RU2833052C2 - Imidazopyridinyl compounds and use thereof for treating neurodegenerative disorders - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. In formula (I) the values of radicals are as follows: R¹ is cyclopropyl substituted with one or two halogen groups; R² and R³ are -H; R⁴ is selected from a group consisting of 6-membered aryl, , , , and , wherein said 6-membered aryl is optionally substituted with one to three groups selected from the group consisting of halogen, hydroxyl, C₁-C₁₂alkyl, C₃-C₁₂cycloalkyl, C₁-C₁₂haloalkyl, C₁-C₁₂hydroxyalkyl, C₁-C₁₂alkoxy-C₁-C₁₂alkyl, C₁-C₁₂alkoxy-C₁-C₁₂alkoxy, di-C₁-C₁₂alkylaminoC₁-C₁₂alkyl, -CH₂NHC(O)CH₃, -NR_aR_b, -NR_aC(=O)R_b, -OR_a, -CN, -C(=O)R_a, -C(=O)OR_a, -SR_a, furanyl, pyrrolyl and pyrazolyl; R^a and R^b independently represent -H or C₁-C₁₂alkyl; R⁵ is H, halogen or C₁-C₁₂alkyl. Also disclosed is a compound selected from a group of individual compounds specified in the claim, and a pharmaceutical composition containing said compounds.

EFFECT: disclosed compounds are c-abl and/or LRRK2 kinase inhibitors and can be used to treat neurodegenerative diseases.

24 cl, 2 tbl, 14 ex

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62/809,230, filed February 22, 2019. The entire disclosure of the application referenced in this paragraph is incorporated herein by reference.

AREA OF TECHNOLOGY

[0002] The present description generally relates to compounds having enzyme inhibitory activity, pharmaceutical compositions containing said compound, and methods of using said compounds to treat diseases.

LEVEL OF TECHNOLOGY

[0003] α-synuclein is a member of a large family of proteins that includes β- and γ-synuclein and synoretin. α-synuclein is normally expressed in association with synapses and is thought to play a role in neuroplasticity, learning, and memory. Several studies have shown that α-synuclein plays a central role in the pathogenesis of Parkinson's disease. Molecular alterations in the α-synuclein protein that enhance protein misfolding and aggregation play a direct role in the pathogenesis of the disease. Aggregation of α-synuclein promotes the formation of Lewy bodies and neurites, the pathological hallmarks of Parkinson's disease and α-synucleinopathies. Activation of the tyrosine kinase c-abl promotes α-synuclein-induced neurodegeneration.

[0004] The tyrosine kinase c-abl is a tightly regulated non-receptor protein tyrosine kinase involved in a wide range of cellular processes including growth, survival, and stress response (Nat Rev Mol Cell Biol, 2004, 5:33-44), and c-abl is involved in the regulation of several cellular processes and is also involved in central nervous system development by controlling neurogenesis. Recently, there has also been increasing evidence from various experimental model systems that c-abl is activated in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Neumann-Pick disease type C, and tauopathies. (Human Molecular Genetics, 2014, Vol. 23, No. 11)

[0005] The stress signaling non-receptor tyrosine kinase c-abl implicates parkin in the development of sporadic Parkinson's disease through tyrosine phosphorylation. Tyrosine phosphorylation of parkin by the tyrosine kinase c-abl is a major post-translational modification that leads to loss of parkin function and disease progression in sporadic Parkinson's disease. Inhibition of c-abl opens new therapeutic options to block the progression of Parkinson's disease. (The Journal of Neuroscience, 2011, 31 (1): 157-163) Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by progressive motor neuron loss. Knockdown of c-abl using small interfering RNA (siRNA) also prevented motor neuron degeneration in ALS. (Imamura et al., Sci, Transl. Med, 9, 2017) Multiple system atrophy (MSA) is a rare, rapidly progressive neurodegenerative disease for which there is currently no cure. In MSA, α-synuclein accumulates in neurons and oligodendrocytes of the substantia nigra, striatum, olivopontocerebellar structures, and spinal cord. (J Neural Trans Vienna Austria 1996. 2016; 123(6))

[0006] Administration of the tyrosine kinase inhibitor nilotinib reduces c-abl activity and improves α-synuclein clearance via autophagy in transgenic and lentiviral gene transfer models. Activation of c-abl in the mouse forebrain induces neurodegeneration in the hippocampus and striatum. Therefore, increased c-abl activity via phosphorylation may be associated with α-synuclein pathology found in Parkinson's disease and other neurodegenerative diseases. (Hum Mol Genet. 2013 Aug 15).

[0007] c-abl is a potential therapeutic target for α-synucleinopathy, Parkinson's disease, Alzheimer's disease, ALS, Lewy body dementia and MSA.

[0008] Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of familial Parkinson's disease with autosomal dominant inheritance. LRRK2 played an important role in neuronal cell death by directly phosphorylating apoptosis signal-regulated kinase 1 at Thr832 and activating kinase activity. The G2019S mutation in LRRK2 impairs the internalization of the dopamine D1 receptor, resulting in altered signal transduction. Parkinson's disease-associated LRRK2 mutations increase the expression of mitochondrial calcium uniporter, a mitochondrial calcium transporter, and subsequently promote dendritic and mitochondrial calcium uptake in cortical neurons and fibroblasts from patients with familial Parkinson's disease. (Frontiers in aging Neuroscience, 2018 April (10)) Accordingly, LRRK2 has emerged as a promising therapeutic target for disease-causing modification in Parkinson's disease.

ESSENCE OF THE INVENTION

[0009] According to the present description, there is provided a compound having inhibitory activity against c-abl LRRK2 kinases, a composition containing said compound, and a method useful for treating a neurodegenerative disease.

[0010] According to one embodiment, a compound of formula (I) and a pharmaceutically acceptable salt thereof are provided:

where R ¹ , R ² , R ³ , R ⁴ and R ⁵ are as defined below in this application.

[0011] According to another embodiment, the present disclosure provides pharmaceutical compositions comprising a therapeutically effective amount of a compound described herein and a pharmaceutically acceptable carrier.

[0012] According to another embodiment, the present disclosure provides methods for suppressing or treating a neurodegenerative disease comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds described herein.

DETAILED DESCRIPTION

[0013] The following description is illustrative only and is not intended to limit the present disclosure, application, or uses.

Definitions

[0014] General terms used in this description are defined in this application for the purpose of clarity.

[0015] In the present description, the terms “substituent,” “radical,” “group,” “moiety,” and “molecule moiety” are used interchangeably.

[0016] As used herein, the term "alkenyl" refers to a linear or branched hydrocarbon group with at least one site of unsaturation, i.e., a carbon-carbon sp2 double bond. In one embodiment, the alkenyl contains from 2 to 12 carbon atoms. In some embodiments, the alkenyl is a _C2 - _C10 alkenyl group or a _C2 - _{C6 alkenyl} group. Examples of an alkenyl group include, but are not limited to _, ethylene or vinyl (-CH= _CH2 ), allyl ( _-CH2CH = _CH2 ), _{cyclopentenyl} ( _-C5H7 ), and 5-hexenyl ( _{-CH2CH2CH2CH2CH} = _{CH2 )} .

[0017] As used herein, the term "alkoxy" refers to RO-, where R is alkyl. Non-limiting examples of alkoxy groups include methoxy, ethoxy, and propoxy.

[0018] As used herein, the term "alkoxyalkyl" refers to an alkyl moiety substituted with an alkoxy group. Examples of alkoxyalkyl groups include methoxymethyl, methoxyethyl, methoxypropyl, and ethoxyethyl.

[0019] As used herein, the term "alkoxycarbonyl" refers to ROC(O)-, wherein R is an alkyl group as defined herein. In various embodiments, R is a _C1 - _C10 alkyl group or a _C1 - _C6 alkyl group.

[0020] As used herein, the term "alkyl" refers to a straight or branched hydrocarbon group. In one embodiment, alkyl contains from 1 to 12 carbon atoms. In some embodiments, alkyl is a C ₁ -C ₁₀ alkyl group or a C ₁ -C ₆ alkyl group. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl. "Lower alkyl" means alkyl containing from 1 to 4 carbon atoms.

[0021] As used herein, the term "alkylamino" refers to an amino group substituted with one or more alkyl groups. "N-(alkyl)amino" is RNH- and "N,N-(alkyl) _2amino " is _R2N- , wherein the R groups are alkyl as defined herein and are the same or different. In various embodiments, R is a _C1 - _C10 alkyl group or a _C1 - _C6 alkyl group. Examples of alkylamino groups include methylamino, ethylamino, propylamino, butylamino, dimethylamino, diethylamino, and methylethylamino.

[0022] As used herein, the term "alkylaminoalkyl" refers to an alkyl moiety substituted with an alkylamino group, wherein alkylamino is as defined herein. Examples of alkylaminoalkyl groups include methylaminomethyl and ethylaminomethyl.

[0023] As used herein, the term "alkynyl" refers to a group having a straight or branched carbon chain with at least one site of unsaturation, i.e., a carbon-carbon triple bond sp. In one embodiment, an alkynyl contains from 2 to 12 carbon atoms. In some embodiments, an alkynyl is a C ₂ -C ₁₀ alkynyl group or a C ₂ -C ₆ alkynyl group. Examples of alkynyl groups include acetylenic (-C≡CH) and propargyl (-CH ₂ C≡CH).

[0024] As used herein, the term "aryl" refers to any monocyclic or bicyclic carbon ring of no more than 7 atoms in each ring, wherein at least one ring is aromatic, or an aromatic ring system of 5 to 14 carbon atoms that includes a carbocyclic aromatic group fused to a 5- or 6-membered cycloalkyl group. Representative examples of aryl groups include, but are not limited to, phenyl, tolyl, xylyl, naphthyl, tetrahydronaphthyl, anthracenyl, fluorenyl, indenyl, azulenyl, and indanyl. The carbocyclic aromatic group may be unsubstituted or optionally substituted.

[0025] As used herein, the term "cycloalkyl" refers to a non-cyclic hydrocarbon group containing at least one saturated or partially unsaturated ring structure and attached via a carbon atom in the ring. In various embodiments, it refers to a saturated or partially unsaturated _C3 - _C12 cyclic moiety, examples of which include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, and cyclooctyl. "Cycloalkyloxy" is RO-, where R is cycloalkyl.

[0026] As used herein, the terms "halogen" and "halo" refer to chlorine (-Cl), bromine (-Br), fluorine (-F), or iodine (-I). "Haloalkoxy" refers to an alkoxy group substituted with one or more halogen-containing groups, wherein examples of haloalkoxy groups include, but are not limited to, _-OCF3 , _-OCHF2 , and _-OCH2F . "Haloalkoxyalkyl" refers to an alkyl moiety substituted with a haloalkoxy group, wherein haloalkoxy is as defined herein. Examples of haloalkoxyalkyl groups include trifluoromethoxymethyl, trifluoroethoxymethyl, and trifluoromethoxyethyl. "Haloalkyl" refers to an alkyl moiety substituted with one or more halogen-containing groups. Examples of haloalkyl groups include _-CF3 and _-CHF2 .

[0027] As used herein, the term "heteroalkyl" refers to a straight or branched chain alkyl group having from 2 to 14 carbon atoms (in some embodiments, from 2 to 10 carbon atoms) in the chain, of which one or more have been replaced by a heteroatom selected from S, O, P, and N. Typical heteroalkyls include alkyl ethers, secondary and tertiary alkyl amines, amides, alkyl sulfides, and the like.

[0028] As used herein, the term "heterocyclyl" includes heteroaryls, as defined below, and refers to a saturated or partially unsaturated monocyclic, bicyclic, or tricyclic group containing from 2 to 14 ring carbon atoms and, in addition to the ring carbon atoms, from 1 to 4 heteroatoms selected from P, N, O, and S. In various embodiments, the heterocyclic group is attached to another moiety via a carbon atom or via a heteroatom and is optionally substituted at the carbon atom or heteroatom. Examples of heterocyclyl include azetidinyl, benzoimidazolyl, benzofuranyl, benzofurazanyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazolyl, carbolinyl, cinnolinyl, furanyl, imidazolyl, indolinyl, indolyl, indolazinyl, indazolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxetanyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridopyridinyl, pyridazinyl, pyridyl, pyrimidyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydroisoquinolinyl, tetrazolyl, tetrazolopyridyl, thiadiazolyl, thiazolyl, thienyl, triazolyl, azetidinyl, 1,4-dioxanyl, hexahydroazepinyl, piperazinyl, piperidinyl, pyridin-2-onyl, pyrrolidinyl, morpholinyl, thiomorpholinyl, dihydrobenzoimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyl, dihydroisooxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl, dihydrothienyl, dihydrotriazolyl, dihydroazetidinyl, methylenedioxybenzoyl, tetrahydrofuranyl and tetrahydrothienyl, and their N-oxides. "Heterocyclyloxy" is RO-, where R is heterocyclyl. "Heterocyclylthio" is RS-, where R is heterocyclyl.

[0029] As used herein, the term "3- or 4-membered heterocyclyl" refers to a monocyclic ring containing 3 or 4 ring atoms, wherein at least one ring atom is a heteroatom selected from the group consisting of N, O, and S. Non-limiting examples of 3- or 4-membered heterocyclyl include aziridinyl, 2H-azirinyl, oxiranyl, thiiranyl, azetidinyl, 2,3-dihydroazetyl, azetyl, 1,3-diazetidinyl, oxetanyl, 2H-oxetyl, thietanyl, and 2H-thiethyl.

[0030] As used herein, the term "heteroaryl" refers to a monocyclic, bicyclic, or tricyclic ring containing no more than 7 atoms in each ring, wherein at least one ring is aromatic and contains from 1 to 4 heteroatoms in the ring selected from the group consisting of N, O, and S. Non-limiting examples of heteroaryl include pyridyl, thienyl, furanyl, pyrimidyl, imidazolyl, pyranyl, pyrazolyl, thiazolyl, thiadiazolyl, isothiazolyl, oxazolyl, isoxazoyl, pyrrolyl, pyridazinyl, pyrazinyl, quinolinyl, isoquinolinyl, benzofuranyl, dibenzofuranyl, dibenzothiophenyl, benzothienyl, indolyl, benzothiazolyl, benzooxazolyl, benzimidazolyl, isoindolyl, benzotriazolyl, purinyl, thianaphthenyl and pyrazinyl. Attachment of the heteroaryl may be via an aromatic ring or, if the heteroaryl is bicyclic or tricyclic and one of the rings is not aromatic or contains no heteroatoms, via a non-aromatic ring or a ring containing no heteroatoms. The term "heteroaryl" is also intended to include the N-oxide derivative of any nitrogen-containing heteroaryl. "Heteroaryloxy" is RO-, where R is heteroaryl.

[0031] As used herein, the term "hydroxyalkoxy" refers to an alkoxy group substituted with a hydroxyl group (-OH), wherein alkoxy is as defined herein. An example of hydroxyalkoxy is hydroxyethoxy.

[0032] As used herein, the term "hydroxyalkyl" refers to a linear or branched monovalent _C1 - _C10 hydrocarbon group substituted with at least one hydroxy group, wherein examples of hydroxyalkyl groups include, but are not limited to, hydroxymethyl, hydroxyethyl, hydroxypropyl, and hydroxybutyl.

[0033] As used herein, the term "pharmaceutically acceptable" means suitable for use in pharmaceutical preparations, generally regarded as safe for such use, officially approved by a regulatory agency of a national or state government for such use, or included in the United States Pharmacopeia or other generally recognized pharmacopeia for use in animals, and especially in humans.

[0034] As used herein, the term "pharmaceutically acceptable carrier" refers to a diluent, adjuvant, excipient, or carrier or other ingredient that is pharmaceutically acceptable and with which a compound of the present invention is administered.

[0035] As used herein, the term "pharmaceutically acceptable salt" refers to a salt that can enhance a desired pharmacological activity. Examples of pharmaceutically acceptable salts include acid addition salts formed with inorganic or organic acids, metal salts, and amine salts. Examples of acid addition salts formed with inorganic acids include salts of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of acid addition salts formed with organic acids include salts of acids such as acetic acid, propionic acid, hexanoic acid, heptanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, o-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, 4-Methylbicyclo[2.2.2]oct-2-ene-1-carboxylic acid, glucoheptonic acid, 4,4'-methylenebis(3-hydroxy-2-naphthoic) acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfonic acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and muconic acid. Examples of metal salts include salts with sodium, potassium, calcium, magnesium, aluminum, iron, and zinc ions. Examples of amine salts include salts with ammonia and organic nitrogenous bases strong enough to form salts with carboxylic acids.

[0036] As used herein, the term "therapeutically effective amount" when used with respect to a compound of the present invention is intended to mean an amount of the compound that is sufficient to ameliorate, alleviate, stabilize, modify the course of, slow down, or delay the progression of a disorder or disease state or the symptoms of a disorder or disease state. In one embodiment, the method of the present invention comprises administering combinations of compounds. In such cases, a "therapeutically effective amount" is an amount of a compound of the present invention in a combination that is sufficient to produce the intended biological effect.

[0037] As used herein, the terms "treating" or "treating" mean improving or altering the progression or severity of a disease or disorder, or improving or altering one or more symptoms or side effects of such a disease or disorder. The terms "treating" or "treating" as used herein also mean suppressing or blocking, such as by delaying, arresting, restraining, hindering, or impeding the progression of a system, condition, or disease state or disorder. For the purposes of the present invention, "treating" or "treating" further means an approach to achieving beneficial or desired clinical results, wherein "beneficial or desired clinical results" include, but are not limited to, alleviation of a symptom, reduction in the severity of a disorder or disease, stabilization (i.e., not worsening) of a disease state or disorder, delay or slowing of a disease state or disorder, amelioration or alleviation of a disease state or disorder, and remission of a disease or disorder, whether partial or complete.

[0038] According to another embodiment, the compounds of formula (I) are used to modulate the activity of protein kinase c-abl.

[0039] As used herein, the term "modulating" or "modulation" refers to a change in the catalytic activity of a protein kinase. In particular, modulation refers to the activation or inhibition of the catalytic activity of a protein kinase depending on the concentration of a compound or salt to which the protein kinase is exposed, or more preferably to the inhibition of the catalytic activity of a protein kinase. The term "catalytic activity" as used herein refers to the rate of phosphorylation of tyrosine, serine, or threonine by a protein kinase, directly or indirectly.

[0040] The three major classes into which pharmacological inhibitors of kinase activity are classified are: (1) type I, or ATP-competitive "DFG-in" inhibitors, which directly compete with ATP at the ATP binding site (i.e., the Src and Abl inhibitor dasatinib, (2) type II, or ATP-competitive "DFG-out" inhibitors, which, in addition to binding to the ATP binding site, also utilize an adjacent hydrophobic binding site that is only accessible when the kinase is in the inactivated configuration (i.e., the activation loop is oriented in a conformation that blocks substrate binding) (i.e., imatinib, nilotinib), and (3) ATP-noncompetitive inhibitors, which bind at sites that affect kinase activity located outside of the ATP binding site (i.e., GNF-2).

[0041] As used herein, the phrase "compound(s) according to this/the present disclosure" includes any compound(s) of Formula (I), as well as clathrates, hydrates, solvates, or polymorphs thereof. And even if the term "compound(s) according to this disclosure" does not refer to a pharmaceutically acceptable salt thereof, the term includes salts thereof. In one embodiment, the compounds according to this disclosure include stereochemically pure compounds, such as those that are substantially free (e.g., greater than 85% ee, greater than 90% ee, greater than 95% ee, greater than 97% ee, or greater than 99% ee) of other stereoisomers. That is, if the compounds of Formula (I) according to this disclosure or their salts are tautomeric isomers and/or stereoisomers (e.g., geometric isomers and conformational isomers), such isolated isomers and mixtures thereof are also included within the scope of this disclosure. If the compounds according to the present description or their salts contain an asymmetric carbon atom in their structures, their active optical isomers and their racemic mixtures are also included within the scope of the present description.

[0042] As used herein, the term "polymorph" refers to solid crystalline forms of a compound as described herein or a complex thereof. Different polymorphs of the same compound may exhibit different physical, chemical, and/or spectroscopic properties. Different physical properties include, but are not limited to, stability (e.g., when exposed to heat or light), compressibility and density (which are important in formulation and product manufacturing), and dissolution rates (which may affect bioavailability). Differences in stability may result from changes in chemical reactivity (e.g., differential oxidation such that a dosage form discolors more quickly when composed of one polymorph than when composed of another polymorph) or mechanical properties (e.g., tablets disintegrate upon storage as a kinematically favored polymorph converts to a thermodynamically more stable polymorph), or both (e.g., tablets of one polymorph are more susceptible to disintegration in high humidity). Different physical properties of polymorphs may affect their processing. For example, one polymorph may be more likely to form solvates, or may be more difficult to filter or wash free of impurities than another, for example due to its shape or particle size distribution.

[0043] As used herein, the term "solvate" means a compound or a salt thereof as described herein that further comprises a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. Preferred solvents are volatile, non-toxic, and/or acceptable for administration to humans in trace amounts.

[0044] As used herein, the term "hydrate" means a compound or salt thereof as described herein that further comprises a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces.

[0045] As used herein, the term "clathrate" means a compound or a salt thereof in a form with a crystal lattice that contains spaces (e.g., channels) in which a guest molecule (e.g., a solvent or water) is trapped within.

Connections according to this description

[0046] According to the present description, compounds according to formula (I) are provided:

[0047] or a pharmaceutically acceptable salt thereof, wherein:

[0048] R ¹ is cyclopropyl, cyclobutyl, or 4-membered heterocyclyl, wherein R ¹ is optionally substituted with one or more groups selected from the group consisting of halogen, alkyl, hydroxyalkyl, haloalkyl, and monoalkylaminoalkyl,

[0049] R ² and R ³ are independently -H, halogen, alkyl, alkoxy, -CF ₃ , -CHF ₂ , -CH ₂ F or -OCF ₃ ,

[0050] R ⁴ is aryl, heteroaryl, cycloalkyl, heterocyclyl or heteroalkyl, wherein R ⁴ is optionally substituted with one or more groups selected from the group consisting of halogen, hydroxyl, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, hydroxyalkyl, dialkylaminoalkyl, trimethylsilylethoxymethyl, -CH ₂ NHC(O)CH ₃ , -NO ₂ , -NR _a R _b , -NR _a C(=O)R _b , -NR _a C(=O)NR _a R _b , -NR _a C(=O)OR _b , -OR _a , -CN, -C(=O)R _a , -C(=O)OR _a , -C(=O)NR _a R _b , -OC(=O)R _a , -OC(=O)OR _a , -OC(=O)NR _a R _b , -SR _a . azetidinyl, oxetanyl, tetrahydrofuranyl, furanyl, pyrrolidinyl, pyrrolyl, pyrazolyl, thiophenyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, furazanyl, oxadiazolyl, thiadiazolyl, phenyl, tetrahydropyranyl, pyranyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl a, wherein R _a and R _b independently represent -H, halogen, amino, alkyl or haloalkyl, and

[0051] R ⁵ is H, halogen or alkyl.

[0052] According to some embodiments, R ¹ is cyclopropyl or cyclobutyl, wherein R ¹ is optionally substituted with one or more groups selected from the group consisting of halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ hydroxyalkyl, and C ₁ -C ₃ haloalkyl; R ² and R ³ are independently -H, halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ alkoxy, -CF ₃ , -CHF ₂ , -CH ₂ F, or -OCF ₃ ; R ⁴ is aryl, heteroaryl, cycloalkyl or heterocyclyl, wherein R ⁴ is optionally substituted with one or more groups selected from the group consisting of halogen, hydroxyl, C ₁ -C ₃ alkyl, C ₂ -C ₃ alkenyl, C ₂ -C ₃ alkynyl, C ₃ -C ₄ cycloalkyl, C ₁ -C ₃ haloalkyl, mono- C ₁ -C ₃ alkylamino, di- C ₁ -C ₃ alkylamino, -NO ₂ , -NR _a R _b , -NR _a C(=O)R _b , -NR _a C(=O)NR _a R _b , -NR _a C(=O)OR _b , -OR _a , -CN, -C(=O)R _a , -C(=O)OR _a , -C(=O)NR _a R _b , -OC(=O)R _a , -OC(=O)OR _a , -OC(=O)NR _a R _b , -SR _a , azetidinyl, oxetanyl, tetrahydrofuranyl, furanyl, pyrrolidinyl, pyrrolyl, pyrazolyl, thiophenyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, furazanyl, oxadiazolyl, thiadiazolyl, phenyl, tetrahydropyranyl, pyranyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl; wherein R _a and R _b are independently -H, halogen, amino, C ₁ -C ₃ alkyl or C ₁ -C ₃ haloalkyl; and R ⁵ is H, F-, Cl-, Br- or methyl.

[0053] In various embodiments, R ¹ is cyclopropyl or cyclobutyl, wherein R ¹ is optionally substituted with one or more groups selected from the group consisting of halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ hydroxyalkyl, and C ₁ -C ₃ haloalkyl. In particular embodiments, R ¹ is cyclopropyl, fluorocyclopropyl, hydroxycyclopropyl, hydroxymethyl cyclopropyl, difluorocyclopropyl, methylaminomethylcyclopropyl, cyclobutyl, fluorocyclobutyl, or difluorocyclobutyl. In other particular embodiments, R ¹ is cyclopropyl, fluorocyclopropyl, cyclobutyl, or fluorocyclobutyl.

[0054] In certain other embodiments, R ¹ is a 4-membered heterocyclyl that is optionally substituted with one or more groups selected from the group consisting of halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ hydroxyalkyl, and C ₁ -C ₃ haloalkyl. In particular embodiments, the 4-membered heterocyclyl is selected from the group consisting of aziridinyl, 2H-azirinyl, oxiranyl, thiiranyl, azetidinyl, 2,3-dihydroazetyl, azetyl, 1,3-diazetidinyl, oxetanyl, 2H-oxetyl, thietanyl, and 2H-thiethyl.

[0055] In some embodiments, R2 and R3 are independently -H, methyl, or fluoro.

[0056] According to some embodiments, R ⁴ is phenyl, pyridinyl, pyrimidinyl, indolinyl, pyrazolyl, thiazolyl, oxoindolinyl, pyrrolopyridinyl, pyrazolyl, pyrazolopyridinyl, oxodihydropyrrolopyridinyl, oxodihydrobenzothiazolyl, benzoimidazolyl, benzooxazolyl, benzothiazolyl, thiophenyl, pyrrolopyridinyl, or isothiazolyl, wherein R ⁴ is optionally substituted with one or more groups selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, amino, cyano, acetyl, hydroxy, and haloalkyl. In certain embodiments, R ⁴ is fluoromethylphenyl, fluorohydroxymethylphenyl, chlorohydroxymethylphenyl, methylhydroxymethylphenyl, difluorohydroxymethylphenyl, chlorofluorohydroxymethylphenyl, fluoromethylhydroxymethylphenyl, chloromethylphenyl, dimethylphenyl, acetamidomethylphenyl, hydroxymethylphenyl, hydroxypropanylmethylphenyl, methylpropenylphenyl, methylpyridinylethynylphenyl, methylpyrrolylphenyl, methylthiazolylphenyl, imidazolylmethylphenyl, cyanomethylphenyl, methylpyrazolylphenyl, ethynylmethylphenyl, methylpyridinyl, fluoromethylmethylaminophenyl, dimethylpyridinyl, fluoromethylpyridinyl, fluoromethylmethylpyridinyl, cyanopyridinyl, trifluoromethylmethylpyridinyl, hydroxymethylpyridinyl, hydroxymethylmethylpyridinyl, hydroxyethylmethylpyridinyl, chloromethylpyridinyl, aminopyridinyl, acetylmethylpyridinyl, aminodimethylpyridinyl, hydroxyethylmethylpyridinyl, methylindolyl, methyloxoindolyl, trimethylsilylethoxymethylindolyl, acetylmethylindolinyl, methylpyrimidinyl, dimethylpyrimidinyl, trifluoromethylpyrimidinyl, pyrazolyl, methylthiazolyl, methyloxoindolinyl, pyrrolopyridinyl, methylpyrrolopyridinyl, methyltetrahydropyranyl, methylpyrazolyl, methyloxodihydrodibenzothiazolyl, pyrazolopyridinyl, oxodihydropyrrolopyridinyl, methylisothiazolyl, chloromethylisothiazolyl, dimethylisothiazolyl or fluoromethylindolyl. In certain embodiments, R ⁴ is fluoromethylphenyl, fluorohydroxymethylphenyl, chlorohydroxymethylphenyl, methylhydroxymethylphenyl, difluorohydroxymethylphenyl, chlorofluorohydroxymethylphenyl, fluoromethylhydroxymethylphenyl, chloromethylphenyl, dimethylphenyl, acetamidomethylphenyl, hydroxylmethylphenyl, methylpropenylphenyl, ethynylmethylphenyl, fluoromethylmethylaminophenyl, fluorohydroxylmethylphenyl, methylmethylaminophenyl, methylpyrrolylphenyl, methylthiazolylphenyl, cyanomethylphenyl, imidazolylmethylphenyl, methylpyridinyl, chloromethylpyridinyl, fluoromethylpyridinyl, fluoromethylmethylpyridinyl, dimethylpyridinyl, aminopyridinyl, aminodimethylpyridinyl, methoxypyridinyl, acetylmethylpyridinyl, hydroxymethylpyridinyl, hydroxymethylmethylpyridinyl, hydroxyethylmethylpyridinyl, cyanopyridinyl, trifluoromethylpyridinyl, methylthiophenyl, methylindolinyl, methylpyrimidinyl, dimethylpyrimidinyl, pyrazolyl, methylpyrazolyl, methylindolinyl, methyloxoindolinyl, pyrrolopyridinyl, methylpyrrolopyridinyl, methylpyrrolyl, pyrazolopyridinyl, dihydropyrrolopyridinyl, methylisothiazolyl, dimethylisothiazolyl, methylindazolyl or methylbenzothiazolyl. In certain embodiments, R ⁴ is pyridinyl or phenyl, which are characterized by one or more substitutions selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, halogen, hydroxyl, hydroxyalkyl, halogenalkyl, cyano, amino, alkoxy, alkoxyalkoxyalkyl, alkoxyalkyl, and haloalkoxy. In some certain embodiments, R4 is selected from the group consisting of:

[0057] In some embodiments, R ¹ is cyclopropyl, fluorocyclopropyl, difluorocyclopropyl, cyclobutyl, fluorocyclobutyl, or difluorocyclobutyl; R ² and R ³ are independently -H, methyl, or fluoro; and R ⁴ is fluoromethylphenyl, fluorohydroxymethylphenyl, chloromethylphenyl, dimethylphenyl, acetamidomethylphenyl, hydroxylmethylphenyl, methylpropenylphenyl, ethynylmethylphenyl, fluoromethylmethylaminophenyl, methylpyrrolylphenyl, methylthiazolylphenyl, cyanomethylphenyl, imidazolylmethylphenyl, methylpyridinyl, chloromethylpyridinyl, fluoromethylpyridinyl, fluoromethylmethylpyridinyl, dimethylpyridinyl, aminopyridinyl, aminodimethylpyridinyl, methoxypyridinyl, acetylmethylpyridinyl, hydroxymethylpyridinyl, hydroxymethylmethylpyridinyl, hydroxyethylmethylpyridinyl, cyanopyridinyl, trifluoromethylpyridinyl, methylthiophenyl, methyl indolinyl, methylpyrimidinyl, dimethylpyrimidinyl, pyrazolyl, methyl pyrazolyl, methylindolinyl, methyloxoindolinyl, pyrrolopyridinyl, methylpyrrolopyridinyl, methylpyrrolyl, pyrazolopyridinyl, dihydropyrrolopyridinyl, methylisothiazolyl, dimethylisothiazolyl, methylindazolyl or methyldibenzothiazolyl.

[0058] The compounds described in this application have c-abl inhibitory activity and c-abl selectivity. The compounds are effective for the treatment of neurodegenerative diseases.

[0059] According to one embodiment, R ¹ is cyclopropyl, fluorocyclopropyl, cyclobutyl, fluorocyclobutyl, or difluorocyclobutyl; R ² and R ³ are -H; R ⁴ is phenyl, pyridinyl, pyrazolyl, pyrrolopyridinyl, indolinyl, oxoindolinyl, benzothiazolyl, benzoimidazolyl, benzooxazolyl or thiophenyl, wherein R ⁴ is optionally substituted with one or more groups selected from the group consisting of halogen, hydroxyl, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, alkoxyalkyl, alkoxyalkoxy, alkylaminoalkyl, -NR _a R _b , -NR _a C(=O)R _b , -OR ^a , -SR ^a , -CN, -C(=O)R ^a , -C(=O)OR _a , -C(=O)NR _a R _b , -OC(=O)R _a , furanyl or pyrrolyl; wherein R _a and R _b independently represent -H, halogen, amino, alkyl or haloalkyl; and R ⁵ represents -H, halogen or C ₁ -C ₃ alkyl.

[0060] According to various embodiments, R ¹ is fluorocyclopropyl, wherein such compounds include, but are not limited to, the following compounds and their salts:

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(3-chloro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(3-chloro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(3-methyl-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(3-chloro-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-fluoro-4-methylpyridin-3-yl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

methyl 3-(2-(2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-4-methylbenzoate;

2-fluoro-N-(6-(5-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-methyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(3-chloro-6-(5-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(5-cyano-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-methyl-1H-pyrazol-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(4-chloropyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(5-amino-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-methyl-5-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

N-(6-(5-acetamido-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(5-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-methyl-5-(1H-pyrazol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(4-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2,4-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(3-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2,5-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-oxoindolin-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

N-(6-(4-cyanopyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-fluoro-2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-fluoro-2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-methyl-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-methylthiophen-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(3,4-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3,6-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(4-chloro-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-methoxypyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(6-amino-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(5-amino-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-methyl-2-oxoindolin-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2-chloro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

2-fluoro-N-(6-(2-oxo-2,3-dihydrobenzo[d]thiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

N-(6-(6-aminopyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-methyl-5-(1H-pyrazol-1-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(3-bromo-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-fluoro-2-methoxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-cyano-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

N-(6-(2-chloro-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

N-(6-(2,3-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

N-(6-(3,5-dimethyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-(methoxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-(furan-2-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-(methylthio)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(6-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-acetyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

N-(6-(6-(dimethylamino)-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-(aminomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

N-(6-(2-(acetamidomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

2,2-difluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-((methylamino)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-((isopropylamino)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-((2-methoxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-((2-hydroxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-((dimethylamino)methyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

N-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

2-fluoro-N-(6-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

2-fluoro-N-(6-(o-tolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-hydroxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-amino-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

2-fluoro-N-(6-(5-methyl-1H-indol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(6-methyl-1H-indol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-(dimethylamino)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-ethyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-cyclopropyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-methylbenzo[d]oxazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

2-fluoro-N-(6-(6-methylbenzo[d]thiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-methylbenzo[d]oxazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(7-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-isopropylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-methyl-3-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-fluoro-2-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-fluoro-2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2-ethyl-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide

N-(6-(4-acetyl-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(2-chloro-3,4-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(2-chloro-3,6-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(furan-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(thiophen-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

2-fluoro-N-(6-(thiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

2-fluoro-N-(6-(3-methylisothiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-methylthiazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(8-(difluoromethyl)-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-8-(fluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(8-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(7-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-fluoro-2-methylphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(8-(difluoromethyl)-6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-fluoro-2-methylphenyl)-8-(fluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(8-fluoro-6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(7-fluoro-6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-fluoro-2-methylphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(8-(difluoromethyl)-6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-fluoro-2-methylphenyl)-8-(fluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(8-fluoro-6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(7-fluoro-6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(8-(difluoromethyl)-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-8-(fluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(8-fluoro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(7-fluoro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(4-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(4-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(3-chloro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarbosamide;

N-(6-(3-chloro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(4-chloro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(4-chloro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(5-chloro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(5-chloro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(2-chloro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-chloro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(2-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2-(hydroxymethyl)-5-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-(hydroxymethyl)-5-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2-(hydroxymethyl)-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-(hydroxymethyl)-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(3,4-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(3,4-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(4,5-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(4,5-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(2,3-difluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2,3-difluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3,6-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(3,6-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3-chloro-4-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(3-chloro-4-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(4-chloro-5-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(4-chloro-5-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3-chloro-2-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(3-chloro-2-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(6-chloro-3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(6-chloro-3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(4-fluoro-2-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(4-fluoro-2-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-fluoro-2-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-fluoro-2-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2-fluoro-6-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-fluoro-6-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(3-fluoro-2-(hydroxymethyl)-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-(hydroxymethyl)-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(4-chloro-3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(4-chloro-3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3-fluoro-2-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(3,5-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(3,5-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(5-chloro-3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(5-chloro-3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3-fluoro-2-(hydroxymethyl)-5-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-(hydroxymethyl)-5-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-chloro-4-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(5-chloro-4-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3,4-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(3,4-difluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(2,4-difluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2,4-difluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(2-chloro-4-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-chloro-4-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(4-fluoro-2-(hydroxymethyl)-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(4-fluoro-2-(hydroxymethyl)-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2-chloro-3-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(2-chloro-3-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3,5-difluoro-2-(hydroxymethyl)-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(3,5-difluoro-2-(hydroxymethyl)-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3-chloro-5-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-(6-(3-chloro-5-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-6-(5-fluoro-2-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-fluoro-2-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-6-(5-fluoro-2-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-fluoro-2-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N(6-(3-chloro-6-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-6-(3-chloro-6-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-6-(6-fluoro-2-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(6-fluoro-2-(hydroxymethyl)-3-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-6-(4-chloro-2-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

N-6-(4-chloro-2-fluoro-6-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-6-(2-fluoro-6-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-fluoro-6-(hydroxymethyl)-4-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N(6-(5-(hydroxymethyl)-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(4-(hydroxymethyl)-1H-pyrazol-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(4-(hydroxymethyl)-1H-pyrazol-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N(6-(2-(hydroxymethyl)-5-(1H-pyrazol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-(hydroxymethyl)-5-(1H-pyrazol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-6-(2-(hydroxymethyl)-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-(hydroxymethyl)-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(3-(hydroxymethyl)thiophen-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-(hydroxymethyl)thiophen-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

N-(6-(5-(hydroxymethyl)-2-oxoindolin-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)-2-oxoindolin-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

N-(6-(3-(hydroxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-(hydroxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1- carboxamide;

N-(6-(2-(hydroxymethyl)-5-(1H-pyrazol-1-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(2-(hydroxymethyl)-5-(1H-pyrazol-1-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-(hydroxymethyl)-3-methyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)-3-methyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(4-(hydroxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(4-(hydroxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1- carboxamide;

N-(6-(5-(hydroxymethyl)-1H-indol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)-1H-indol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(6-(hydroxymethyl)-1H-indol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(6-(hydroxymethyl)-1H-indol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-(hydroxymethyl)-1H-benzo[d]imidazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)-1H-benzo[d]imidazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-(hydroxymethyl)benzo[d]oxazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)benzo[d]oxazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-(hydroxymethyl)-1H-benzo[d]imidazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)-1H-benzo[d]imidazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-(hydroxymethyl)benzo[d]thiazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)benzo[d]thiazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-(hydroxymethyl)benzo[d]oxazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)benzo[d]oxazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-(hydroxymethyl)benzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-(hydroxymethyl)benzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(7-(hydroxymethyl)benzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(7-(hydroxymethyl)benzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-(hydroxymethyl)thiazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide and

2-fluoro-N-(6-(5-(hydroxymethyl)thiazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide.

[0061] In one embodiment, R ¹ is fluorocyclopropyl; R ² and R ³ are -H; R ⁴ is phenyl, indolinyl, oxoindolinyl, or benzothiazolyl, wherein R ⁴ is optionally substituted with one or more groups selected from the group consisting of halogen, hydroxyl, alkyl, alkylamino, and pyrrolyl; and R ⁵ is -H, halogen, or C ₁ -C ₃ alkyl. In various embodiments, such compounds include, but are not limited to, the following compounds and salts thereof:

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(3-chloro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(3-chloro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-methyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(3-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-methyl-5-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

N-(6-(2,4-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(3-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2,5-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(2-oxoindolin-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

2-fluoro-N-(6-(2-methyl-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

2-fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-fluoro-N-(6-(5-methyl-2-oxoindolin-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(3-bromo-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

N-(6-(3,5-dimethyl-1 H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(5-methyl-1H-indol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

2-fluoro-N-(6-(6-methyl-1H-indol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide and

2-fluoro-N-(6-(5-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridine-2-methyl)cyclopropanecarboxamide.

[0062] According to one embodiment, the compound of formula (I) is selected from compounds according to formula (II) and pharmaceutically acceptable salts thereof:

[0063] wherein R ⁶ is selected from the group consisting of halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ hydroxyalkyl and C ₁ -C ₃ haloalkyl, and R ² , R ³ , R ⁴ and R ⁵ are as defined above.

[0064] In one embodiment, the compound of formula (I) is a compound in which R ¹ is cyclopropyl. In one embodiment, the compound of formula (I) is N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide or a salt thereof.

[0065] According to another embodiment, the compound of formula (I) is a compound wherein R ¹ is cyclobutyl which is optionally substituted with one or more groups selected from the group consisting of halogen, alkyl, hydroxyalkyl, haloalkyl, and monoalkylaminoalkyl; and R ² , R ³ , R ⁴ and R ⁵ are as defined above. According to various embodiments, the compound of formula (I) is selected from the group consisting of the following compounds and salts thereof:

N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclobutanecarboxamide;

3-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclobutanecarboxamide and

3,3-difluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclobutanecarboxamide.

[0066] The compounds of the present disclosure include stereoisomers of the compounds described herein. In some embodiments, the compounds are stereochemically pure compounds, such as those that are substantially free (e.g., greater than 85% ee, greater than 90% ee, greater than 95% ee, greater than 97% ee, or greater than 99% ee) of other stereoisomers. Examples of such stereoisomers include, but are not limited to,

where R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are as defined above.

[0067] According to one embodiment, the compound of formula (I) is selected from compounds according to formula (III) and pharmaceutically acceptable salts thereof:

[0068] wherein R ⁶ is selected from the group consisting of halogen, C ₁ -C ₃ alkyl, C ₁ -C ₃ hydroxyalkyl and C ₁ -C ₃ haloalkyl, and R ² , R ³ , R ⁴ and R ⁵ are as defined above. Table 1 provides representative compounds having the stereochemistry of formula (III). Examples of the compound of formula (III) include, but are not limited to, the following compounds and their salts: (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(3-chloro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(3-chloro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-

fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(3-methyl-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(3-chloro-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-3-methyl imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-3-methyl imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(5-fluoro-4-methylpyridin-3-yl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

methyl 3-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-4-methylbenzoate;

(1S,2S)-2-fluoro-N-(6-(5-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(3-chloro-6-(5-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(5-cyano-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(4-methyl-1H-pyrazol-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(3-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(6-(4-chloropyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(5-amino-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-methyl-5-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(6-(5-acetamido-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(5-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide ;

(1S,2S)-2-fluoro-N-(6-(2-methyl-5-(1 H-pyrazol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(6-(4-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(3-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

(1S,2S)-N-(6-(2,4-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(3-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(6-(2,5-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-oxoindolin-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

(1S,2S)-N-(6-(4-cyanopyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(4-fluoro-2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(4-fluoro-2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-methyl-5-(1 H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(3-methylthiophen-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(6-(2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(6-(3,4-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(3,6-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(4-chloro-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(4-methoxypyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

(1S,2S)-N-(6-(6-amino-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-N-(6-(5-amino-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(5-methyl-2-oxoindolin-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide;

(1S,2S)-N-(6-(2-chloro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-oxo-2,3-dihydrobenzo[d]thiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan- 1-carboxamide;

(1S,2S)-N-(6-(6-aminopyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-methyl-5-(1H-pyrazol-1-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N-(3-bromo-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methoxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-N-(6-(2-cyano-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-N-(6-(2-chloro-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-N-(6-(2,3-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-N-(6-(3,5-dimethyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(methoxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(furan-2-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(methylthio)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(6-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-N-(6-(2-acetyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-N-(6-(6-(dimethylamino)-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide (1S,2S)-N-(6-(2-(aminomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-N-(6-(2-(acetamidomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((methylamino)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((isopropylamino)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((2-methoxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((2-hydroxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-N-(6-(2-((dimethylamino)methyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-N-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-N-(6-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(o-tolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-hydroxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-N-(6-(2-amino-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(6-methyl-1H-indol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-N-(6-(2-(dimethylamino)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-N-(6-(2-ethyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-N-(6-(2-cyclopropyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]oxazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(6-methylbenzo[d]thiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]oxazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(6-(7-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide and

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-isopropylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide.

[0069] According to specific embodiments, the compound of formula (I) is selected from the group consisting of the following compounds and their salts:

(1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-methyl-5-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-N(6-(2,5-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(2-methyl-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(6-(6-methyl-1H-indol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide and

(1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide.

[0070] Provided herein are pharmaceutically acceptable salts of the compounds described above. Pharmaceutically acceptable salts are as defined above in the definitions section. In some embodiments, the salt is a hydrochloric acid salt, a tartaric acid salt, a phosphoric acid salt, or a maleic acid salt.

[0071] Treatment methods

[0072] The present disclosure further provides methods for treating a neurodegenerative disease or disorder in a subject having or predisposed to such disease or disorder by administering to the subject a therapeutically effective amount of one or more compounds as described above. In one embodiment, the treatment is a prophylactic treatment. In another embodiment, the treatment is a palliative treatment. In another embodiment, the treatment is a restorative treatment.

[0073] 1. Diseases or conditions

[0074] A compound of the present disclosure for inhibiting c-abl and/or LRRK2 activity is useful for treating or preventing a neurodegenerative disease or disorder. The compound can be used to inhibit or reduce the activity of c-abl and/or LRRK2 kinases, as well as to treat a neurodegenerative disease or disorder or to prevent an exacerbation of such a disease. Thus, according to the present disclosure, there is provided a method for inhibiting or reducing the activity of c-abl and/or LRRK2 in a cell, which comprises contacting the cell with an effective amount of a compound of the present disclosure. In one embodiment, such a cell is in a subject (e.g., in patients with Alzheimer's disease). In another embodiment, there is provided a medical use for treating or preventing a neurodegenerative disease or disorder in a subject using a compound of the present disclosure. The method according to the present disclosure comprises administering to a subject in need of treatment or prevention of a neurodegenerative disease or disorder, a pharmaceutical composition comprising a therapeutically or prophylactically effective amount of a c-abl and/or LRRK2 inhibitor. The neurodegenerative disease or disorder includes, but is not limited to, α-synucleopathy, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy (MSA), Alzheimer's disease or amyotrophic lateral sclerosis (ALS). The medical use for the present disclosure also includes inflammatory disease, inflammatory bowel disease, Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriasis, contact dermatitis or a delayed-type hypersensitivity reaction.

[0075] 2. Subjects

[0076] Suitable subjects to be treated according to the present disclosure include mammalian subjects. Mammals according to the present disclosure include, but are not limited to, humans, canines, felines, bovines, caprines, equines, ovines, pigs, rodents, lagomorphs, primates, and the like, and also include mammals in utero. Subjects can be of either sex and at any stage of development. In one embodiment, a suitable subject to be treated according to the present disclosure is a human.

[0077] 3. Administration and dosage

[0078] The compounds of the present disclosure are generally administered in a therapeutically effective amount. The compounds of the present disclosure can be administered by any suitable route in the form of a pharmaceutical composition adapted to such route and in a dose effective for the intended treatment. An effective dosage is generally in the range of from about 0.001 to about 100 mg per kg of body weight per day, preferably from about 0.01 to about 50 mg/kg/day in single or divided doses. Depending on the age, species, and disease or condition being treated, dosage levels below the lower end of this range may be appropriate. In other cases, even higher doses can be used without deleterious side effects. Higher doses can also be divided into several smaller doses for administration throughout the day. Methods for determining appropriate dosages are well known in the art to which the present disclosure pertains. For example, Remington: The Science and Practice of Pharmacy, Mack Publishing Co., 20th ed., 2000.

[0079] Pharmaceutical compositions, dosage forms and routes of administration

[0080] For the treatment of the diseases or conditions mentioned above, the compounds described in this application, or pharmaceutically acceptable salts thereof, can be administered as follows:

[0081] Oral administration

[0082] The compounds of the present disclosure may be administered orally, including by ingestion such that the compound enters the gastrointestinal tract or is absorbed into the bloodstream directly from the oral cavity (e.g., buccal or sublingual administration).

[0083] Suitable compositions for oral administration include solid, liquid, gel or powder compositions and are presented in a dosage form such as a tablet, lozenge, capsule, granule or powder.

[0084] Compositions for oral administration may be formulated to be immediate or modified release, including delayed or sustained release, optionally with an enteric coating.

[0085] Liquid formulations may include solutions, syrups, and suspensions that can be used in soft or hard capsules. Such formulations may include a pharmaceutically acceptable carrier, such as water, ethanol, polyethyleneglycol, cellulose, or oil. The formulation may also include one or more emulsifying agents and/or suspending agents.

[0086] In a tablet dosage form, the amount of drug present may be from about 0.05% to about 95% by weight, more typically from about 2% to about 50% by weight of the dosage form. In addition, the tablets may contain a disintegrant comprising from about 0.5% to about 35% by weight, more typically from about 2% to about 25% of the dosage form. Examples of disintegrants include, but are not limited to, lactose, starch, sodium starch glycolate, crospovidone, croscarmellose sodium, maltodextrin, or mixtures thereof.

[0087] Suitable lubricants for use in tablets may be present in amounts from about 0.1% to about 5% by weight and include, but are not limited to, talc, silicon dioxide, stearic acid, calcium, zinc or magnesium stearate, sodium stearyl fumarate and the like.

[0088] Suitable binders for use in tablets include, but are not limited to, gelatin, polyethylene glycol, sugars, gums, starch, polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and the like. Suitable diluents for use in tablets include, but are not limited to, mannitol, xylitol, lactose, dextrose, sucrose, sorbitol, microcrystalline cellulose, and starch.

[0089] Suitable solubilizers for use in tablets may be present in amounts from about 0.1% to about 3% by weight and include, but are not limited to, polysorbates, sodium lauryl sulfate, sodium dodecyl sulfate, propylene carbonate, diethylene glycol monoethyl ether, dimethyl isosorbide, polyethylene glycol, castor oil (natural or hydrogenated), HCOR™ (Nikkol), oleyl ether, Gelucire™, mono/diglyceride of caprylic/caprylic acid, sorbitan esters of fatty acids, and Solutol HS™.

[0090] Parenteral administration

[0091] The compounds of the present disclosure can be administered directly into the bloodstream, muscles, or internal organs. Suitable routes for parenteral administration include intravenous, intramuscular, subcutaneous, intraarterial, intraperitoneal, intrathecal, intracranial, and the like. Suitable devices for parenteral administration include injectors (including needle and needle-free type injectors) and infusion methods.

[0092] Compositions for parenteral administration can be prepared with immediate or modified release, including delayed or sustained release. Most parenteral formulations are aqueous solutions containing excipients including salts, buffering agents and isotonic agents. Parenteral formulations can also be prepared in dehydrated form (e.g., by lyophilization) or as sterile non-aqueous solutions. These formulations can be used with a suitable vehicle, such as sterile water. Solubility enhancing agents can also be used in the preparation of parenteral solutions.

[0093] Transdermal administration

[0094] The compounds of the present disclosure can be applied topically to the skin or administered transdermally. Topical formulations can include lotions, solutions, creams, gels, hydrogels, ointments, foams, implants, patches, and the like. Pharmaceutically acceptable carriers for topical formulations can include water, alcohol, mineral oil, glycerin, polyethylene glycol, and the like. Topical application or transdermal administration can also be accomplished by electroporation, iontophoresis, phonophoresis, and the like.

[0095] Compositions for topical use may be prepared with immediate or modified release, including delayed or sustained release.

[0096] Combination therapy

[0097] The pharmaceutical composition according to the present description may contain one or more additional therapeutic agents, for example, to increase the effectiveness or reduce side effects. According to some embodiments, accordingly, the pharmaceutical composition further comprises one or more additional therapeutic agents selected from active ingredients useful for the treatment or suppression of diseases mediated directly or indirectly by c-abl and/or LRRK2 kinases. Examples of such active ingredients include, but are not limited to, agents such as DNL151 and DNL201 for the treatment of a neurodegenerative disease or disorder.

[0098] References relating to the preparation of pharmaceutical compositions

[0099] Methods for preparing pharmaceutical compositions for treating or preventing a disease or condition are well known in the art to which this disclosure pertains. For example, based on Handbook of Pharmaceutical Excipients ( ^7th ed.), Remington: The Science and Practice of Pharmacy ( ^20th ed.), Encyclopedia of Pharmaceutical Technology ( ^3rd ed.), or Sustained and Controlled Release Drug Delivery Systems (1978), pharmaceutically acceptable excipients, carriers, additives, and so forth can be selected and then mixed with the compounds according to the present disclosure to prepare pharmaceutical compositions.

[0100] According to the present description, there are provided a compound having various pharmacological effects due to inhibition of c-abl and/or LRRK2 activity, a pharmaceutical composition comprising said compound as an effective agent, a medical use, in particular for the treatment of a neurodegenerative disease or disorder, of said compound, and a method of treatment or prevention comprising administering said compound to a subject in need of such treatment or prevention. The compounds according to the present description and their pharmaceutically acceptable salts are characterized by appropriate safety and high selectivity for c-abl and/or LRRK2, and thus exhibit excellent properties as a drug.

EXAMPLES

[0101] The present description is now illustrated in some detail by means of examples in order to facilitate the understanding of the present description by those skilled in the art. However, the following examples are offered by way of illustration and are not intended to limit the scope of protection of the present invention. It is understood that various changes can be made without departing from the spirit and scope of protection of the present invention or without departing from all its material advantages.

[0102] Synthesis of compounds of formula (I)

[0103] Synthetic methods A - N were used to prepare the following compounds. Illustrative examples of the synthesis of some compounds according to the present disclosure are described below, while other compounds can be prepared in a manner similar to that described below using different starting materials or reactants. [0104] Synthetic method A

[0105] Example 1. (1S,2S)-2-Fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide hydrochloride

[0106] Step 1): 6-iodimidazo[1,2-a]pyridin-2-amine

[0107] A mixture of compound 1 (10.000 g, 28.164 mmol) and lithium hydroxide monohydrate (4.727 g, 112.657 mmol) in water (100 mL)/methanol (300 mL) was heated under reflux for 18 h, cooled to room temperature, concentrated under reduced pressure, and partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer was washed with aqueous saturated sodium chloride, separated, dried over anhydrous MgSO ₄ , filtered, and concentrated in vacuo. The residue was diluted with dichloromethane (30 mL) and hexane (200 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with hexane and dried to give compound 2 as a brown solid (5.890 g, 80.7%).

[0108] Step 2): (1S,2S)-2-fluoro-N-(6-iodimidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide

[0109] A mixture of compound 2 (5.890 g, 22.737 mmol), (1S,2S)-2-fluorocyclopropane-1-carboxylic acid (3.076 g, 29.558 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC-HCl, 6.538 g, 34.105 mmol) in dichloromethane (100 mL) was treated with N,N-diisopropylethylamine (2.376 mL, 13.642 mmol) at room temperature and stirred at the same temperature for 40 h. The precipitates were collected by filtration, washed with dichloromethane and dried to give compound 3 as a beige solid (3.870 g, 49.3%).

[0110] 1H NMR (400 MHz, DMSO-d6) δ 10.99 (s, 1H), 8.87 (s, 1H), 8.02 (s, 1H), 7.36-7.23 (m, 2H), 4.97-4.77 (m, 1H), 2.09-2.07 (m, 1H), 1.65-1.57 (m, 1H), 1.16-1.09 (m, 1H).

[0111] Step 3): (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

[0112] Compound 3 (1.000 g, 2.898 mmol), (3-fluoro-2-methylphenyl)boronic acid (0.535 g, 3.477 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf) _Cl2 , 0.212 g, 0.290 mmol) and cesium carbonate (1.416 g, 4.346 mmol) in tetrahydrofuran (12 mL)/water (3 mL) were mixed at room temperature and then heated at 100 °C in the microwave for 30 min, cooled to room temperature, filtered through a pad of celite to remove solids and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed with aqueous saturated sodium chloride solution, separated, dried (using anhydrous _MgSO4 ), filtered and concentrated in vacuo. The residue was chromatographed ( _SiO2 , 45 g cartridge; ethyl acetate/hexane gradient from 70% to 100%) to give the crude product, which was crystallized at room temperature using diethyl ether (5 mL). The resulting precipitates were filtered, washed with diethyl ether and dried to give compound 4 as a white solid (0.700 g, 73.8%).

[0113] Step 4): (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide hydrochloride

[0114] A solution of compound 4 (0.600 g, 1.833 mmol) in ethyl acetate (100 mL) was mixed with hydrochloric acid (1.00 M solution in EtOAc, 1.925 mL, 1.925 mmol) at room temperature. The reaction mixture was stirred at the same temperature for 3 h. The precipitates were collected by filtration, washed with diethyl ether and dried to give Example 1 as a white solid (0.665 g, 99.7%).

[0115] 1H NMR (400 MHz, DMSO-d6) δ 11.67 (s, 1H), 8.74 (s, 1H), 8.13 (s, 1H), 7.69 (d, J=9.2 Hz, 1 H), 7.55 (d, J=9.2 Hz, 1 H), 7.35-7.30 (m, 1H), 7.23 (t, J=9.2 Hz, 1H), 7.15 (d, J=7.2 Hz, 1H), 5.05-4.85 (m, 1H), 7.21-7.14 (t, 4H), 1.69-1.63 (m, 1H), 1.21-1.18 (m, 1H).

[0116] Method of synthesis B

[0117] Example 3. (1S,2S)-N-(3-Chloro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide

[0118] Step 1): (1S,2S)-N-(3-chloro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide

[0119] A solution of Example 1 (0.060 g, 0.183 mmol) in acetonitrile (8 mL) was mixed at room temperature with 1-chloropyrrolidine-2,5-dione (NCS, 0.027 g, 0.202 mmol), stirred at the same temperature for 3 h and partitioned between ethyl acetate and a saturated aqueous solution of sodium bicarbonate. The organic layer was washed with an aqueous saturated solution of sodium chloride, separated, dried (using anhydrous MgSO ₄ ), filtered and concentrated in vacuo. The residue was chromatographed (SiO ₂ , 12 g cartridge; ethyl acetate/hexane gradient from 70% to 100%) to give the crude product, which was crystallized at room temperature using diethyl ether (5 mL). The resulting precipitates were filtered, washed with diethyl ether and dried to give Example 3 as a white solid (0.015 g, 22.6%).

[0120] 1H NMR (400 MHz, DMSO-d6) δ 10.44 (s, 1H), 8.21 (s, 1H), 7.62 (d, J=9.6 Hz, 1H), 7.35 (dd, J=9.2, 1.6 Hz, 1H), 7.30 (t, J=7.0 Hz, 1H), 7.24-7.19 (m, 2H), 5.01-4.83 (m, 1H), 2.15 (d, J=2.4 Hz, 3H), 2.06-2.03 (m, 1H), 1.64-1.56 (m, 1H), 1.15-1.08 (m, 1H).

[0121] Method for synthesizing C

[0122] Example 5. (1S,2S)-2-Fluoro-N-(3-methyl-6-(4-methylpyridin-3-yl)imidazo[1,2-a1pyridin-2-yl)cyclopropane-1-carboxamide

Step 1): (E)-2-(5-iodo-2-(tosylimino)pyridin-1(2H)-yl)propanamide

[0123] A mixture of compound 5 and 2-bromopropanamide (4.549 g, 29.931 mmol) in N,N-dimethylformamide (40 mL) was treated with N,N-diisopropylethylamine (5.213 mL, 29.931 mmol) at room temperature and stirred at the same temperature for 24 h. The reaction mixture was diluted with water (500 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with water and dried to give the crude product, which was redissolved in ethyl acetate (100 mL) and diethyl ether (300 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with diethyl ether and dried to give compound 6 as a pale pink solid (4.220 g, 35.5%).

[0124] 1H NMR (400 MHz, DMSO-d6) δ 8.15 (d, J=1.6 Hz, 1 H), 7.87 (dd, J=9.6, 2.4 Hz, 1 H), 7.75 (s, 1H), 7.62 (d, J=8.0 Hz, 2H), 7.38 (s, 1H), 7.24 (d, J=8.4 Hz, 2H), 7.16 (d, J=9.6 Hz, 1H), 5.63 (m, 1H), 2.30 (s, 3H), 1.60 (d, J=7.2 Hz, 3H).

[0125] Step 2): 2,2,2-trifluoro-N-(6-iodo-3-methylimidazo[1,2-a]pyridin-2-yl)acetamide

[0126] A stirred slurry of compound 6 (4.220 g, 9.477 mmol) in dichloromethane (50 mL) was mixed with trifluoroacetic anhydride (8.032 mL, 56.863 mmol) at room temperature. The reaction mixture was heated under reflux for 4 h, cooled to room temperature, and concentrated under reduced pressure. The residue was diluted with diethyl ether (300 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with diethyl ether, and dried to give the crude product, which was redissolved in water (300 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with water, and dried to give compound 7 as a beige solid (3.098 g, 88.6%).

[0127] Step 3): 6-iodo-3-methylimidazo[1,2-a]pyridin-2-amine

[0128] Compound 7 (3.098 g, 8.394 mmol) and lithium hydroxide monohydrate (1.057 g, 25.181 mmol) in water (15 mL)/ethanol (30 mL) were mixed at room temperature and then heated at 140 °C in a microwave for 30 min, cooled to room temperature and concentrated under reduced pressure. The residue was diluted with aqueous saturated ammonium chloride solution (20 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with water and dried to give compound 8 as a light yellow solid (1.400 g, 61.1%).

[0129] Step 4): (1S,2S)-2-fluoro-N-(6-iodo-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

[0130] A mixture of compound 8 (1.400 g, 5.127 mmol), (1S,2S)-2-fluorocyclopropane-1-carboxylic acid (0.640 g, 6.152 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU, 2.924 g, 7.690 mmol) in N,N-dimethylformamide (20 mL) was treated at room temperature with N,N-diisopropylethylamine (2.679 mL, 15.380 mmol), stirred at 60 °C for 48 h, cooled to room temperature and concentrated under reduced pressure. The residue was diluted with water (100 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with water and dried to give the crude product, which was redissolved in ethyl acetate (50 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with ethyl acetate and dried to give compound 9 as a white solid (1.070 g, 58.1%).

[0131] 1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.51 (s, 1H), 7.36 (dd, J=9.2, 1.6 Hz, 1H), 7.27 (d, J=9.2 Hz, 1H), 4.97-4.80 (m, 1H), 2.25 (s, 3H), 2.03 (m, 1H), 1.60-1.53 (m, 1H), 1.11-1.06 (m, 1H).

[0132] Step 5): (1S,2S)-2-fluoro-N-(3-methyl-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

[0133] Compound 9 (0.200 g, 0.557 mmol), (4-methylpyridin-3-yl)boronic acid (0.099 g, 0.724 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl ₂ , 0.041 g, 0.056 mmol) and potassium carbonate (0.231 g, 1.671 mmol) in a mixture of water (3 mL)/tetrahydrofuran (12 mL) were mixed at room temperature and then heated at 120 °C in the microwave for 1 h, cooled to room temperature and partitioned between ethyl acetate and water. The organic layer was washed with aqueous saturated sodium chloride solution, separated, dried (using anhydrous _MgSO4 ), filtered and concentrated in vacuo. The residue was chromatographed ( _SiO2 , 10 g cartridge; tetrahydrofuran/ethyl acetate gradient from 0% to 10%) to give the crude product, which was dissolved in diethyl ether (5 mL) and hexane (20 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with hexane and dried to give example 5 as a beige solid (0.100 g, 55.4%).

[0134] 1H NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.47 (s, 1H), 8.44 (d, J=5.2 Hz, 1H), 8.26 (s, 1H), 7.51 (d, J=9.2 Hz, 1H), 7.34 (d, J=5.2 Hz, 1H), 7.24 (d, J=9.2 Hz, 1H), 4.99-4.81 (m, 1H), 2.29 (s, 6H), 2.07-2.03 (m, 1H), 1.63-1.56 (m, 1H), 1.15-1.05 (m, 1H).

[0135] Synthesis Method D

[0136] Example 29. (1S,2S)-2-Fluoro-N-(6-(2-methyl-5-(1H-pyrazol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

[0137] Step 1): (1S,2S)-2-fluoro-N-(6-(2-methyl-5-(1H-pyrazol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

[0138] Example 26 (0.100 g, 0.291 mmol), (1H-pyrazol-3-yl)boronic acid (0.042 g, 0.378 mmol), [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (Pd(dtbpf) _Cl2 , 0.019 g, 0.029 mmol) and cesium carbonate (0.284 g, 0.873 mmol) in a mixture of 1,4-dioxane (12 mL)/water (3 mL) were mixed at room temperature and then heated at 140 °C in the microwave for 1 h, cooled to room temperature and partitioned between ethyl acetate and water. The organic layer was washed with aqueous saturated sodium chloride solution, separated, dried (using anhydrous _MgSO4 ), filtered and concentrated in vacuo. The residue was chromatographed ( _SiO2 , 10 g cartridge; tetrahydrofuran/ethyl acetate gradient from 0% to 20%) to give the crude product, which was dissolved in dichloromethane (3 mL) and hexane (20 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with diethyl ether and dried to give Example 29 as a beige solid (0.005 g, 4.6%).

[0139] 1H NMR (400 MHz, DMSO-d6) δ 12.82 (s, 1H), 10.99 (s, 1H), 8.58 (s, 1H), 8.08 (s, 1H), 7.73-7.69 (m, 2H), 7.46-7.23 (m, 4H), 6.70 (s, 1H), 4.97-4.80 (m, 1H), 2.25 (s, 3H), 2.14-2.09 (m, 1H), 1.66-1.59 (m, 1H), 1.13-1.08 (m, 1H).

[0140] Synthesis method E

[0141] Example 34. (1S,2S)-2-Fluoro-N-(3-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0142] Step 1): (1 S,2S)-2-fluoro-N-(3-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0143] A solution of Example 1 (0.1 g, 0.3055 mmol) in tetrahydrofuran (4 mL) was mixed at 0 °C with 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octaneditetrafluoroborate (Selectfluor®, 0.162 g, 0.4582 mmol), stirred at room temperature for 3 h, and partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic layer was washed with saturated aqueous sodium chloride, separated, dried (using anhydrous Na ₂ SO ₄ ), filtered, and concentrated in vacuo. The residue was chromatographed ( _SiO2 , 12 g cartridge; ethyl acetate/hexane gradient from 0% to 30%) to give Example 34 as a yellow solid (0.021 g, 15%).

[0144] 1H NMR (400 MHz, DMSO-d6) δ 10.56 (s, 1H), 8.23 (s, 1H), 7.49 (d, J=9.6 Hz, 1H), 7.33-7.27 (m, 1H), 7.24-7.16 (m, 3H), 5.01-4.81 (m, 1H), 2.15 (s, 3H), 2.05-2.05 (m, 1H), 1.63-1.56 (m, 1H), 1.17-1.09 (m, 1H).

[0145] Method for synthesizing F

[0146] Example 41. (1S,2S)-2-Fluoro-N-(6-(2-methyl-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

[0147] Step 1): 3-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-4-methylphenyl trifluoromethanesulfonate

[0148] A mixture of Example 12 (0.842 g, 2.588 mmol) and pyridine (0.313 mL, 3.882 mmol) in dichloromethane (100 mL) was treated at 0 °C with trifluoromethanesulfonic anhydride (0.479 mL, 2.847 mmol), stirred at the same temperature for 1 h and partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The organic layer was washed with aqueous saturated sodium chloride solution, separated, dried (using anhydrous MgSO ₄ ), filtered and concentrated in vacuo. The residue was chromatographed ( _SiO2 , 10 g cartridge; ethyl acetate/hexane gradient from 80% to 100%) to afford compound 10 as a purple solid (0.056 g, 4.7%).

[0149] Step 2): (1S,2S)-2-fluoro-1N-(6-(2-methyl-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

[0150] Compound 10 (0.056 g, 0.122 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole (0.031 g, 0.159 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(H) (Pd(dppf) _Cl2 , 0.009 g, 0.012 mmol) and potassium carbonate (0.051 g, 0.367 mmol) in a mixture of water (3 mL)/tetrahydrofuran (12 mL) were mixed at room temperature and then heated at 120 °C in the microwave for 30 min, cooled to room temperature and partitioned between ethyl acetate and water. The organic layer was washed with aqueous saturated sodium chloride solution, separated, dried (using anhydrous _MgSO4 ), filtered and concentrated in vacuo. The residue was chromatographed ( _SiO2 , cartridge 10g; tetrahydrofuran/ethyl acetate gradient from 0% to 10%) to give the crude product, which was dissolved in diethyl ether (5 mL) and hexane (5 mL) and stirred at ambient temperature. The resulting precipitates were collected by filtration, washed with diethyl ether and dried to give Example 41 as a white solid (0.005 g, 10.9%).

[0151] 1H NMR (400 MHz, DMSO-d6) δ 10.97 (s, 1H), 10.86 (bs, 1H), 8.54 (s, 1H), 8.07 (s, 1H), 7.44-7.40 (m, 3H), 7.23-7.19 (m, 3H), 6.74 (dd, J=4.4, 2.8 Hz, 1H), 6.41 (dd, J=4.4, 2.8 Hz, 1H), 4.97-4.79 (m, 1H), 2.20 (s, 3H), 2.11 (m, 1H), 1.66-1.59 (m, 1H), 1.15-1.10 (m, 1H).

[0152] Method for synthesizing G

[0153] Example 44. (1S,2S)-2-Fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a-pyridin-2-yl)cyclopropanecarboxamide

[0154] Step 1): (1S,2S)-2-fluoro-N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2 -a]pyridin-2-yl)cyclopropan-1-carboxamide

[0155] Compound 3 (0.800 g, 2.318 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane, 1.177 g, 4.636 mmol), [1.1'-

[bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2, 0.169 g, 0.231 mmol) and potassium acetate (0.796 g, 8.113 mmol) were mixed at room temperature in DMSO (20 mL) and then stirred at 90 °C for 24 h, cooled to room temperature, filtered through a pad of celite to remove solids, and partitioned between ethyl acetate and water. The organic layer was washed with aqueous saturated sodium chloride solution, separated, dried using anhydrous _MgSO4 , filtered, and concentrated in vacuo. The residue was chromatographed ( _SiO2 , 12 g cartridge; ethyl acetate/hexane gradient from 0% to 100%) to give compound 11 as a brown solid (0.560 g, 69.9%).

[0156] Step 2): (1S,2S)-2-fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0157] Compound 11 (0.080 g, 0.231 mmol), 5-bromo-2-fluoro-4-methylphenol (0.056 g, 0.277 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl ₂ , 0.017 g, 0.023 mmol) and Na ₂ CO ₃ (0.049 g, 0.462 mmol) in dioxane (2 mL)/water (0.5 mL) were mixed at room temperature and then the mixture was degassed and purged with N ₂ for 1 min, after which the mixture was stirred at 80 °C for 12 h under N ₂ . The reaction mixture was concentrated to give a residue. The residue was purified. The residue was chromatographed ( _SiO2 , 12 g cartridge; ethyl acetate/hexane gradient from 80% to 100%) to give Example 44 as a white solid (0.031 g, 39.8%).

[0158] 1H NMR (400 MHz, DMSO-d6) δ 10.98 (s, 1H), 9.75 (bs, 1H), 8.47 (s, 1H), 8.05 (s, 1H), 7.40 (d, J=9.2 Hz, 1H), 7.13 (dd, J=9.2, 2.0 Hz, 1H), 7.06 (d, J=12.4 Hz, 1H), 6.81 (d, J=9.2 Hz, 1H), 4.98-4.78 (m, 1H), 2.14-2.07 (m, 4H), 1.65-1.58 (m, 1H), 1.16-1.07 (m, 1H).

Method of synthesis of H

[0159] Example 66. (1S,2S)-2-Fluoro-N-(6-(3-fluoro-2-(methoxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0160] Step 1): 1-bromo-3-fluoro-2-(methoxymethyl)benzene

[0161] To a solution of compound 12 (500 mg, 2.44 mmol, 1 equiv.) in THF (10 mL), NaH (146.31 mg, 3.66 mmol, 60% purity, 1.5 equiv.) was added portionwise at 0 °C under N ₂ atmosphere and the reaction mixture was stirred at 0 °C for 0.5 h under N ₂ atmosphere, after which Mel (692.30 mg, 4.88 mmol, 303.64 μL, 2 equiv.) was added dropwise, then the mixture was stirred at 20 °C for another 1 h under N ₂ atmosphere. Saturated aqueous _NH4Cl solution (30 mL) was added to the reaction mixture, then the mixture was extracted with ethyl acetate (20 mL*2), _the combined organic layers were dried over _Na2SO4 , filtered and concentrated under reduced pressure to give a residue. Compound 13 (510 mg, crude) was obtained as a yellow oil.

[0162] 1H NMR (400 MHz, CDCl ₃ ) δ 7.41 (d, J=8.1 Hz, 1H), 7.18 (dt, J=5.9, 8.2 Hz, 1H), 7, 10-7.00 (m, 1H), 4.64 (d, J=2.3 Hz, 2H), 3.42 (s, 3H).

[0163] Step 2): (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(methoxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0164] To a solution of compound 13 (80 mg, 365.21 μmol, 1 equiv.) and compound 11 (151.27 mg, 438.25 μmol, 1.2 equiv.) in dioxane (2 mL) and H ₂ O (0.4 mL) were added Pd(dppf)Cl ₂ (26.72 mg, 36.52 μmol, 0.1 equiv.) and Na ₂ CO ₃ (77.42 mg, 730.42 μmol, 2 equiv.), and the mixture was stirred at 90 °C for 12 h under N ₂ atmosphere. The reaction mixture was diluted with ethyl acetate (300 mL), and the mixture was filtered through silica gel, and the filtrate was concentrated to give a residue. The residue was purified by preparative HPLC (column: Phenomenex luna C18 150*40 mm*15 μm; mobile phase: [water (0.1% TFA) - ACN]; B%: 17-47%, 10 min). Example 66 (91.3 mg, 193.69 μmol, yield 53.03%, purity 100%, TFA) was obtained as a white solid.

[0165] 1H NMR (400 MHz, DMSO-d6) δ 11.25 (s, 1H), 8.68 (s, 1H), 8.14 (s, 1H), 7.60 (d, J=9.2 Hz, 1H), 7.52 (dt, J=6.0, 7.9 Hz, 1H), 7.44 (dd, J=1.6, 9.2 Hz, 1H), 7.33 (d, J=8.7 Hz, 1H), 7.30-7.25 (m, 1H), 5.11-4.76 (m, 1H), 4.30 (br d, J=1.3 Hz, 2H), 3.25 (s, 3H), 2.23-2.08 (m, 1H), 1.76-1.59 (m, 1H), 1.20 (tdd, J=6.3, 9.1, 12.4 Hz, 1H).

[0166] Synthesis Method I

[0167] Example 67. (1S,2S)-2-Fluoro-N-(6-(3-fluoro-2(furan-2-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0168] Step 1): 2-(2-bromo-6-fluorophenyl)furan

[0169] Pd(dppf)Cl2 (113.13 mg, 154.61 μmol, 0.1 equiv) and Na2CO3 (491.61 mg, 4.64 mmol, 3 equiv) were added to a solution of compound ₁₄ (511.74 mg, 1.70 mmol, 1.1 equiv) and 2-(furan-2-yl)-4,4,5,5-tetramethyl-1,3,2- _{dioxaborolane} (300 mg, 1.55 mmol, 1 equiv) in dioxane ( ₃ mL) and H2O (0.6 mL), and the reaction mixture was stirred at 80 °C for 3 h under _N2 atmosphere. The reaction mixture was poured into water (50 mL), then the mixture was extracted with ethyl acetate (50 mL*2), _the combined organic layers were dried over _Na2SO4 , filtered and concentrated under reduced pressure to give a residue. The residue was purified by preparative TLC ( _SiO2 , petroleum ether:ethyl acetate - 3:1). The residue was purified by preparative TLC ( _SiO2 , petroleum ether:ethyl acetate - 1:0). Compound 15 (70 mg, 290.39 μmol, yield 18.78%) was obtained as a yellow oil.

[0170] 1H NMR (400 MHz, CDCl ₃ ) δ 7.61 (dd, J=0.8, 1.8 Hz, 1H), 7.48 (td, J=1.1, 8.0 Hz, 1H), 7.21 (dt, J=5.8, 8.1 Hz, 1H), 7.15-7.08 (m, 1H), 6.70 (td, J=0.9, 3.3 Hz, 1H), 6.56 (dd, J=1.8, 3.3 Hz, 1H).

[0171] Step 2): (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(furan-2-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0172] Pd(dppf)Cl2 (21.25 mg, 29.04 μmol, 0.1 equiv) and _Na2CO3 (92.33 mg, 871.17 μmol, 3 equiv) were added to a solution of compound ₁₅ (70 mg, 290.39 μmol, 1 equiv) and compound ₁₁ (110.26 mg, 319.43 μmol, 1.1 equiv) in _dioxane (1 mL) and H2O (0.2 mL), and the reaction mixture was stirred at 80 °C for 12 h under _N2 atmosphere. The reaction mixture was poured into brine (10 mL), then the mixture was extracted with ethyl acetate (10 mL*2), _the combined organic layers were dried over _Na2SO4 , filtered and concentrated under reduced pressure to give a residue. The residue was dissolved in methanol:dichloromethane (1:10, 100 mL), then the mixture was filtered through silica gel and the filtrate was concentrated to give a residue. The residue was purified by preparative HPLC (column: Phenomenex Synergi C18 150*25*10 μm; mobile phase: [water (0.1% TFA)-ACN]; B%: 34-54%, 9 min). Example 67 (38.3 mg, 77.63 μmol, yield 26.73%, purity 100%, TFA) was obtained as a white solid.

[0173] 1H NMR (400 MHz, DMSO-d6) δ 11.20 (s, 1H), 8.61 (s, 1H), 8.08 (s, 1H), 7.61 (dd, J= 0.9, 1.6 Hz, 1H), 7.60-7.54 (m, 1H), 7.45-7.41 (m, 1H), 7.40-7.36 (t, 2H), 6.93 (dd, J=1.3, 9.3 Hz, 1H), 6.56- 6.48 (t, 2H), 5.05-4.83 (m, 1H), 2.19-2.09 (m, 1H), 1.75-1.59 (m, 1H), 1.19 (tdd, J=6.3, 9.1, 12.4 Hz, 1H). Method of synthesis of J

[0174] Example 72. N-(6-(3-Fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0175] Step 1): 2,2,2-trifluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)acetamide

[0176] To a solution of compound 1 (1 g, 2.82 mmol, 1 equiv.) in dioxane (10 mL) and H ₂ O (1 mL) were added compound 2 (520.30 mg, 3.38 mmol, 1.2 equiv.), Pd(dppf)Cl ₂ (206.08 mg, 281.65 μmol, 0.1 equiv.) and Na ₂ CO ₃ (298.52 mg, 2.82 mmol, 1 equiv.). The mixture was stirred at 80 °C for 16 h under N ₂ atmosphere. The reaction mixture was diluted with 30 mL of water and extracted with ethyl acetate (30 mL * 2). The combined organic layers were washed with brine (30 mL * 2), dried over Na ₂ SO ₄ , filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (silica gel, gradient petroleum ether:ethyl acetate from 20:1 to 5:1). Compound 16 (500 mg, 1.48 mmol, yield 52.64%) was obtained as a white solid.

[0177] Step 2): 6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-amine

[0178] To a solution of compound 16 (500 mg, 1.48 mmol, 1 equiv.) in MeOH (10 mL) and H ₂ O (10 mL) was added K ₂ CO ₃ (1.02 g, 7.41 mmol, 5 equiv.). The mixture was stirred at 75 °C for 2 h. 50 mL of water was added to the reaction mixture, and it was extracted with ethyl acetate (50 mL * 2). The combined organic layers were washed with brine (50 mL * 2), dried over Na ₂ SO ₄ , filtered, and the filtrate was concentrated under reduced pressure to give a residue. Compound 17 (300 mg, 1.24 mmol, yield 83.88%) was obtained as a yellow solid.

[0179] Step 3): N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0180] Cyclopropanecarboxylic acid (53.52 mg, 621.73 μmol, 49.10 μL, 1.5 equiv) and DCC (85.52 mg, 414.49 μmol, 83.84 μL, 1 equiv) were added to a solution of compound 17 (100 mg, 414.49 μmol, 1 equiv) in EtOAc (2 mL). The mixture was stirred at 20 °C for 32 h. Then, DMAP (5.06 mg, 41.45 μmol, 0.1 equiv) was added to the mixture and stirred at 20 °C for 16 h. The reaction mixture was diluted with 20 mL of water and extracted with ethyl acetate (20 mL * 2). The combined organic layers were washed with brine (20 mL*2), dried over _{Na2SO4 ,} filtered, and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (column: Phenomenex Luna C18 150*25 mm*10 μm; mobile phase: [water (0.1% TFA)-ACN]; B%: 22-52%, 10 min). Example 72 (45.9 mg, 106.25 μmol, yield 25.63%, purity 98%, TFA) was obtained as a pink solid.

[0181] 1H NMR (400 MHz, DMSO-d6) δ 11.22 (br s, 1H), 8.66 (s, 1H), 8.09 (s, 1H), 7.59 (d, J=9.2 Hz, 1H), 7.40 (br d, J=9.3 Hz, 1H), 7.38-7.30 (m, 1H), 7.28-7.21 (m, 1H), 7.17 (d, J=7.5 Hz, 1H), 2.18 (d, J=2.3 Hz, 3H), 1.94 (quin, J=6.2 Hz, 1H), 0.85 (d, J=6.1 Hz, 4H).

Method of synthesis of K

[0182] Example 77: (1S,2S)-N-(6-(2-(Acetamidomethyl)3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide

[0183] Step 1: N-(2-bromo-6-fluorobenzyl)acetamide

[0184] Ac ₂ O (85.26 mg, 835.13 μmol, 78.22 μL, 1.2 equiv) was added to a solution of compound 18 (200 mg, 695.94 μmol, 1 equiv) in pyridine (5 mL). The mixture was stirred at 25 °C for 3 h. The desired MS was detected by LC-MS. The mixture was concentrated under reduced pressure to give a residue. The pH of the residue was adjusted to 6 with HCl and the residue was extracted with EA (30 mL*3). The organic phase was concentrated under reduced pressure to give a residue. Compound 19 (130 mg, 412.07 μmol, yield 59.21%, purity 78%) was obtained as a light yellow solid.

[0185] Step 2): (1S,2S)-N-(6-(2-(acetamidomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide

[0186] A mixture of compound 19 (100 mg, 361.68 μmol, 1 equiv), compound 11 (122.35 mg, 354.44 μmol, 0.98 equiv), Pd(dppf) _Cl2 (26.46 mg, 36.17 μmol, 0.1 equiv) and _Na2CO3 (76.67 mg, 723.35 μmol, 2 equiv) in water (1 mL) and dioxane (4 mL) was degassed and purged with _N2 3 times and then the mixture was stirred at 80 °C for 16 h under _N2 . _The desired MS was detected by LC-MS. The mixture was filtered and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (column: Phenomenex luna C18 250 * 50 mm * 10 μm; mobile phase: [water (0.1% TFA) - ACN]; B%: 10-40%, 9 min). Example 77 (15.3 mg, 29.84 μmol, yield 8.25%, purity 97.2%, TFA) was obtained as a white solid.

[0187] 1H NMR (400 MHz, CD30D) δ 8.67 (s, 1H), 7.81-7.71 (m, 2H), 7.49-7.47 (m, 1H), 7.31-7.22 (m, 2H), 5.04-5.01 (m, 0.5H), 4.87-4.85 (m, 0.5H), 4.38 (s, 2H), 2.16-2.12 (m, 1H), 1.90-1.84 (m, 1H), 1.31-1.28 (m, 1H).

Method of synthesis of L

[0188] Example 84: (1S,2S)-2-Fluoro-N-(6-(3-fluoro-2-((2-methoxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridine-2- yl)cyclopropanecarboxamide, TFA salt

[0189] Step 1): 1-bromo-3-fluoro-2-((2-methoxyethoxy)methyl)benzene

[0190] Compound 20 (445.00 mg, 2.17 mmol, 1 equiv) was dissolved in DMF (15 mL), to which NaH (130.22 mg, 3.26 mmol, 60% purity, 1.5 equiv) was added portionwise at 0 °C. The resulting mixture was then stirred under N ₂ for 30 min before adding 1-bromo-2-methoxyethane (362.01 mg, 2.60 mmol, 244.60 µL, 1.2 equiv) at 0 °C. The mixture was then stirred under N ₂ at 15 °C for another 11.5 h. The mixture was quenched with EtOH (5 mL), diluted with water (20 mL), and extracted with EA (20 mL x 3). The combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (pure PE - PE/EA: 4/1) to give compound 21 (178 mg, 676.54 μmol, yield 31.17%) as a light yellow oil.

[0191] Step 2): (15,25)-2-fluoro-N-(6-(3-fluoro-2-((2-methoxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridine-2 -yl)cyclopropanecarboxamide, TFA salt

[0192] A mixture of compound 21 (178 mg, 676.54 μmol, 1 equiv.) and compound 11 (210.17 mg, 608.89 μmol, 0.9 equiv.) was dissolved in dioxane (10 mL) and H ₂ O (2 mL), to which Pd(dppf)Cl ₂ (99.01 mg, 135.31 μmol, 0.2 equiv.) and Na ₂ CO ₃ (215.12 mg, 2.03 mmol, 3 equiv.) were added portionwise. The resulting mixture was then stirred under N ₂ at 80 °C for 16 h. LC-MS detection was performed at the desired m/z ratio. The mixture was filtered and the filtrate was diluted with water (20 mL) and extracted with EA (20 mL × 3). The combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (PE/EA 10/1 to 1/1) and then by preparative HPLC (column: Phenomenex Gemini-NX C18 75 * 30 mm * 3 μm; mobile phase: [water (0.1% TFA) - ACN]; B%: 18-48%, 7 min) and lyophilized to give Example 84 (32.2 mg, 62.10 μmol, yield 9.18%, purity 99.4%, TFA) as an off-white solid.

[0193] 1H NMR (400 MHz, DMSO) δ 11.23-11.19 (br s, 1H), 8.72 (s, 1H), 8.10 (s, 1H), 7.56-7.50 (m, 3H), 7.32-7.28 (m, 2H), 5.04-4.84 (m, 1H), 4.35 (s, 2H), 3.47-3.44 (m, 4H), 3.25 (s, 3H), 2.16-2.11 (m, 1H), 1.70-1.64 (m, 1H), 1.21-1.16 (m, 1H).

Method of synthesis M

[0194] Example 85. (1S,2S)-2-Fluoro-N-(6-(3-fluoro-2-((2-hydroxyethoxy)methyl)phenyl)imidazo[1,2-a1pyridin-2-yl)cyclopropanecarboxamide

[0195] Step 1: (2-((2-bromo-6-fluorobenzyl)oxy)ethoxy)(tert-butyl)dimethylsilane

[0196] Compound 22 (1 g, 4.88 mmol, 1 equiv) was dissolved in DMF (50 mL) and NaH (292.65 mg, 7.32 mmol, 60% pure, 1.5 equiv) was added portionwise at 0 °C. The resulting mixture was then stirred under N ₂ for 30 min before adding 2-bromoethoxy-tert-butyl-dimethylsilane (1.40 g, 5.85 mmol, 109.93 µL, 1.2 equiv) at 0 °C. The mixture was then stirred under N ₂ at 15 °C for another 11.5 h. TLC showed new spots (PE/EA = 4/1). The mixture was quenched with EtOH (5 mL), diluted with water (20 mL) and extracted with EA (20 mL × 3). The combined organic layers were concentrated under reduced pressure. The residue was purified together with the previous batch by silica gel chromatography (pure PE - PE/EA: 4/1) to give compound 23 (372 mg, 1.02 mmol, 20.99% yield) as a white solid.

[0197] 1H NMR (400 MHz, DMSO-d6) δ 7.52-7.50 (m, 1H), 7.37-7.36 (m, 1H), 7.34-7.30 (m, 1H), 4.61-4.60 (m, 2H), 3.90-3.80 (m, 2H), 3.58-3.47 (m, 2H), 0.835 (s, 9H), 0.02 (s, 6H).

[0198] Step 2: 2-((2-bromo-6-fluorobenzyl)oxy)ethanol

[0199] Compound 23 (352 mg, 968.80 μmol, 1 equiv) was dissolved in DMF (10 mL), CsF (147.16 mg, 968.80 μmol, 35.72 μL, 1 equiv) was added. The resulting mixture was then stirred at 80 °C for 12 h. The starting material was consumed according to the result of TLC (PE/EA = 4/1). The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (PE - PE/EA: 5/1) to give compound 24 (120 mg, 481.78 μmol, yield 49.73%) as an off-white solid.

[0200] 1H NMR (400 MHz, DMSO-d6) δ 7.52-7.50 (m, 1H), 7.36-7.28 (m, 2H), 4.60-4.59 (m, 2H), 3.52-3.47 (m, 4H).

[0201] Step 3: (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((2-hydroxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0202] A mixture of compound 24 (120 mg, 481.78 μmol, 1 equiv.) and compound 11 (149.67 mg, 433.60 μmol, 0.9 equiv.) was dissolved in a mixture of dioxane (10 mL) and H ₂ O (2 mL), to which Pd(dppf)Cl ₂ (35.25 mg, 48.18 μmol, 0.1 equiv.) and Na ₂ CO ₃ (153.19 mg, 1.45 mmol, 3 equiv.) were added portionwise. The resulting mixture was then stirred under N ₂ at 80 °C for 12 h. LC-MS detection was performed at the desired m/z ratio. The mixture was filtered and the filtrate was diluted with water (20 mL) and extracted with EA (20 mL × 3). The combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (PE/EA = 2/1 to EA/MeOH = 10/1) and then by preparative HPLC (column: Phenomenex Gemini-NX C18 75 * 30 mm * 3 μm; mobile phase: [water (0.1% TFA) - ACN]; B%: 12-42%, 9 min) and lyophilized to give example 85 (74.1 mg, 143.65 μmol, yield 29.82%, purity 97.2%, TFA) as an off-white solid.

[0203] 1H NMR (400 MHz, DMSO-d6) δ 11.21 (s, 1H), 8.78 (s, 1H), 8.14 (s, 1H), 7.58-7.47 (m, 3H), 7.33-7.29 (m, 2H), 5.05-4.85 (m, 1H), 4.36 (s, 2H), 3.55-3.52 (m, 2H), 3.47-3.45 (m, 2H), 2.16-2.13 (m, 1H), 1.71-1.69 (m, 1 H), 1.65-1.64 (m, 1H).

Method of synthesis of N

[0204] Example 105. (18.28)-2-Fluoro-N-(6-(2-methyl-5-(1H-pyrazol-1-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

[0205] Step 1): 3-bromo-4-methyl-2-nitrophenol

[0206] To a solution of compound 25 (5 g, 26.73 mmol, 1 equiv.) in CHCl _{3 (} 50 mL) was added dropwise HNO ₃ (2.85 g, 29.41 mmol, 2.04 mL, 1.1 equiv.) at -50 °C, then the reaction mixture was stirred at -50 °C for 1 h. The reaction mixture was slowly poured into ice water (200 mL), then the mixture was extracted with dichloromethane (100 mL*2), the combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO ₂ , petroleum ether/ethyl acetate: 1/0 to 100/1). Compound 26 (550 mg, 2.37 mmol, yield 8.87%) was obtained as a yellow oil.

[0207] 1H NMR (400 MHz, CDCl ₃ ) δ 8.84-8.20 (m, 1H), 7.31 (d, J=8.7 Hz, 1H), 7.00 (d, J=8.6 Hz, 1H), 2.41 (s, 3H).

[0208] Step 2): 2-amino-3-bromo-4-methylphenol

[0209] To a solution of compound 26 (450 mg, 1.94 mmol, 1 equiv.) in EtOH (5 mL) and H ₂ O (5 mL) were added Fe (649.83 mg, 11.64 mmol, 6 equiv.) and NH ₄ Cl (622.44 mg, 11.64 mmol, 6 equiv.). The suspension was degassed and purged with N ₂ 3 times. The reaction mixture was stirred under N ₂ at 80 °C for 2 h. The reaction mixture was filtered, the filter cake was washed with methanol (50 mL * 3), and the filtrate was concentrated under reduced pressure to give a residue. The residue was poured into water (50 mL), then the mixture was extracted with ethyl acetate (50 mL * 2), the combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was purified by reverse phase flash chromatography (MeCN/H ₂ O, CF ₃ COOH), then the mixture was concentrated to remove MeCN, after which the pH of the mixture was adjusted to pH = 7 using saturated aqueous sodium bicarbonate solution, then the mixture was extracted with ethyl acetate (100 mL * 2), the combined organic layers were dried over saturated sodium sulfate, filtered and concentrated under reduced pressure to give a residue. Compound 27 (210 mg, 1.02 mmol, yield 52.52%, purity 98%) was obtained as a yellow solid.

[0210] 1H NMR (400 MHz, CDCl ₃ ) δ 6.64-6.59 (m, 1H), 6.54-6.50 (m, 1H), 2.30 (s, 3H).

[0211] Step 3): 4-bromo-5-methylbenzo[d]oxazole

[0212] Tris(trifluoromethylsulfonyloxy)ytterbium (14.19 mg, 22.87 μmol, 2.25*10 -2 equiv) was added to a solution of compound 27 (210 mg, 1.02 mmol, ¹ equiv) and trimethoxymethane (162.14 mg, 1.53 mmol, 167.50 μL, 1.5 equiv) in EtOH (3 mL), and the reaction mixture was stirred at 90 °C for 12 h. LCMS showed that 19% of compound 3 remained, and 81% of the desired mass was found. Trimethoxymethane (108.09 mg, 1.02 mmol, 111.66 μl, 1 equiv) was added to the reaction mixture, then the reaction mixture was stirred at 90 °C for another 2 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. Saturated aqueous _NaHCO3 solution (50 ml) was added to the residue, then the mixture was extracted with ethyl acetate (30 ml * 3), _the combined organic layers were dried over _Na2SO4 , filtered and concentrated under reduced pressure to give a residue. Compound 28 (160 mg, crude) was obtained as a brown solid.

[0213] 1H NMR (400 MHz, CDCl ₃ ) δ 8.12 (s, 1 H), 7.43 (d, J=8.3 Hz, 1 H), 7.29 (d, J=8, 4 Hz, 1H), 2.54 (s, 3H).

[0214] Step 4): (1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]oxazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide

[0215] Pd(dppf)Cl2 (44.86 mg, 61.31 μmol, 0.1 equiv) and _Na2CO3 (194.94 mg, 1.84 mmol, 3 equiv) were added to a solution of compound ₂₈ (130 mg, 613.08 μmol, 1 equiv) and compound ₁₁ (253.95 mg, 735.70 μmol, 1.2 equiv) in _dioxane (2 mL) and H2O (0.4 mL), and the reaction mixture was stirred at 90 °C for 12 h under _N2 atmosphere. The reaction mixture was poured into brine (30 mL), then the mixture was extracted with ethyl acetate (30 mL * 2), the combined organic layers were dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was dissolved in methanol: dichloromethane (1:10, 100 mL), then the mixture was filtered through silica gel and the filtrate was concentrated to give a residue. The residue was purified by preparative HPLC (Column: Xtimate C18 150 * 40 mm * 10 μm; Mobile Phase: [Water (0.05% v/v ammonium hydroxide) - ACN]; B%: 25-55%, 10 min). Example 105 (118.4 mg, 333.33 μmol, yield 54.37%, purity 98.633%) was obtained as a white solid.

[0216] 1H NMR (400 MHz, DMSO-d6) δ 11.07 (s, 1H), 8.70 (s, 1H), 8.65 (s, 1H), 8.13 (s, 1H), 7.71 (d, J=8.3 Hz, 1H), 7.53 (d, J=9.2 Hz, 1H), 7.43 (d, J=8.4 Hz, 1H), 7.29 (dd, J=1.6, 9.2 Hz, 1H), 5.05-4.81 (m, 1H), 2.38 (s, 3H), 2.20-2.10 (m, 1H), 1.73-1.59 (m, 1H), 1.17 (tdd, J=6.2, 9.1,12.2 Hz, 1 N).

[0217] Table 1 below presents the compounds of the examples along with the general synthetic methods used to prepare the compound and characterizing data.

[0218]

[0219] Evaluation of connections

[0220] c-abl kinase assay

[0221] The ADP-Glo assay kit was purchased from Promega. Magnesium chloride (MgCl ₂ ), bovine serum albumin (BSA), ethylene glycol bis(B-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), Triton X-100, 1,4-dithiothreitol (DTT), and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich. HEPES buffer was purchased from Gibco. ABL1 kinase and Abltide were purchased from Signalchem.

[0222] c-Abl kinase activity was measured using the ADP-Glo™ assay from Promega. In this assay, His-tagged recombinant human ABL1 (0.25 ng/μl) was incubated with 5 μl of compounds (0.5% DMSO), 5 μl of Abltide (0.01 μg/μl), and 5 μl of ATP (25 μM) in buffer (50 mM HEPES, 7.5; 10 mM _MgCl2 ; 1 mM EGTA; 0.05% BSA; 0.01% Triton X-100; 2 mM DTT). The assay was started by incubating the reaction mixture in a 96-well plate at 30°C for 30 min. After incubation, 25 μl of ADP-Glo reagent were added and the reaction was incubated at room temperature for 40 min to stop the reaction and decompose residual ATP. The ADP product was then converted to ATP by adding 50 μl per well of detection reagent. Luminescence was detected after incubation for 30 min at room temperature using a Molecular device I3X plate reader. IC ₅₀ values were calculated from a series of percent inhibition values determined over a range of inhibitor concentrations using standard procedures using software implemented in GraphPad Prism 7 and Sigma Plot 13.0 software.

[0223] LRRK2 Kinase Assay with G2019S and LRRK2

[0224] LRRK2 with G2019S and LRRK2 kinase assays were performed using Adapta™ technology from ThermoFisher Scientific. This experiment was performed according to the supplier's protocol. Briefly, the assay conditions were as follows. The substrate (LRRKtide) and each kinase mixture were prepared in 50 mM Tris pH 8.5, 0.01% BRIJ-35, 10 mM _MgCl2 , 1 mM EGTA, 0.02% NaN. Assays were performed in the presence of 70 μM ATP and 100 μM ATP (KtATP) in LRRK2 and LRRK2 with G2019S, respectively. The reactions were allowed to progress at room temperature for 1 hour. After completion of the kinase reaction, 5 µl of detection mixture was added and after 60 min of incubation time, the emission coefficient at 665/615 nm was calculated.

[0225] Table 2 provides IC ₅₀ values for the compounds of the present invention, which are + for >1000 nM, ++ for 101-1000 nM, +++ for 10-100 nM, ++++ for <10 nM.

[0226]

Claims (296)

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof: Formula I, where R ¹ is cyclopropyl substituted with one or two halogen groups; R ² and R ³ independently represent -H; R ⁴ is selected from the group consisting of 6-membered aryl, , , , And , wherein said 6-membered aryl is optionally substituted with one to three groups selected from the group consisting of halogen, hydroxyl, _C1 - _C12 alkyl, _C3 - _C12 cycloalkyl, _C1 - _C12 haloalkyl, _C1 - _C12 hydroxyalkyl, _C1 - _C12 alkoxy- _C1 - _C12 alkyl, _C1 - _C12 alkoxy _{- C1} - _C12 alkoxy, di _{- C1} - _C12 alkylaminoC1- _C12 alkyl, _-CH2NHC (O) _{CH3 , -NRaRb, -NRaC(=O)Rb , -ORa ,} -CN, -C(=O) _Ra , -C(=O) _ORa , _-SRa , furanyl, pyrrolyl and pyrazolyl; R _a and R _b are independently -H or C ₁ -C ₁₂ alkyl; and R ⁵ is H, halogen or C ₁ -C ₁₂ alkyl. 2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R ⁴ is a 6-membered aryl, wherein R ⁴ is optionally substituted with one to three groups selected from the group consisting of halogen, hydroxyl, C ₁ -C ₃ alkyl, C ₃ -C ₄ cycloalkyl, C ₁ -C ₃ haloalkyl, mono-C ₁ -C ₃ alkylamino, di-C ₁ -C ₃ alkylamino, -CH ₂ NHC(O)CH ₃ , -NR _a R _b , -NR _a C(=O)R _b , -OR _a , -CN, -C(=O)R _a , -C(=O)OR _a , -SR _a , furanyl, pyrrolyl and pyrazolyl; and R ⁵ is H, F-, Cl-, Br- or methyl. 3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R ⁴ is phenyl, wherein R ⁴ is optionally substituted with one to three groups selected from the group consisting of halogen, hydroxyl, C ₁ -C ₃ alkyl, C ₁ -C ₃ haloalkyl, mono(C ₁ -C ₃ )alkylamino, di(C ₁ -C ₃ )alkylamino, -NR _a R _b , -OR _a , -CN, -C(=O)R _a , -C(=O)OR _a , -SR _a , furanyl and pyrazolyl. 4. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R ¹ is cyclopropyl substituted with one or two fluorine groups. 5. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R ¹ is fluorocyclopropyl. 6. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R ⁴ is fluoromethylphenyl, fluorohydroxymethylphenyl, chloromethylphenyl, dimethylphenyl, acetamidomethylphenyl, hydroxymethylphenyl, hydroxypropanylmethylphenyl, methylpyrrolylphenyl, cyanomethylphenyl, methylpyrazolylphenyl or fluoromethylmethylaminophenyl. 7. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R ⁴ is fluoromethylphenyl, fluorohydroxymethylphenyl, chloromethylphenyl, dimethylphenyl, acetamidomethylphenyl, hydroxylmethylphenyl, fluoromethylmethylaminophenyl, fluorohydroxylmethylphenyl, methylmethylaminophenyl, methylpyrrolylphenyl or cyanomethylphenyl. 8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R ⁴ is selected from the group consisting of phenyl, wherein R ⁴ is optionally substituted with one or more groups selected from the group consisting of halogen, C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ hydroxyalkyl, amino, cyano, acetyl, hydroxy and C ₁ -C ₁₂ haloalkyl. 9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R ⁴ is selected from the group consisting of: And . 10. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R ¹ is fluorocyclopropyl. 11. The compound of claim 10 or a pharmaceutically acceptable salt thereof, wherein R ⁴ is phenyl, wherein R ⁴ is optionally substituted with one or more groups selected from the group consisting of halogen, hydroxyl, C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ haloalkyl, C ₁ -C ₁₂ hydroxyalkyl, C ₃ -C ₁₂ cycloalkyl, C ₁ -C ₁₂ alkoxy-C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkoxy-C ₁ -C ₁₂ alkoxy, C ₁ -C ₁₂ alkylamino-C ₁ -C ₁₂ alkyl, -NR _a R _b , -NR _a C(=O)R _b , -OR _a , -SR _a , -CN, -C(=O)R _a , -C(=O)OR _a , furanyl or pyrrolyl; and R ⁵ is -H, halogen or methyl. 12. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is represented by a compound of formula (II) Formula II, where R ⁶ is a halogen. 13. The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein R ⁴ is phenyl, wherein R ⁴ is optionally substituted with one or more groups selected from the group consisting of halogen, hydroxyl, C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ haloalkyl, C ₁ -C ₁₂ hydroxyalkyl, C ₃ -C ₁₂ cycloalkyl, C ₁ -C ₁₂ alkoxy-C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkoxy-C ₁ -C ₁₂ alkoxy, C ₁ -C ₁₂ alkylamino-C ₁ -C ₁₂ alkyl, -NR _a R _b , -NR _a C(=O)R _b , -OR _a , -SR _a , -CN, -C(=O)R _a , -C(=O)OR _a , furanyl or pyrrolyl; and R ⁵ is -H, halogen or C ₁ -C ₁₂ alkyl. 14. The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: 2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(3-chloro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(3-chloro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; methyl 3-(2-(2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-4-methylbenzoate; N-(6-(5-cyano-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(3-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; N-(6-(2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(5-amino-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-methyl-5-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; N-(6-(5-acetamido-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(5-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(4-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(3-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(2,4-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(3-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(2,5-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-fluoro-2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-fluoro-2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-methyl-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; N-(6-(3,4-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(3,6-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(4-chloro-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(5-amino-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(2-chloro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-methyl-5-(1H-pyrazol-1-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(3-bromo-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(3-fluoro-2-methoxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; N-(6-(2-cyano-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; N-(6-(2-chloro-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; N-(6-(2,3-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-(methoxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-(furan-2-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-(methylthio)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; N-(6-(2-acetyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; N-(6-(2-(aminomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; N-(6-(2-(acetamidomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; 2,2-difluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-((methylamino)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-((isopropylamino)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-((2-methoxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-((2-hydroxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; N-(6-(2-((dimethylamino)methyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; 2-fluoro-N-(6-(o-tolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-hydroxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; N-(6-(2-amino-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; N-(6-(2-(dimethylamino)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; N-(6-(2-ethyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; N-(6-(2-cyclopropyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-isopropylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(3-fluoro-2-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(3-fluoro-2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(2-ethyl-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(4-acetyl-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(2-chloro-3,4-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(2-chloro-3,6-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(8-(difluoromethyl)-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-8-(fluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(8-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(7-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-fluoro-2-methylphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(8-(difluoromethyl)-6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-fluoro-2-methylphenyl)-8-(fluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(8-fluoro-6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(7-fluoro-6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(5-fluoro-2-methylphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(8-(difluoromethyl)-6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(5-fluoro-2-methylphenyl)-8-(fluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(8-fluoro-6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(7-fluoro-6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-8-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(8-(difluoromethyl)-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-8-(fluoromethyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(8-fluoro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; And 2-fluoro-N-(7-fluoro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide. 15. The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: 2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(3-chloro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(3-chloro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(3-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; N-(6-(2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-methyl-5-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; N-(6-(2,4-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(3-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(2,5-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-methyl-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; N-(3-bromo-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; And 2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide. 16. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is represented by a compound of formula (III) Formula III, where R ⁶ is a halogen. 17. The compound of claim 16 or a pharmaceutically acceptable salt thereof, wherein R ⁴ is phenyl, wherein R ⁴ is optionally substituted with one or more groups selected from the group consisting of halogen, hydroxyl, C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ haloalkyl, C ₁ -C ₁₂ hydroxyalkyl, C ₃ -C ₁₂ cycloalkyl, C ₁ -C ₁₂ alkoxyC ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkoxyC ₁ -C ₁₂ alkoxy, C ₁ -C ₁₂ alkylaminoC ₁ -C ₁₂ alkyl, -NR _a R _b , -NR _a C(=O)R _b , -OR _a , -SR _a , -CN, -C(=O)R _a , -C(=O)OR _a , furanyl or pyrrolyl; and R ⁵ is -H, halogen, or C ₁ -C ₁₂ alkyl. 18. The compound of claim 16 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-N-(3-chloro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-N-(3-chloro-6-(2-fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(2-fluoro-6-methylphenyl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; methyl 3-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamido)imidazo[1,2-a]pyridin-6-yl)-4-methylbenzoate; (1S,2S)-N-(6-(5-cyano-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(3-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-N-(6-(2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-N-(6-(5-amino-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(2-methyl-5-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-N-(6-(5-acetamido-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-N-(6-(5-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(2-methyl-5-(1H-pyrazol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-N-(6-(4-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-N-(6-(3-chloro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-N-(6-(2,4-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(3-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-N-(6-(2,5-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(4-fluoro-2,3-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(4-fluoro-2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(4-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(2-methyl-5-(1H-pyrrol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(3-methylthiophen-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-N-(6-(2,6-dimethylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-N-(6-(3,4-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-N-(6-(3,6-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-N-(6-(4-chloro-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-N-(6-(5-amino-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-N-(6-(2-chloro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(2-methyl-5-(1H-pyrazol-1-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(hydroxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-N-(3-bromo-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methoxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-N-(6-(2-cyano-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-N-(6-(2-chloro-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-N-(6-(2,3-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(methoxymethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(furan-2-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(methylthio)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-N-(6-(2-acetyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-N-(6-(2-(aminomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-N-(6-(2-(acetamidomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((methylamino)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((isopropylamino)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((2-methoxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((2-hydroxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-N-(6-(2-((dimethylamino)methyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(o-tolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-hydroxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-N-(6-(2-amino-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-N-(6-(2-(dimethylamino)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-N-(6-(2-ethyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(trifluoromethyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-N-(6-(2-cyclopropyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; and (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-isopropylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide. 19. The compound of claim 16 or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of: (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(5-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(2-methyl-5-(methylamino)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(3-methylthiophen-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; And (1S,2S)-N-(6-(3,4-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide. 20. The compound of claim 1, wherein the salt is a hydrochloric acid salt, a tartaric acid salt, a phosphoric acid salt, or a maleic acid salt. 21. A compound selected from the group consisting of: 2-fluoro-N-(6-(5-methyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-methyl-1H-pyrazol-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(2-methyl-5-(1H-pyrazol-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(2-oxoindolin-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(3-methylthiophen-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(5-methyl-2-oxoindolin-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(2-oxo-2,3-dihydrobenzo[d]thiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; N-(6-(3,5-dimethyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; N-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; 2-fluoro-N-(6-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; N-(6-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; 2-fluoro-N-(6-(5-methyl-1H-indol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(6-methyl-1H-indol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(5-methylbenzo[d]oxazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(6-methylbenzo[d]thiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(5-methylbenzo[d]oxazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(5-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(6-(7-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; 2-fluoro-N-(3-methyl-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(3-chloro-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropan-1-carboxamide; 2-fluoro-N-(6-(5-fluoro-4-methylpyridin-3-yl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; 2-fluoro-N-(6-(5-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(3-chloro-6-(5-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; N-(6-(4-chloropyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(4-cyanopyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropan-1-carboxamide; 2-fluoro-N-(6-(2-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-fluoro-N-(6-(4-methoxypyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(6-amino-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropan-1-carboxamide; N-(6-(6-aminopyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; 2-fluoro-N-(6-(6-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; And N-(6-(6-(dimethylamino)-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide. 22. The compound according to claim 21, selected from the group consisting of: (1S,2S)-N-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide ; (1S,2S)-2-fluoro-N-(6-(2-oxoindolin-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(5-methyl-2-oxoindolin-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl) cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(2-oxo-2,3-dihydrobenzo[d]thiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan- 1-carboxamide; (1S,2S)-N-(6-(3,5-dimethyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-N-(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-N-(6-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(6-methyl-1H-indol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]oxazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(6-methylbenzo[d]thiazol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]oxazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(7-methylbenzo[d]thiazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(3-methyl-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-N-(3-chloro-6-(4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropan-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(5-fluoro-4-methylpyridin-3-yl)-3-methylimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(5-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-N-(3-chloro-6-(5-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide ; (1S,2S)-N-(6-(4-chloropyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-N-(6-(4-cyanopyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(2-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(4-methoxypyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropan-1-carboxamide; (1S,2S)-N-(6-(6-amino-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropan-1-carboxamide; (1S,2S)-N-(6-(6-aminopyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(6-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; and (1S,2S)-N-(6-(6-(dimethylamino)-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropanecarboxamide. 23. A pharmaceutical composition for inhibiting c-abl and/or LRRK2 kinase, comprising a therapeutically effective amount of a compound according to any one of claims 1-22 or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier. 24. The pharmaceutical composition according to claim 23, further comprising one or more active ingredients that are useful for treating a neurodegenerative disease.