixture at 0° C. and stirring was continued at room temperature for 2 hours. The reaction mixture was diluted with water (5 mL) and extracted with ethyl acetate (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude product was purified by preparative LCMS (Method I). After purification by preparative LCMS, fractions containing isomers 1 and 2 were collected and dried using a centrifugal evaporator (Genevac). Example 184 (Isomer 1): (9.9 mg, 0.021 mmol, 17.19% yield). LCMS retention time 1.348 min [A]; MS (E - ) m / z: 465.3(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.30(s, 1H), 8.72(s, 1H), 8.46(s, 1H), 4.65(t, J=6.7Hz, 2H), 4.35(t, J=6.1Hz, 2H), 4.07-3.96(m, 1H), 2.95 (tt, J=11.9, 3.6Hz, 2H), 2.76-2.66(m, 2H), 2.57(s, 3H), 2.18(s, 3H), 2.15-2.04(m, 2H), 1.86(d, J=11.0Hz, 2H), 1.63-1.42(m, 2H), 1.41-1.12(m, 7H), 1.12-0.97(m, 1H) Example 185 (Isomer 2): (9.1 mg, 0.018 mmol, 14.64% yield). LCMS retention time 1.514 min [A]; MS (E - ) m / z: 465.3(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.37(s, 1H), 8.72(d, J=8.8Hz, 1H), 8.47(d, J=0.7Hz, 1H), 4.68-4.59(m, 2H), 4.55(d, J=4.9Hz, 2H), 3.63 (qd, J=11.5, 5.4Hz, 1H), 3.25-3.18(m, 1H), 2.97-2.86(m, 1H), 2.79-2.68(m, 1H), 2.65-2.55(m, 3H), 2.40-2.32(m, 1H), 2.19(s, 3H), 1.9 (d, J=9.3Hz, 1H), 1.93-1.82(m, 3H), 1.82-1.59(m, 2H), 1.34(d, J=6.8Hz, 6H), 1.17(t, J=7.2Hz, 2H)

[0222] The following examples were prepared according to the general procedures described in Examples 184 and 185. [Table 35] [Table 36] [Table 37] [Table 38] [Table 39] [Table 40] [Table 41] [Table 42]

[0223] The following examples were prepared according to the general procedures described in Intermediate 162. [Table 43] [Table 44]

[0224] Examples 241 and 242 5-(6-Isopropyl-2-(4-(oxetan-3-ylamino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one [ka] To a mixture of 5-(6-isopropyl-2-(4-oxocyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (50 mg, 0.126 mmol) and oxetan-3-amine (92 mg, 1.258 mmol) in DMF (1 mL) and THF (1 mL) was added AcOH (7.20 μL, 0.126 mmol) at 0° C. and stirred overnight at room temperature. Sodium cyanoborohydride (15.42 mg, 0.245 mmol) was added to the reaction mixture at 0° C. and stirring was continued at room temperature for 2 hours. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product obtained was purified by preparative LCMS (Method I). After purification by preparative LCMS, fractions containing isomers 1 and 2 were collected and dried using a centrifugal evaporator (Genevac). Example 241 (Isomer 1): (13.6 mg, 0.028 mmol, 22.29% yield). LCMS retention time 1.523 min [A]; MS (E - ) m / z: 455.3(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.02(s, 1H), 7.52(s, 1H), 4.64(t, J=6.6Hz, 2H), 4.34(t, J=6.4Hz, 2H), 4.06-3.94(m, 1H), 3.94-3.86(m, 1H), 3.46(s, 3H), 2.98-2.87(m, 2H), 2.74-2.68(m, 1H), 2.18-1.97(m, 6H), 1.93(s, 2H), 1.85(d, J=10.3Hz, 2H), 1.61-1.45(m, 2H), 1.36-1.08(m, 8H) Example 242 (Isomer 2): (7.8 mg, 0.016 mmol, 12.89% yield). LCMS retention time 1.702 min [A]; MS (E - ) m / z: 455.3(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.03(s, 1H), 7.53(s, 1H), 4.64(t, J=6.6Hz, 2H), 4.35(t, J=6.2Hz, 2H), 3.97(br. s., 1H), 3.46(s, 3H), 3.12-3.05(m, 2H), 2.79-2.64(m, 2H), 2.13-1.86(m, 8H), 1.85-1.69(m, 2H), 1.57(d, J=4.6Hz, 4H), 1.37-1.24(m, 6H)

[0225] The following examples were prepared according to the general procedures described in Examples 241 and 242. [Table 45] [Table 46] [Table 47] [Table 48] [Table 49]

[0226] Examples 269 and 270 6-(4-(6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane [ka]

[0227] Intermediate 269A: tert-butyl 5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-6-vinyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 6-bromo-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (220 mg, 0.373 mmol) in dioxane (10 mL) and water (2.500 mL) was added vinylboronic acid (34.8 mg, 0.484 mmol) and potassium phosphate tribasic (237 mg, 1.118 mmol). The solution was degassed with argon for 10 minutes, and PdCl(dppf)-CHCl adduct (30.4 mg, 0.037 mmol) was added and heated at 90 °C for 12 hours. The reaction was concentrated, diluted with water (100 mL), and extracted with DCM (3 x 100 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was purified by Combiflash (40 g silica column, elution solvent: 40% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl 5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-6-vinyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (0.18 g, 90% yield) was recovered as a pale yellow solid. LCMS retention time 3.35 min [C]; MS (E - ) m / z: 538.2(M+H)

[0228] Intermediate 269B: tert-butyl 6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] A solution of tert-butyl 5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-6-vinyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (0.18 g, 0.335 mmol) in THF (10 mL) and methanol (2.5 mL) was purged with nitrogen gas, and Pd-C (0.036 g, 0.335 mmol) was added. The system was evacuated and purged with hydrogen gas, and the mixture was stirred under a hydrogen atmosphere for 24 hours. The reaction was filtered through Celite to give tert-butyl 6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (0.15 g, 83%) as a yellow solid. LCMS retention time 1.48 min [C]; MS (E - ) m / z: 540.2(M+H)

[0229] Intermediate 269C: 4-(6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one [ka] To a solution of tert-butyl 6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (120 mg, 0.222 mmol) in DCM (5.00 mL) was added TFA (5 mL) and stirred at room temperature for 12 hours. The reaction was concentrated to give 4-(6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (80 mg, 91%) as a yellow solid. LCMS retention time 2.31 min [C]; MS (E - ) m / z: 396.2 (M+H)

[0230] Examples 269 and 270: 6-(4-(6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane To a solution of 4-(6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (100 mg, 0.253 mmol) in THF (5 mL) and DMF (5.00 mL) was added acetic acid (0.014 mL, 0.253 mmol) followed by 2-oxa-6-azaspiro[3.3]heptane (376 mg, 3.79 mmol) and stirred at ambient temperature for 12 h. The reaction mixture was concentrated to remove DMF and THF, and the resulting residue was taken up in dry methanol (3 mL), cooled to −78 °C under a nitrogen atmosphere, and NaCNBH (79 mg, 1.264 mmol) was added in one portion. The reaction was continued at the same temperature (-78°C) for 3 hours and then warmed to 0°C over 1 hour. The reaction was quenched with ice-cold water (10 mL) and concentrated. The resulting residue was extracted with 10% methanol / DCM (10 mL x 2), the organic layer was concentrated, and the resulting crude product was purified by preparative LCMS (Method I). After purification by preparative LCMS, fractions containing isomers 1 and 2 were collected and dried using a centrifugal evaporator (Genevac). Example 269 (Isomer 1) was obtained as a pale yellow solid (3 mg, 2.3%). LCMS retention time 1.12 min [A]; MS (E - ) m / z: 479.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.68(s, 1H), 8.53(d, J=1.5Hz, 1H), 8.50-8.44(m, 1H), 7.17(d, J=1.2Hz, 1H), 4.61(s, 4H), 4.06(s, 3H), 2.95-2.80(m, 4H), 2.15-2.07(m, 2H), 1.91(s, 1H), 1.85-1.77(m, 2H), 1.57-1.41(m, 2H), 1.36-1.28(m, 3H), 1.15-0.97(m, 3H) Example 270 (Isomer 2) was obtained as a pale yellow solid (2.5 mg, 1.9%). LCMS retention time 1.02 min [A]; MS (E - ) m / z: 479.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.69(s, 1H), 8.53(d, J=1.5Hz, 1H), 8.47(s, 1H), 7.18(d, J=1.2Hz, 1H), 4.62(s, 4H), 4.10-4.01(m, 4H), 3.30-3.21(m, 4H), 3.08-3.00(m, 1H), 2.90-2.79(m, 4H), 2.74(s, 1H), 2.29-2.14(m, 1H), 1.97-1.84(m, 3H), 1.81-1.63(m, 3H), 1.61-1.41(m, 4H), 1.37-1.29(m, 3H), 1.17-1.06(m, 3H)

[0231] The following examples were prepared according to the general procedures described in Examples 269 and 270. [Table 50]

[0232] Example 273 N-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine [ka]

[0233] Intermediate 273A: tert-butyl 5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 6-bromo-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (600 mg, 1.016 mmol) in THF (30 mL) and water (7.5 mL) was added methylboronic acid (304 mg, 5.08 mmol), potassium phosphate tripotassium (702 mg, 3.05 mmol). The solution was degassed with argon for 10 minutes, and then chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (80 mg, 0.102 mmol) was added and heated at 70°C for 12 hours. The reaction was concentrated, diluted with water (100 mL), and extracted with DCM (3 x 100 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was purified by combiflash (40 g silica column, elution solvent: 40% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl 5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (0.35 g, 65% yield) was recovered as a pale yellow solid. LCMS retention time 2.78 min [C]; MS(E-) m / z: 526.2 (M+H).

[0234] Intermediate 273B: 4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one [ka] To a solution of tert-butyl 5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-(1,4-dioxaspiro[4.5]decan-8-yl)-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (350 mg, 1.142 mmol) in DCM (10.00 mL) was added TFA (10 mL) and stirred at room temperature for 12 hours. The reaction was concentrated to give 4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (250 mg, 58%) as a yellow solid. LCMS retention time 1.64 min [C]; MS (E - ) m / z: 382.2(M+H)

[0235] Example 273: N-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine To a solution of 4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-one (80 mg, 0.210 mmol) in THF (2 mL) and DMF (2.00 mL) was added acetic acid (0.012 mL, 0.210 mmol) followed by oxetan-3-amine (0.012 mL, 0.210 mmol), and the solution was stirred at ambient temperature for 12 hours. NaCNBH3 (13.18 mg, 0.210 mmol) was added, and the reaction was continued at room temperature for 1 hour. The reaction was quenched with water (10 mL) and extracted with 10% methanol / DCM (10 mL x 2). The organic layer was concentrated, and the resulting crude product was purified by preparative LCMS (Method I). After purification by preparative LCMS, fractions containing isomers 1 and 2 were collected and dried using a centrifugal evaporator (Genevac), respectively, to give Example 273 (isomer 1: 3.5 mg, 3.7%) as a pale yellow solid and Example 273 (isomer 2: 3.5 mg, 3.7%) as a pale yellow solid. Example 273 (Isomer 1): LCMS retention time 1.20 min [A]; MS(E-) m / z: 439.2 (M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.72(s, 1H), 8.59(d, J=1.2Hz, 1H), 8.46(s, 1H), 7.23(d, J=1.2Hz, 1H), 4.64(t, J=6.5Hz, 2H), 4.32(t, J=6.2Hz, 2H), 4.07(s, 3H), 3.98 (quin, J=6.8Hz, 1H), 2.97-2.90(m, 1H), 2.47-2.36(m, 4H), 2.16-2.04(m, 2H), 1.91(s, 2H), 1.88-1.78(m, 2H), 1.61-1.45(m, 2H), 1.27-1.11(m, 2H)

[0236] The following examples were prepared according to the general procedures described in Example 273. [Table 51]

[0237] Intermediate 277B 6-ethynyl-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine TIFF0007629007000178.tif26153

[0238] Intermediate 277A: 7,8-dimethyl-6-((trimethylsilyl)ethynyl)-[1,2,4]triazolo[1,5-a]pyridine [ka] To a solution of 6-bromo-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (15 g, 66.3 mmol) in triethanolamine (TEA) (100 mL) was added copper(I) iodide (1.264 g, 6.63 mmol) and degassed with argon for 10 minutes. Bis(triphenylphosphine)palladium(II) dichloride (3.26 g, 4.64 mmol) was then added, followed by trimethylsilylacetylene (13.03 g, 133 mmol), and the mixture was heated at 80 °C for 12 hours. The reaction mixture was filtered through Celite and washed with ethyl acetate (200 mL). The filtrate was diluted with water (250 mL) and extracted with ethyl acetate (2 x 200 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give 7,8-dimethyl-6-((trimethylsilyl)ethynyl)-[1,2,4]triazolo[1,5-a]pyridine (16 g, 55.9 mmol, 84% yield) as a brown oil. LCMS 1.90 min [F]; MS (E - ) m / z: 244.2 (M+H)

[0239] Intermediate 277B: 6-ethynyl-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine To a solution of 7,8-dimethyl-6-((trimethylsilyl)ethynyl)-[1,2,4]triazolo[1,5-a]pyridine (16 g, 65.7 mmol) in methanol (150 mL) was added potassium carbonate (18.17 g, 131 mmol) and stirred at room temperature for 2 h. The reaction was concentrated, diluted with water (150 mL), and extracted with DCM (3 x 250 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was purified using Combiflash (120 g silica column, elution solvent: 75% EtOAc / petroleum ether). After concentration of the fractions, 6-ethynyl-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (7.2 g, 42.1 mmol, 64.0% yield) was recovered as a white solid. LCMS 1.81 min[C];MS(E - ) m / z: 172.2 (M+H)

[0240] The following intermediates were prepared following the general procedure described in Intermediate 277B. [Table 52]

[0241] Example 278 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole [ka]

[0242] Intermediate 278A: methyl 5-((tert-butoxycarbonyl)amino)thiazole-2-carboxylate [ka] To a solution of tert-butyl (2-bromothiazol-5-yl)carbamate (10 g, 35.8 mmol) in methanol (75 mL) and DMF (75 mL) was added DPPF (3.97 g, 7.16 mmol) and PdOAc (0.804 g, 3.58 mmol). The solution was degassed with argon for 10 minutes. The reaction was saturated with CO gas, followed by the addition of TEA (19.97 mL, 143 mmol), and the mixture was heated under CO pressure (10 kg / cm). 2 ) and stirred at 80 °C for 7 h. The reaction was concentrated, and the resulting residue was dissolved in DCM (100 mL), washed with water (2 x 100 mL), dried over sodium sulfate, filtered, and concentrated to give the crude compound. The resulting crude was purified by ISCO (120 g silica column) by eluting the compound with 35% ethyl acetate / petroleum ether, collecting and concentrating the fractions to give methyl 5-((tert-butoxycarbonyl)amino)thiazole-2-carboxylate (7.5 g, 29.0 mmol, 81% yield) as an off-white solid. LCMS retention time 2.10 min [C]; MS (E - ) m / z: 259.1 (M+H)

[0243] Intermediate 278B: methyl 5-((tert-butoxycarbonyl)amino)-4-iodothiazole-2-carboxylate [ka] To a solution of methyl 5-((tert-butoxycarbonyl)amino)thiazole-2-carboxylate (7.5 g, 29.0 mmol) in acetonitrile (150 mL) was added dropwise NIS (6.53 g, 29.0 mmol) in acetonitrile (50 mL) at 0 °C and stirred at the same temperature for 10 min. The reaction was quenched with water (250 mL) and extracted with ethyl acetate (3 × 200 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude product. The crude product was purified by Combiflash (80 g silica column, elution solvent: 31% EtOAc / petroleum ether). After concentration of the fractions, methyl 5-((tert-butoxycarbonyl)amino)-4-iodothiazole-2-carboxylate (8.2 g, 21.34 mmol, 73.5% yield) was recovered as a pale yellow solid. LCMS retention time 1.64 min[F];MS(E - ) m / z: 384.1 (M+H)

[0244] Intermediate 278C: methyl 5-((tert-butoxycarbonyl)amino)-4-((7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)ethynyl)thiazole-2-carboxylate [ka] To a solution of methyl 5-((tert-butoxycarbonyl)amino)-4-iodothiazole-2-carboxylate (2.0 g, 5.21 mmol) in toluene (50 mL) and DIPEA (10.00 mL) was added triphenylphosphine (0.137 g, 0.521 mmol) and copper(I) iodide (0.099 g, 0.521 mmol) and degassed with argon for 10 minutes. 6-Ethynyl-7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine (1.159 g, 6.77 mmol) was then added, followed by bis(triphenylphosphine)palladium(II) dichloride (0.183 g, 0.260 mmol), and the mixture was again degassed for 5 minutes. The resulting reaction mixture was heated at 45 °C for 3 hours. The reaction mixture was filtered, washed with ethyl acetate (100 mL), and the filtrate was concentrated to give the crude product. The crude product was purified by combiflash (40 g silica column, elution solvent: 4% MeOH / CHCl3). After concentration of the fractions, methyl 5-((tert-butoxycarbonyl)amino)-4-((7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)ethynyl)thiazole-2-carboxylate (1.4 g, 3.28 mmol, 62.9% yield) was recovered as a pale yellow solid. LCMS retention time 2.71 min [C]; MS (E - ) m / z: 428.2.1(M+H)

[0245] Intermediate 278D: 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate [ka] To a solution of methyl 5-((tert-butoxycarbonyl)amino)-4-((7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)ethynyl)thiazole-2-carboxylate (1.3 g, 3.04 mmol) in toluene (15 mL) was added silver acetate (0.508 g, 3.04 mmol), and the resulting solution was heated at 100° C. for 45 minutes. The reaction was filtered through Celite, washed with ethyl acetate (10 mL), and the filtrate was concentrated to give 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate (1.3 g, 2.80 mmol, 92% yield) as a pale yellow solid. LCMS retention time 2.71 min[C];MS(E - ) m / z: 428.2.1(M+H)

[0246] Intermediate 278E: 4-(tert-butyl) 2-methyl 6-bromo-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate [ka] To a solution of 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate (1.3 g, 3.04 mmol) in DMF (15 mL), NBS (0.541 g, 3.04 mmol) in DMF (5 mL) was added dropwise at 0° C. and stirred at room temperature for 12 hours. The reaction was quenched with ice water (70 mL), stirred for 10 min, and the resulting precipitate was filtered and dried to give 4-(tert-butyl) 2-methyl 6-bromo-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate (0.9 g, 1.777 mmol, 58.4% yield) as a pale yellow solid. LCMS retention time 3.01 min [C]; MS (E - ) m / z: 508.2(M+2H)

[0247] Intermediate 278F: 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(prop-1-en-2-yl)-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate [ka] To a solution of 4-(tert-butyl) 2-methyl 6-bromo-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate (2.1 g, 4.15 mmol) in THF (15 mL) and water (1.667 mL) was added potassium phosphate tribasic (1.445 g, 8.29 mmol), degassed for 10 minutes, and then chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.326 g, 0.415 mmol) was added. The reaction mixture was again degassed for 5 minutes, followed by the addition of 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (3.48 g, 20.74 mmol) and heating at 70° C. for 4 hours. The reaction was concentrated, diluted with water (100 mL), and extracted with DCM (3×100 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The crude product was purified by Combiflash (24 g silica column, elution solvent: 41% EtOAc / petroleum ether). After concentration of the fractions, 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(prop-1-en-2-yl)-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate (1.3 g, 2.78 mmol, 67.0% yield) was recovered as a pale yellow solid. LCMS retention time 1.86 min [F]; MS (E - ) m / z: 468.2(M+H)

[0248] Intermediate 278G: 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate [ka] A solution of 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(prop-1-en-2-yl)-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate (1.3 g, 2.78 mmol) in methanol (75 mL) was purged with nitrogen gas, and Pd / C (0.444 g, 0.417 mmol) was added. The system was evacuated, purged with hydrogen gas, and stirred under a hydrogen atmosphere for 24 hours. The reaction was filtered through Celite, the Celite was rinsed with additional methanol, and the filtrate was concentrated to dryness to give 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate (1.15 g, 2.449 mmol, 88% yield) as a white solid. LCMS retention time 1.92 min [F]; MS (E - ) m / z: 470.2 (M+H)

[0249] Intermediate 278H: methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxylate [ka] To a solution of 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate (1.1 g, 2.343 mmol) in DCM (10 mL) was added TFA (1.805 mL, 23.43 mmol) dropwise and stirred at room temperature for 12 h. The reaction was diluted with DCM (20 mL) and washed with 10% NaHCO (20 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxylate (0.86 g, 2.328 mmol, 99% yield) as a pale yellow solid. LCMS retention time 2.39 min [C]; MS (E - ) m / z: 370.2 (M+H)

[0250] Intermediate 278I: 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxylic acid [ka] To a solution of methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxylate (0.86 g, 2.328 mmol) in methanol (10 mL) was added 10% sodium hydroxide (5 mL, 2.328 mmol) dropwise and stirred at room temperature for 3 hours. The reaction was concentrated, the aqueous layer was acidified to pH ~4 to 5, and the resulting precipitate was filtered and dried to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxylic acid (0.7 g, 1.970 mmol, 85% yield) as an off-white solid. LCMS retention time 0.94 min [C]; MS (E - ) m / z: 355.2(M+H)

[0251] The following intermediates were prepared following the general procedures described in Intermediate 278I. [Table 53]

[0252] Intermediate 278K: 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole [ka] A solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxylic acid (400 mg, 1.125 mmol) in THF (10 mL) was heated at 70° C. for 1 hour. The reaction was concentrated to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (340 mg, 1.092 mmol, 97% yield) as a pale yellow solid. LCMS retention time 1.26 min [F]; MS (E - ) m / z: 3122(M+H)

[0253] Intermediate 278L: 2-Bromo-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (340 mg, 1.092 mmol) in DMF (10 mL) was added NBS (194 mg, 1.092 mmol) in DMF (3 mL) dropwise at 0 °C and stirred at room temperature for 2 h. The reaction was quenched with water (50 mL) and stirred for 10 min. The resulting precipitate was filtered and dried to give 2-bromo-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (275 mg, 0.705 mmol, 64.5% yield) as an off-white solid. LCMS retention time 1.52 min[G];MS(E - ) m / z: 390.2 (M+H)

[0254] The following intermediates were prepared following the general procedure described in Intermediate 278L. [Table 54]

[0255] Intermediate 278N: tert-butyl 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazine-1-carboxylate [ka] To a solution of 2-bromo-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (250 mg, 0.641 mmol) and tert-butyl piperazine-1-carboxylate (179 mg, 0.961 mmol) in toluene (7 mL) was added cesium carbonate (417 mg, 1.281 mmol). The resulting solution was degassed with N for 10 min, and Pd(dba) (58.7 mg, 0.064 mmol) was added, followed by BINAP (399 mg, 0.641 mmol), at which point the solution was again degassed for 5 min. The resulting mixture was heated at 90°C for 12 hours. The reaction mixture was cooled, diluted with ethyl acetate (500 mL), washed with water (2 x 50 mL), brine (50 mL), dried over sodium sulfate, and concentrated to give the crude product. The crude product was purified by combiflash (24 g silica column) and the compound was eluted with 75% ethyl acetate / petroleum ether. The fractions were collected and concentrated to give tert-butyl 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazine-1-carboxylate (210 mg, 0.424 mmol, 66.1% yield) as a pale yellow solid. LCMS retention time 3.48 min [C]; MS (E - ) m / z: 496.2(M+H)

[0256] Example 278: 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole To a solution of tert-butyl 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazine-1-carboxylate (210 mg, 0.424 mmol) in DCM (10 mL) was added HCl / dioxane (2 mL, 8.00 mmol) dropwise and stirred at room temperature for 1 h. The reaction was diluted with DCM (20 mL) and washed with 10% NaHCO (20 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (170 mg, 100% yield) as a pale yellow solid. LCMS retention time 1.62 min [C]; MS (E - ) m / z: 396.2 (M+H)

[0257] The following examples were prepared according to the general procedures described in Example 278. [Table 55]

[0258] Example 280 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (68 mg, 0.172 mmol) and dimethylglycine (17.73 mg, 0.172 mmol) in DMF (1 mL) was added HATU (65.4 mg, 0.172 mmol) followed by TEA (0.024 mL, 0.172 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. LCMS retention time 1.76 min [C]; MS (E - ) m / z: 481.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 10.97(s, 1H), 8.68(s, 1H), 8.44(s, 1H), 4.17(s, 4H), 3.91 (s,4H), 3.37(br. s., 2H), 2.77-2.58(m, 4H), 2.27(s, 6H), 2.18(s, 3H), 1.98(s, 2H), 1.26(d, J=6.8Hz, 6H)

[0259] Example 281 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-2-methylpropan-2-ol [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (25 mg, 0.063 mmol) and 1-chloro-2-methylpropan-2-ol (6.86 mg, 0.063 mmol) in DMF (1 mL) was added potassium carbonate (17.47 mg, 0.126 mmol), and the solution was heated at 80° C. for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The reaction was purified by preparative LCMS (Method I) and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-2-methylpropan-2-ol (16.7 mg, 0.035 mmol, 55.9% yield) as a pale yellow solid. LCMS retention time 2.01 min [A]; MS (E - ) m / z: 468.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 10.97(s, 1H), 8.68(s, 1H), 8.44(s, 1H), 4.17(s, 1H), 3.91 (s,1H), 3.37(br. s., 3H), 2.77-2.58(m, 5H), 2.58-2.53(m, 3H), 2.27(s, 2H), 2.18(s, 3H), 1.26(d, J=6.8Hz, 6H), 1.13(s, 6H)

[0260] Example 282 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (25 mg, 0.063 mmol) and 1-chloro-2-(methylsulfonyl)ethane (9.01 mg, 0.063 mmol) in DMF (1 mL) was added TEA (8.81 μL, 0.063 mmol), and the solution was heated at 90° C. for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The reaction was purified by preparative LCMS (Method I) and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole as a pale yellow solid. LCMS retention time 1.70 min [A]; MS (E - ) m / z: 502.3(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.06(s, 1H), 8.69(s, 1H), 8.46(s, 1H), 3.36(br. s., 8H), 3.13(s, 3H), 2.68-2.61(m, 2H), 2.60-2.53(m, 6H), 2.17(s, 3H), 1.34-1.18(m, 6H)

[0261] Example 283 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-N,N-dimethylacetamide [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (25 mg, 0.063 mmol) and 2-chloro-N,N-dimethylacetamide (7.68 mg, 0.063 mmol) in DMF (1 mL) was added TEA (8.81 μL, 0.063 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The reaction was purified by preparative LCMS (Method I) and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-N,N-dimethylacetamide (19.5 mg, 0.039 mmol, 62.3% yield) as a pale yellow solid. LCMS retention time 1.72 min [A]; MS (E - ) m / z: 481.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 10.98(s, 1H), 8.68(s, 1H), 8.44(s, 1H), 3.39(br. s., 4H), 3.23(s, 2H), 3.03(s, 3H), 2.83(s, 3H), 2.66-2.58(m, 5H), 2.56(s, 3H), 2.18(s, 3H), 1.26(d, J=6.8Hz, 6H)

[0262] The following examples were prepared according to the general procedures described in Example 283. [Table 56]

[0263] Example 286 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (65 mg, 0.164 mmol) and oxetan-3-one (11.84 mg, 0.164 mmol) in methanol (2 mL) was added TEA (0.023 mL, 0.164 mmol) followed by acetic acid (9.41 μL, 0.164 mmol) at 0° C., and the solution was stirred at room temperature for 12 hours. Sodium cyanoborohydride (10.33 mg, 0.164 mmol) was then added at 0° C. and stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated. LCMS retention time 2.16 min[C];MS(E - ) m / z: 452.2(M+H); 1 H NMR (400MHz, DMSO-d6)δ 10.97(s, 1H), 8.68(s, 1H), 8.44(s, 1H), 4.59(s, 2H), 4.48 (s,2H), 3.37(m, 5H), 2.81(s, 1H), 2.52(s, 3H), 2.27(m, 4H),2.18(s, 3H),1.26(d, J=6.8Hz, 6H)

[0264] The following examples were prepared according to the general procedures described in Example 286. [Table 57]

[0265] Example 290 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(3-methyloxetan-3-yl)piperidin-4-amine [ka]

[0266] Intermediate 290A: 8-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-1,4-dioxa-8-azaspiro[4.5]decane [ka] To a solution of 2-bromo-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (500 mg, 1.281 mmol) and 1,4-dioxa-8-azaspiro[4.5]decane (275 mg, 1.922 mmol) in toluene (15 mL) was added cesium carbonate (835 mg, 2.56 mmol). The solution was degassed for 10 min, and then Pd(dba) (117 mg, 0.128 mmol) was added, followed by BINAP (80 mg, 0.128 mmol). The reaction mixture was degassed again for 5 min and heated at 90 °C for 16 h. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (2 × 100 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude product. The crude product was purified by Combiflash (24 g silica column, elution solvent: 45% ethyl acetate / DCM). After concentration of the fractions, 8-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-1,4-dioxa-8-azaspiro[4.5]decane (490 mg, 1.083 mmol, 85% yield) was recovered as a pale yellow solid. LCMS retention time 1.54 min [F]; MS (E -) m / z: 453.2(M+H)

[0267] Intermediate 290B: 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-4-one [ka] To a solution of 8-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-1,4-dioxa-8-azaspiro[4.5]decane (450 mg, 0.994 mmol) in DCM (10 mL) was added TFA (3 mL, 38.9 mmol) dropwise and stirred at room temperature for 12 hours. The reaction was concentrated to give 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-4-one (400 mg, 0.979 mmol, 98% yield) as a yellow oil. LCMS retention time 1.36 min[F];MS(E - ) m / z: 409.2(M+H)

[0268] Example 290: 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(3-methyloxetan-3-yl)piperidin-4-amine To a solution of 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-4-one (25 mg, 0.061 mmol) and 3-methyloxetan-3-amine (5.33 mg, 0.061 mmol) in methanol (1 mL) was added acetic acid (3.50 μL, 0.061 mmol) at 0° C., and the solution was stirred at room temperature for 12 hours. Sodium cyanoborohydride (7.69 mg, 0.122 mmol) was then added at 0° C., and the mixture was stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The reaction was purified by preparative LCMS (Method I) and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(3-methyloxetan-3-yl)piperidin-4-amine (14.1 mg, 48%) as a pale yellow solid. LCMS retention time 1.75 min [A]; MS (E - ) m / z: 480.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 10.95(s, 1H), 8.67(s, 1H), 8.44(s, 1H), 4.42(d, J=5.1Hz,2H), 4.21(d, J=5.4Hz, 2H), 3.91(s, 1H), 3.82(d, J=12.2Hz, 2H), 3.01(t, J=11.6Hz, 2H), 2.81(br. s., 1H), 2.63 (dt, J=13.6, 6.8Hz, 1H), 2.59-2.53(m, 2H), 2.18(s, 3H), 1.70(d, J=12.5Hz, 2H), 1.46(s, 2H), 1.37(d, J=11.2Hz, 2H), 1.26(d, J=6.8Hz, 6H)

[0269] The following examples were prepared according to the general procedures described in Example 290. [Table 58] [Table 59]

[0270] Example 300 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-isobutyl-2,6-diazaspiro[3.3]heptan-2-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole [ka]

[0271] Intermediate 300A: tert-butyl 6-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate [ka] To a solution of 2-bromo-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (0.85 g, 2.178 mmol) and tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate (0.518 g, 2.61 mmol) in toluene (15 mL) was added cesium carbonate (1.419 g, 4.36 mmol). The mixture was degassed for 10 min, then Pd(dba) (0.199 g, 0.218 mmol) was added, followed by BINAP (0.136 g, 0.218 mmol). The solution was then degassed again for 5 min and heated at 90 °C for 16 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2×100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude product. The crude product was purified by Combiflash (24 g silica column, elution solvent: 45% ethyl acetate / DCM). After concentration of the fractions, tert-butyl 6-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (550 mg, 1.083 mmol, 49.7% yield) was recovered as a yellow solid. LCMS retention time 1.80 min [F]; MS (E - ) m / z: 508.2(M+H)

[0272] Intermediate 300B: 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of tert-butyl 6-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (400 mg, 0.788 mmol) in DCM (10 mL) was added TFA (3 mL, 38.9 mmol) dropwise and the solution was stirred at room temperature for 12 h. The reaction was concentrated to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (400 mg, 0.979 mmol, 98% yield) as a yellow solid. LCMS retention time 1.32 min [A]; MS (E - ) m / z: 408.2(M+H); 1 H NMR (400MHz, DMSO-d6)δ 11.00(d, J=4.2Hz, 1H), 8.67(s, 1H), 8.44(d, J=2.0Hz, 1H), 4.32(s, 1H), 4.18(s, 2H), 4.15(s, 3H), 4.05(s, 1H), 2.65-2.59(m, 1H), 2.58-2.54(m, 2H), 2.16(d, J=2.4Hz, 3H), 1.91(s, 1H), 1.76(s, 1H), 1.25(d, J=7.1Hz, 6H)

[0273] Example 300: 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-isobutyl-2,6-diazaspiro[3.3]heptan-2-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.123 mmol) and isobutyraldehyde (8.85 mg, 0.123 mmol) in methanol (1 mL) was added acetic acid (7.02 μL, 0.123 mmol) at 0° C., and the solution was stirred at room temperature for 12 hours. Sodium cyanoborohydride (15.42 mg, 0.245 mmol) was then added at 0° C., and the reaction mixture was stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The reaction was purified by preparative LCMS (Method I) and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-isobutyl-2,6-diazaspiro[3.3]heptan-2-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (18.9 mg, 0.039 mmol, 31.9% yield) as a pale yellow solid. LCMS retention time 1.52 min [A]; MS (E - ) m / z: 464.2(M+H)

[0274] The following examples were prepared according to the general procedures described in Example 300. [Table 60]

[0275] Example 303 1-(6-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-methylpropan-2-ol [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.123 mmol) and 1-chloro-2-methylpropan-2-ol (13.32 mg, 0.123 mmol) in DMF (1 mL) was added potassium carbonate (16.96 mg, 0.123 mmol), and the solution was heated at 80° C. for 12 hours. The reaction mixture was diluted with water (5 mL) and extracted with ethyl acetate (3×10 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude product was purified by preparative LCMS (Method I) and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 1-(6-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-methylpropan-2-ol (5.6 mg, 0.011 mmol, 9.04% yield) as a pale yellow solid. LCMS retention time 1.28 min [A]; MS (E - ) m / z: 480.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.00-10.95(m, 1H), 8.66(s, 1H), 8.44(s, 1H), 4.14-4.05(m, 2H), 3.91(s, 2H), 2.65-2.59(m, 2H), 2.56(s, 3H), 2.19-2.13(m, 2H), 1.92(s, 2H), 1.25(d, J=6.8Hz, 5H), 1.15-1.00(m, 6H)

[0276] Example 304 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(6-(2-(methylsulfonyl)ethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (100 mg, 0.245 mmol) and 1-chloro-2-(methylsulfonyl)ethane (35.0 mg, 0.245 mmol) in THF (1 mL) and DMF (1 mL) was added TEA (0.034 mL, 0.245 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(6-(2-(methylsulfonyl)ethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (23 mg, 0.044 mmol, 18.02% yield) as a pale yellow solid. LCMS retention time 1.81 min [C]; MS (E - ) m / z: 514.2(M+H)

[0277] Example 305 5-(6-Isopropyl-2-(6-(2-(methylsulfonyl)ethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one [ka] To a solution of 5-(6-isopropyl-2-(2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (25 mg, 0.063 mmol) and 1-chloro-2-(methylsulfonyl)ethane (8.97 mg, 0.063 mmol) in THF (1 mL) and DMF (1 mL) was added TEA (8.77 μL, 0.063 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(6-isopropyl-2-(6-(2-(methylsulfonyl)ethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (13.3 mg, 0.026 mmol, 41.6% yield) as a pale yellow solid. LCMS retention time 1.24 min [A]; MS (E - ) m / z: 504.2(M+H)

[0278] Example 306 5-(6-Isopropyl-2-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one [ka] To a solution of 5-(6-isopropyl-2-(2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (30 mg, 0.075 mmol) and oxetan-3-one (5.44 mg, 0.075 mmol) in methanol (1 mL) was added TEA (10.52 μL, 0.075 mmol) followed by acetic acid (4.32 μL, 0.075 mmol) at 0° C. The solution was stirred at room temperature for 12 hours, then sodium cyanoborohydride (9.48 mg, 0.151 mmol) was added at 0° C. and stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 5-(6-isopropyl-2-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (1.0 mg, 2.205 μmol, 2.92% yield) as a pale yellow solid. LCMS retention time 1.27 min [A]; MS (E - ) m / z: 454.2(M+H)

[0279] The following examples were prepared according to the general procedures described in Example 306. [Table 61]

[0280] Example 308 (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole HCl [ka]

[0281] Intermediate 308A: tert-butyl (R)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazine-1-carboxylate [ka] To a solution of 2-bromo-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (2.0 g, 5.12 mmol) and tert-butyl (R)-3-methylpiperazine-1-carboxylate (1.539 g, 7.69 mmol) in dioxane (60 mL) was added potassium carbonate (2.125 g, 15.37 mmol). The solution was degassed for 10 min, then XPhos Pd G2 (0.403 g, 0.512 mmol) was added, degassed again for 5 min, and the mixture was heated at 110 °C for 16 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2 x 100 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude product. The crude product was purified by combiflash (40 g silica column, elution solvent: 65% ethyl acetate / DCM). After concentration of the fractions, tert-butyl (R)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazine-1-carboxylate (2.2 g, 4.32 mmol, 84% yield) was recovered as a yellow solid. LCMS retention time 3.62 min [C]; MS (E - ) m / z: 508.2(MH)

[0282] The following intermediates were prepared following the general procedure described in Intermediate 308A. [Table 62]

[0283] Example 308: (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole HCl To a solution of tert-butyl (R)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazine-1-carboxylate (2.2 g, 4.32 mmol) in DCM (10 mL) was added 4 M hydrochloric acid in dioxane (10 mL, 329 mmol) dropwise and stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole·HCl (1.9 g, 4.18 mmol, 97% yield) as a pale yellow solid. LCMS retention time 1.31 min [A]; MS (E - ) m / z: 410.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ 10.91(s, 1H) 8.65(s, 1H) 8.43(s, 1H) 3.92(br dd, J=5.14, 2.69Hz, 1H) 3.45-3.49(m, 1H) 2.93-2.98(m, 1H) 2.85-2.91(m, 1H) 2.74-2.80(m, 1H) 2.60-2.71(m, 1H) 2.56(s, 3H) 2.19(s, 3H) 1.26(d, J=6.85Hz, 9H)

[0284] The following examples were prepared according to the general procedures described in Example 308. [Table 63]

[0285] Example 312 (R)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide [ka] To a solution of (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.122 mmol) and 2-chloro-N,N-dimethylacetamide (14.84 mg, 0.122 mmol) in DMF (1 mL) and THF (2 mL) was added TEA (0.017 mL, 0.122 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I) to give (R)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide (27 mg, 0.054 mmol, 44.3% yield) as a pale yellow solid. LCMS retention time 1.71 min [A]; MS (E - ) m / z: 495.3(M+H); 1H NMR(400MHz, DMSO-d6)δ 10.94(s, 1H) 8.66(s, 1H) 8.43(s, 1H) 3.99-4.10(m, 1H) 3.51-3.62(m, 1H) 3.12-3.28(m, 3H) 3.08(s, 3H) 2.89(br d, J=11.49Hz, 1H) 2.84(s, 3H) 2.74(br d, J=11.00Hz, 1H) 2.63 (dt, J=13.63, 6.76Hz, 1H) 2.56(s, 3H) 2.39 (dd, J=11.25, 3.42Hz, 1H) 2.19-2.29(m, 1H) 2.19(s, 2H) 1.24-1.31(m, 9H)

[0286] The following examples were prepared according to the general procedures described in Example 312. [Table 64]

[0287] Example 316 (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.122 mmol) and oxetan-3-one (8.80 mg, 0.122 mmol) in methanol (1 mL) was added TEA (0.017 mL, 0.122 mmol) at 0° C., and the solution was stirred at room temperature for 12 hours. Sodium cyanoborohydride (15.34 mg, 0.244 mmol) was then added at 0° C., and the reaction mixture was stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (22 mg, 0.043 mmol, 35.6% yield) as a pale yellow solid. LCMS retention time 1.78 min [A]; MS (E - ) m / z: 466.2(M+H)

[0288] The following examples were prepared according to the general procedures described in Example 316. [Table 65]

[0289] Example 325 (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol [ka] To a solution of (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.122 mmol) and 1-chloro-2-methylpropan-2-ol (13.25 mg, 0.122 mmol) in DMF (1 mL) was added potassium carbonate (16.87 mg, 0.122 mmol) and the solution was heated at 80° C. for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol (14.9 mg, 0.030 mmol, 24.83% yield) as a pale yellow solid. LCMS retention time 2.03 min [A]; MS (E - ) m / z: 482.2(M+H); 1 H NMR(400MHz, DMSO-d6)δ ppm 10.92(s, 1H) 8.66(s, 1H) 8.43(s, 1H) 4.16(s, 1H) 3.95-4.04(m, 1H) 3.52(br d, J=12.23Hz, 1H) 3.27(td, J=12.10, 2.93Hz, 1H) 3.18(d, J=5.14Hz, 1H) 2.99(br d, J=11.00Hz, 1H) 2.90(br d, J=11.00Hz, 2H) 2.59-2.67(m, 1H) 2.56(s, 2H) 2.43 (dd, J=11.37, 3.30Hz, 1H) 2.16-2.32(m, 4H) 2.08(s, 2H) 1.24-1.36(m, 6H) 1.14(d, J=6.11Hz, 6H)

[0290] Example 326 (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(methylamino)ethan-1-one [ka]

[0291] Intermediate 326A: tert-butyl (R)-(2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-oxoethyl)(methyl)carbamate [ka] To a solution of (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.122 mmol) and N-(tert-butoxycarbonyl)-N-methylglycine (23.10 mg, 0.122 mmol) in DMF (1 mL) was added HATU (46.4 mg, 0.122 mmol) followed by TEA (0.017 mL, 0.122 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated to give tert-butyl (R)-(2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-oxoethyl)(methyl)carbamate (50 mg, 0.086 mmol, 70.5% yield) as a yellow solid. LCMS retention time 1.88 min [F]; MS (E - ) m / z: 581.2

[0292] Example 326: (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(methylamino)ethan-1-one To a solution of tert-butyl (R)-(2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-oxoethyl)(methyl)carbamate (50 mg, 0.086 mmol) in DCM (2 mL) was added 4 M hydrochloric acid in dioxane (1 mL, 32.9 mmol) dropwise and stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(methylamino)ethan-1-one (27 mg, 0.053 mmol, 61.3% yield) as a pale yellow solid. LCMS retention time 1.29 min [A]; MS(E-) m / z: 481.2 (M+H); 1 H NMR(400MHz, DMSO-d6)δ ppm 10.96-11.03(m, 1H) 8.64-8.84(m, 3H) 8.45(s, 1H) 6.96-7.27(m, 1H) 3.96-4.44(m, 5H) 3.65-3.80(m, 3H) 3.33(br d, J=9.54Hz, 1H) 3.09-3.25(m, 2H) 2.80-3.05(m, 1H) 2.54-2.69(m, 6H) 2.18(s, 3H) 1.21-1.30(m, 6H)

[0293] The following examples were prepared according to the general procedures described in Example 326. [Table 66]

[0294] Example 328 2-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-((2S,5R)-2,5-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.118 mmol) and oxetan-3-one (8.51 mg, 0.118 mmol) in methanol (1 mL) was added acetic acid (6.76 μL, 0.118 mmol) at 0° C., and the solution was stirred at room temperature for 12 hours. Sodium cyanoborohydride (14.84 mg, 0.236 mmol) was then added at 0° C. and stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole as a pale yellow solid. LCMS retention time 1.88 min [A]; MS (E - ) m / z: 480.2 (M+H)

[0295] The following examples were prepared according to the general procedures described in Example 328. [Table 67]

[0296] Example 335 2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-N,N-dimethylacetamide [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-((2S,5R)-2,5-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.118 mmol) and 2-chloro-N,N-dimethylacetamide (14.35 mg, 0.118 mmol) in DMF (1 mL) and THF (2 mL) was added TEA (0.016 mL, 0.118 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-N,N-dimethylacetamide (19 mg, 0.037 mmol, 31.3% yield) as a pale yellow solid. LCMS retention time 1.79 min [A]; MS (E - ) m / z: 509.2(M+H)

[0297] The following examples were prepared according to the general procedures described in Example 335. [Table 68]

[0298] Example 339 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-methylpropan-2-ol [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-((2S,5R)-2,5-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.118 mmol) and 1-chloro-2-methylpropan-2-ol (12.82 mg, 0.118 mmol) in DMF (1 mL) was added potassium carbonate (32.6 mg, 0.236 mmol) and the solution was heated at 80° C. for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-methylpropan-2-ol (14 mg, 0.027 mmol, 22.97% yield) as a pale yellow solid. LCMS retention time 2.13 min [A]; MS (E - ) m / z: 496.2(M+H)

[0299] Example 340 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-(methylamino)ethan-1-one [ka]

[0300] Intermediate 340A: tert-butyl (2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-oxoethyl)(methyl)carbamate [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-((2S,5R)-2,5-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.118 mmol) and N-(tert-butoxycarbonyl)-N-methylglycine (22.33 mg, 0.118 mmol) in DMF (1 mL) was added HATU (44.9 mg, 0.118 mmol) followed by TEA (0.016 mL, 0.118 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and evaporated to give tert-butyl (2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-oxoethyl)(methyl)carbamate (45 mg, 0.076 mmol, 64.1% yield) as a yellow solid. LCMS retention time 2.09 min [F]; MS(E-) m / z: 595.2

[0301] Example 340: 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-(methylamino)ethan-1-one To a solution of tert-butyl (2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-oxoethyl)(methyl)carbamate (45 mg, 0.076 mmol) in DCM (2 mL) was added 4 M hydrochloric acid in dioxane (1 mL, 32.9 mmol) dropwise and stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-(methylamino)ethan-1-one (22 mg, 0.044 mmol, 58.2% yield) as a pale yellow solid. LCMS retention time 1.34 min [A]; MS (E - ) m / z: 495.2(M+H)

[0302] The following examples were prepared according to the general procedures described in Example 340. [Table 69]

[0303] Example 342 (S)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide [ka] To a solution of (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (30 mg, 0.073 mmol) and 2-bromo-N-methylacetamide (11.13 mg, 0.073 mmol) in DMF (1 mL) and THF (2 mL) was added TEA (10.21 μL, 0.073 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (S)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (8 mg, 0.017 mmol, 22.72% yield) as a pale yellow solid. LCMS retention time 1.60 min [A]; MS (E - ) m / z: 481.2 (M+H)

[0304] The following examples were prepared according to the general procedures described in Example 342. [Table 70]

[0305] Example 345 (S)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol [ka] To a solution of (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (30 mg, 0.073 mmol) and 1-chloro-2-methylpropan-2-ol (11.21 mg, 0.073 mmol) in DMF (1 mL) was added potassium carbonate (10.12 mg, 0.073 mmol) and the solution was heated at 80° C. for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (S)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol (4.1 mg, 8.51 μmol, 11.62% yield) as a pale yellow solid. LCMS retention time 2.09 min [A]; MS (E - ) m / z: 482.2(M+H)

[0306] Example 346 (S)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(dimethylamino)ethan-1-one [ka] To a solution of (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (30 mg, 0.073 mmol) and dimethylglycine (7.55 mg, 0.073 mmol) in DMF (1 mL) was added HATU (27.9 mg, 0.073 mmol) followed by TEA (10.21 μL, 0.073 mmol), and the solution was stirred at room temperature for 12 h. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (S)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(dimethylamino)ethan-1-one (17 mg, 0.032 mmol, 44.1% yield) as a pale yellow solid. LCMS retention time 1.50 min [A]; MS (E - ) m / z: 495.2(M+H)

[0307] The following examples were prepared according to the general procedures described in Example 346. [Table 71]

[0308] Example 348 (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (30 mg, 0.073 mmol) and oxetan-3-one (5.28 mg, 0.073 mmol) in methanol (1 mL) was added TEA (10.21 μL, 0.073 mmol) at 0° C., and the solution was stirred at room temperature for 12 hours. Sodium cyanoborohydride (9.21 mg, 0.147 mmol) was then added at 0° C., and the reaction mixture was stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (15 mg, 0.032 mmol, 44.0% yield) as a pale yellow solid. LCMS retention time 1.78 min [A]; MS (E - ) m / z: 466.2(M+H)

[0309] The following examples were prepared according to the general procedures described in Example 348. [Table 72]

[0310] Example 353 (R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide [ka] To a solution of (R)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.126 mmol) and 2-bromo-N-methylacetamide (19.21 mg, 0.126 mmol) in DMF (1 mL) and THF (2 mL) was added TEA (0.018 mL, 0.126 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with ethyl acetate (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (24 mg, 0.047 mmol, 37.5% yield) as a pale yellow solid. LCMS retention time 1.45 min [A]; MS (E - ) m / z: 467.2(M+H)

[0311] The following examples were prepared according to the general procedures described in Example 353. [Table 73]

[0312] Example 359 (R)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol [ka] To a solution of (R)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.126 mmol) and 1-chloro-2-methylpropan-2-ol (13.72 mg, 0.126 mmol) in DMF (1 mL) was added potassium carbonate (34.9 mg, 0.253 mmol) and the solution was heated at 80° C. for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (R)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol (4.2 mg, 8.98 μmol, 7.10% yield) as a pale yellow solid. LCMS retention time 1.68 min [A]; MS (E - ) m / z: 468.2(M+H)

[0313] Example 360 (R)-2-(Dimethylamino)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)ethan-1-one [ka] To a solution of (R)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.126 mmol) and dimethylglycine (13.04 mg, 0.126 mmol) in DMF (1 mL) was added HATU (48.1 mg, 0.126 mmol) followed by TEA (0.018 mL, 0.126 mmol), and the solution was stirred at room temperature for 12 hours. The reaction was diluted with water (5 mL) and extracted with EtOAc (3×10 mL). The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (R)-2-(dimethylamino)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)ethan-1-one (18 mg, 0.037 mmol, 29.3% yield) as a pale yellow solid. LCMS retention time 1.27 min [A]; MS (E - ) m / z: 481.2 (M+H)

[0314] Example 361 (R)-2-(4-Isobutyl-2-methylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole [ka] To a solution of (R)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (50 mg, 0.126 mmol) and isobutyraldehyde (9.12 mg, 0.126 mmol) in methanol (1 mL) was added TEA (0.018 mL, 0.126 mmol) at 0° C., and the solution was stirred at room temperature for 12 hours. Sodium cyanoborohydride (15.89 mg, 0.253 mmol) was then added at 0° C., and the mixture was stirred at room temperature for 2 hours. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with ethyl acetate (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give (R)-2-(4-isobutyl-2-methylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (27 mg, 0.060 mmol, 47.3% yield) as a pale yellow solid. LCMS retention time 1.27 min [B]; MS (E - ) m / z: 452.2(M+H)

[0315] The following examples were prepared according to the general procedures described in Example 361. [Table 74]

[0316] Examples 368 and 369 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-(dimethylamino)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxamide [ka] To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxylic acid (20 mg, 0.056 mmol) and N1,N1-dimethylcyclohexane-1,4-diamine (8.00 mg, 0.056 mmol) in DMF (1 mL) was added DIPEA (9.83 μL, 0.056 mmol) followed by HATU (21.40 mg, 0.056 mmol), and the solution was stirred at room temperature for 4 h. The reaction was concentrated to give the crude product. The resulting crude sample was purified by preparative LCMS (Method I). After purification by preparative LCMS, fractions containing isomers 1 and 2 were collected and dried using a centrifugal evaporator (Genevac), respectively, to give Example 368A (isomer 1, 7.0 mg, 0.014 mmol, 25.7% yield) as a pale yellow solid and Example 368B (isomer 2, 6.1 mg, 0.013 mmol, 22.60% yield) as a pale yellow solid. Example 368 (Isomer 1): LCMS retention time 1.26 min [A]; MS(E-) m / z: 480.2 (M+H); 1 H NMR (400MHz, DMSO-d6)δ 11.66(s, 1H), 8.83(s, 1H), 8.53-8.42(m, 1H), 8.12(d, J=7.8Hz, 1H), 3.94(d, J=3.7Hz, 1H), 2.86-2.71(m, 1H), 2.59(s, 3H), 2.23(br. s., 5H), 2.17(s, 3H),2.14-1.97(m, 2H), 1.93-1.73(m, 4H), 1.54(d, J=11.5Hz, 4H), 1.37(d, J=6.8Hz, 5H) Example 369 (Isomer 2): LCMS retention time 1.29 min [A]; MS (E - ) m / z: 480.2(M+H); 1H NMR(400MHz, DMSO-d6)δ 11.66(s, 1H), 8.83(s, 1H), 8.47(s, 1H), 8.23(d, J=9.3Hz,1H), 3.91(s, 1H), 3.78(br. s., 2H), 2.84-2.72(m, 1H), 2.59(s, 3H), 2.34(br. s., 1H), 2.27(br. s., 4H), 2.17(s, 3H), 1.89(br. s., 4H), 1.63-1.49(m, 3H), 1.42-1.28(m, 6H)

[0317] The following examples were prepared according to the general procedures described in Example 368. [Table 75] [Table 76] [Table 77]

[0318] Example 391 6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide [ka] To a solution of 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxylic acid (30 mg, 0.088 mmol), ammonium acetate (33.9 mg, 0.439 mmol), and ammonium chloride (23.50 mg, 0.439 mmol) in DMF (1 mL) was added DIPEA (0.012 mL, 0.088 mmol), followed by HATU (33.4 mg, 0.088 mmol), and the solution was stirred at room temperature for 4 hours. The reaction was concentrated to give the crude product. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (2.9 mg, 8.52 μmol, 9.69% yield) as a pale yellow solid. LCMS retention time 1.37 min [A]; MS (E - ) m / z: 341.2 (M+H); 1 H NMR(400MHz, DMSO-d6)δ 11.93(s, 1H), 8.83(s, 1H), 8.53(s, 1H), 7.90(br s, 1H), 7.61(s, 2H), 3.22-3.13(m, 1H), 2.63(s, 3H), 1.48(d, J=6.8Hz, 6H)

[0319] The following examples were prepared according to the general procedures described in Example 391. [Table 78] [Table 79]

[0320] Example 401 N-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-1-isopropylpiperidin-4-amine [ka]

[0321] Intermediate 401A: tert-butyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(hydroxymethyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of 4-(tert-butyl) 2-methyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2,4-dicarboxylate (1.0 g, 2.130 mmol) in toluene (25 mL) was added diisobutylaluminum hydride (4.44 mL, 5.32 mmol) dropwise at −78° C., and the resulting mixture was stirred at the same temperature for 3 h. The reaction was quenched with HCl (1.5 N, 15 mL) at −78° C., and the reaction mixture was extracted with EtOAc (3×50 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give tert-butyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(hydroxymethyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (0.9 g, 2.038 mmol, 96% yield) as a yellow solid. LCMS retention time 1.54 min [F]; MS (E - ) m / z: 442.2 (M+H)

[0322] Intermediate 401B: tert-butyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-formyl-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(hydroxymethyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (1.0 g, 2.265 mmol) in DCM (25 mL) was added Celite (0.488 g, 1.310 mmol), followed by portionwise addition of pyridinium chlorochromate (0.488 g, 2.265 mmol). The resulting solution was stirred at room temperature for 3 hours, and the reaction mixture was filtered through Celite, washing with additional DCM (60 mL). The filtrate was concentrated to give the crude product. The crude product was purified by Combiflash (24 g silica column, elution solvent: 40% ethyl acetate / petroleum ether). After concentration of the fractions, tert-butyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-formyl-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (0.65 g, 1.479 mmol, 65.3% yield) was recovered as a pale yellow solid. LCMS retention time 3.43 min [C]; MS (E - ) m / z: 44202(M+H)

[0323] Intermediate 401C: 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carbaldehyde [ka] To a solution of tert-butyl 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-formyl-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-4-carboxylate (0.65 g, 1.479 mmol) in DCM (10 mL) was added TFA (3 mL, 38.9 mmol) dropwise and stirred at room temperature for 12 hours. The reaction was diluted with DCM (25 mL) and washed with cold 10% sodium bicarbonate solution. The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carbaldehyde (0.42 g, 1.237 mmol, 84% yield) as a pale yellow solid. LCMS retention time 2.41 min [C]; MS(E-) m / z: 440.2 (M+H).

[0324] Example 401: N-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-1-isopropylpiperidin-4-amine To a solution of 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carbaldehyde (30 mg, 0.088 mmol) in methanol (1 mL) was added 1-isopropylpiperidin-4-amine (12.57 mg, 0.088 mmol) followed by acetic acid (5.06 μL, 0.088 mmol) at 0° C. The resulting solution was stirred at room temperature for 12 hours, then sodium cyanoborohydride (11.11 mg, 0.177 mmol) was added at 0° C. and stirring was continued for 2 hours at room temperature. The reaction was concentrated, and the residue was dissolved in water (5 mL) and extracted with ethyl acetate (3×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting crude sample was purified by preparative LCMS (Method I), and the product-containing fractions were combined and dried using a centrifugal evaporator (Genevac) to give N-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-1-isopropylpiperidin-4-amine (7.8 mg, 0.017 mmol, 18.70% yield) as a pale yellow solid. LCMS retention time 1.44 min [A]; MS (E - ) m / z: 466.3(M+H); 1 H NMR (400MHz, DMSO-d6)δ 11.27(s, 1H), 8.72(s, 1H), 8.45(s, 1H), 4.06(s, 2H), 2.79-2.64(m, 4H), 2.57(s, 3H), 2.47-2.38(m, 1H), 2.18(s, 3H),2.13-2.03(m, 2H), 1.90(s, 2H), 1.88-1.79(m, 2H), 1.30(d, J=6.8Hz, 6H), 0.95(d, J=6.6Hz, 6H)

[0325] The following examples were prepared according to the general procedures described in Example 401. [Table 80] [Table 81]

[0326] Example 410 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[2,3-d]thiazole [ka]

[0327] Intermediate 410A: Ethyl 2-bromothiazole-4-carboxylate [ka] To a solution of ethyl 2-aminothiazole-4-carboxylate (12.5 g, 72.6 mmol) and copper(II) bromide (24.32 g, 109 mmol) in acetonitrile (350 mL) was added tert-butyl nitrite (11.23 g, 109 mmol) dropwise at 0 °C, and the reaction mixture was stirred at 0 °C for 2 h. The reaction was diluted with water (150 mL), acidified to pH 1 with concentrated HCl, and the aqueous layer was extracted with dichloromethane (3 × 150 mL). The combined organic layers were dried over sodium sulfate, filtered, and the solvent removed under reduced pressure. The crude material was purified by Combiflash (80 g silica column, elution solvent: 10% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl ethyl 2-bromothiazole-4-carboxylate (10.5 g, 43.1 mmol, 59.4% yield) was recovered as a white solid. LCMS retention time 1.79 min[F];MS(E-)m / z: 237.2(M+H)

[0328] Intermediate 410B: 2-Bromothiazole-4-carboxylic acid [ka] To a solution of ethyl 2-bromothiazole-4-carboxylate (10.5 g, 44.5 mmol) in methanol (150 mL) was added dropwise 10% NaOH (45 mL, 44.5 mmol) at 0 °C, and the reaction mixture was stirred at 0 °C for 2 h. The reaction was concentrated under reduced pressure to remove volatiles, and the aqueous layer was acidified to pH 4-5 with HCl (1.5 N). The precipitated solid was filtered and dried to give 2-bromothiazole-4-carboxylic acid (8.7 g, 41.4 mmol, 93% yield) as a white solid product. LCMS retention time 0.33 min [C]; MS (E - ) m / z: 208.0(M+2H)

[0329] Intermediate 410C: tert-butyl (2-bromothiazol-4-yl)carbamate [ka] To a solution of 2-bromothiazole-4-carboxylic acid (8.7 g, 41.8 mmol) in t-BuOH (130 mL) was added TEA (6.99 mL, 50.2 mmol) and diphenylphosphoryl azide (10.13 mL, 46.0 mmol) at 0 °C, and the solution was heated at 80 °C for 12 h. The reaction was quenched with water (250 mL), the mixture was concentrated under reduced pressure to remove volatiles, and the aqueous layer was extracted with DCM (3 × 200 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude product. The crude product was purified by Combiflash (80 g silica column, elution solvent: 12% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl (2-bromothiazol-4-yl)carbamate (7.2 g, 24.24 mmol, 58.0% yield) was recovered as a white solid. LCMS retention time 2.84 min[C];MS(E - ) m / z: 278.2(MH)

[0330] Intermediate 410D: tert-butyl 4-(4-((tert-butoxycarbonyl)amino)thiazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate [ka] To a stirred solution of tert-butyl (2-bromothiazol-4-yl)carbamate (7.2 g, 25.8 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (11.96 g, 38.7 mmol) in dioxane (150 mL) and water (16.67 mL) was added potassium phosphate tribasic (16.42 g, 77 mmol), and the solution was degassed with nitrogen for 10 min. Next, PdCl(dppf)-CHCl adduct (2.106 g, 2.58 mmol) was added, and the mixture was degassed again for 5 min. The resulting brown reaction mixture was heated at 110° C. for 12 hours, the reaction diluted with EtOAc (250 mL), washed with water (250 mL), and the aqueous layer extracted with ethyl acetate (2×200 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give the crude product. The crude product was purified by Combiflash (80 g silica column, eluting solvent: 45% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl 4-(4-((tert-butoxycarbonyl)amino)thiazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (7.8 g, 17.99 mmol, 69.8% yield) was recovered as a yellow oil. LCMS retention time 3.31 min [C]; MS (E - ) m / z: 382.2(M+H)

[0331] Intermediate 410E: tert-butyl 4-(4-((tert-butoxycarbonyl)amino)thiazol-2-yl)piperidine-1-carboxylate [ka] A solution of tert-butyl 4-(4-((tert-butoxycarbonyl)amino)thiazol-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (7.8 g, 20.45 mmol) in ethyl acetate (150 mL) was purged with nitrogen gas, and Pd / C (3.92 g, 3.68 mmol) was added. The mixture was purged with N2 three times, and hydrogen gas was introduced into the mixture via a balloon. The mixture was stirred at room temperature for 8 hours. The reaction was filtered through Celite, rinsing with additional methanol, and the filtrate was concentrated to dryness to give tert-butyl 4-(4-((tert-butoxycarbonyl)amino)thiazol-2-yl)piperidine-1-carboxylate (7.4 g, 19.30 mmol, 94% yield) as a yellow oil. LCMS retention time 3.44 min [C]; MS (E - ) m / z: 384.2(M+H)

[0332] Intermediate 410F: tert-butyl 4-(4-((tert-butoxycarbonyl)amino)-5-iodothiazol-2-yl)piperidine-1-carboxylate [ka] To a solution of tert-butyl 4-(4-((tert-butoxycarbonyl)amino)thiazol-2-yl)piperidine-1-carboxylate (1.0 g, 2.61 mmol) in acetonitrile (20 mL) was added NIS (0.587 g, 2.61 mmol) in acetonitrile (10 mL) dropwise at 0° C., and the mixture was stirred at 0° C. for 10 minutes. Sodium thiosulfate solution (50 mL) was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate (2×100 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude product. The crude product was purified by Combiflash (24 g silica column, elution solvent: 16% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl 4-(4-((tert-butoxycarbonyl)amino)-5-iodothiazol-2-yl)piperidine-1-carboxylate (0.75 g, 1.458 mmol, 55.9% yield) was recovered as a pale yellow solid. LCMS retention time 3.09 min [C]; MS (E - ) m / z: 510.1(M+H)

[0333] Intermediate 410G: tert-butyl 4-(4-((tert-butoxycarbonyl)(3-methylbut-2-en-1-yl)amino)-5-iodothiazol-2-yl)piperidine-1-carboxylate [ka] To a solution of tert-butyl 4-(4-((tert-butoxycarbonyl)amino)-5-iodothiazol-2-yl)piperidine-1-carboxylate (0.3 g, 0.589 mmol) in DMF (10 mL) was added NaH (0.024 g, 0.589 mmol) at 0° C., and the mixture was stirred at 0° C. for 10 minutes. Then, 1-bromo-3-methylbut-2-ene (0.069 mL, 0.589 mmol) was added dropwise, and the reaction mixture was stirred at 0° C. for 10 minutes. The reaction was quenched with ice water (25 mL) and extracted with DCM (2×50 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give tert-butyl 4-(4-((tert-butoxycarbonyl)(3-methylbut-2-en-1-yl)amino)-5-iodothiazol-2-yl)piperidine-1-carboxylate (0.25 g, 0.429 mmol, 72.8% yield) as a pale yellow oil. LCMS retention time 4.10 min [C]; MS (E - ) m / z: 578.1(M+H)

[0334] Intermediate 410H: tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[2,3-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 4-(4-((tert-butoxycarbonyl)(3-methylbut-2-en-1-yl)amino)-5-iodothiazol-2-yl)piperidine-1-carboxylate (3.0 g, 5.19 mmol) and potassium carbonate (0.790 g, 5.71 mmol) in DMF (25 mL) was added tetrabutylammonium bromide (5.02 g, 15.58 mmol). The mixture was degassed for 10 min, and PdOAc2 (0.117 g, 0.519 mmol) was added. The reaction mixture was degassed for an additional 5 min, and the resulting mixture was heated at 100 °C for 12 h. The reaction was filtered through Celite to remove inorganics, washing with DCM (100 mL), and the filtrate was concentrated to give the crude product. The crude product was purified by Combiflash (40 g silica column, elution solvent: 15% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[2,3-d]thiazole-4-carboxylate (0.72 g, 1.601 mmol, 30.8% yield) was recovered as a yellow solid. LCMS retention time 4.24 min [C]; MS (E - ) m / z: 450.2(M+H)

[0335] Intermediate 410I: tert-butyl 5-bromo-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[2,3-d]thiazole-4-carboxylate [ka] To a solution of tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[2,3-d]thiazole-4-carboxylate (0.9 g, 2.002 mmol) in DCE (2 mL) was added NBS (0.392 g, 2.202 mmol) in DCE (2 mL) at 0° C., and the mixture was stirred at 0° C. for 15 min. The reaction was quenched with water, and the reaction mixture was extracted with DCM (2×10 mL). The extracted organic layer was dried over sodium sulfate, filtered, and concentrated to give the crude product. The crude product was purified by Combiflash (24 g silica column, elution solvent: 10% EtOAc / petroleum ether). After concentration of the fractions, tert-butyl 5-bromo-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[2,3-d]thiazole-4-carboxylate (29 mg, 0.055 mmol, 49.3% yield) was recovered as a pale yellow solid. LCMS retention time 4.66 min [C]; MS (E - ) m / z: 530.1(M+H)

[0336] Intermediate 410J: tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[2,3-d]thiazole-4-carboxylate [ka] A mixture of tert-butyl 5-bromo-2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[2,3-d]thiazole-4-carboxylate (25 mg, 0.047 mmol), 8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (15.62 mg, 0.057 mmol), and potassium phosphate tribasic (24.72 mg, 0.142 mmol) in dioxane (2 mL) and water (0.222 mL) was degassed for 10 min, followed by the addition of PdCl(dppf)-CHCl adduct (1.931 mg, 2.365 μmol). The mixture was degassed again for 5 min and heated at 85 °C for 3 h. The reaction was filtered through Celite to remove inorganics, washed with EtOAc (20 mL), and the filtrate was concentrated to give tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[2,3-d]thiazole-4-carboxylate (22 mg, 0.037 mmol, 78% yield) as a brown solid product. LCMS retention time 1.80 min [F]; MS (E - ) m / z: 597.1(M+H)

[0337] Example 410: 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[2,3-d]thiazole To a solution of tert-butyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[...

Claims

1. Formula (I) 【Chemistry 1】 [In the formula, X is N and Y is S; or X is S and Y is N or CH; R 1 are F, Cl, -CN, C 1-4 Alkyl, C 1-3 Fluoroalkyl, -OCH 3 , or -S(O) 2 (C 1-3 alkyl); G is (i) 【Chemistry 2】 (ii) 【Chemistry 3】 (iii) 【Chemistry 4】 (iv) 【Chemistry 5】 【Chemistry 6】 【Chemistry 7】 【Chemistry 8】 or a 9-membered heterocycle selected from (v) 【Chemistry 9】 【Chemistry 10】 【Chemistry 11】 is a 10-membered heterocycle selected from Each R 2 are independently halogen, -CN, -OH, -NO 2 , C 1-4 Alkyl, C 1-2 Fluoroalkyl, C 1-2 Cyanoalkyl, C 1-3 Hydroxyalkyl, C 1-3 Aminoalkyl, -O(CH 2 ) 1-2 OH, -(CH 2 ) 0-4 O(C 1-4 Alkyl), C 1-3 Fluoroalkoxy, -(CH 2 ) 1-4 O(C 1-3 alkyl), -O(CH 2 ) 1-2 O.C.(O)(C 1-3 alkyl), -O(CH 2 ) 1-2 NR x R x , -C(O)O(C 1-3 alkyl), -(CH 2 ) 0-2 C(O)NR y R y , -C(O)NR x (C 1-5 Hydroxyalkyl), -C(O)NR x (C 2-6 Alkoxyalkyl), -C(O)NR x (C 3-6 Cycloalkyl), -NR y R y , -NR y (C 1-3 Fluoroalkyl), -NR y (C 1-4 Hydroxyalkyl), -NR x CH 2 (phenyl), -NR x S(O) 2 (C 3-6 Cycloalkyl), -NR x C(O)(C 1-3 alkyl), -NR x CH 2 (C 3-6 Cycloalkyl), -(CH 2 ) 0-2 S(O) 2 (C 1-3 alkyl), -(CH 2 ) 0-2 (C 3-6 Cycloalkyl), -(CH 2 ) 0-2 (phenyl), morpholinyl, dioxothiomorpholinyl, dimethylpyrazolyl, methylpiperidinyl, methylpiperazinyl, amino-oxadiazolyl, imidazolyl, pyrimidinyl, triazolyl, or -C(O)(thiazolyl); R 2a is C 1-6 Alkyl, C 1-3 Fluoroalkyl, C 1-6 Hydroxyalkyl, C 1-3 Aminoalkyl, -(CH 2 ) 0-4 O(C 1-3 Alkyl), C 3-6 Cycloalkyl, -(CH 2 ) 1-3 C(O)NR y R y , -CH 2 (C 3-6 Cycloalkyl), -CH 2 (phenyl), tetrahydrofuranyl, tetrahydropyranyl, or phenyl; Each R 2b are independently H, halogen, -CN, -NR x R x , C 1-6 Alkyl, C 1-3 Fluoroalkyl, C 1-3 Hydroxyalkyl, C 1-3 Fluoroalkoxy, -(CH 2 ) 0-2 O(C 1-3 alkyl), -(CH 2 ) 0-3 C(O)NR x R x , -(CH 2 ) 1-3 (C 3-6 Cycloalkyl), -C(O)O(C 1-3 alkyl), -C(O)NR x (C 1-3 alkyl), -CR x =CR x R x , or -CR x =CH(C 3-6 cycloalkyl); R 2c is R 2a or R 2b and; R 2d is R 2a or R 2b where R 2c and R 2d One of them is R 2a and R 2c and the other of R 2d is R 2b and; A is, (i) H, -NR y R y , or -CH 2 NHCH 2 C(O)NR x R x ; (ii)-CR x R x R 3 , -CR x R x NR x R 3 , -CR x R x NR x CH 2 R 3 , -C(O)NR x R 3 , -C(O)NR x R 4 , -C(O)R 3 , or -NR x C(O)R 3 or (iii)R 3 and; R 3 teeth, (I C 3-5 cycloalkyl, azetidinyl, oxetanyl, pyrrolidinyl, pyrrolidinonyl, piperidinyl, piperazinyl, piperazinonyl, morpholinyl, dioxidethiomorpholinyl, oxazepanyl, diazaspiro[3.3]heptanyl, dioxidethiazaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, or oxazaspiro[3.5]nonanyl, each of which has zero to two R 3a and 0 to 2 R 3b Replaced with; (ii) cyclohexyl (such a group is -NR y R y , -NR x (C 1-6 Hydroxyalkyl), -NR x (CR x R x ) 1-2 O(C 1-3 alkyl), -NR x (C 1-6 Hydroxy-fluoroalkyl), -NR x CH 2 C(O)NR x R x , -NR x (CH 2 ) 1-2 S(O) 2 (C 1-3 alkyl), -NR x C(O)(C 1-3 alkyl), -NR x C(O)CH 2 NR x R x , -NR x C(O)CH 2 NR x R y , -NR x (CH 2 ) 1-2 C(O)NR x R x , -NR x (CH 2 ) 1-2 NR x R x , -NR x S(O) 2 (C 1-3 alkyl), -S(O) 2 (C 1-3 alkyl), -NR x (cyanocyclopropyl), -NR x (azetidinyl), -NR x (Oxetanyl), -NR x (Methyloxetanyl), -NR x (Ethyloxetanyl), -NR x (isopropyloxetanyl), -NR x (Tetrahydropyranyl), -NR x (bicyclo[1.1.1]pentyl), -NR x (CH 2 (methyloxetanyl), -NR x (tetrahydrothiophenyl dioxide), -NR x CH 2 (hydroxymethylcyclopropyl), -NR x CH 2 (methylsulfonylcyclopropyl), -NR x CH 2 (Methylcyclobutyl), -NR x HCH 2 or substituted with C(O)(morpholinyl), azetidinyl, fluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, pyrrolidinyl, piperazinonyl, morpholinyl, dioxothiomorpholinyl, oxazepanyl, bicyclo[1.1.1]pentanyl, azaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, dioxidothiazaspiro[3.3]heptanyl, oxazabicyclo[3.2.1]octanyl, oxazaspiro[3.5]nonanyl, or diazaspiro[4.4]nonanyl; or (iii) diazaspiro[3.3]heptanyl (such groups are 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(CH 2 ) 1-3 S(O) 2 (C 1-6 alkyl), oxetanyl, or -CH 2 (substituted with tetrahydropyranyl); Each R 3a are independently F, Cl, and C 1-6 Alkyl, C 1-6 Cyanoalkyl, C 1-6 Fluoroalkyl, C 1-6 Hydroxyalkyl, -(CH 2 ) 1-3 O(C 1-3 alkyl), -C(O)(C 1-6 alkyl), -CH 2 C(O)NR y R y , -NR y R y , -NR x (C 1-4 hydroxyalkyl), -C(O)(CH 2 ) 1-3 NR y R y , -C(O)(C 1-6 alkyl), -(CH 2 ) 0-2 S(O) 2 (C 1-3 alkyl), -(CH 2 ) 1-2 NR x S(O) 2 (C 1-3 alkyl), -NR x CH 2 C(O)NR y R y , -NR x (CH 2 ) 1-3 S(O) 2 (C 1-3 alkyl), -NR x (C 3-6 Cycloalkyl), -NR x (Oxetanyl), -CH 2 (Methyltriazolyl), C 3-6 Cycloalkyl, oxetanyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, -CH 2 (C 3-6 Cycloalkyl), -CH 2 (Oxetanyl), -CH 2 (methyloxetanyl), -CH 2 (Tetrahydropyranyl), -NR x (C 3-6 Cycloalkyl), -NR x (Oxetanyl), -NR x (Methyloxetanyl), -NR x CH 2 (methyloxetanyl), or -C(O)(dioxidetetrahydrothiopyranyl); Each R 3b is -CH 3 and; R 4 , H, C 1-2 Fluoroalkyl, -(CR x R x ) 1-2 NR y R y , or -(CR x R x ) 1-3 R 3 and; R 5 , H, C 1-3 Alkyl, or C 1-3 is a fluoroalkyl; Each R x are independently H or -CH 3 and; Each R y are independently H or C 1-6 is alkyl; and p is 0, 1, or 2. a compound of the formula (I), its N-oxide, or a salt thereof.

2. 2. The compound according to claim 1, wherein X is N and Y is S, an N-oxide, or a salt thereof.

3. During the ceremony, R 1 But -CH 3 , -CH 2 CH 3 , -CH(CH 3 ) 2 , -CF 3 , -OCH 3 , or -S(O) 2 (C 1-2 alkyl); G, (i) 【Chemistry 12】 (ii) 【Chemistry 13】 (iii) 【Chemistry 14】 (iv) 【Chemistry 15】 【Chemistry 16】 【Chemistry 17】 or a 9-membered heterocycle selected from (v) 【Chemistry 18】 【Chemistry 19】 is a 10-membered heterocycle selected from Each R 2 are independently F, Cl, -CN, -OH, C 1-3 Alkyl, C 1-2 Fluoroalkyl, C 1-2 Cyanoalkyl, C 1-3 Hydroxyalkyl, C 1-2 Aminoalkyl, -(CH 2 ) 0-2 O(C 1-3 Alkyl), C 3-6 Cycloalkyl, -NR x R x , -(CH 2 ) 0-2 C(O)NR x R x , -(CH 2 ) 0-2 S(O) 2 (C 1-3 alkyl), -CH 2 (C 3-6 Cycloalkyl), -CH 2 (phenyl), phenyl, pyrimidinyl, or triazolyl; R 2a But, C 1-4 Alkyl, C 1-2 Fluoroalkyl, C 1-4 Hydroxyalkyl, -(CH 2 ) 1-3 OCH 3 , C 3-6 Cycloalkyl, -CH 2 C(O)NR x R x , -CH 2 (C 3-6 Cycloalkyl), -CH 2 (phenyl), tetrahydrofuranyl, or phenyl; Each R 2b are independently H, F, Cl, -CN, -NR x R x , C 1-6 Alkyl, C 1-2 Fluoroalkyl, C 1-3 Hydroxyalkyl, -(CH 2 ) 0-2 O(C 1-2 alkyl), -(CH 2 ) 0-2 C(O)NR x R x , -(CH 2 ) 1-3 (cyclopropyl), -C(O)O(C 1-2 alkyl), or -C(O)NR x (C 1-3 alkyl); A, (i)-CH 2 NHCH 2 C(O)NR x R x ; (ii)-CR x R x R 3 , -CH 2 NR x R 3 , -CH 2 NR x CH 2 R 3 , -C(O)NR x R 3 , -C(O)NR x R 4 , -C(O)R 3 , or -NR x C(O)R 3 or (iii)R 3 and R 3 but, (i) azetidinyl, oxetanyl, cyclopropyl, pyrrolidinyl, pyrrolidinonyl, piperidinyl, piperazinyl, piperazinonyl, morpholinyl, dioxidethiomorpholinyl, oxazepanyl, diazaspiro[3.3]heptanyl, dioxidethiazaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, or oxazaspiro[3.5]nonanyl, each of which has zero to one R 3a and 0 to 2 R 3b Replaced with; (ii) cyclohexyl (such a group is -NR y R y , -NR x (C 1-4 Hydroxyalkyl), -NR x (CR x R x ) 1-2 O(C 1-2 alkyl), -NR x (C 1-6 Hydroxy-fluoroalkyl), -NR x CH 2 C(O)NR x R x , -NR x (CH 2 ) 1-2 S(O) 2 (C 1-2 alkyl), -NR x C(O)(C 1-2 alkyl), -NR x C(O)CH 2 NR x R x , -NR x C(O)CH 2 NR x R y , -NR x (CH 2 ) 1-2 C(O)NR x R x , -NR x (CH 2 ) 1-2 NR x R x , -NR x S(O) 2 (C 1-2 alkyl), -S(O) 2 (C 1-2 alkyl), -NR x (cyanocyclopropyl), -NR x (azetidinyl), -NR x (Oxetanyl), -NR x (Methyloxetanyl), -NR x (Ethyloxetanyl), -NR x (isopropyloxetanyl), -NR x (Tetrahydropyranyl), -NR x (bicyclo[1.1.1]pentyl), -NR x (CH 2 (methyloxetanyl), -NR x (tetrahydrothiophenyl dioxide), -NR x CH 2 (hydroxymethylcyclopropyl), -NR x CH 2 (methylsulfonylcyclopropyl), -NR x CH 2 (Methylcyclobutyl), -NR x HCH 2 or substituted with C(O)(morpholinyl), azetidinyl, fluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, pyrrolidinyl, piperazinonyl, morpholinyl, dioxothiomorpholinyl, oxazepanyl, bicyclo[1.1.1]pentanyl, azaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, dioxidothiazaspiro[3.3]heptanyl, oxazabicyclo[3.2.1]octanyl, oxazaspiro[3.5]nonanyl, or diazaspiro[4.4]nonanyl; or (iii) diazaspiro[3.3]heptanyl (such groups are 1-4 Alkyl, C 1-4 Hydroxyalkyl, -(CH 2 ) 1-2 S(O) 2 (C 1-3 alkyl), oxetanyl, or -CH 2 (substituted with tetrahydropyranyl); Each R 3a However, F, Cl, and C are independent 1-5 Alkyl, C 1-3 Cyanoalkyl, C 1-3 Fluoroalkyl, C 1-4 Hydroxyalkyl, -(CH 2 ) 1-2 O(C 1-2 alkyl), -C(O)(C 1-3 alkyl), -CH 2 C(O)NR x R x , -NR y R y , -NH(C 1-4 hydroxyalkyl), -C(O)(CH 2 ) 1-3 NR x R x , -C(O)(C 1-3 alkyl), -(CH 2 ) 0-2 S(O) 2 (C 1-2 alkyl), -(CH 2 ) 1-2 NR x S(O) 2 (C 1-2 alkyl), -NR x CH 2 C(O)NR y R y , -NR x CH 2 CH 2 S(O) 2 (C 1-2 alkyl), -NR x (C 3-6 Cycloalkyl), -NR x (Oxetanyl), -CH 2 (methyltriazolyl), cyclobutyl, oxetanyl, pyrrolidinyl, morpholinyl, tetrahydropyranyl, -CH 2 (C 3-4 Cycloalkyl), -CH 2 (Oxetanyl), -CH 2 (methyloxetanyl), -CH 2 (Tetrahydropyranyl), -NR x (cyclobutyl), -NR x (Oxetanyl), -NR x (Methyloxetanyl), -NR x CH 2 (methyloxetanyl), or -C(O)(dioxidetetrahydrothiopyranyl); and R 5 H, -CH 3 , -CH 2 CH 3 , -CF 3 , -CH 2 CHF 2 , or -CH 2 CF 3 That is, 2. The compound of claim 1, its N-oxide, or a salt thereof.

4. During the ceremony, R 1 But -CH 3 , -CH 2 CH 3 , or -CH(CH 3 ) 2 and; G, 【Chemistry 20】 and; Each R 2 However, independently, -CN, -CH 3 , or -OCH 3 and; A, (i)-CH 2 NHCH 2 C(O)NH 2 ; (ii)-CH 2 R 3 , -CH 2 NHR 3 , -CH 2 NHCH 2 R 3 , -C(O)NHR 3 , -C(O)NR x R 4 , or -C(O)R 3 or (iii) cyclohexyl, piperidinyl, piperazinyl, methylpiperazinyl, dimethylpiperazinyl, or diazaspiro[3.3]heptanyl, each of which is 0 to 1 R 3a Replaced with; R 3 is azetidinyl, oxetanyl, cyclopropyl, cyclobutyl, pyrrolidinyl, pyrrolidinonyl, piperidinyl, piperazinyl, piperazinonyl, morpholinyl, dioxidethiomorpholinyl, oxazepanyl, diazaspiro[3.3]heptanyl, dioxidethiazaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, or oxazaspiro[3.5]nonanyl, each of which is selected from 0 to 1 R 3a and 0 to 2 R 3b Replaced with; R 3a が、F、-CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 、-CH(CH 3 ) 2 、-CH 2 CH(CH 3 ) 2 、-CH 2 C(CH 3 ) 3 、-CH 2 CH(CH 2 CH 3 ) 2 、-CH 2 CF 3 、-CH 2 CN、-CH 2 C(CH 3 ) 2 OH、-CH 2 CH 2 OCH 3 、-CH 2 CH 2 S(O) 2 CH 3 、-CH 2 C(O)NR x R x 、-OCH 3 、-C(O)CH 3 、-C(O)CH 2 N(CH 3 ) 2 、-NH 2 、-NH(CH 3 )、-NH(CH(CH 3 ) 2 )、-NH(CH 2 C(CH 3 ) 3 )、-NH(CH 2 C(CH 3 ) 2 OH)、-NH(CH 2 CHFC(CH 3 ) 2 OH)、-NH(CH 2 C(CH 3 ) 2 OCH 3 )、-N(CH 3 )(CH 2 CH 3 )、-N(CH 3 )(CH(CH 3 ) 2 )、-N(CH 3 )CH 2 CH(CH 3 ) 2 、-N(CH 3 )CH 2 C(O)N(CH 3 ) 2 、-N(CH 3 )CH 2 CH 2 S(O) 2 CH 3 、-NHC(O)CH 2 N(CH 3 ) 2 、-NHC(O)CH 2 N(CH 3 )(CH 2 CH 3 )、-NHC(O)CH 2 NH(CH 2 CH(CH 3 ) 2 )、-NHCH 2 C(O)NH 2 、-NHCH 2 C(O)NH(CH 3 )、-NHCH 2 C(O)N(CH 3 ) 2 、-NHCH 2 CH 2 NH(CH 3 )、-NHS(O) 2 CH 3 、-S(O) 2 CH 3 、-CH 2 (シクロプロピル)、-CH 2 (メチルオキセタニル)、-CH 2 (tetrahydropyranyl), -C(O)(dioxidetetrahydrothiopyranyl), -NH(cyanocyclopropyl), -NH(cyclobutyl), -NH(methylcyclobutyl), -NH(oxetanyl), -NH(methyloxetanyl), -NH(ethyloxetanyl), -NH(isopropylpiperidinyl), -NH(tetrahydropyranyl), -NH(bicyclo[1.1.1]pentyl), -NHCH 2 (Methyloxetanyl), -NH(Dioxidetetrahydrothiophenyl), -NHCH 2 (hydroxymethylcyclopropyl), -NHCH 2 (methylsulfonylcyclopropyl), -NHCH 2 (Methylcyclobutyl), -NHCH 2 C(O)(morpholinyl), cyclobutyl, azetidinyl, fluoroazetidinyl, difluoroazetidinyl, hydroxyazetidinyl, methoxyazetidinyl, hydroxy(trifluoromethyl)azetidinyl, bis(hydroxymethyl)azetidinyl, oxetanyl, pyrrolidinyl, acetamidopyrrolidinyl, piperazinonyl, tetrahydropyranyl, morpholinyl, dioxothiomorpholinyl, oxazepanyl, bicyclo[1.1.1]pentanyl, azaspiro[3.3]heptanyl, oxazaspiro[3.3]heptanyl, dioxidothiazaspiro[3.3]heptanyl, oxazabicyclo[3.2.1]octanyl, oxazaspiro[3.5]nonanyl, or diazaspiro[4.4]nonanyl; R 4 H, -CH 2 CHF 2 , -CH 2 CF 3 , -CH 2 CH 2 N(CH 3 ) 2 , -CH 2 R 3 , -CH 2 CR x R x R 3 , or -(CH 2 ) 3 R 3 and; R 5 is H or -CH 2 CF 3 and p is 0, 1, or 2; 2. The compound of claim 1, its N-oxide, or a salt thereof.

5. wherein A is cyclohexyl, piperidinyl, piperazinyl, methylpiperazinyl, dimethylpiperazinyl, or diazaspiro[3.3]heptanyl, each of which contains 0 to 1 R 3a 2. The compound of claim 1, an N-oxide, or a salt thereof, substituted with:

6. In the formula, A is -CH 2 R 3 , -CH 2 NHR 3 , -CH 2 NHCH 2 R 3 , or -CH 2 NHCH 2 C(O)NH 2 2. The compound of claim 1, an N-oxide, or a salt thereof,

7. In the formula, A is -C(O)NHR 3 or -C(O)NR x R 4 2. The compound of claim 1, an N-oxide, or a salt thereof,

8. In the formula, A is -C(O)R 3 2. The compound of claim 1, an N-oxide, or a salt thereof,

9. 2. The compound according to claim 1, wherein X is S and Y is N, its N-oxide, or salt.

10. 2. The compound according to claim 1, wherein X is S and Y is CH, an N-oxide, or a salt thereof.

11. The compound is 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (1); 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (2); 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (3); 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (4); 5-(6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (5); 2-(dimethylamino)-1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (6); 2-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (7); 2-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N-methylacetamide (8); 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-(2,2,2-trifluoroethyl)-2-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (9); 6-isopropyl-2-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (10);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (11); 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (12); 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-neopentylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (13); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (14); 1-(4-(6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol (15); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (16); 2-(4-(6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (17); 1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol (18); 2-(dimethylamino)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (19);6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (20); 6-isopropyl-2-(1-isopropylpiperidin-4-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (21); 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (22); 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (23); 2-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (24); 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(1-isopropylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (25); 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (26); 5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (27); 2-(dimethylamino)-1-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (28); 1-(4-(5-(2,6-dimethylpyridin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-2-methylpropan-2-ol (29);2-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (30); 2-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)acetamide (31); 2-(dimethylamino)-1-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (32); 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (33); 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (34); 6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (35); 6-isopropyl-2-(1-isopropylpiperidin-4-yl)-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazole (36); 5-(6-isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (37); 5-(6-isopropyl-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (38); 5-(2-(1-(dimethylglycyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)quinoline-8-carbonitrile (39);2-(4-(5-(8-cyanoquinolin-5-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (40); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol (41); 5-(6-isopropyl-2-(piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (42); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (43); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-isopropylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (44); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(methylsulfonyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (45); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (46); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (47); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (48);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-methylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (49); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-ethylpiperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (50); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-propylpiperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (51); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-isobutylpiperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (52); 2-(1-(cyclopropylmethyl)piperidin-4-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (53); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-(2-ethylbutyl)piperidin-4-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (54); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazole (55); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N-methylacetamide (56); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (57);2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)acetamide (58); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)ethan-1-one (59); 5-(6-isopropyl-2-(1-(oxetan-3-yl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (60); 5-(6-isopropyl-2-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (61); 2-(4-(6-isopropyl-5-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N,N-dimethylacetamide (62); 2-(4-(6-isopropyl-5-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)-N-methylacetamide (63); 2-(4-(6-isopropyl-5-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-1-yl)acetamide (64); N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (65-66); (1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)azetidine-3,3-diyl)dimethanol (67);6-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (68-69); N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-methyloxetan-3-amine (70-71); N-ethyl-4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (72-73); 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (74-75); 2-(4-(azetidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6; -yl)-4H-pyrrolo[3,2-d]thiazole (76-77); N-isopropyl-4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl-1-amine (78-79); 4-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)thiomorpholine 1,1-dioxide (82-83); 1-((4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (84-85); 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(2-methoxy-2-methylpropyl)cyclohexan-1-amine (86-87); N-isopropyl-4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (88-89); (R)-3-fluoro-4-((4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylbutan-2-ol (90-91); 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexan-1-amine (92-93); 3-ethyl-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (94-95);6-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide (96-97); 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-(pyrrolidin-1-yl)cyclohexyl)-4H-pyrrolo[3,2-d]thiazole (98-99); (R)-N-(1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)pyrrolidin-3-yl)acetamide (100-101); 4-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-1,4-oxazepane (102-103); (1R,5S)-8-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-oxa-8-azabicyclo[3.2.1]octane (104-105); 1-((4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)cyclopropane-1-carbonitrile (106-107); 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(1-methylcyclobutyl)cyclohexan-1-amine (108-109); 2-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-7-oxa-2-azaspiro[3.5]nonane (110-111);7-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-7-azaspiro[3.5]nonane (112-113); 2-(4-(2,7-diazaspiro[4.4]nonan-2-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (114-115); N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-azaspiro[3.3]heptan-6-amine (116-117); 1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-(trifluoromethyl)azetidin-3-ol (118-119); 4-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (120-121); 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-4H-pyrrolo[3,2-d]thiazole (122-123); N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-N-methyloxetan-3-amine (124-125); 2-(dimethylamino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (126);N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)methanesulfonamide (127); trans 2-(ethyl(methyl)amino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (128); 2-(Isobutylamino)-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)acetamide (129); N-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (130-131); N-ethyl-4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (132); 4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine (134-135); 6-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (136-137); N-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)bicyclo[1.1.1]pentan-1-amine (138-139);1-((4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (140-141); (1-(((4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)methyl)cyclopropyl)methanol (142-143); N-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-methyloxetan-3-amine (144-145); 4-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-1,4-oxazepane (146-147); 4-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (148-149); 6-isopropyl-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (150-151); N-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (152-153); 6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-(pyrrolidin-1-yl)cyclohexyl)-4H-pyrrolo[3,2-d]thiazole (154-155);1-((4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (156-157); N-isopropyl-4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (158-159); N-(4-(6-isopropyl-5-(7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (160-161); 2-((4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)(methyl)amino)-N,N-dimethylacetamide (162-163); 4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methyl-N-(2-(methylsulfonyl)ethyl)cyclohexan-1-amine (164-165); 1-isopropyl-N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperidin-4-amine (166-167); N-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)bicyclo[1.1.1]pentan-1-amine (168-169); N1-(4-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-N2-methylethane-1,2-diamine (170-171);4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((3-methyloxetan-3-yl)methyl)cyclohexan-1-amine (172-173); N-ethyl-4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-methylcyclohexan-1-amine (174-175); N-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)bicyclo[1.1.1]pentan-1-amine (176-177); N-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (178-179); 6-(4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (180-181); 1-((4-(6-isopropyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (182-183); N-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (184-185); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(2-methoxy-2-methylpropyl)cyclohexan-1-amine (186-187);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-4H-pyrrolo[3,2-d]thiazole (188-189); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-ethyl-N-methylcyclohexan-1-amine (190-191); 6-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (192-193); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isopropylcyclohexan-1-amine (194-195); 1-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-2-methylpropan-2-ol (196-197); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-neopentylcyclohexan-1-amine (198-199); N-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)- Lysin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)tetrahydro-2H-pyran-4-amine (200-201); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((1-methylcyclobutyl)methyl)cyclohexan-1-amine (202-203); 2-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-N,N-dimethylacetamide (204-205); 2-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-1-morpholinoethan-1-one (206-207); 2-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)-N-methylacetamide (208-209); 2-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)acetamide (210-211); 4-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)morpholine (212-213); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)cyclohexan-1-amine (214-215);2-(4-(azetidin-1-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (216-217); 2-(4-(3,3-difluoroazetidin-1-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (218-219); 4-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (220-221); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isopropyl-N-methylcyclohexan-1-amine (222-223); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)azetidin-3-ol (224-225); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-(3-fluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (226-227); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isobutyl-N-methylcyclohexan-1-amine (228-229); 3-((4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)amino)tetrahydrothiophene 1,1-dioxide (230-232);6-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide (233-234); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-3-(trifluoromethyl)azetidin-3-ol (235-236); 7-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-7-azaspiro[3.5]nonane (237-238); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-7-oxa-2-azaspiro[3.5]nonane (239-240); 5-(6-isopropyl-2-(4-(oxetan-3-ylamino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (241-242); 5-(6-isopropyl-2-(4-((2-methoxy-2-methylpropyl)amino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (243-244); 5-(2-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (245-246); 5-(2-(4-(ethyl(methyl)amino)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (247-248);5-(6-isopropyl-2-(4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (249-250); 5-(2-(4-((2-hydroxy-2-methylpropyl)amino)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (251-252); 5-(6-isopropyl-2-(4-(isopropylamino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (253-254); 5-(2-(4-(azetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (255-256); 5-(6-isopropyl-2-(4-(((1-(methylsulfonyl)cyclopropyl)methyl)amino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (257-258); 4-(4-(6-isopropyl-5-(1,4,5-trimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (259-260); 5-(6-isopropyl-2-(4-(isopropyl(methyl)amino)cyclohexyl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (261-262); 5-(2-(4-(3-hydroxyazetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (263-264); 5-(2-(4-(3-fluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (265-266);5-(2-(4-(3-hydroxy-3-(trifluoromethyl)azetidin-1-yl)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (267-268); 6-(4-(6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)-2-oxa-6-azaspiro[3.3]heptane (269-270); N-(4-(6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (271-272); N-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)oxetan-3-amine (273); 4-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-4H-pyrrolo[3,2-d]thiazol-2-yl)cyclohexyl)piperazin-2-one (275-276); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazol (278); 5-(6-isopropyl-2-(piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (279); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-2-(dimethylamino)ethan-1-one (280); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-2-methylpropan-2-ol (281);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (282); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-N,N-dimethylacetamide (283); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)-N-methylacetamide (284); 2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-1-yl)acetamide (285); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (286); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (287); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-isopropylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (288); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-((3-methyloxetan-3-yl)methyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (289); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(3-methyloxetan-3-yl)piperidin-4-amine (290);1-((1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-4-yl)amino)-2-methylpropan-2-ol (291); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isopropyl-N-methylpiperidin-4-amine (292); N-cyclobutyl-1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperidin-4-amine (293); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(2-methoxy-2-methylpropyl)piperidin-4-amine (294); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((3-methyloxetan-3-yl)methyl)piperidin-4-amine (295); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-(oxetan-3-yl)piperidin-4-amine (296); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-isopropylpiperidin-4-amine (297); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-ethyl-N-methylpiperidin-4-amine (298); 1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-piperidin-4-amine (299);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-isobutyl-2,6-diazaspiro[3.3]heptan-2-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (300); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(6-((tetrahydro-2H-pyran-4-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (301); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazole (302); 1-(6-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-2-methylpropan-2-ol (303); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(6-(2-(; 5-(6-isopropyl-2-(6-(2-(methylsulfonyl)ethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (305); 5-(6-isopropyl-2-(6-(oxetan-3-yl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (306); 5-(6-isopropyl-2-(6-((tetrahydro-2H-pyran-4-yl)methyl)-2,6-diazaspiro[3.3]heptan-2-yl)-4H-pyrrolo[3,2-d]thiazol-5-yl)-1,3,4-trimethylpyridin-2(1H)-one (307); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole.HCl (308); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-((2S,5R)-2,5-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (309); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (310); (R)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (311); (R)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide (312);(R)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)acetamide (313); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (314); (R)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (315); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (316); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (317); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (318); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(2,4-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (319); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(4-ethyl-2-methylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (320);(R)-2-(4-(cyclopropylmethyl)-2-methylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (321); (R)-2-(4-cyclobutyl-2-methylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (322); (R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-(1-isopropylpiperidin-4-yl)-2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (323); (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol (325); (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(methylamino)ethan-1-one (326); (R)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(dimethylamino)ethan-1-one (327); 2-((2S,5R)-2,5-dimethyl-4-(oxetan-3-yl)piperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (328); 2-((2S,5R)-2,5-dimethyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (329);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-((2S,5R)-4-isopropyl-2,5-dimethylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (330); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-((2S,5R)-4-ethyl-2,5-dimethylpiperazin-1-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (331); 2-((2S,5R)-4-(cyclopropylmethyl)-2,5-dimethylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (332); 2-((2S,5R)-4-cyclobutyl-2,5-dimethylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (333); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-((2S,5R)-4-isopropyl-2,5-dimethylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (334); 2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-N,N-dimethylacetamide (335); 2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-N-methylacetamide (336); 2-((2S,5R)-2,5-dimethyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (337);2-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)acetamide (338); 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-methylpropan-2-ol (339); 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-(methylamino)ethan-1-one (340); 1-((2R,5S)-4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-2,5-dimethylpiperazin-1-yl)-2-(dimethylamino)ethan-1-one (341); (S)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (342); (S)-2-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide (343); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (344);(S)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol (345); (S)-1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-(dimethylamino)ethan-1-one (346); (S)-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)(1,1-dioxidetetrahydro-2H-thiopyran-4-yl)methanone (347); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (348); (S)-2-(4-cyclobutyl-2-methylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (349); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(2-methyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (350); (S)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-2-(4-isopropyl-2-methylpiperazin-1-yl)-4H-pyrrolo[3,2-d]thiazole (351); (S)-2-(4-(cyclopropylmethyl)-2-methylpiperazin-1-yl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (352);(R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N-methylacetamide (353); (R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-N,N-dimethylacetamide (354); (R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)acetamide (355); (R)-6-isopropyl-2-(2-methyl-4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (356); (R)-6-isopropyl-2-(4-(2-methoxyethyl)-2-methylpiperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (357); (R)-2-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)acetonitrile (358); (R)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)-2-methylpropan-2-ol (359); (R)-2-(dimethylamino)-1-(4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)-3-methylpiperazin-1-yl)ethan-1-one (360);(R)-2-(4-isobutyl-2-methylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (361); (R)-2-(4-cyclobutyl-2-methylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (362); (R)-6-isopropyl-2-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (363); (R)-6-isopropyl-2-(2-methyl-4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (364); (R)-2-(4-(cyclopropylmethyl)-2-methylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (365); (R)-6-isopropyl-2-(4-isopropyl-2-methylpiperazin-1-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-; d]thiazole (366); (R)-2-(2,4-dimethylpiperazin-1-yl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole (367); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-(dimethylamino)cyclohexyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (368-369); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(2-(pyrrolidin-1-yl)ethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (370); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(3-(2-oxopyrrolidin-1-yl)propyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (371); 5-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(2-(dimethylamino)ethyl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (372); (5-(7,8-Dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(1,1-dioxidethiomorpholino)methanone (373); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(2-methyl-2-morpholinopropyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (374); 1-(4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carbonyl)piperazin-1-yl)ethan-1-one (375); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(4-(dimethylamino)piperidin-1-yl)methanone (376);(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(pyrrolidin-1-yl)methanone (377); 4-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)piperazin-2-one (378); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(3-fluoroazetidin-1-yl)methanone (379); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(4-isopropylpiperazin-1-yl)methanone (380); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(2-(1-methylpiperidin-4-yl)ethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (381); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(2-(dimethylamino)ethyl)-6-isopropyl-N-methyl-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (382); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(3-(dimethylamino)azetidin-1-yl)methanone (383); (5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)(4-(methylsulfonyl)piperazin-1-yl)methanone (384); 5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (385);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-N-(morpholin-2-ylmethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (386); 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(2-(pyrrolidin-1-yl)ethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (387); N-(2-(dimethylamino)ethyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (388); N-(2,2-difluoroethyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (389); 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(2,2,2-trifluoroethyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (390); 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (391); 4-(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carbonyl)piperazin-2-one (392); (6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)(pyrrolidin-1-yl)methanone (393); (6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)(1,4-oxazepan-4-yl)methanone (394); (4-(dimethylamino)piperidin-1-yl)(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)methanone (395);(6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)(3-methoxyazetidin-1-yl)methanone (396); 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(oxetan-3-yl)-4H-pyrrolo[3,2-d]thiazol-2-yl)(morpholino)methanone (398); 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (399); N-(2-(dimethylamino)ethyl)-6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-4H-pyrrolo[3,2-d]thiazole-2-carboxamide (400); N-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-1-isopropylpiperidin-4-amine (401); 2-(((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)amino)acetamide (402); 6-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide (403); 2-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-7-oxa-2-azaspiro[3.5]nonane (404);1-(5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)-N-((1-(methylsulfonyl)cyclopropyl)methyl)methanamine (405); 4-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)piperazin-2-one (406); 4-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)morpholine (407); 6-((5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazol-2-yl)methyl)-2-oxa-6-azaspiro[3.3]heptane (408); 2-((2,6-diazaspiro[3.3]heptan-2-yl)methyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-4H-pyrrolo[3,2-d]thiazole (409); 6-Isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[2,3-d]thiazole (410); 6-Isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-pyrrolo[2,3-d]thiazole (411); 6-isopropyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(1-((3-methyloxetan-3-yl)methyl)piperidin-4-yl)-4H-pyrrolo[2,3-d]thiazole (412); or 6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(piperidin-4-yl)-4H-thieno[3,2-b]pyrrole (413); 2. The compound of claim 1, an N-oxide, or a salt thereof,

12. A pharmaceutical composition comprising a compound according to any one of claims 1 to 11, or a pharma- ceutically acceptable salt thereof, and a pharma- ceutically acceptable carrier.

13. 12. A pharmaceutical composition comprising a compound according to any one of claims 1 to 11, or a pharma- ceutically acceptable salt thereof, for use in the treatment of an autoimmune disease or a chronic inflammatory disease.

14. 14. The pharmaceutical composition of claim 13, wherein the autoimmune disease or chronic inflammatory disease is selected from systemic lupus erythematosus (SLE), rheumatoid arthritis, multiple sclerosis (MS), and Sjogren's syndrome.

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