HK40058867B - Imidazopyridinyl compounds and use thereof for treatment of proliferative disorders - Google Patents

Description

Imidazolidine compounds and their use in the treatment of proliferative disorders

Cross-reference to related applications

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

Technical Field

This invention generally relates to compounds having enzyme-inhibiting activity, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat cancer and/or proliferative diseases.

Background Technology

c-Abl is a tightly regulated, non-receptor tyrosine kinase involved in regulating cell proliferation, cell survival, cell adhesion, cell migration, and apoptosis. c-Abl is located in both the nucleus and cytoplasm. In the nucleus, c-Abl is known to be activated by DNA damage and contribute to apoptosis (Wang, 2000). Cytoplasmic c-Abl is associated with growth factor receptor signaling that can affect cell fluidity and cell adhesion (Taagepera et al., 1998). The oncogenic effects of Abl are thought to originate in the cytoplasmic form of c-Abl. Several studies have shown that c-Abl is partially downregulated through intramolecular interactions that provide a self-inhibiting kinase effect (Pendergast, 2002; Pluk et al., 2002; Hantschel et al., 2003). The study also found that c-Abl kinase activity is regulated by intermolecular interactions with negative regulators, including Bcr (Liu et al., 1996; Ling et al., 2003), PAG (Wen and Van Etten, 1997), F-actin (Woodring et al., 2003), and phosphatidylinositol (Plattner and Pendergast, 2003).

c-Abl protein is widely expressed in all tissues, and until recently it was thought that the oncogenic activation of Abl was limited to hematopoietic malignancies, primarily chronic myeloid leukemia (CML) and lesser-degree acute lymphoblastic B-cell leukemia. More than 95% of CML patients have an abnormal chromosome 22 called the Philadelphia chromosome (Ph). Ph fuses 50 portions of the BCR with the second exon of the c-ABL gene. The first exon of c-ABL encodes sequences involved in the autoinhibition of the c-Abl tyrosine kinase, and therefore deletions of these sequences are thought to contribute to the activation state of the Abl tyrosine kinase domain.

Recent findings suggest that activated c-Abl tyrosine kinase may also play a role in non-small cell lung cancer (NSCLC) in China (Lin et al., 2005, 2007). c-Abl tyrosine kinase is activated in certain solid tumors, a finding further supported by the work of Plattner and colleagues (Srinivasan and Plattner, 2006; Srinivasan et al., 2008), whose findings indicate that activated c-Abl tyrosine kinase plays a role in invasive human breast cancer cell lines (J Lin and R Arlinghaus; Oncogene 2008, 27, 4385).

KIT enzyme (also known as CD117) is a receptor tyrosine kinase expressed in a variety of cell types. The KIT molecule comprises a long extracellular domain, a transmembrane segment, and an intracellular portion. KIT's ligand is stem cell factor (SCF), and the binding of SCF to the KIT extracellular domain induces receptor dimerization and activation of downstream signaling pathways. KIT mutations commonly occur in DNA encoding the juxtamembrane domain (exon 11). KIT mutations also occur at lower frequencies in exons 7, 8, 9, 13, 14, 17, and 18. Mutations render KIT function unaffected by SCF activation, leading to high cell division rates and potentially genomic instability. Mutated KIT is associated with the pathogenesis of various diseases and conditions, including systemic mastocytosis, GIST (gastrointestinal stromal tumor), AML (acute myeloid leukemia), melanoma, and seminoma. Therefore, a therapeutic agent that inhibits KIT, and especially one that inhibits mutant KIT, is needed.

Studies have shown that platelet-derived growth factor (PDGF) is involved in tumor angiogenesis, binding to a wide range of mesodermal-derived cells, such as fibroblasts, pericytes, glial cells, or mesangial cells. PDGF isoforms bind to two different receptors, PDGF-α and -β, a mechanism that induces receptor autophosphorylation and activation of several signaling molecules. PDGF receptors are expressed in tumor cells and stromal cells in both normal and tumor tissues. They play an important role in tumor progression as part of a group of receptors expressed along the tumor cell membrane (Adina Octavia et al. Rom J Morphol Embryol 2012, 53(3Suppl):749), and tumor cells include non-Hodgkin lymphoma (NHL), particularly B-cell lymphoma (BCL), T-cell lymphoma, and natural killer cell lymphoma.

The PDGFRA D842V mutation has been found in different subsets of GISTs, which typically originate from the stomach. The D842V mutation is known to be associated with resistance to tyrosine kinase inhibitors. Therefore, an agent targeting this mutation is needed. (Valentina et al., Int. J. Mol. Sci. 2018, 19, 732).

Summary of the Invention

This disclosure provides compounds having c-abl, KIT and/or PDGFR inhibitory activities, compositions comprising the compounds, and methods for treating cancer and/or proliferative diseases.

In one embodiment, a compound of formula (I) is provided:

Or a pharmaceutically acceptable salt thereof, wherein ^R1 , ^R2 , ^R3 , ^R4 and ^R5 are defined as follows.

In another embodiment, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound described herein and a pharmaceutically acceptable carrier.

In another embodiment, the present invention provides a method for inhibiting or treating cancer and/or proliferative diseases, comprising administering a therapeutically effective amount of one or more of the compounds described herein to a subject in need.

Detailed Implementation

The following description is merely illustrative in nature and is not intended to limit the invention, application, or use.

definition

For clarity, the general terms used in this invention are defined herein.

The terms “substituent”, “free radical”, “group”, “part” and “fragment” may be used interchangeably in this specification.

As used herein, the term "alkenyl" refers to a straight-chain or branched hydrocarbon group having at least one unsaturated site, namely a carbon-carbon, sp2 double bond. In one embodiment, the alkenyl group has 2 to 12 carbon atoms. In some embodiments, the alkenyl group is a _C2 - _C10 alkenyl or a _C2 - _C6 alkenyl. Examples of alkenyl groups include, but are not limited to _, ethylene or vinyl (-CH= _CH2 ), allyl ( _-CH2CH = _CH2 ), cyclopentenyl _{( -C5H7} ), and 5- _hexenyl ( _{-CH2CH2CH2CH2CH = CH2} ).

As used herein, the term "alkoxy" is RO- where R is an alkyl group. Non-limiting examples of alkoxy groups include methoxy, ethoxy, and propoxy.

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.

As used herein, the term "alkoxycarbonyl" is ROC(O)-, where R is an alkyl group as defined in this invention. In various embodiments, R is a _C1 - _C10 alkyl group or a _C1 - _C6 alkyl group.

As used herein, the term "alkyl" refers to a straight-chain or branched hydrocarbon group. In one embodiment, the alkyl group has 1 to 12 carbon atoms. In some embodiments, the alkyl group is a _C1 - _C10 alkyl or a _C1 - _C6 alkyl. 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" refers to an alkyl group having 1 to 4 carbon atoms.

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 group is an alkyl group as defined herein and may be the same or different. In various embodiments, R is a _C1 - _C10 alkyl or a _C1 - _C6 alkyl. Examples of alkylamino groups include methylamino, ethylamino, propylamino, butylamino, dimethylamino, diethylamino, and methylethylamino.

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

As used herein, the term "alkynyl" refers to a straight-chain or branched carbon chain group having at least one unsaturated site, namely a carbon-carbon-sp triple bond. In one embodiment, the alkynyl group has 2 to 12 carbon atoms. In some embodiments, the alkynyl group is a _C2 - _C10 alkynyl or a _C2 - _C6 alkynyl. Examples of alkynyl groups include alkynyl (-C≡CH) and propynyl ( _-CH2C≡CH ).

As used herein, the term "aryl" refers to any monocyclic or bicyclic carbocyclic ring with up to seven atoms per ring, wherein at least one ring is aromatic, or an aromatic ring system with five to fourteen carbon atoms, comprising a carbocyclic aromatic group fused with a five- or six-membered cycloalkyl group. Representative examples of aryl groups include, but are not limited to, phenyl, tolyl, xylyl, naphthyl, tetrahydronaphthyl, anthracel, fluorenyl, indene, azulel, and indanyl. The carbocyclic aromatic group may be unsubstituted or optionally substituted.

As used herein, the term "cycloalkyl" is a hydrocarbon group comprising at least one saturated or partially unsaturated ring structure and linked via a ring carbon. 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. "Cycloalkoxy" is RO-, where R is a cycloalkyl group.

As used herein, the terms “halogen” and “halogenated” refer to chlorine (-Cl), bromine (-Br), fluorine (-F), or iodine (-I). “Haloalkoxy” refers to an alkoxy group substituted with one or more halogen groups, and 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 the haloalkoxy group 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 groups. Examples of haloalkyl groups include _-CF3 and _-CHF2 .

As used herein, the term "heteroalkyl" refers to a straight-chain or branched alkyl group having 2 to 14 carbons (2 to 10 carbons in some embodiments) in the chain, wherein one or more of these carbons are substituted with heteroatoms selected from S, O, P, and N. Exemplary heteroalkyl groups include alkyl ethers, secondary and tertiary alkylamines, amides, alkyl sulfides, etc.

As used herein, the term "heterocyclic group" includes heteroaryl groups as defined below, and refers to a saturated or partially unsaturated monocyclic, bicyclic, or tricyclic group having 2 to 14 ring carbon atoms, and having 1 to 4 heteroatoms selected from P, N, O, and S in addition to the ring carbon atoms. In various embodiments, the heterocyclic group is attached to another part via carbon or via a heteroatom, and is optionally substituted by carbon or a heteroatom. Examples of heterocyclic groups include azirrobutane, benzimidazolyl, benzofuranyl, benzofuranazonyl, benzopyrazolyl, benzotriazolyl, benzothiophenyl, benzoxazolyl, carbazoyl, carbaolinyl, cinnamolinyl, furanyl, imidazoyl, dihydroindolyl, indolyl, indolazinyl, indolazolyl, indolazolyl, isobenzofuranyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthiaridinyl, oxadiazolyl, oxazolyl, oxazoline, isoxazoline, oxazoline, oxazoline, oxazoline, oxadiazolyl, pyranyl, pyrazinyl, pyridazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrroleyl, quinazolinyl, quinolinyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydroisoquinolinyl, tetrazolyl, tetrazo[pyridinyl]pyridinyl, thiadiazolyl, thiazolyl Thiophene, triazolyl, aziridine, 1,4-dioxane, hexahydroaziridine, piperazinyl, piperidinyl, pyridin-2-yl, pyrrolyl, morpholinyl, thiomorpholinyl, dihydrobenzimidazolyl, dihydrobenzofuranyl, dihydrobenzothiophene, dihydrobenzoxazolyl, dihydrofuranyl, dihydroimidazolyl, dihydroindolyldihydroisoxazolyl, dihydroisothiazolyl, dihydrooxadiazolyl, dihydrooxazolyl, dihydropyrazinyl, dihydropyrazolyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrroleyl, dihydroquinolinyl, dihydrotetrazolyl, dihydrothiadiazolyl, dihydrothiazolyl, dihydrothiazolyl, dihydrothiaphene, dihydrotriazolyl, dihydroaziridine, methylenedioxybenzoyl, tetrahydrofuranyl and tetrahydrothiaphene and their N-oxides. "Heterocyclic oxy group" is RO-, where R is a heterocyclic group. "Heterocyclic thio group" is RS-, where R is a heterocyclic group.

As used herein, the term "3- or 4-membered heterocyclic group" refers to a monocyclic ring having 3 or 4 ring atoms, wherein at least one ring atom is a heteroatom selected from N, O, and S. Non-limiting examples of 3- or 4-membered heterocyclic groups include acridinel, 2H-acridinyl, oxetyl, thiaranyl, aziridine, 2,3-diacetyl, aziridine, 1,3-diazacyclobutane, oxetyl, 2H-oxetyl, thioheterobutane, and 2H-thienyl.

As used herein, the term "heteroaryl" refers to a monocyclic, bicyclic, or tricyclic ring having up to seven atoms in each ring, wherein at least one ring is aromatic and contains 1-4 heteroatoms selected from N, O, and S. Non-limiting examples of heteroaryl groups include pyridinyl, thiopheneyl, furanyl, pyrimidinyl, imidazolyl, pyranyl, pyrazolyl, thiazolyl, thiadiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrroleyl, pyridazinyl, quinolinyl, isoquinolinyl, benzofuranyl, dibenzofuranyl, dibenzothiopheneyl, benzothiopheneyl, indolyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, isoydinolyl, benzotriazolyl, purinel, thiazoindyl, and pyrazinyl. The linkage of heteroaryl groups can occur via an aromatic ring, or, if the heteroaryl group is bicyclic or tricyclic and one of the rings is not aromatic or does not contain a heteroatom, it can be linked via a non-aromatic ring or a ring without a heteroatom. "Heteroaryl" should also be understood to include any N-oxide derivative of a nitrogen-containing heteroaryl group. "Heteroaryloxy group" is RO-, where R is a heteroaryl group.

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

As used herein, the term "hydroxyalkyl" refers to a straight-chain or branched monovalent _C1 - _C10 hydrocarbon group substituted with at least one hydroxyl group, and examples of hydroxyalkyl include, but are not limited to, hydroxymethyl, hydroxyethyl, hydroxypropyl, and hydroxybutyl.

As used herein, the term “pharmaceutical acceptable” means that a pharmaceutical preparation is generally considered safe for such use, has been formally approved for use by a national or state regulatory agency, or is listed in the United States Pharmacopeia or other recognized pharmacopoeia for use in animals, and especially in humans.

As used herein, the term "pharmaceuticalally acceptable carrier" means a diluent, adjuvant, excipient, or carrier, or other pharmaceutically acceptable ingredients that are administered together with the compounds of the present invention.

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, metal salts, and amine salts that form with inorganic or organic acids. Examples of acid addition salts that form with inorganic acids include salts formed with hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of acid addition salts formed with organic acids include 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-hydroxy-benzoyl)-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-methyl-bicyclo[2.2.2]oct-2-en-1-carboxylic acid, glucono-heptanoic acid, 4,4'-methylenebis(3-hydroxy-2-naphthalene) acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, and mucoconic 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 that are strong enough to form salts with carboxylic acids.

As used herein, the term "therapeuticly effective amount" refers to, when applied to the compounds of the present invention, an amount intended to indicate sufficient to improve, alleviate, stabilize, reverse, slow, or delay the development of a condition or disease state, or symptoms of a condition or disease. In one embodiment, the method of the present invention provides administration of a combination of compounds. In this case, the "therapeuticly effective amount" is the amount of the compound of the present invention in the combination sufficient to cause the desired biological effect.

As used herein, the term "treatment" means improving or reversing the progression or severity of a disease or condition, or improving or reversing one or more symptoms or side effects of such a disease or condition. As used herein, "treatment" also means inhibiting or blocking the progression of a system, condition, or state of a disease or condition by delaying, preventing, restraining, inhibiting, or hindering it. For the purposes of this invention, "treatment" further means a method of obtaining a beneficial or desired clinical outcome, wherein "beneficial or desired clinical outcome" includes, but is not limited to, relief of symptoms, reduction of the severity of a disease or condition, stabilization (i.e., non-worsening) of a disease or condition state, delay or slowing of a disease or condition state, improvement or relief of a disease or condition state, and partial or complete relief of a disease or condition.

In another embodiment, the compound shown in formula (I) is used to regulate the activity of protein kinases c-abl, KIT, and PDFGR.

As used herein, the term "regulation" refers to a change in the catalytic activity of a protein kinase. Specifically, regulation refers to the activation or inhibition of the catalytic activity of a protein kinase, depending on the concentration of the compound or salt to which the protein kinase is exposed, or more preferably, on the inhibition of its catalytic activity. As used herein, the term "catalytic activity" refers to the phosphorylation rate of tyrosine, serine, or threonine under the direct or indirect influence of a protein kinase.

Pharmacological inhibitors of kinase activity can be classified into three main categories: (1) Type I or “DFG-in” ATP-competitive inhibitors, which directly compete with ATP at the ATP-binding site (i.e., SRrc and Abl inhibitors, dasatinib); (2) Type II or “DFG-out” ATP-competitive inhibitors, which bind to adjacent hydrophobic binding sites in addition to ATP-binding sites, and these binding sites can only bind when the kinase is in an inactivated configuration (i.e., the orientation of the activation loop prevents substrate binding) (e.g., imatinib, nilotinib); and (3) Non-ATP-competitive inhibitors (e.g., GNF-2), which bind at sites other than the ATP-binding sites that affect kinase activity.

As used herein, the phrase “compound of the invention” includes any compound represented by formula (I), as well as its inclusion compounds, hydrates, solvates, or polymorphs. Furthermore, the term “compound of the invention” includes its salts even if the term does not specifically refer to a pharmaceutically acceptable salt. In one embodiment, the compounds of the invention include stereochemically pure compounds, such as those substantially free of (e.g., greater than 85%, 90%, 95%, 97%, or 99% ee) other stereoisomers. That is, if a compound represented by formula (I) according to the invention or a salt thereof is a tautomer and/or a stereoisomer (e.g., a geometric isomer and a conformational isomer), then these separate isomers and mixtures thereof are also included within the scope of the invention. If a compound of the invention or a salt thereof has an asymmetric carbon in its structure, then their active optical isomers and racemic mixtures thereof are also included within the scope of the invention.

As used herein, the term "polymorph" refers to the solid crystalline form of the compound or its complex of the present invention. Different polymorphs of the same compound can exhibit different physical, chemical, and/or spectroscopic properties. Different physical properties include, but are not limited to, stability (e.g., stability to heat or light), compressibility and density (important in formulation and product manufacturing), and dissolution rate (affecting bioavailability). Differences in stability may be due to changes in chemical reactivity (e.g., differential oxidation, causing the dosage form to discolor faster when containing one polymorph than when containing another) or mechanical properties (e.g., tablets pulverize during storage because a kinetically favorable polymorph transforms into a thermodynamically more stable polymorph) or both (e.g., tablets of one polymorph are more prone to decomposition at high humidity). Different physical properties of polymorphs can affect their processing. For example, one polymorph may be more likely to form solvates or may be more difficult to filter or remove impurities from than another polymorph, for example, due to the shape or size distribution of the polymorph's particles.

As used herein, the term "solvent" refers to a compound or salt thereof according to the invention, which also includes stoichiometric or non-stoichiometric solvents bound by non-covalent intermolecular forces. Preferred solvents are volatile, non-toxic, and/or acceptable in trace amounts for human use.

As used herein, the term "hydrate" refers to a compound or salt thereof according to the invention, which also includes stoichiometric or nonstoichiometric water bound by noncovalent intermolecular forces.

As used herein, the term “inclusion compound” refers to a compound or salt thereof in lattice form that contains spaces (e.g., channels) with guest molecules (e.g., solvents or water) trapped therein.

The compounds of the present invention

This invention provides compounds represented by formula (I):

Or its pharmaceutically acceptable salt, wherein:

^R1 is a cyclopropyl, cyclobutyl, or 4-membered heterocyclic group, wherein ^R1 is optionally substituted by one or more groups selected from halogens, alkyl, hydroxyalkyl, haloalkyl, and monoalkylaminoalkyl groups.

^R2 and ^R3 are independently selected from H, halogen, alkyl, alkoxy, _-CF3 , _-CHF2 , _-CH2F , or _-OCF3 .

^R4 is aryl, heteroaryl, cycloalkyl, heterocycloyl, or heteroalkyl, wherein ^R4 is optionally substituted by one or more groups selected from: halogen, hydroxyl, alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, hydroxyalkyl, dialkylaminoalkyl, trimethylsilylethoxymethyl, _-CH2NHC (O) _CH3 , _-NO2 , _-NRaRb , -NRaC(=O)Rb, _-NRaC (=O) _NRaRb , _-NRaC (=O) _ORb , _-ORa , _-CN , _-C (=O) _{Ra ,} -C(=O) _ORa , -C(=O) _NRaRb , _-OC (=O) _Ra , _-OC (=O) _ORa , -OC(=O _{) NRaRb} , _-SRa Aza-butane, oxa-butane, tetrahydrofuranyl, furanyl, pyrrolyl, pyrrolyl, pyrazolyl, thiophenyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, furanyl, oxadiazolyl, thiadiazolyl, phenyl, tetrahydropyranyl, pyranyl, pyridinyl, pyridinyl, piperidinyl, pyrazinyl, morpholinyl, and thiomorpholinyl, _Ra and _Rb are independently -H, halogen, amino, alkyl, or haloalkyl, and

^R5 is H, halogen, or alkyl.

In some embodiments, ^R1 is cyclopropyl or cyclobutyl, wherein ^R1 is optionally substituted with one or more groups selected from halogen, _C1 - _C3 alkyl, _C1 - _C3 hydroxyalkyl, and _C1 - _C3 haloalkyl; ^R2 and ^R3 are independently -H, halogen, _C1 - _C3 alkyl, _C1 - _C3 alkoxy, _-CF3 , _-CHF2 , _-CH2F , or _-OCF3 ; ^R4 is aryl, heteroaryl, cycloalkyl, or heterocyclic, wherein ^R4 is optionally substituted with one or more groups selected from: halogen, hydroxyl, _C1 - _C3 alkyl, _C2 - _C3 alkenyl, _C2 -C3 alkynyl, _C3 - _C4 cycloalkyl, _C1 - _C3 haloalkyl, mono- _C1 - _C3 alkylamino, bis- _{C1 - C3} alkylamino, _-NO2 , _-NRaRb , _-NRa C(＝O) _Rb , -NR _a C(＝O)NR _{a Rb} , -NR _a C(＝O)OR _b , -OR _a , -CN, -C(＝O)R _a , -C(＝O)OR _a , -C(＝O)NR _{a Rb} , -OC(＝O) _{R a} , -OC(＝O)OR _a , -OC(＝O)NR _{a Rb} , -SR a, azahexacyclobutane, oxacyclobutane, tetrahydrofuranyl, furanyl, pyrrolyl, pyrrolyl, pyrazolyl, thiophene, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, furazolyl, furazolyl, oxadiazolyl, phenyl, tetrahydropyranyl, pyranyl, piperidinyl, pyridinyl, pyrazinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl; _Ra and _Rb are respectively -H, halogen, amino, _C1 -C _3- alkyl or _C1 - _C3 haloalkyl; ^R5 is H, F-, Cl-, Br- or methyl.

In various embodiments, ^R1 is cyclopropyl or cyclobutyl, wherein ^R1 is optionally substituted with one or more groups selected from halogens, _C1 - _C3 alkyl, _C1 - _C3 hydroxyalkyl, and _C1 - _C3 haloalkyl. In specific embodiments, ^R1 is cyclopropyl, fluorocyclopropyl, hydroxycyclopropyl, hydroxymethylcyclopropyl, difluorocyclopropyl, methylaminomethylcyclopropyl, cyclobutyl, fluorocyclobutyl, or difluorocyclobutyl. In other specific embodiments, ^R1 is cyclopropyl, fluorocyclopropyl, cyclobutyl, or fluorocyclobutyl.

In some other embodiments, ^R1 is a 4-membered heterocyclic group, wherein ^R1 is optionally substituted by one or more groups selected from: halogen, _C1 - _C3 alkyl, _C1 - _C3 hydroxyalkyl, and _C1 - _C3 haloalkyl. In a particular embodiment, the 4-membered heterocyclic group is selected from aziridinyl, 2H-azacyclobutane, ethylene oxide, thiocyclobutane, azacyclobutane, 2,3-dihydroazacyclobutane, azayl, 1,3-diazacyclobutane, oxacyclobutane, 2H-oxacyclobutane, thiocyclobutane, and 2H-thiacyclobutane.

In some implementations, ^R2 and ^R3 are independently –H, methyl, or fluorine.

In some embodiments, ^R4 is phenyl, pyridinyl, pyrimidinyl, indololinyl, pyrazolyl, thiazolyl, oxindololinyl, pyrropyridinyl, pyrazolinyl, pyrazolinyl, oxodihydropyridinyl, oxodihydrobenzothiazole, benzimidazolyl, benzoxazolyl, benzothiazole, thiophene, pyrropyridinyl, or isothiazolyl, wherein ^R4 is optionally substituted with one or more groups selected from the group consisting of halogenated, alkyl, alkenyl, alkynyl, hydroxyalkyl, amino, cyano, acetyl, hydroxyl, and haloalkyl. In particular embodiments, R ⁴ represents fluoromethylphenyl, fluorohydroxymethylphenyl, chlorohydroxymethylphenyl, methylhydroxymethylphenyl, difluorohydroxymethylphenyl, chlorofluorohydroxymethylphenyl, fluoromethylhydroxymethylphenyl, chloromethylphenyl, dimethylphenyl, acetamylmethylphenyl, hydroxymethylphenyl, hydroxypropylmethylphenyl, methpropenylphenyl, methylpyridylethylphenyl, methylpyrrolylphenyl, methylthiazolylphenyl, imidazolylmethylphenyl, cyanomethylphenyl, methylpyridylphenyl, ethynylmethylphenyl, methylpyridyl, fluoromethylaminophenyl, dimethylpyridyl, fluoromethylpyridyl, fluoromethylmethylpyridyl, cyanopyridyl, trifluoromethylmethylpyridyl, hydroxymethylpyridyl, hydroxy Methylmethylpyridyl, hydroxyethylmethylpyridyl, chloromethylpyridyl, aminopyridyl, acetylmethylpyridyl, aminodimethylpyridyl, hydroxyethylmethylpropenyl, methylindolyl, methyloxoindolyl, trimethylsiloxymethylindolyl, acetylmethylindolyl, methylpyrimidinyl, dimethylpyrimidinyl, trifluoromethylpyrimidinyl, pyrazolyl, methylthiazolyl, methyloxoindolinyl, pyrrolopyridyl, methylpyrrolopyridyl, methyltetrahydropyranyl, methylpyrazolyl, methyloxodihydrobiphenylthiazolyl, pyrazolopyridyl, oxodihydropyridyl, methylisothiazolyl, chloromethylisothiazolyl, dimethylisothiazolyl, or fluoromethylindolyl. In a particular embodiment, R ⁴ represents fluoromethylphenyl, fluorohydroxymethylphenyl, chlorohydroxymethylphenyl, methylhydroxymethylphenyl, difluorohydroxymethylphenyl, chlorofluorohydroxymethylphenyl, fluoromethylhydroxymethylphenyl, chloromethylphenyl, dimethylphenyl, acetamylmethylphenyl, hydroxymethylphenyl, methpropenylphenyl, ethynylmethylphenyl, fluoromethylaminophenyl, fluorohydroxymethylphenyl, methylmethylaminophenyl, methylpyrrolylphenyl, methylthiazolylphenyl, cyanomethylphenyl, imidazolylmethylphenyl, methylpyridyl, chloromethylpyridyl, fluoromethylpyridyl, fluoromethylmethylpyridyl, dimethylpyridyl, amino Pyridyl, aminodimethylpyridyl, methoxypyridyl, acetylmethylpyridyl, hydroxymethylpyridyl, hydroxymethylmethylpyridyl, hydroxyethylmethylpyridyl, cyanopyridyl, trifluoromethylpyridyl, methylthiophenyl, methylindololinyl, methylpyrimidinyl, dimethylpyrimidinyl, pyrazolyl, methylpyrazolyl, methylpyrazolyl, methylindololinyl, methyloxoindololinyl, pyrrolopyridyl, methylpyrrolopyridyl, methylpyrrolopyridyl, methylpyrrolopyridyl, pyrazolopyridyl, dihydropyrrolopyridyl, methylisothiazolyl, dimethylisothiazolyl, methylindololinyl, or methylbenzothiazolyl. In certain embodiments, ^R4 is pyridyl or phenyl having one or more substitutions selected from alkyl, alkenyl, alkynyl, cycloalkyl, halogenated, hydroxyl, hydroxyalkyl, haloalkyl, cyano, amino, alkoxy, alkoxyalkyl, alkoxyalkyl, and haloalkyl. In some specific embodiments, ^R4 is selected from:

In some embodiments, ^R1 is cyclopropyl, fluorocyclopropyl, difluorocyclopropyl, cyclobutyl, fluorocyclobutyl, or difluorocyclobutyl; ^R2 and ^R3 are independently –H, methyl, or fluorine; ^R4 is fluoromethylphenyl, fluorohydroxymethylphenyl, chloromethylphenyl, dimethylphenyl, acetamide methylphenyl, hydroxymethylphenyl, methacrylylphenyl, ethynylmethylphenyl, fluoromethylmethylaminophenyl, methylpyrrolylphenyl, methylthiazolylphenyl, cyanomethylphenyl, imidazolylmethylphenyl, methylpyridyl, chloromethylpyridyl, fluoromethylpyridyl, fluoromethylmethylpyridyl, dimethylpyridyl, aminopyridyl, aminodimethylpyridyl, methoxypyridyl, acetylmethyl Pyridyl, hydroxymethylpyridyl, hydroxymethylmethylpyridyl, hydroxyethylmethylpyridyl, cyanopyridyl, trifluoromethylpyridyl, methylthiophenyl, methylindololinyl, methylpyrimidinyl, dimethylpyrimidinyl, pyrazolyl, methylpyrazolyl, methylindololinyl, methyloxoindololinyl, pyrrolidinyl, methylpyrrolidinyl, methylpyrrolidinyl, pyrazolopyridyl, dihydropyrrolidinyl, methylisothiazolyl, dimethylisothiazolyl, methylindololinyl, or methylbibenzothiazolyl.

The compounds described herein possess c-abl inhibitory activity and selectivity for c-abl. These compounds may be effective in treating cancer and/or proliferative diseases.

In one embodiment, ^R1 is cyclopropyl, fluorocyclopropyl, cyclobutyl, fluorocyclobutyl, or difluorocyclobutyl; ^R2 and ^R3 are –H; ^R4 is phenyl, pyridinyl, pyrazolyl, pyrrolopyridinyl, dihydroindolyl, oxondolyl, benzothiazolyl, benzimidazolyl, benzoxazolyl, or thiophene, wherein R4 is optionally composed of one or more elements selected from halogen, hydroxyl, alkyl, haloalkyl, cycloalkyl, alkoxyalkyl, alkoxyalkoxy, alkylaminoalkyl, -NR _a R b, -NR _a C(=O)R _b , -OR a, -SR a, -CN, -C(=O) _Ra , -C(=O) _{OR a ,} -C(=O)NR _a R _b , -OC(=O) _Ra , furanyl, or pyrroleyl; _Ra and R _b are respectively -H, halogen, _amino , alkyl _, or haloalkyl; R ⁵ is -H, halogen, or _C1 - _C3 alkyl.

In various embodiments, ^R1 is a fluorocyclopropyl group, and 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;

3-(2-(2-fluorocyclopropane-1-carboxamide)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)cyclopropane-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-oxoindol-6-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-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-pyrrolo-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-oxoindol-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)cyclopropane-1-carboxamide;

2-Fluoro-N-(6-(2-oxo-2,3-dihydrobenzo[d]thiazolyl-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-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)cyclopropaneformamide;

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-fluorocyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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

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)cyclopropaneformamide

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

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

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

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-fluorocyclopropaneformamide;

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

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

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-fluorocyclopropaneformamide;

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

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

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

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

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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

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

2-Fluoro-N-(6-(6-methylbenzothiazo-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide;

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

2-Fluoro-N-(6-(5-methylbenzothiazo-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide;

2-Fluoro-N-(6-(7-methylbenzothiazo-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide;

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-(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)cyclopropane-1-carboxamide;

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

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

2-Fluoro-N-(6-(5-methylthiazolyl-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)cyclopropaneformamide;

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

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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

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

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)cyclopropaneformamide;

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-pyrrolo-3-yl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide;

2-Fluoro-N-(6-(2-(hydroxymethyl)-5-(1H-pyrrolo-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)cyclopropaneformamide;

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

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

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

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

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

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

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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

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

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)cyclopropaneformamide;

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)benzothiazo-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide;

2-Fluoro-N-(6-(5-(hydroxymethyl)benzothiazo-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)cyclopropaneformamide;

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]thiazo-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide;

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

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

2-Fluoro-N-(6-(7-(hydroxymethyl)benzothiazo-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

N-(6-(5-(hydroxymethyl)thiazo-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; and

2-Fluoro-N-(6-(5-(hydroxymethyl)thiazolyl-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide.

In one embodiment, ^R1 is fluorocyclopropyl; ^R2 and ^R3 are -H; ^R4 is phenyl, dihydroindolyl, oxodihydroindolyl, or benzothiazolyl, wherein ^R4 is optionally substituted by one or more groups selected from halogen, hydroxyl, alkyl, alkylamino, and pyrroleyl; _R5 is -H, halogen, or C1-C3 alkyl. In various embodiments, 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-(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)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-oxoindol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide;

2-Fluoro-N-(6-(2-methyl-5-(1H-pyrrolo-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-oxoindol-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-1H-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)cyclopropaneformamide;

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

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

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)cyclopropaneformamide; and

2-Fluoro-N-(6-(5-methylbenzothiazo-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide.

In one embodiment, the compound represented by formula (I) is selected from the compounds represented by formula (II) and their pharmaceutically acceptable salts:

Equation (II)

^R6 is selected from halogens, ^C1 - ^C3 alkyl, ^C1 - ^C3 hydroxyalkyl and ^C1 - ^C3 haloalkyl, and ^R2 , ^R3 , ^R4 and ^R5 are as defined above.

In one embodiment, the compound represented by formula (I) is a compound wherein ^R1 is cyclopropyl. In one embodiment, the compound represented by formula (I) is N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide or a salt thereof.

In another embodiment, the compound of formula (I) is a compound in which ^R1 is a cyclobutyl group, optionally substituted by one or more groups selected from halogens, alkyl groups, hydroxyalkyl groups, haloalkyl groups, and monoalkylaminoalkyl groups; ^R2 , ^R3 , ^R4 , and ^R5 are as defined above. In various embodiments, the compound represented by formula (I) is selected from the group consisting of the following compounds and their salts:

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.

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

^R2 , ^R3 , ^R4 , ^R5 and ^R6 are defined as above.

In one embodiment, the compound represented by formula (I) is selected from the compounds represented by formula (III) and their pharmaceutically acceptable salts:

^R6 is selected from halogens, ^C1 - ^C3 alkyl, ^C1 - ^C3 hydroxyalkyl, and ^C1 - ^C3 haloalkyl, and ^R2 , ^R3 , ^R4 , and ^R5 are as defined above. Table 1 shows exemplary compounds having the stereochemistry shown in formula (III). Examples of compounds shown in 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-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-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;

3-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamide)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-(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)-2-fluoro-N-(6-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-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-oxoindol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-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-(1H-pyrrolo-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)cyclopropane-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-oxoindol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-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-dihydrobenzothiazo-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-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)cyclopropaneformamide;

(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-fluorocyclopropaneformamide;

(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)cyclopropaneformamide;

(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)cyclopropaneformamide;

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

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

(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)cyclopropaneformamide

(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-fluorocyclopropaneformamide;

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

(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-fluorocyclopropaneformamide;

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

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

(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)cyclopropaneformamide;

(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)cyclopropaneformamide;

(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)cyclopropaneformamide;

(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)cyclopropaneformamide;

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

(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-methylbenzothiazo-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide;

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

(1S,2S)-2-fluoro-N-(6-(5-methylbenzothiazo-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide;

(1S,2S)-2-fluoro-N-(6-(7-methylbenzothiazo-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; and

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

In a particular embodiment, the compound represented by 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-pyrrolo-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)cyclopropaneformamide; and

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

This invention provides pharmaceutically acceptable salts of the above-described compounds. Pharmaceutically acceptable salts are as defined in the definition section above. In some embodiments, the salt is a hydrochloride, tartrate, phosphate, or maleate.

Treatment

The present invention also provides a method for treating cancer and/or proliferative disorders in subjects who have or are susceptible to such diseases or disorders by administering to a subject a therapeutically effective amount of one or more of the compounds described above.

1. Disease or symptoms

The compounds of this invention for inhibiting c-abl, KIT, and/or PDGFR activity can be used to treat or prevent cancerous diseases and proliferative diseases. These compounds can be used to inhibit or block the activity of c-abl, KIT, and/or PDGFR kinases and are used to treat cancerous diseases and proliferative diseases, or to prevent the worsening of such diseases. Therefore, this invention provides a method for inhibiting or blocking the activity of c-abl, KIT, and/or PDGFR in cells, wherein the cells are contacted with an effective amount of the compounds of this invention. In one embodiment, such cells are present in a subject (e.g., a CML patient). In another embodiment, medical use is provided for treating or preventing cancerous diseases and proliferative diseases in a subject using compounds according to the invention. The method of this invention comprises administering to a subject requiring treatment or prevention of cancerous diseases and proliferative diseases a pharmaceutical composition containing a therapeutically or preventively effective amount of a c-abl, KIT, and/or PDGFR inhibitor. Cancerous diseases and proliferative diseases include, but are not limited to, breast cancer, ovarian cancer, NSCLC, acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia.

On the other hand, the compounds described herein can be used to treat human and non-human conditions associated with abnormal KIT activity. Activating mutations in KIT have been found in a variety of indications, including systemic mastocytosis, GIST (gastrointestinal stromal tumor), AML (acute myeloid leukemia), melanoma, seminoma, intracranial germ cell tumors, and non-Hodgkin's lymphomas (NHL), such as B-cell lymphoma (BCL), T-cell lymphoma, and natural killer cell lymphoma. Furthermore, KIT mutations are associated with Ewing's sarcoma, DLBCL (diffuse large B-cell lymphoma), dysgerminoma, MDS (myelodysplastic syndrome), NKTCL (nasal NK/T-cell lymphoma), CMML (chronic myelomonocytic leukemia), and brain cancer.

Mastocytosis is a group of diseases characterized by an excessive accumulation of mast cells in one or more tissues. Mastocytosis is subdivided into two groups of diseases: (1) cutaneous mastocytosis (CM), which is described only in the form of the skin; and (2) systemic mastocytosis (SM), which is described in the form of mast cell infiltration of extradermal organs, with or without skin involvement. SM is further subdivided into five forms: indolent (ISM), smoldering (SSM), aggressive (ASM), SM with hematologic non-mastocytic spectrum disorders (SM-AHNMD), and SM of mast cell leukemia (MCL).

The diagnosis of systemic mastocytosis is partly based on histological and cytological studies of the bone marrow, which often show atypical mast cell infiltration that frequently expresses non-mast cell markers (CD25 and/or CD2). SM can be diagnosed when bone marrow mast cell infiltration occurs in one of the following ways: (1) abnormal mast cell morphology (fusiform cells); (2) serum trypsin levels above 20 ng/mL; or (3) the presence of an activated KIT D816V mutation.

Activating mutations at position D816 have been found in the vast majority (90-98%) of mastocytosis cases, with the most common mutations being D816V, D816H, and D816Y. The D816V mutation is located in the activation loop of the kinase domain, leading to constitutive activation of KIT kinase.

The compounds described in this article can also be used to treat gastrointestinal stromal tumors (GISTs). Complete surgical resection remains the preferred treatment for patients with primary GIST. Surgery is effective in approximately 50% of GIST patients; in the remaining patients, tumor recurrence is frequent. For initial treatment, the use of KIT inhibitors (such as imatinib) has proven sufficient. However, resistance to imatinib can develop within months through somatic mutations. These secondary imatinib resistance mutations are most common in exons 11, 13, 14, 17, or 18. Sunitinib is the standard second-line treatment for most imatinib-resistant tumors and is effective against tumors containing mutations in exons 11, 13, and 14. However, secondary KIT mutations in exons 17 and 18 are resistant to sunitinib treatment, and in addition, tumors containing tertiary resistance mutations in exons 17 and 18 emerge several months after sunitinib treatment. Regorafenib demonstrated satisfactory efficacy in a phase 3 clinical trial of GIST resistant to imatinib and sunitinib, exhibiting activity against several, but not all, exon 17 and 18 mutations, including D816. Therefore, therapeutic agents are needed to treat GIST patients with exon 17 mutations unresolved by regorafenib. In addition to using the compounds described herein as monotherapy in refractory GIST settings, the use of combinations of imatinib, sunitinib, and/or regorafenib with the compounds disclosed herein can prevent resistance to exon 17 mutations.

The compounds described in this article can also be used to treat AML. AML patients also have KIT mutations, most of which are located at position D816.

A subset of GIST patients have the D842V mutation in PDGFRa; this mutation can be used to stratify this subgroup of GIST patients. All currently available tyrosine kinase inhibitors are ineffective against this subset of patients. Because the compounds described herein possess PDGFRa D842V activity, they can be used to treat these patients.

In various implementations, the above method is used to treat gastrointestinal stromal tumors (GIST), gastrointestinal cancers such as gastric and colorectal cancer, melanoma, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), or acute myeloid leukemia (AML). In a specific implementation, the method is used to treat gastrointestinal stromal tumors (GIST), melanoma, or chronic lymphocytic leukemia (CLL).

2. Subjects

Suitable subjects for treatment according to the present invention include mammalian subjects. Mammals according to the present invention include, but are not limited to, humans, dogs, cats, cattle, goats, horses, sheep, pigs, rodents, rabbits, primates, etc., and include mammals in the womb. Subjects can be of any sex and at any developmental stage. In one embodiment, a suitable subject for treatment according to the present invention is a human.

3. Dosage and preparation

The compounds of the present invention are generally administered in therapeutically effective amounts. The compounds of the present invention can be administered via any suitable route in the form of a pharmaceutical composition suitable for that route, and at a dose that is expected to be therapeutically effective. An effective dose is generally from about 0.001 to about 100 mg/kg body weight per day in a single dose or fractional dose, preferably from about 0.01 to about 50 mg/kg/day. Depending on the age, type, and disease or condition of the patient being treated, dose levels below the lower limit of this range may be appropriate. In other cases, larger doses may be used without adverse side effects. Large doses may also be divided into several smaller doses for administration throughout the day. Methods for determining appropriate doses are well known in the art to which this invention pertains. For example, Remington: The Science and Practice of Pharmaceuticals, Mack Publishing Co., 20th edition, 2000.

Drug composition, dosage form and route of administration

To treat the aforementioned diseases or conditions, the compounds of the present invention or their pharmaceutically acceptable salts may be administered in the following manner:

Oral administration

The compounds of the present invention can be administered orally, including by swallowing, so that the compound enters the gastrointestinal tract, or be absorbed directly from the mouth into the bloodstream (e.g., buccal or sublingual administration).

Suitable compositions for oral administration include solid, liquid, gel, or powder formulations, and have dosage forms such as tablets, lozenges, capsules, granules, or powders.

Compositions for oral administration can be formulated to release immediately or modulated release, including delayed release or sustained release, and optionally have an enteric coating.

Liquid formulations can include solutions, syrups, and suspensions, which can be used in soft or hard capsules. Such formulations may contain pharmaceutically acceptable carriers such as water, ethanol, polyethylene glycol, cellulose, or oil. The formulation may also contain one or more emulsifiers and/or suspending agents.

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

The amount of a suitable lubricant for tablets is from about 0.1% to about 5% by weight, and includes, but is not limited to, talc, silica, stearic acid, calcium, zinc or magnesium stearate, sodium stearate, etc.

Suitable binders for tablets include, but are not limited to, gelatin, polyethylene glycol, sugar, gum, starch, polyvinylpyrrolidone, hydroxypropyl cellulose, and hydroxypropyl methylcellulose. Suitable diluents for tablets include, but are not limited to, mannitol, xylitol, lactose, dextrose, sucrose, sorbitol, microcrystalline cellulose, and starch.

The amount of a suitable solubilizer used in tablets may be from about 0.1% to about 3% by weight, and includes, but is not limited to, polysorbate, sodium lauryl sulfate, sodium dodecyl sulfate, propylene carbonate, diethylene glycol monoethyl ether, dimethyl isosorbide, polyethylene glycol (natural or hydrogenated) castor oil, HCOR ^™ (Nikkol), oleate, Gelucire ^™ , caprylic acid/caprylic acid monoglyceride/diglyceride, sorbitan fatty acid ester and Solutol HS ^™ .

Parenteral administration

The compounds of this invention can be directly administered into the bloodstream, muscles, or internal organs. Suitable methods of parenteral administration include intravenous, intramuscular, subcutaneous intra-arterial, intraperitoneal, intrathecal, and intracranial administration. Suitable devices for parenteral administration include syringes (including needle-tipped and needleless syringes) and infusion methods.

Compositions for parenteral administration can be formulated for immediate or modulated release, including delayed or sustained release. Most parenteral formulations are aqueous solutions containing excipients, including salts, buffers, 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 suitable media such as sterile water. Solubilizers can also be used to prepare parenteral solutions.

transdermal drug delivery

The compounds of this invention can be applied topically to the skin or transdermally. Formulations for this topical administration can include lotions, solutions, creams, gels, hydrogels, ointments, foams, implants, patches, etc. Pharmaceutically acceptable carriers for topical administration formulations can include water, alcohol, mineral oil, glycerin, polyethylene glycol, etc. Topical or transdermal administration can also be performed via electroporation, iontophoresis, ultrasound transdermal therapy, etc.

Compositions for local administration can be formulated to release immediately or modulatedly, including delayed release or sustained release.

combination therapy

The pharmaceutical compositions according to the invention may contain one or more additional therapeutic agents, for example, to enhance efficacy or reduce side effects. Therefore, in some embodiments, the pharmaceutical composition further contains one or more other therapeutic agents selected from the active ingredient, which can be used to treat or inhibit diseases directly or indirectly mediated by c-abl, KIT, and/or PDGFR kinases. Examples of such active ingredients are, but are not limited to, imatinib, sunitinib, and regorafenib. Other agents include compound 1 as described in WO2014/039714 and WO2014/100620.

References for the preparation of pharmaceutical compositions

Methods for preparing pharmaceutical compositions for treating or preventing diseases or conditions are well known in the art to which this invention pertains. For example, pharmaceutically acceptable excipients, carriers, additives, etc., can be selected according to the Handbook of Pharmaceutical Excipients (7th edition), Remington: The Science and Practice of Pharmaceuticals (20th edition), the Encyclopedia of Pharmaceutical Technology (3rd edition), or Sustained-Release and Controlled-Release Drug Delivery Systems (1978), and then mixed with the compounds of this invention to prepare pharmaceutical compositions.

This invention provides compounds with various pharmacological effects by inhibiting c-abl, KIT, and/or PDGFR activity; pharmaceutical compositions having the compounds as active agents; medical uses of the compounds, particularly for the treatment of cancerous diseases and proliferative diseases; and methods of treatment or prevention comprising administering the compounds to a subject in need of such treatment or prevention. The compounds of this invention and their pharmaceutically acceptable salts exhibit good safety and high selectivity for c-ab, KIT, and/or PDGFR, thus demonstrating excellent performance as medicines.

Example

The invention is described in considerable detail below by way of examples to aid those skilled in the art in understanding it. However, the following embodiments are merely illustrative and are not intended to limit the scope of the invention. It will be apparent that various changes can be made without departing from the spirit and scope of the invention or without sacrificing all its material advantages.

Synthesis of the compound shown in formula (I)

Synthetic methods A to N are used to prepare the following compounds. Exemplary synthetic examples of some compounds of the present invention are described below, and other compounds can be prepared using different starting or reactant materials by methods similar to those described below.

Synthesis Method A

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

Step 1) 6-Iodoimidazole[1,2-a]pyridine-2-amine

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 refluxed and heated for 18 hours, cooled to room temperature, concentrated under reduced pressure, and separated between ethyl acetate and a saturated aqueous solution of ammonium chloride. The organic layer was washed with a saturated aqueous solution of sodium chloride, separated, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was diluted with dichloromethane (30 mL) and hexane (200 mL) and stirred at ambient temperature. The resulting precipitate was collected by filtration, washed with hexane, and dried to give compound 2 (5.890 g, 80.7%) as a brown solid.

Step 2)(1S,2S)-2-fluoro-N-(6-iodoimidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide

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 at room temperature with N,N-diisopropylethylamine (2.376 mL, 13.642 mmol) and stirred at the same temperature for 40 hours. The precipitate was collected by filtration, washed with dichloromethane, and dried to give compound 3 (3.870 g, 49.3%) as a pale yellow solid.

¹ H NMR (400MHz, DMSO-d6) δ10.99 (s, 1H), 8.87 (s, 1H), 8.02 (s, 1H), 7.36~7.23 (m, 2 H), 4.97~4.77(m, 1H), 2.09~2.07(m, 1H), 1.65~1.57(m, 1H), 1.16~1.09(m, 1H).

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

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) were mixed at room temperature and then heated in a microwave at 100 °C for 30 min. After cooling to room temperature, the mixture was filtered through a diatomaceous earth mat to remove solids and partitioned between ethyl acetate and a saturated sodium bicarbonate aqueous solution. The organic layer was washed with a saturated sodium chloride aqueous solution, separated, dried (anhydrous magnesium sulfate), filtered, and concentrated under vacuum. The residue was subjected to chromatographic analysis (SiO₂ ₎ . The crude product was obtained by crystallization with diethyl ether (5 mL) at room temperature using a 45 g cartridge (ethyl acetate/hexane = 70%-100%). The resulting precipitate was filtered, washed with diethyl ether, and dried to give compound 4 (0.700 g, 73.8%) as a white solid.

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

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 hours. The precipitate was collected by filtration, washed with diethyl ether, and dried to give Example 1 (0.665 g, 99.7%) as a white solid.

1H NMR (400MHz, DMSO-d6) δ11.67 (s, 1H), 8.74 (s, 1H), 8.13 (s, 1H), 7.69 (d, J = 9.2Hz, 1H), 7.55 (d, J = 9.2Hz, 1H), 7.35 ~ 7.30 (m , 1H), 7.23 (t, J=9.2Hz, 1H), 7.15 (d, J=7.2Hz, 1H), 5.05～4.85 (m, 1H), 7.21～7.14 (m, 4H), 1.69～1.63 (m, 1H), 1.21～1.18 (m, 1H).

Synthesis Method B

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

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

The solution of Example 1 (0.060 g, 0.183 mmol) in acetonitrile (8 mL) was mixed with 1-chloropyrrolidine-2,5-dione (NCS, 0.027 g, 0.202 mmol) at room temperature and stirred for 3 hours at the same temperature, and partitioned between ethyl acetate and saturated sodium bicarbonate aqueous solution. The organic layer was washed with saturated sodium chloride aqueous solution, separated, dried (anhydrous magnesium sulfate), filtered, and concentrated under vacuum. The residue was subjected to chromatographic analysis ( _SiO₂ , 12 g cartridge; ethyl acetate/hexane = 70%–100%), yielding a crude product that crystallized at room temperature using diethyl ether (5 mL). The resulting precipitate was filtered, washed with diethyl ether, and dried to give Example 3 (0.015 g, 22.6%) as a white solid.

1H NMR (400MHz, DMSO-d6) δ10.44 (s, 1H), 8.21 (s, 1H), 7.62 (d, J＝9.6Hz, 1H), 7.35 (dd, J＝9.2, 1.6Hz, 1H), 7.30 (t, J＝7.0Hz , 1H), 7.24~7.19(m, 2H), 5.01~4.83(m, 1H), 2.15(d, J=2.4Hz, 3H), 2.06~2.03(m, 1H), 1.64~1.56(m, 1H), 1.15~1.08(m, 1H).

Synthesis method C

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

Step 1)(E)-2-(5-iodo-2-(tolylamino)pyridin-1(2H)-yl)propylamine

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

1H NMR (400MHz, DMSO-d6) δ8.15 (d, J＝1.6Hz, 1H), 7.87 (dd, J＝9.6, 2.4Hz, 1H), 7.75 (s, 1H), 7.62 (d, J＝8.0Hz, 2 H), 7.38 (s, 1H), 7.24 (d, J=8.4Hz, 2H), 7.16 (d, J=9.6Hz, 1H), 5.63 (m, 1H), 2.30 (s, 3H), 1.60 (d, J=7.2Hz, 3H).

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

Compound 6 (4.220 g, 9.477 mmol) was mixed in a stirred slurry of dichloromethane (50 mL) with trifluoroacetic anhydride (8.032 mL, 56.863 mmol) at room temperature. The reaction mixture was refluxed and heated for 4 hours, cooled to room temperature, and concentrated under reduced pressure. The residue was diluted with diethyl ether (300 mL) and stirred at ambient temperature. The precipitate was collected by filtration, washed with diethyl ether, and dried to give a crude product. The crude product was redissolved in water (300 mL) and stirred at ambient temperature. The precipitate was collected by filtration, washed with water, and dried to give compound 7 (3.098 g, 88.6%) as a pale yellow solid.

Step 3) 6-Iodo-3-methylimidazo[1,2-a]pyridine-2-amine

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

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

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]pyridine 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). The mixture was 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 precipitate was collected by filtration, washed with water, and dried to give a crude product. The crude product was redissolved in ethyl acetate (50 mL) and stirred at ambient temperature. The precipitate was collected by filtration, washed with ethyl acetate and dried to give compound 9 (1.070 g, 58.1%) as a white solid.

1H NMR (400MHz, DMSO-d6) δ10.24 (s, 1H), 8.51 (s, 1H), 7.36 (dd, J＝9.2, 1.6Hz, 1H), 7.27 (d, J＝ 9.2Hz, 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).

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

Compound 9 (0.200 g, 0.557 mmol), (4-methylpyridin-3-yl)boronic acid (0.099 g, 0.724 mmol), [1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium(II) (Pd(dppf) _Cl2 , 0.041 g, 0.056 mmol), and potassium carbonate (0.231 g, 1.671 mmol) were mixed in water (3 mL)/tetrahydrofuran (12 mL) at room temperature, then heated in a microwave at 120 °C for 1 hour. After cooling to room temperature, the mixture was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous sodium chloride solution, separated, dried (anhydrous magnesium sulfate), filtered, and concentrated under vacuum. The residue was subjected to chromatographic analysis ( _SiO₂ , 10 g cartridge; tetrahydrofuran/ethyl acetate = 0%–10%) to obtain a crude product, which was dissolved in diethyl ether (5 mL) and hexane (20 mL) and stirred at ambient temperature. The precipitate was collected by filtration, washed with hexane, and dried to give Example 5 (0.100 g, 55.4%) as a beige solid.

1H NMR (400MHz, DMSO-d6) δ10.25 (s, 1H), 8.47 (s, 1H), 8.44 (d, J＝5.2Hz, 1H), 8.26 (s, 1H), 7.51 (d, J＝9.2Hz, 1H), 7.34 (d, J＝ 5.2Hz, 1H), 7.24 (d, J=9.2Hz, 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).

Synthesis method D

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

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

In 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) were mixed in 1,4-dioxane (12 mL)/water (3 mL) at room temperature, then heated in a microwave at 140 °C for 1 hour, cooled to room temperature, and partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous sodium chloride solution, separated, dried (anhydrous magnesium sulfate), filtered, and concentrated under vacuum. The residue was subjected to chromatographic analysis ( _SiO₂ , 10 g cartridge; tetrahydrofuran/ethyl acetate = 0%–20%), yielding a crude product dissolved in dichloromethane (3 mL) and hexane (20 mL) under stirring at ambient temperature. The precipitate was collected by filtration, washed with diethyl ether, and dried to give Example 29 (0.005 g, 4.6%) as a pale yellow solid.

1H NMR (400MHz, DMSO-d6) δ12.82(s,1H),10.99(s,1H),8.58(s,1H),8.08(s,1H),7.73～7.69(m,2H),7.46～7.2 3(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).

Synthesis Method E

Example 34 (1S,2S)-2-fluoro-N-(3-fluoro-6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-2- (Base) cyclopropane formamide

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

The 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-diazobicyclo[2.2.2]octane difluoroborate (0.162 g, 0.4582 mmol), stirred at room temperature for 3 hours, and partitioned between dichloromethane and a saturated aqueous sodium bicarbonate solution. The organic layer was washed with a saturated aqueous sodium chloride solution, separated, dried ( _{anhydrous Na₂SO₄} ), filtered, and concentrated under vacuum. The residue was subjected to chromatographic analysis ( _SiO₂ , 12 g cartridge; ethyl acetate/hexane = 0%–30%), yielding Example 34 (0.021 g, 15%) as a yellow solid.

1H NMR (400MHz, DMSO-d6) δ10.56 (s, 1H), 8.23 (s, 1H), 7.49 (d, J = 9.6Hz, 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).

Synthesis method F

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

Step 1) 3-(2-((1S,2S)-2-fluorocyclopropane-1-carboxamide)imidazo[1,2-a]pyridin-6-yl)-4-methylphenyltrifluoromethanesulfonate

A mixture of dichloromethane (100 mL) from Example 12 (0.842 g, 2.588 mmol) and pyridine (0.313 mL, 3.882 mmol) was treated with trifluoromethanesulfonic anhydride (0.479 mL, 2.847 mmol) at 0 °C, stirred at the same temperature for 1 hour, and partitioned between dichloromethane and a saturated aqueous sodium bicarbonate solution. The organic layer was washed with a saturated aqueous sodium chloride solution, separated, dried (anhydrous magnesium sulfate), filtered, and concentrated under vacuum. The residue was subjected to chromatographic analysis ( _SiO₂ , 10 g cartridge; ethyl acetate/hexane = 80%–100%) to give compound 10 (0.056 g, 4.7%) as a purple solid.

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

Compound 10 (0.056 g, 0.122 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxobenzofuran-2-yl)-1H-pyrrole (0.031 g, 0.159 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf) _Cl₂ , 0.009 g, 0.012 mmol), and potassium carbonate (0.051 g, 0.367 mmol) in water (3 mL)/tetrahydrofuran (12 mL) were mixed at room temperature, then heated in a microwave oven at 120 °C for 30 min, cooled to room temperature, and partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous sodium chloride solution, separated, dried (anhydrous magnesium sulfate), filtered, and concentrated under vacuum. The residue was subjected to chromatographic analysis ( _SiO₂ , 10 g cartridge; tetrahydrofuran/ethyl acetate = 0%–10%), yielding a crude product dissolved in diethyl ether (5 mL) and hexane (5 mL) under stirring at ambient temperature. The precipitate was collected by filtration, washed with diethyl ether, and dried to give Example 41 (0.005 g, 10.9%) as a white solid.

1H NMR (400MHz, DMSO-d6) δ10.97(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＝4.4,2.8Hz,1H),6.41(dd,J＝4.4,2.8Hz,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).

Synthesis method G

Example 44. (1S,2S)-2-fluoro-N-(6-(4-fluoro-5-hydroxy-2-methylphenyl)imidazo[1,2-a]pyridine- 2-yl)cyclopropaneformamide

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

Compound 3 (0.800 g, 2.318 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxoboronylcyclopentane) (1.177 g, 4.636 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloro(Pd(dppf) _Cl₂ , 0.169 g, 0.231 mmol), and potassium acetate (0.796 g, 8.113 mmol) were mixed in DMSO (20 mL) at room temperature and stirred at 90 °C for 24 h. After cooling to room temperature, the solids were removed by filtration through a diatomaceous earth mat and separated between ethyl acetate and water. The organic layer was washed with saturated sodium chloride aqueous solution, separated, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residues were analyzed by chromatography (SiO₂ ₎ . , 12g cartridge; ethyl acetate/hexane = 0%-100%), to obtain compound 11 (0.560g, 69.9%) as a brown solid.

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

Compound 11 (0.080 g, 0.231 mmol), 5-bromo-2-fluoro-4-methylphenol (0.056 g, 0.277 mmol), [1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium(II) (Pd(dppf) _Cl₂ (0.017 g, 0.023 mmol)) and _{Na₂CO₃ (} 0.049 g, 0.462 mmol) in dioxane (2 mL)/water (0.5 mL) at room temperature were mixed, degassed, and purged with _N₂ for 1 min. The mixture was then stirred at 80 °C under _N₂ atmosphere for 12 h. The reaction mixture was concentrated to give a residue. The residue was purified. Chromatographic analysis of the residue ( _SiO₂ , 12 g cartridge; ethyl acetate/hexane = 80%–100%) gave Example 44 (0.031 g, 39.8%) as a white solid.

1H NMR (400MHz, DMSO-d6) δ10.98 (s, 1H), 9.75 (bs, 1H), 8.47 (s, 1H), 8.05 (s, 1H), 7.40 (d, J=9.2Hz, 1H), 7.13 (dd, J=9.2, 2.0Hz , 1H), 7.06 (d, J=12.4Hz, 1H), 6.81 (d, J=9.2Hz, 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).

Synthesis method H

Example 66. (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(methoxymethyl)phenyl)imidazo[1,2-a]pyridine (Pyridine-2-yl)cyclopropaneformamide

Step 1) 1-Bromo-3-fluoro-2-(methoxymethyl)benzene

NaH (146.31 mg, 3.66 mmol, 60% purity, 1.5 eq) was added dropwise to a solution of compound 12 (500 mg, 2.44 mmol, 1 eq) in THF (10 mL) at 0 °C under _N2. The reaction mixture was stirred at 0 °C under _N2 for half an hour, followed by dropwise addition of MeI (692.30 mg, 4.88 mmol, 303.64 μL, 2 eq). The mixture was then stirred at 20 °C under _N2 for another hour. A saturated aqueous solution of _NH4Cl (30 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL x 2) _. The combined organic layers were dried over _Na2SO4 , filtered, and concentrated under reduced pressure to obtain the residue. Compound 13 (510 mg, crude product) was obtained as butter.

1H NMR (400MHz, CDCl ₃ ) δ7.41 (d, J=8.1Hz, 1H), 7.18 (dt, J=5.9, 8.2Hz, 1H), 7.10-7.00 (m, 1H), 4.64 (d, J=2.3Hz, 2H), 3.42 (s, 3H).

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

Pd(dppf) _Cl₂ (26.72 mg, 36.52 μmol, 0.1 eq) and Na₂CO₃ (77.42 mg, 730.42 μmol, 2 eq) were added to a solution of compound 13 (80 mg, 365.21 μmol, 1 eq) and compound ₁₁ (151.27 mg, 438.25 μmol, 1.2 eq) in _dioxane ( ₂ mL) and H₂O (0.4 mL). The mixture was then stirred at 90 °C for 12 h under _N₂ . The reaction mixture was diluted with ethyl acetate (300 mL) and filtered through silica gel. The filtrate was concentrated to give the residue. The residue was purified by prep 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, 53.03% yield, 100% purity, TFA) was obtained as a white solid.

1H NMR(400MHz,DMSO-d6)δ11.25(s,1H),8.68(s,1H),8.14(s,1H),7.60(d,J＝9 .2Hz,1H),7.52(dt,J＝6.0,7.9Hz,1H),7.44(dd,J＝1.6,9.2Hz,1H),7.33(d,J＝8. 7Hz,1H),7.30-7.25(m,1H),5.11-4.76(m,1H),4.30(br d,J＝1.3Hz,2H),3.25( s,3H),2.23-2.08(m,1H),1.76-1.59(m,1H),1.20(tdd,J=6.3,9.1,12.4Hz,1H).

Synthesis Method I

Example 67. (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-(furan-2-yl)phenyl)imidazo[1,2-a]pyridine- 2-yl)cyclopropaneformamide

Step 1) 2-(2-bromo-6-fluorophenyl)furan

To a solution of compound 14 (511.74 mg, 1.70 mmol, 1.1 eq) and 2-(furan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxane (300 mg, 1.55 mmol, 1 eq) in dioxane (3 mL) and _H₂O (0.6 mL), Pd(dppf) _Cl₂ (113.13 mg, 154.61 μmol, 0.1 eq) and _Na₂CO₃ (491.61 _mg , 4.64 mmol, 3 eq) were added, and the reaction mixture was stirred at 80 °C for 3 hours under _N₂ . The reaction mixture was poured into water (50 mL), and the mixture was extracted with ethyl acetate (50 mL x 2) _. The combined organic layers were dried over _Na₂SO₄ , filtered, and concentrated under reduced pressure to give the residue. The residue was purified by prep-TLC ( _SiO₂ , petroleum ether:ethyl acetate = 3:1). The residue was purified by prep-TLC ( _SiO2 , petroleum ether: ethyl acetate = 1:0). Compound 15 was given as butter (70 mg, 290.39 μmol, 18.78% yield).

1H NMR (400MHz, CDCl ₃ )δ7.61 (dd, J=0.8, 1.8Hz, 1H), 7.48 (td, J=1.1, 8.0Hz, 1H), 7.21 (dt, J=5.8, 8.1Hz , 1H), 7.15-7.08 (m, 1H), 6.70 (td, J=0.9, 3.3Hz, 1H), 6.56 (dd, J=1.8, 3.3Hz, 1H).

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

Pd(dppf) _Cl₂ (21.25 mg, 29.04 μmol, 0.1 eq) and Na₂CO₃ (92.33 mg, 871.17 μmol, 3 eq) were added to a solution of compound 15 (70 mg, 290.39 μmol, 1 eq) and compound ₁₁ (110.26 mg, 319.43 μmol, 1.1 eq) in _dioxane (1 mL) and _H₂O (0.2 mL). The reaction mixture was then stirred at 80 °C for 12 hours under _N₂ . The reaction mixture was poured into brine (10 mL), and 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 the residue. The residue was dissolved in methanol:dichloromethane (1:10, 100 mL), and the mixture was filtered through silica gel. The filtrate was concentrated to give the residue. The residue was purified by prep-HPLC (column: Phenomenex Synergi C18150*25*10um; mobile phase: [water (0.1% TFA)-ACN]; B%: 34%-54%, 9 min). Example 67 (38.3 mg, 77.63 μmol, 26.73% yield, 100% purity, TFA) was given as a white solid.

1H NMR (400MHz, DMSO-d6) δ11.20 (s, 1H), 8.61 (s, 1H), 8.08 (s, 1H), 7.61 (dd, J=0.9, 1.6Hz, 1H), 7.60-7.54(m, 1H), 7.45-7.41(m, 1H), 7.40-7.36( m, 2H), 6.93 (dd, J=1.3, 9.3Hz, 1H), 6.56-6.48 (m, 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, 12.4Hz, 1H).

Synthesis Method J

Example 72. N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide

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

Pd(dppf) _Cl₂ (206.08 mg, 281.65 μmol, 0.1 eq) and Na₂CO₃ (298.52 mg, 2.82 mmol, 1 eq) were added to a solution of compound ₁ ( ₁ g, 2.82 mmol, 1 eq) in dioxane (10 mL) and _H₂O (1 mL). The mixture was stirred at 80 °C for 16 h under _N₂ . The reaction mixture was diluted with 30 mL of water and extracted with ethyl acetate (30 mL x 2). The combined organic layers were washed with brine (30 mL x 2), dried over _Na₂SO₄ , _filtered , and the filtrate was concentrated under reduced pressure to give the residue. The residue was purified by column chromatography (silica gel, petroleum ether:ethyl acetate = 20:1 to 5:1). Compound 16 was given as a white solid (500 mg, 1.48 mmol, yield 52.64%).

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

To a solution of compound 16 (500 mg, 1.48 mmol, 1 eq) in MeOH (10 mL) and _H₂O (10 mL) _{, K₂CO₃} (1.02 g, 7.41 mmol, 5 eq) was added. The mixture was stirred at 75 °C for 2 hours. 50 mL of water was added to the reaction mixture, and the mixture was extracted with ethyl acetate (50 mL x 2). The combined organic layers were washed with brine (50 mL x 2), dried over _Na₂SO₄ , filtered, and the filtrate was concentrated under reduced pressure to give the residue. Compound 17 (300 mg, 1.24 mmol, 83.88% yield) was given as _a yellow solid.

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

Cyclopropanecarboxylic acid (53.52 mg, 621.73 μmol, 49.10 μL, 1.5 eq) and DCC (85.52 mg, 414.49 μmol, 83.84 μL, 1 eq) were added to a solution of compound 17 (100 mg, 414.49 μmol, 1 eq) in EtOAc (2 mL). The mixture was stirred at 20 °C for 32 h. Then DMAP (5.06 mg, 41.45 μmol, 0.1 eq) was added to the mixture, and the mixture was stirred at 20 °C for 16 h. The reaction mixture was diluted with 20 mL of water and extracted with ethyl acetate (20 mL x 2). The combined organic layers were washed with brine (20 mL x ₂ ), dried over _Na₂SO₄ , filtered, and the filtrate was concentrated under reduced pressure to give the residue. The residue was purified by prep HPLC (column: Phenomenex Luna C18 150*25mm*10um; mobile phase: [water (0.1% TFA)-ACN]; B%: 22%-52%, 10 min). Example 72 (45.9 mg, 106.25 μmol, 25.63% yield, 98% purity, TFA) was obtained as a pink solid.

1H NMR (400MHz, DMSO-d6) δ11.22 (br s, 1H), 8.66 (s, 1H), 8.09 (s, 1H), 7.59 (d, J＝9.2Hz, 1H), 7.40 (br d, J＝9.3Hz, 1H), 7.38- 7.30 (m, 1H), 7.28-7.21 (m, 1H), 7.17 (d, J=7.5Hz, 1H), 2.18 (d, J=2.3Hz, 3H), 1.94 (quin, J=6.2Hz, 1H), 0.85 (d, J=6.1Hz, 4H).

Synthesis method K

Example 77. (1S,2S)-N-(6-(2-(acetamidomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridine-2- 2-Fluorocyclopropaneformamide

Step 1) N-(2-bromo-6-fluorobenzyl)acetamide

To a solution of compound 18 (200 mg, 695.94 μmol, 1 eq) in Py (5 mL) _{, Ac₂O} (85.26 mg, 835.13 μmol, 78.22 μL, 1.2 eq) was added. The mixture was stirred at 25 °C for 3 hours. The desired MS concentration was determined by LC-MS. The mixture was concentrated under reduced pressure to obtain a residue. The residue was adjusted to pH 6 with hydrochloric acid and extracted with EA (30 mL x 3). The organic phase was concentrated under reduced pressure to obtain a residue. Compound 19 (130 mg, 412.07 μmol, yield 59.21%, purity 78%) was given as a pale yellow solid.

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

Pd(dppf) _Cl₂ (26.46 mg, 36.17 μmol, 0.1 eq) and Na₂CO₃ (76.67 mg, 723.35 μmol, 2 eq) were added to a solution of compound 19 (100 mg, 361.68 μmol, 1 eq) and compound ₁₁ (122.35 mg, 354.44 μmol, 0.98 eq) in water (1 mL) and _dioxane (4 mL). The mixture was degassed and purged three times with _N₂ . The mixture was then stirred at 80 °C for 16 h under _N₂ atmosphere. The desired MS was determined by LC-MS. The mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain the residue. The residue was purified by prep HPLC (column: Phenomenex Luna C18 250*50mm*10μm; mobile phase: [water (0.1% TFA)-ACN]; B%: 10%-40%, 9 min). Example 77 (15.3 mg, 29.84 μmol, 8.25% yield, 97.2% purity, TFA) was obtained as a white solid.

1H NMR (400MHz, CD3OD) δ8.67 (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).

Synthesis method L

Example 84. (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((2-methoxyethoxy)methyl)phenyl)imidazo [1,2-a]pyridin-2-yl)cyclopropaneformamide.

Step 1) 1-Bromo-3-fluoro-2-((2-methoxyethoxy)methyl)benzene

Compound 20 (445.00 mg, 2.17 mmol, 1 eq) was dissolved in DMF (15 mL). NaH (130.22 mg, 3.26 mmol, 60% purity, 1.5 eq) was added in portions to the DMF at 0 °C. The resulting mixture was stirred in _N₂ for 30 min before adding 1-bromo-2-methoxy-ethane (362.01 mg, 2.60 mmol, 244.60 μL, 1.2 eq) at 0 °C. The mixture was then stirred again in _N₂ at 15 °C for 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 to PE/EA = 4/1) to give compound 21 as a pale yellow oil (178 mg, 676.54 μmol, 31.17% yield).

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

A mixture of compound 21 (178 mg, 676.54 μmol, 1 eq) and compound 11 (210.17 mg, 608.89 μmol, 0.9 eq) was dissolved in dioxane (10 mL) and _H₂O (2 mL), to which Pd(dppf) _Cl₂ (99.01 _mg , 135.31 μmol, 0.2 eq) and _Na₂CO₃ (215.12 mg, 2.03 mmol, 3 eq) were added in portions. The resulting mixture was then stirred at 80 °C for 16 hours under _N₂ conditions. The desired m/z was determined by LC-MS. The mixture was filtered, the filtrate was 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 (PE/EA = 10/1 to 1/1), and then purified by Prep-HPLC (column: Phenomenex Gemini NX C18 75*30mm*3um; mobile phase: [water (0.1% TFA)-ACN]; B%: 18%-48%, 7min) and lyophilized to give Example 84 (32.2 mg, 62.10 μmol, 9.18% yield, 99.4% purity, TFA) as a grayish-white solid.

1H NMR (400MHz, DMSO) δ11.23-11.19 (br s, 1H), 8.72 (s, 1H), 8.10 (s, 1H), 7.56-7.50 (m, 3H), 7.32-7.28 (m, 2H), 5.0 4-4.84 (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).

Synthesis method M

Example 85. (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((2-hydroxyethoxy)methyl)phenyl)imidazo[1, 2-a]pyridin-2-yl)cyclopropaneformamide

Step 1)(2-((2-bromo-6-fluorobenzyl)oxy)ethoxy)(tert-butyl)dimethylsilane

Compound 22 (1 g, 4.88 mmol, 1 eq) was dissolved in DMF (50 mL), and NaH (292.65 mg, 7.32 mmol, 60% purity, 1.5 eq) was added in portions at 0 °C. The resulting mixture was stirred in _N₂ for 30 min before adding 2-bromoethoxy-tert-butyldimethylsilane (1.40 g, 5.85 mmol, 109.93 μL, 1.2 eq) at 0 °C. The mixture was then stirred in _N₂ at 15 °C for 11.5 h. New spots were formed according to TLC results (PE/EA = 4/1). 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 together with the previous batch by silica gel chromatography (pure PE and PE/EA = 4/1) to give compound 23 as a white solid (372 mg, 1.02 mmol, 20.99%).

1H NMR (400MHz, DMSO-d6) δ7.52-7.50 (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).

Step 2) 2-((2-bromo-6-fluorobenzyl)oxy)ethanol

Compound 23 (352 mg, 968.80 μmol, 1 eq) was dissolved in DMF (10 mL), and CsF (147.16 mg, 968.80 μmol, 35.72 μL, 1 eq) was added. The resulting mixture was then stirred at 80 °C for 12 hours. The starting material was consumed according to TLC results (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 to PE/EA = 5/1) to give compound 24 (120 mg, 481.78 μmol, 49.73% yield) as a grayish-white solid.

1H NMR (400MHz, DMSO-d6) δ7.52-7.50 (m, 1H), 7.36-7.28 (m, 2H), 4.60-4.59 (m, 2H), 3.52-3.47 (m, 4H).

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

A mixture of compound 24 (120 mg, 481.78 μmol, 1 eq) and compound 11 (149.67 mg, 433.60 μmol, 0.9 eq) was dissolved in a mixture of dioxane (10 mL) and H₂O ( ₂ mL), and Pd(dppf)Cl₂ (35.25 _mg , 48.18 μmol, 0.1 eq) and _Na₂CO₃ (153.19 mg, 1.45 mmol, 3 eq) were added in portions. The resulting mixture was then stirred at 80 °C for 12 hours under _N₂ conditions. The desired m/z was determined by LC-MS. The mixture was filtered, the filtrate was 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 (PE/EA = 2/1 to EA/MeOH = 10/1), and then purified by Prep-HPLC (column: Phenomenex Gemini NX C18 75*30mm*3um; mobile phase: [water (0.1% TFA)-ACN]; B%: 12%-42%, 9min) and lyophilized to obtain Example 85 (74.1 mg, 143.65 μmol, 29.82% yield, 97.2% purity, TFA) as a grayish-white solid.

1H NMR (400MHz, DMSO-d6) δ11.21 (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, 1H), 1.65-1.64 (m, 1H).

Synthesis method N

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

Step 1) 3-Bromo-4-methyl-2-nitrophenol

_HNO₃ (2.85 g, 29.41 mmol, 2.04 mL, 1.1 eq) was added dropwise to a solution of compound 25 (5 g, 26.73 mmol, 1 eq) in _CHCl₃ (50 mL) at -50 °C, and the reaction mixture was stirred at -50 °C for 1 hour. The reaction mixture was slowly poured into ice water (200 mL), and the mixture was extracted with dichloromethane (100 mL × 2). The combined organic layers were dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give the residue. The residue was purified by column chromatography (SiO₂, petroleum ether/ethyl acetate = 1/0 to 100/1). Compound 26 (550 mg, 2.37 mmol, 8.87% yield) was given as a yellow oil.

1H NMR (400MHz, CDCl3) δ8.84-8.20 (m, 1H), 7.31 (d, J=8.7Hz, 1H), 7.00 (d, J=8.6Hz, 1H), 2.41 (s, 3H).

Step 2) 2-Amino-3-bromo-4-methylphenol

Fe (649.83 mg, 11.64 mmol, 6 eq) and _NH₄Cl (622.44 mg, 11.64 mmol, 6 eq) were added to a solution of compound 26 (450 mg, 1.94 mmol, 1 eq) in EtOH (5 mL) and _H₂O (5 mL). The suspension was degassed and purged three times with nitrogen. The reaction mixture was stirred at 80 °C for 2 hours under _N₂ . The reaction mixture was filtered, the filter cake was washed with methanol (50 mL x 3), and the filtrate was concentrated under reduced pressure to obtain the residue. The residue was poured into water (50 mL), and the mixture was extracted with ethyl acetate (50 mL x 2) _. The combined organic layers were dried over _Na₂SO₄ , filtered, and concentrated under reduced pressure to obtain the residue. The residue was purified by backflushing (MeCN/ _H₂O , _CF₃COOH ), the mixture was concentrated to remove MeCN, and the pH of the mixture was adjusted to pH 7 with a saturated aqueous sodium bicarbonate solution. It was then extracted with ethyl acetate (100 mL * 2), and the combined organic layers were dried over saturated sodium sulfate, filtered, and concentrated under reduced pressure to obtain the residue. Compound 27 was given as a yellow solid (210 mg, 1.02 mmol, 52.52% yield, 98% purity).

1hnmr (400mhz, CDCl ₃ ) δ 6.64-6.59 (m, 1H), 6.54-6.50 (m, 1H), 2.30 (s, 3H).

Step 3) 4-Bromo-5-methylbenzo[d]oxazole

To a solution of compound 27 (210 mg, 1.02 mmol, 1 eq) and trimethoxymethane (162.14 mg, 1.53 mmol, 167.50 μL, 1.5 eq) in EtOH (3 mL), tris(trifluoromethanesulfonyloxy)ytterbium (14.19 mg, 22.87 μmol, 2.25e-2 eq) was added, and the reaction mixture was stirred at 90 °C for 12 h. LCMS showed that the residual amount of compound 3 was 19%, and the desired mass was detected to be 81%. Trimethoxymethane (108.09 mg, 1.02 mmol, 111.66 μL, 1 eq) was added to the reaction mixture, and the reaction mixture was stirred at 90 °C for another 2 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. A saturated aqueous solution of _NaHCO3 (50 mL) was added to the residue, and the mixture was then extracted with ethyl acetate (30 mL x 3) _. The combined organic layers were dried over _Na2SO4 , filtered, and concentrated under reduced pressure to obtain the residue. Compound 28 (160 mg, crude product) was obtained as a brown solid.

1H NMR (400MHz, CDCl ₃ ) δ 8.12 (s, 1H), 7.43 (d, J=8.3Hz, 1H), 7.29 (d, J=8.4Hz, 1H), 2.54 (s, 3H).

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

Pd(dppf) _Cl₂ (44.86 mg, 61.31 μmol, 0.1 eq) and Na₂CO₃ (194.94 mg, 1.84 mmol, 3 eq) were added to a solution of compound 28 (130 mg, 613.08 μmol, 1 eq) and compound ₁₁ (253.95 mg, 735.70 μmol, 1.2 eq) in dioxane ( ₂ mL) and _H₂O (0.4 mL). The reaction mixture was then stirred at 90 °C for 12 hours under _N₂ . The reaction mixture was poured into brine (30 _mL ), and the mixture was extracted with ethyl acetate (30 mL x 2). The combined organic layers were dried over _Na₂SO₄ , filtered, and concentrated under reduced pressure to obtain the residue. The residue was dissolved in methanol:dichloromethane (1:10, 100 mL), filtered through silica gel, and the filtrate was concentrated to obtain the residue. The residue was purified by prep-HPLC (column: Ultimate C18 150*40mm*10um; mobile phase: [water (0.05% ammonium hydroxide v/v)-ACN]; B%: 25%-55%, 10 min). Example 105 (118.4 mg, 333.33 μmol, yield 54.37%, purity 98.633%) was given as a white solid.

1H NMR (400MHz, DMSO-d6) δ11.07(s,1H),8.70(s,1H),8.65(s,1H),8.13(s,1H),7.71(d,J＝8.3Hz,1H),7.53(d,J＝9.2Hz,1H),7.43(d,J＝8.4H z,1H),7.29(dd,J＝1.6,9.2Hz,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＝6.2,9.1,12.2Hz,1H).

Table 1 below shows example compounds and the general synthetic methods and characterization data used to prepare the compounds.

Table 1. Compounds from Examples

Evaluation of compounds

c-abl kinase assay

The ADP-Glo assay kit was purchased from Promega. Magnesium chloride ( _MgCl₂ ), bovine serum albumin (BSA), ethylene glycol-bis(β-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.

c-abl kinase activity was detected using Promega's ADP-Glo ^™ assay kit. During the assay, His-tagged recombinant human ABL1 (0.25 ng/μl) was incubated with 5 μL of the compound (0.5% DMSO), 5 μL of abiraterone (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 first step of the assay involved incubating the reaction mixture in a 96-well plate at 30°C for 30 minutes. After incubation, 25 μL of ADP-Glo reagent was added, and the reaction was incubated at room temperature for 40 minutes to terminate the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 μL of the assay reagent to each well. The luminescence was detected after incubation for 30 minutes at room temperature using an I3X microplate reader. _IC50 values were calculated using software routines implemented in GraphPad Prism 7 or SigmaPlot 13.0, based on a series of inhibition percentages determined within a defined inhibitor concentration range.

C-Kit kinase assay

The ADP-Glo assay kit was purchased from Promega. Magnesium chloride ( _MgCl₂ ), ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), manganese dichloride ( _MnCl₂ ), bovine serum albumin (BSA), 1,4-dithiothreitol (DTT), and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich. HEPES buffer was purchased from Gibco. C-Kit kinase and multiple (4:1Glu,Tyr) peptides were purchased from Signalchem.

The activity of c-Kit kinase was detected using Promega's ADP-Glo ^™ assay kit. In the assay, 100 ng of recombinant human c-Kit was incubated with 5 μL of the compound (0.5% DMSO), a poly(4:1 Glu, Tyr) peptide (50 ng/μL), and 5 μL of ATP (50 μM) in buffer (50 mM HEPES, pH 7.5; 10 mM _MgCl₂ ; 1 mM EGTA; 0.05% BSA; 50 μM DTT; 2 mM _MnCl₂ ). The first step of the assay involved incubating the reaction mixture in a 96-well plate at 30°C for 120 min. After incubation, 25 μL of ADP-Glo reagent was added, and the reaction was incubated at room temperature for 40 min to terminate the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 μL of assay reagent to each well. The luminescence was detected after incubation for 30 min at room temperature using a microplate reader (I3X). Using software routines implemented in GraphPad Prism 8 or SigmaPlot 13.0, _IC50 values are calculated based on a series of inhibition percentage values determined within a certain range of inhibitor concentrations.

C-Kit(D816V) kinase assay

The ADP-Glo assay kit was purchased from Promega. Magnesium chloride ( _MgCl₂ ), ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), bovine serum albumin (BSA), 1,4-dithiothreitol (DTT), and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich. HEPES buffer was purchased from Gibco. C-Kit (D816V) kinase and multiple (4:1Glu,Tyr) peptides were purchased from Signalchem.

The activity of c-Kit (D816V) kinase was detected using Promega's ADP-Glo ^™ assay kit. During the assay, 2.5 ng of recombinant human c-Kit (D816V) was incubated with 5 μL of the compound (0.5% DMSO), 5 μL of a poly(4:1Glu,Tyr) peptide (50 ng/μL), and 5 μL of ATP (50 μM) in buffer (50 mM HEPES, pH 7.5; 10 mM _MgCl₂ ; 1 mM EGTA; 0.05% BSA; 50 μM DTT). The first step of the assay involved incubating the reaction mixture in a 96-well plate at 30°C for 120 min. After incubation, 25 μL of ADP-Glo reagent was added, and the reaction was incubated at room temperature for 40 min to terminate the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 μL of the assay reagent to each well. At room temperature, luminescence was detected after incubation for 30 minutes using an I3X microplate reader. _IC50 values were calculated using software routines implemented in GraphPad Prism 8 or SigmaPlot 13.0, based on a series of inhibition percentages determined within a defined inhibitor concentration range.

PDGFRα kinase assay

The ADP-Glo assay kit was purchased from Promega. Magnesium chloride ( _MgCl₂ ), ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), bovine serum albumin (BSA), 1,4-dithiothreitol (DTT), and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich. HEPES buffer was purchased from Gibco. PDGFRα kinase and multiple (4:1Glu,Tyr) peptides were purchased from Signalchem.

PDGFRα kinase activity was detected using Promega's ADP-Glo ^™ assay kit. In the assay, 40 ng of recombinant human PDGFRα was incubated with 5 μL of the compound (0.5% DMSO), 5 μL of a poly(4:1 Glu, Tyr) peptide (100 ng/μL), and 5 μL of ATP (25 μM) in buffer (50 mM HEPES, pH 7.5; 10 mM _MgCl₂ ; 1 mM EGTA; 0.05% BSA; 50 μM DTT). The first step of the assay involved incubating the reaction mixture in a 96-well plate at 30°C for 60 min. After incubation, 25 μL of ADP-Glo reagent was added, and the reaction was incubated at room temperature for 40 min to terminate the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 μL of the assay reagent to each well. Brilliance was detected after incubation for 30 min at room temperature using an I3X microplate reader. Using software routines implemented in GraphPad Prism 8 or SigmaPlot 13.0, _IC50 values are calculated based on a series of inhibition percentage values determined within a certain range of inhibitor concentrations.

PDGFRα(D842V) kinase assay

The ADP-Glo assay kit was purchased from Promega. Magnesium chloride ( _MgCl₂ ), ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), bovine serum albumin (BSA), 1,4-dithiothreitol (DTT), and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich. HEPES buffer was purchased from Gibco. PDGFRα (D842V) kinase and multiple (4:1Glu,Tyr) peptides were purchased from Signalchem.

PDGFRα (D842V) kinase activity was detected using Promega's ADP-Glo ^™ assay kit. In the assay, 10 ng of recombinant human PDGFRα was incubated with 5 μL of the compound (0.5% DMSO), 5 μL of a poly(4:1Glu,Tyr) peptide (100 ng/μL), and 5 μL of ATP (3 μM) in buffer (50 mM HEPES, pH 7.5; 10 mM _MgCl₂ ; 1 mM EGTA; 0.05% BSA; 50 μM DTT). The first step of the assay involved incubating the reaction mixture in a 96-well plate at 30°C for 120 min. After incubation, 25 μL of ADP-Glo reagent was added, and the reaction was incubated at room temperature for 40 min to terminate the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 μL of the assay reagent to each well. Brilliance was detected after incubation for 30 min at room temperature using an I3X microplate reader. Using software routines implemented in GraphPad Prism 8 or SigmaPlot 13.0, _IC50 values are calculated based on a series of inhibition percentage values determined within a certain range of inhibitor concentrations.

Table 2 shows the IC ₅₀ values of the compounds of the present invention, where + indicates >1000 nM, ++ indicates 101-1000 nM, +++ indicates 10-100 nM, and ++++ indicates <10 nM.

Table 2. In vitro kinase activity

K562 cell proliferation assay

The K562 human leukemia cell line was purchased from the Korean Cell Bank (KCLB) and cultured in a humidified incubator at 37°C and 5% _CO2 in Roswell Park Memorial Institute (RPMI) 1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin. Cells were seeded in 100 μl of medium at a density of ² x 10³ cells/well in 96-well plates. The compound was diluted twice in 100 μl of medium and added to each well. The compound was serially diluted 5-fold at 6 wells, and the concentration was increased from 5 μM to 1.6 nM in K562 cells. After 48 hours of incubation, the cells treated with the compound were analyzed for antiproliferative assays. Cell viability was studied using a Cell Titer 96 Aqueous One Solution Reagent. Briefly, 40 μl of MTS solution was added to 200 μl of medium, incubated for 4 hours, and then the absorbance was recorded at 490 nm using a 96-well plate reader. GI50 values are calculated based on a range of cell viability percentages within a compound concentration range. GraphPad Prism 8 software or SigmaPlot 13.0 is used to generate GI50 values.

Table 3 shows the _IC50 values of the compounds of the present invention, where + indicates >1000 nM, ++ indicates 101-1000 nM, +++ indicates 10-100 nM, and ++++ indicates <10 nM. Table 3 K562 cell activity.

Example <![CDATA[K562IC₅₀(nM)]]> 1 ++ 11 ++ 12 +++ 15 +++ twenty four +++ 40 +++ 57 ++ 70 ++ 77 ++ 85 ++ 92 +++ 94 ++ 103 +++

Claims (21)

1. The use of the compound represented by formula (I) or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating leukemia. Formula (I) in ^R1 is a cyclopropyl group substituted with one or more halogen groups. ^R2 and ^R3 are -H. ^R4 is selected from hexaaryl, pyridyl, and, wherein the hexaaryl or pyridyl is optionally substituted by one or more groups selected from: halogen, hydroxyl, _C1 - _C10 alkyl, _C3 - _C12 cycloalkyl, _C1 - _C10 haloalkyl, _C1 - _C10 hydroxyalkyl, _-CH2NHC (O) _CH3 , _-NO2 , _-NRaRb , -NRaC(=O) _Rb , _-NRaC (=O) _{ORb , -ORa} , -CN, _-C (=O) _Ra , -C(=O) _ORa , -C(=O) _NRaRb , -OC(=O) _Ra , pyrazolyl _, and furanyl; _Ra and _Rb are independently -H, halogen, amino, _C1 - _C10 alkyl or _C1 - _C10 haloalkyl, and ^R5 is -H, halogen, or _C1 - _C10 alkyl. 2. The application according to claim 1, wherein ^R1 is a cyclopropyl group substituted with one or more halogen groups; ^R2 and ^R3 are -H; ^R4 is a hexa-aryl or pyridyl group, wherein ^R4 is optionally substituted by one or more groups selected from the following: halogen, hydroxyl, _C1 - _C3 alkyl, _C3 - _C4 cycloalkyl, _C1 - _C3 haloalkyl, _-CH2NHC (O)CH3 _{, -NO2} , -NRaRb, _-NRaC (=O) _Rb , _-NRaC (=O) _ORb , _-ORa , _-CN , -C(=O) _Ra , -C(=O) _ORa , -C(=O) _NRaRb , -OC ₍ =O) _Ra , _pyrazolyl , and furanyl; _Ra and _Rb are independently -H, halogen, amino, _C1 - _C3 alkyl, or _C1 - _C3 haloalkyl; and ^R5 is -H, F, Cl, Br, or methyl. 3. The application according to claim 1, characterized in that, ^R1 is a cyclopropyl group substituted with one or more fluorine groups; ^R2 and ^R3 are -H; ^R4 is phenyl or pyridyl, wherein ^R4 is optionally substituted by one or more groups selected from: halogen, hydroxyl, _C1 - _C3 alkyl, _C1 - _C3 haloalkyl, -NRaRb, _-ORa , -CN, -C(=O) _Ra , _-C (= _O ) _ORa , -OC(=O) _Ra , furanyl, and pyrazolyl; and _Ra and _Rb are independently -H, halogen, amino, _C1 - _C3 alkyl, or _C1 - _C3 haloalkyl. 4. The application according to claim 1, wherein ^R1 is fluorocyclopropyl; ^R2 and ^R3 are –H. 5. The application according to claim 1, wherein ^R4 is selected from phenyl and pyridyl, wherein ^R4 is optionally substituted by one or more groups selected from the following groups: halogen, _C1 - _C10 alkyl, _C1 - _C10 hydroxyalkyl, amino, cyano, acetyl, hydroxyl and _C1 - _C10 haloalkyl. 6. The application according to claim 1, wherein ^R1 is fluorocyclopropyl. 7. The application according to claim 6, characterized in that ^R2 and ^R3 are –H; ^R4 is phenyl or pyridyl, wherein ^R4 is optionally substituted by one or more of the following groups: halogen, hydroxyl, _C1 - _C10 alkyl, _C1 - _C10 haloalkyl, _C1 - _C10 hydroxyalkyl, C3 _{-C12 cycloalkyl} , _-NRaRb , _-NRaC (=O) _Rb , _-ORa , _-CN , -C(=O) _Ra , -C(=O) _ORa , -C( ₌ O) _NRaRb , -OC(=O) _Ra , furanyl or pyrazolyl; _Ra and _Rb are independently -H, halogen, amino, _C1 - _C10 alkyl or _C1 - _C10 haloalkyl; ^R5 is -H, halogen, or methyl. 8. The application according to claim 1, characterized in that the compound is a compound represented by formula (II): Formula II ^R6 is selected from halogens; ^R2 - ^R5 are as described in claim 1. 9. The application according to claim 8, characterized in that ^R2 and ^R3 are –H; ^R4 is phenyl or pyridyl, wherein ^R4 is optionally substituted by one or more of the following groups: halogenated, hydroxylated, _C1 - _C10 alkyl, _C1 - _C10 haloalkyl _{, C1-C10 hydroxyalkyl, C3-C12 cycloalkyl , -NRaRb , -NRaC} (=O) _Rb , _-ORa , _-CN , -C(=O) _Ra , -C(=O) _ORa , -C( _{=O)NRaRb, -OC(=O)Ra, furanyl or pyrazolyl; Ra and Rb are independently -H ,} halogenated, amino, _C1 - _C10 alkyl or _C1 - _C10 haloalkyl; ^R5 is -H, halogenated, or _C1 - _C10 alkyl. 10. The use of a compound or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating leukemia, characterized in that the compound is selected from: 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-carboxamide)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; 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; 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)cyclopropane-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; 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; 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-pyrrolo-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; 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; N-(6-(2-chloro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-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)cyclopropaneformamide; N-(6-(2-cyano-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropaneformamide; 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)cyclopropaneformamide; 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)cyclopropaneformamide; 2-Fluoro-N-(6-(6-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; N-(6-(2-acetyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropaneformamide; N-(6-(6-(dimethylamino)-4-methylpyridin-3-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; N-(6-(2-(acetamidomethyl)-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropaneformamide; 2,2-Difluoro-N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; 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; 2-Fluoro-N-(6-(o-tolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; 2-Fluoro-N-(6-(3-fluoro-2-hydroxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; N-(6-(2-amino-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropaneformamide; 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)cyclopropaneformamide; 2-Fluoro-N-(6-(3-fluoro-2-isopropylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; 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)cyclopropane-1-carboxamide; and 2-Fluoro-N-(7-Fluoro-6-(2-Fluoro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide. 11. The use of a compound or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating leukemia, characterized in that the compound is selected from: 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-(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)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-methyl-5-(1H-pyrrolo-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; 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. 12. The application according to claim 1, characterized in that the compound is a compound represented by formula (III): Formula III ^R6 is selected from halogens; ^R2 - ^R5 are as described in claim 1. 13. The application according to claim 12, characterized in that ^R2 and ^R3 are –H; ^R4 is phenyl or pyridyl, wherein ^R4 is optionally substituted by one or more of the following groups: halogen, hydroxyl, _C1 - _C10 alkyl, _C1 - _C10 haloalkyl, _C1 -C10 hydroxyalkyl, C3 _{- C12} cycloalkyl, -NR _aRb , -NR _aC (=O) _Rb , -OR _a , -CN, -C(=O) _Ra , -C(=O)OR _a , -C(=O)NR _{aRb ,} -OC(=O) _Ra , _furanyl or pyrazolyl; _Ra and _Rb are independently -H, halogen, amino, _C1 - _C10 alkyl or _C1 - _C10 haloalkyl; ^R5 is -H, halogen, or _C1 - _C10 alkyl. 14. The use of a compound or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating leukemia, characterized in that the compound is selected from: (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-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-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-carboxamide)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)-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)-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)-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)-2-fluoro-N-(6-(4-(trifluoromethyl)pyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-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)-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-(1H-pyrrolo-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)cyclopropane-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)-N-(6-(2-chloro-6-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-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)cyclopropaneformamide; (1S,2S)-N-(6-(2-cyano-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropaneformamide; (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)cyclopropaneformamide; (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)cyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(6-fluoro-4-methylpyridin-3-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (1S,2S)-N-(6-(2-acetyl-3-fluorophenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropaneformamide; (1S,2S)-N-(6-(6-(dimethylamino)-4-methylpyridin-3-yl)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-fluorocyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((2-methoxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-((2-hydroxyethoxy)methyl)phenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide; (1S,2S)-2-fluoro-N-(6-(o-tolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-hydroxyphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (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)cyclopropaneformamide; (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)cyclopropaneformamide; and (1S,2S)-2-fluoro-N-(6-(3-fluoro-2-isopropylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide. 15. The use of a compound or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating leukemia, characterized in that it is selected from: (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)-N-(6-(4-chloropyridin-3-yl)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)-2-fluoro-N-(6-(3-methylthiophen-2-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; and (1S,2S)-N-(6-(3,4-difluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide. 16. The application according to claim 1, wherein the salt is a hydrochloride, tartrate, phosphate, or maleate. 17. The application according to claim 1, characterized in that the compound is administered in the form of a pharmaceutical composition comprising at least one pharmaceutically acceptable carrier. 18. The application according to claim 17, wherein the composition further comprises one or more active ingredients that can be used to treat cancer. 19. The application according to claim 1, wherein the leukemia is selected from acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, and chronic lymphocytic leukemia. 20. Use of the compound in the preparation of a medicament for treating leukemia, wherein the compound is selected from: 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)cyclopropane-1-carboxamide; 2-Fluoro-N-(6-(2-oxoindol-6-yl)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; 2-Fluoro-N-(6-(5-methyl-2-oxoindol-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)cyclopropane-1-carboxamide; 2-Fluoro-N-(6-(2-oxo-2,3-dihydrobenzo[d]thiazolyl-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-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-fluorocyclopropaneformamide; 2-Fluoro-N-(6-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; N-(6-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropaneformamide; 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)cyclopropaneformamide; 2-Fluoro-N-(6-(5-methylbenzo[d]oxazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; 2-Fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-Fluoro-N-(6-(6-methylbenzo[d]thiazo-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; 2-Fluoro-N-(6-(5-methylbenzo[d]oxazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; 2-Fluoro-N-(6-(5-methylbenzo[d]thiazo-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; 2-Fluoro-N-(6-(7-methylbenzo[d]thiazolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; 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)cyclopropane-1-carboxamide; 2-Fluoro-N-(6-(thiazolyl-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-Fluoro-N-(6-(3-methylisothiazo-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-Fluoro-N-(6-(5-methylthiazo-4-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; 2-Fluoro-N-(6-(2-oxoindol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; 2-Fluoro-N-(6-(5-methyl-2-oxoindol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; N-(6-(3,5-dimethyl-1H-indol-4-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-methylbenzo[d]thiazo-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; and N-(6-(3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide. 21. The use of a compound or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating leukemia, characterized in that it is selected from: (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-oxoindol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; (1S,2S)-2-fluoro-N-(6-(5-methyl-2-oxoindol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-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]thiazolyl-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-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)cyclopropaneformamide; (1S,2S)-N-(6-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)imidazo[1,2-a]pyridin-2-yl)-2-fluorocyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-indol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(6-methyl-1H-indol-5-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]oxazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (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]thiazolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]oxazol-4-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(5-methylbenzo[d]thiazolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (1S,2S)-2-fluoro-N-(6-(7-methylbenzo[d]thiazolyl)imidazo[1,2-a]pyridin-2-yl)cyclopropaneformamide; (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-oxoindol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropane-1-carboxamide; and (1S,2S)-2-fluoro-N-(6-(5-methyl-1H-benzo[d]imidazol-6-yl)imidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide.