Certain Chemical Substances, Compositions, and Methods

Abstract

Provided herein are inhibitors of c-KIT kinase, pharmaceutical compositions comprising the inhibitory compounds, and methods of using the c-KIT kinase inhibitory compounds for the treatment of cancer, inflammatory, allergic, or autoimmune diseases, and other disorders characterized by aberrant c-KIT pathway signaling.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Patent Application No. 63 / 403,661, filed September 2, 2022, and U.S. Patent Application No. 63 / 335,687, filed April 27, 2022, each of which is incorporated by reference in its entirety. [Background technology]

[0002] Receptor tyrosine kinase c-KIT is involved in multiple signal transduction pathways that are important for cell proliferation and differentiation.In many types of tumors, c-KIT is overexpressed or mutated, and c-KIT inhibition has become an effective treatment modality.Therefore, therapies that target c-KIT kinase activity are desirable for use in the treatment of cancer, inflammatory, allergic, and autoimmune diseases, and other disorders characterized by abnormal c-KIT pathway signal transduction. Summary of the Invention

[0003] Provided herein are inhibitors of c-KIT kinase, pharmaceutical compositions containing the inhibitory compounds, and methods of using the inhibitory compounds for the treatment of disease.

[0004] One embodiment is a compound of formula (I)

[0005] [ka] or a pharmaceutically acceptable salt or solvate thereof, During the ceremony, Ring A is an optionally substituted 5-membered nitrogen-containing heteroaryl; Ring B is an optionally substituted 9- or 10-membered bicyclic nitrogen-containing heteroaryl; R 1is optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; R 2 is hydrogen, halo, cyano, or optionally substituted C1-C6 alkyl; R 3 is a halo, R 4 is an optionally substituted C1-C6 alkyl; R 5 is hydrogen, halo, cyano, or optionally substituted C1-C6 alkyl; The present invention provides a compound or a pharmaceutically acceptable salt or solvate thereof.

[0006] One embodiment provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof and at least one pharmaceutically acceptable excipient.

[0007] One embodiment provides a method of treating a disease or disorder in a patient in need thereof, the method comprising administering to the patient a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof. Another embodiment provides a method wherein the disease or disorder is cancer, inflammatory, allergic, or autoimmune disease, and other disorders characterized by aberrant c-KIT pathway signaling.

[0008] Incorporation by Reference All publications, patents, and patent applications mentioned herein are hereby incorporated by reference for the particular purposes identified herein. DETAILED DESCRIPTION OF THE INVENTION

[0009] As used in this specification and the appended claims, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, a reference to "an agent" includes a plurality of such agents; a reference to "the cell" includes a reference to one or more cells (or cells) and equivalents thereof known to those skilled in the art, and so forth. When ranges are used herein for physical properties, such as molecular weight, or chemical properties, such as chemical formulas, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. When referring to a number or numerical range, the term "about" means that the referenced number or numerical range is approximate within experimental variability (or within statistical experimental error); therefore, the number or numerical range will, in some cases, vary between 1% and 15% of the stated number or numerical range. The term "comprising" (and related terms such as "comprise" or "comprises" or "having" or "including") is not intended to exclude certain other embodiments, such as, for example, any composition of matter, composition, method, or process described herein, "consisting of" or "consisting essentially of" the described features.

[0010] definition As used in this specification and the appended claims, unless otherwise stated, the following terms have the meanings indicated below.

[0011] "Amino" refers to the -NH2 radical.

[0012] "Cyano" refers to the -CN radical.

[0013] "Nitro" refers to the -NO2 radical.

[0014] "Oxa" refers to the -O- radical.

[0015] "Oxo" refers to the =0 radical.

[0016] "Thioxo" refers to the =S radical.

[0017] "Imino" refers to the =NH radical.

[0018] "Oximo" refers to the =N-OH radical.

[0019] "Hydrazino" refers to the =N-NH2 radical.

[0020] "Alkyl" refers to a straight or branched chain hydrocarbon radical, consisting solely of carbon and hydrogen atoms, containing no unsaturation, and having from 1 to 15 carbon atoms (e.g., C1-C 15 In certain embodiments, alkyl includes 1 to 13 carbon atoms (e.g., C-C 13 In certain embodiments, alkyl contains 1 to 8 carbon atoms (e.g., C1-C8 alkyl). In other embodiments, alkyl contains 1 to 5 carbon atoms (e.g., C1-C5 alkyl). In other embodiments, alkyl contains 1 to 4 carbon atoms (e.g., C1-C4 alkyl). In other embodiments, alkyl contains 1 to 3 carbon atoms (e.g., C1-C3 alkyl). In other embodiments, alkyl contains 1 to 2 carbon atoms (e.g., C1-C2 alkyl). In other embodiments, alkyl contains 1 carbon atom (e.g., C1 alkyl). In other embodiments, alkyl contains 5 to 15 carbon atoms (e.g., C5-C 15In other embodiments, an alkyl group contains 5 to 8 carbon atoms (e.g., C5-C8 alkyl). In other embodiments, an alkyl group contains 2 to 5 carbon atoms (e.g., C2-C5 alkyl). In other embodiments, an alkyl group contains 3 to 5 carbon atoms (e.g., C3-C5 alkyl). In other embodiments, an alkyl group is selected from methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (iso-propyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (iso-butyl), 1,1-dimethylethyl (tert-butyl), and 1-pentyl (n-pentyl). An alkyl is attached to the rest of the molecule by a single bond. Unless otherwise stated in the specification, an alkyl group is optionally substituted with one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR, -O- ... a , -SR a , -OC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a , -C(O)N(R a )2, -N(R a )C(O)OR a , -OC(O)-N(R a )2, -N(R a )C(O)R a , -N(R a )S(O) t R a (wherein t is 1 or 2), -S(O) t OR a (wherein t is 1 or 2), -S(O) t R a (wherein t is 1 or 2), and -S(O) t N(R a ) 2 (wherein t is 1 or 2), each R aare independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a ) For two groups, both R a The groups may be linked to form a nitrogen-containing heterocyclyl. In certain embodiments, the optionally substituted alkyl is a haloalkyl. In other embodiments, the optionally substituted alkyl is a fluoroalkyl. In other embodiments, the optionally substituted alkyl is a -CF3 group.

[0021] "Alkoxy" refers to a radical attached through an oxygen atom of the formula --O-alkyl, where alkyl is an alkyl chain as defined above.

[0022] "Alkenyl" refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and having from 2 to 12 carbon atoms. In certain embodiments, an alkenyl contains from 2 to 8 carbon atoms. In other embodiments, an alkenyl contains from 2 to 4 carbon atoms. An alkenyl is attached to the rest of the molecule by a single bond, such as ethenyl (i.e., vinyl), prop-1-enyl (i.e., aryl), but-1-enyl, pent-1-enyl, penta-1,4-dienyl, and the like. Unless stated otherwise in the specification, alkenyl groups are optionally substituted with one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR, -O- ... a , -SR a , -OC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a , -C(O)N(R a )2, -N(R a )C(O)OR a , -OC(O)-N(R a )2, -N(R a )C(O)R a , -N(R a )S(O) t R a (wherein t is 1 or 2), -S(O) t OR a (wherein t is 1 or 2), -S(O) t R a (wherein t is 1 or 2), and -S(O) t N(R a ) 2 (wherein t is 1 or 2), each R aare independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally N(R a ) For two groups, both R a The groups may be joined to form a nitrogen-containing heterocyclyl.

[0023] "Alkynyl" refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and having from 2 to 12 carbon atoms. In certain embodiments, an alkynyl contains from 2 to 8 carbon atoms. In other embodiments, an alkynyl contains from 2 to 6 carbon atoms. In other embodiments, an alkynyl contains from 2 to 4 carbon atoms. An alkynyl is attached to the rest of the molecule by a single bond, such as, for example, ethenyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Unless stated otherwise in the specification, alkynyl groups are optionally substituted with one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR, -O- ... a , -SR a , -OC(O)-Ra , -N(R a )2, -C(O)R a , -C(O)OR a , -C(O)N(R a )2, -N(R a )C(O)OR a , -OC(O)-N(R a )2, -N(R a )C(O)R a , -N(R a )S(O) t R a (wherein t is 1 or 2), -S(O) t OR a (wherein t is 1 or 2), -S(O) t R a (wherein t is 1 or 2), and -S(O) t N(R a ) 2 (wherein t is 1 or 2), each R a are independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a ) For two groups, both R aThe groups can be linked to form a nitrogen-containing heterocyclyl.

[0024] "Alkylene" or "alkylene chain" refers to a straight or branched divalent hydrocarbon chain, consisting solely of carbon and hydrogen, containing no unsaturation, having 1 to 12 carbon atoms, linking the rest of the molecule to a radical group, e.g., methylene, ethylene, propylene, n-butylene, etc. The alkylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. The points of attachment of the alkylene chain to the rest of the molecule and to the radical group are through one carbon atom in the alkylene chain or through any two carbon atoms within the chain. In certain embodiments, alkylene contains 1 to 8 carbon atoms (e.g., C1-C8 alkylene). In other embodiments, alkylene contains 1 to 5 carbon atoms (e.g., C1-C5 alkylene). In other embodiments, alkylene contains 1 to 4 carbon atoms (e.g., C1-C4 alkylene). In other embodiments, alkylene contains 1 to 3 carbon atoms (e.g., C1-C3 alkylene). In other embodiments, an alkylene contains 1 to 2 carbon atoms (e.g., a C1-C2 alkylene). In other embodiments, an alkylene contains 1 carbon atom (e.g., a C1 alkylene). In other embodiments, an alkylene contains 5 to 8 carbon atoms (e.g., a C5-C8 alkylene). In other embodiments, an alkylene contains 2 to 5 carbon atoms (e.g., a C2-C5 alkylene). In other embodiments, an alkylene contains 3 to 5 carbon atoms (e.g., a C3-C5 alkylene). Unless stated otherwise in the specification, an alkylene chain is optionally substituted with one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR, -O, -O- ... a , -SR a , -OC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a , -C(O)N(R a )2, -N(R a )C(O)OR a , -OC(O)-N(R a )2, -N(Ra )C(O)R a , -N(R a )S(O) t R a (wherein t is 1 or 2), -S(O) t OR a (wherein t is 1 or 2), -S(O) t R a (wherein t is 1 or 2), and -S(O) t N(R a ) 2 (wherein t is 1 or 2), each R a are independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a For two groups, both R a groups can be linked to form a nitrogen-containing heterocyclyl.

[0025] "Alkenylene" or "alkenylene chain" refers to a straight or branched divalent hydrocarbon chain, consisting solely of carbon and hydrogen, containing at least one carbon-carbon double bond, having 2 to 12 carbon atoms, that connects the rest of the molecule to a radical group. The alkenylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. In certain embodiments, the alkenylene contains 2 to 8 carbon atoms (e.g., C2-C8 alkenylene). In other embodiments, the alkenylene contains 2 to 5 carbon atoms (e.g., C2-C5 alkenylene). In other embodiments, the alkenylene contains 2 to 4 carbon atoms (e.g., C2-C4 alkenylene). In other embodiments, the alkenylene contains 2 to 3 carbon atoms (e.g., C2-C3 alkenylene). In other embodiments, the alkenylene contains 2 carbon atoms (e.g., C2 alkenylene). In other embodiments, an alkenylene contains 5 to 8 carbon atoms (e.g., C5-C8 alkenylene). In other embodiments, an alkenylene contains 3 to 5 carbon atoms (e.g., C3-C5 alkenylene). Unless stated otherwise in the specification, an alkenylene chain is optionally substituted with one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR a , -SR a , -OC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a , -C(O)N(R a )2, -N(R a )C(O)OR a , -OC(O)-N(R a )2, -N(R a )C(O)R a , -N(R a )S(O) t R a (wherein t is 1 or 2), -S(O) t OR a (wherein t is 1 or 2), -S(O) t R a (wherein t is 1 or 2), and -S(O) t N(Ra ) 2 (wherein t is 1 or 2), each R a are independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally N(R a ) For two groups, both R a The groups may be joined to form a nitrogen-containing heterocyclyl.

[0026] "Alkynylene" or "alkynylene chain" refers to a straight or branched divalent hydrocarbon chain, consisting solely of carbon and hydrogen, containing at least one carbon-carbon triple bond, and having 2 to 12 carbon atoms that links the rest of the molecule to a radical group. The alkynylene chain is attached to the rest of the molecule through a single bond and to the radical group through a single bond. In certain embodiments, alkynylene contains 2 to 8 carbon atoms (e.g., C2-C8 alkynylene). In other embodiments, alkynylene contains 2 to 5 carbon atoms (e.g., C2-C5 alkynylene). In other embodiments, alkynylene contains 2 to 4 carbon atoms (e.g., C2-C4 alkynylene). In other embodiments, alkynylene contains 2 to 3 carbon atoms (e.g., C2-C3 alkynylene). In other embodiments, alkynylene contains 2 carbon atoms (e.g., C2 alkynylene). In other embodiments, an alkynylene contains 5 to 8 carbon atoms (e.g., C5-C8 alkynylene). In other embodiments, an alkynylene contains 3 to 5 carbon atoms (e.g., C3-C5 alkynylene). Unless stated otherwise in the specification, an alkynylene chain is optionally substituted with one or more of the following substituents: halo, cyano, nitro, oxo, thioxo, imino, oximo, trimethylsilanyl, -OR a , -SR a , -OC(O)-R a , -N(R a )2, -C(O)R a , -C(O)OR a , -C(O)N(R a )2, -N(R a )C(O)OR a , -OC(O)-N(R a )2, -N(R a )C(O)R a , -N(R a )S(O) t R a (wherein t is 1 or 2), -S(O) t OR a (wherein t is 1 or 2), -S(O) t R a (wherein t is 1 or 2), and -S(O) t N(Ra ) 2 (wherein t is 1 or 2), each R a are independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, carbocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), carbocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a ) For two groups, both R a The groups may be joined to form a nitrogen-containing heterocyclyl.

[0027] "Aryl" refers to a radical derived from an aromatic monocyclic or polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or polycyclic hydrocarbon ring system contains only hydrogen and carbon from 5 to 18 carbon atoms, and at least one of the rings in the ring system is fully unsaturated, i.e., it contains a cyclic delocalized (4n+2) π-electron system according to Hickel theory. Ring systems from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. Unless otherwise noted herein, the term "aryl" or the prefix "ar-" (e.g., "aralkyl") is meant to include aryl radicals optionally substituted with one or more substituents independently selected from the following: optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, cyano, nitro, -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b -S(O) t R a(wherein t is 1 or 2), -R b -S(O) t OR a (wherein t is 1 or 2), and -R b -S(O) t N(R a ) 2 (wherein t is 1 or 2), each R a are independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a ) For two groups, both R a groups can be linked to form a nitrogen-containing heterocyclyl, and each R b are independently a direct bond or a straight or branched alkylene or alkenylene chain; R c is a linear or branched alkylene or alkenylene chain, and R a , R b , or R c Each of the substituents is unsubstituted unless otherwise indicated.

[0028] "Aralkyl" is a group of the formula -R c-aryl radicals such as methylene, ethylene, etc., where R c is an alkylene chain as defined above. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical is optionally substituted as described above for an aryl group.

[0029] "Aralkenyl" refers to a group of the formula -R d -aryl radical, where R d is an alkenylene chain as defined above. The aryl part of the aralkenyl radical is optionally substituted as defined above for an aryl group. The alkenylene chain part of the aralkenyl radical is optionally substituted as defined above for an alkenylene group.

[0030] "Aralkynyl" refers to a group of the formula -R e -aryl radical, where R e is an alkynylene chain as defined above. The aryl part of the aralkynyl radical is optionally substituted as defined above for an aryl group. The alkynylene chain part of the aralkynyl radical is optionally substituted as defined above for an alkynylene chain.

[0031] "Alkoxy" means a group of the formula -OR c -refers to a radical attached through an oxygen atom of an aryl, e.g., methylene, ethylene, etc., where R c is an alkylene chain as defined above. The alkylene chain part of the aralkyl radical is optionally substituted as described above for an alkylene chain. The aryl part of the aralkyl radical is optionally substituted as described above for an aryl group.

[0032] "Carbocyclyl" refers to a stable non-aromatic monocyclic or polycyclic hydrocarbon radical, consisting solely of carbon and hydrogen atoms, including fused or bridged ring systems having 3 to 15 carbon atoms. In certain embodiments, a carbocyclyl contains 3 to 10 carbon atoms. In other embodiments, a carbocyclyl contains 5 to 7 carbon atoms. A carbocyclyl is attached to the rest of the molecule by a single bond. A carbocyclyl may be saturated (i.e., contain only a single C-C bond) or unsaturated (contain one or more double or triple bonds). A fully saturated carbocyclyl radical is also referred to as a "cycloalkyl." Examples of monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. An unsaturated carbocyclyl is also referred to as a "cycloalkenyl." Examples of monocyclic cycloalkenyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Polycyclic carbocyclyl radicals include, for example, adamantyl, norbornyl (i.e., bicyclo[2.2.1]heptanyl), norbornyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl, etc. Unless stated otherwise herein, the term "carbocyclyl" is meant to include carbocyclyl radicals optionally substituted by one or more substituents independently selected from the following: optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, oxo, thioxo, cyano, nitro, -R b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -Rb -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2), -R b -S(O) t OR a where t is 1 or 2, and -R b -S(O) t N(R a ) 2 (wherein t is 1 or 2), each R a are independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a) For two groups, both R a groups can be linked to form a nitrogen-containing heterocyclyl, and each R b are independently a direct bond or a straight or branched alkylene or alkenylene chain; R c is a linear or branched alkylene or alkenylene chain, and R a , R b , or R c Each of the substituents is unsubstituted unless otherwise indicated.

[0033] A "carbocyclylalkyl" is a group of the formula -R c -carbocyclyl radical, where R c is an alkylene chain as defined above. The alkylene chain and the carbocyclyl radical are optionally substituted as defined above.

[0034] "Carbocyclylalkynyl" refers to a group of the formula -R c -carbocyclyl radical, where R c is an alkynylene chain as defined above. The alkynylene chain and the carbocyclyl radical are optionally substituted as defined above.

[0035] "Carbocyclylalkoxy" refers to a group of the formula -OR c - refers to a radical attached through the oxygen atom of a carbocyclyl, where R c is an alkylene chain as defined above. The alkylene chain and the carbocyclyl radical are optionally substituted as defined above.

[0036] "Halo" or "halogen" refers to a bromo, chloro, fluoro, or iodo substituent.

[0037] "Fluoroalkyl" refers to an alkyl group, as defined above, that is substituted by one or more fluoro radicals, as defined above, e.g., trifluoromethyl, difluoromethyl, fluoromethyl, 2,2,2-trifluoroethyl-1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl radical is optionally substituted as defined above for an alkyl group.

[0038] "Heterocyclyl" refers to a stable 3- to 18-membered non-aromatic ring group containing 2 to 12 carbon atoms and 1 to 6 heteroatoms selected from nitrogen, oxygen, and sulfur. Unless otherwise specified in the specification, a heterocyclyl group is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, optionally including fused or bridged ring systems. The heteroatoms in the heterocyclyl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heterocyclyl radical is partially or fully saturated. The heterocyclyl is attached to the rest of the molecule through any atom of the ring. Examples of such heterocyclyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl. In this specification, unless stated otherwise, the term "heterocyclyl" is meant to include heterocyclyl radicals as defined above, optionally substituted with one or more substituents selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, -Rb -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2), -R b -S(O) t OR a where t is 1 or 2, and -R b -S(O) t N(R a ) 2 (wherein t is 1 or 2), each R aare independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a ) For two groups, both R a groups can be linked to form a nitrogen-containing heterocyclyl, and each R b are independently a direct bond or a straight or branched alkylene or alkenylene chain; R c is a linear or branched alkylene or alkenylene chain, and R a , R b , or R c Each of the substituents is unsubstituted unless otherwise indicated.

[0039] "N-heterocyclyl" or "N-linked heterocyclyl" refers to a heterocyclyl radical, as defined above, containing at least one nitrogen, and the point of attachment of the heterocyclyl radical to the rest of the molecule is through a nitrogen atom in the heterocyclyl radical. The N-heterocyclyl radical is optionally substituted as described above for heterocyclyl radicals. Examples of such N-heterocyclyl radicals include, but are not limited to, 1-morpholinyl, 1-piperidinyl, 1-piperazinyl, 1-pyrrolidinyl, pyrazolidinyl, imidazolinyl, and imidazolidinyl.

[0040] "C-heterocyclyl" or "C-linked heterocyclyl" refers to a heterocyclyl radical as defined above containing at least one heteroatom, and the point of attachment of the heterocyclyl radical to the rest of the molecule is through a carbon atom in the heterocyclyl radical. The C-heterocyclyl radical is optionally substituted as described above for heterocyclyl radicals. Examples of such C-heterocyclyl radicals include, but are not limited to, 2-morpholinyl, 2-, 3-, or 4-piperidinyl, 2-piperazinyl, 2-, or 3-pyrrolidinyl, and the like.

[0041] "Heterocyclylalkyl" refers to a group of the formula -R c -heterocyclyl radical, where R c is an alkylene chain as defined above. If the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heterocyclylalkyl radical is optionally substituted as defined above for an alkylene chain. The heterocyclyl portion of the heterocyclylalkyl radical is optionally substituted as defined above for a heterocyclyl group.

[0042] "Heterocyclylalkoxy" refers to a group of the formula -OR c - refers to a radical attached through an oxygen atom of a heterocyclyl, where R cis an alkylene chain as defined above. If the heterocyclyl is a nitrogen-containing heterocyclyl, the heterocyclyl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heterocyclylalkoxy radical is optionally substituted as defined above for an alkylene chain. The heterocyclyl portion of the heterocyclylalkoxy radical is optionally substituted as defined above for a heterocyclyl group.

[0043] "Heteroaryl" refers to a radical derived from a 3- to 18-membered aromatic ring radical containing 2 to 17 carbon atoms and 1 to 6 heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, a heteroaryl radical is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system in which at least one ring in the ring system is fully unsaturated, i.e., it contains a cyclic delocalized (4n+2) π-electron system according to Hickel theory. Heteroaryl includes fused or bridged ring systems. Heteroatoms in a heteroaryl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. A heteroaryl is attached to the rest of the molecule through any atom of the ring. Examples of heteroaryl include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzoindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, benzo[b][1,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]i midazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, furo[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl,10-Hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyryldinonyl, oxadiazolyl, 2- Oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyri pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohexyl

[0023] Unless otherwise specified herein, the term "heteroaryl" includes optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, halo, optionally substituted fluoroalkyl, optionally substituted haloalkenyl, optionally substituted haloalkynyl, oxo, thioxo, cyano, nitro, -R, b -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b-N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2), -R b -S(O) t OR a where t is 1 or 2, and -R b -S(O) t N(R a )2, where t is 1 or 2, and each R aare independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a ) For two groups, both R a groups can be linked to form a nitrogen-containing heterocyclyl, and each R b are independently a direct bond or a straight or branched alkylene or alkenylene chain; R c is a linear or branched alkylene or alkenylene chain, and R a , R b , or R c Each of the substituents is unsubstituted unless otherwise indicated.

[0044] "N-heteroaryl" refers to a heteroaryl radical, as defined above, containing at least one nitrogen, and the point of attachment of the heteroaryl radical to the rest of the molecule is through a nitrogen atom in the heteroaryl radical. The N-heteroaryl radical is optionally substituted as described above for heteroaryl radicals.

[0045] "C-heteroaryl" refers to a heteroaryl radical as defined above, where the point of attachment of the heteroaryl radical to the rest of the molecule is through a carbon atom in the heteroaryl radical. The C-heteroaryl radical is optionally substituted as described above for heteroaryl radicals.

[0046] "Heteroarylalkyl" refers to a group of the formula -R c -heteroaryl radical, where R c is an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkyl radical is optionally substituted as defined above for an alkylene chain. The heteroaryl portion of the heteroarylalkyl radical is optionally substituted as defined above for a heteroaryl group.

[0047] "Heteroarylalkoxy" refers to a group of the formula -OR c - refers to a radical attached through an oxygen atom of a heteroaryl, where R c is an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl radical at the nitrogen atom. The alkylene chain of the heteroarylalkoxy radical is optionally substituted as defined above for an alkylene chain. The heteroaryl portion of the heteroarylalkoxy radical is optionally substituted as defined above for a heteroaryl group.

[0048] The compounds disclosed herein, in some embodiments, contain one or more asymmetric centers, thus giving rise to enantiomers, diastereomers, and other stereoisomeric forms defined in terms of absolute stereochemistry as (R)- or (S)-. Unless otherwise specified, all stereoisomeric forms of the compounds disclosed herein are intended to be contemplated by the present disclosure. When the compounds described herein contain an alkene double bond, unless otherwise specified, the present disclosure is intended to include both E and Z geometric isomers (e.g., cis or trans). The term "positional isomer" refers to structural isomers around a central ring, such as ortho, meta, and para isomers around a benzene ring.

[0049] "Tautomer" refers to a molecule in which a proton shift from one atom of the molecule to another atom of the same molecule is possible. The compounds presented herein exist as tautomers in certain embodiments. In situations where tautomerization is possible, a chemical equilibrium of tautomers exists. The exact ratio of tautomers depends on several factors, including physical conditions, temperature, solvent, and pH. Some examples of tautomeric equilibrium include the following:

[0050] [ka]

[0051] The compounds disclosed herein are, in some embodiments, used in different isotopically enriched forms, e.g., 2 H, 3 H, 11 C. 13 C and / or 14The compound is enriched in C content. In one particular embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, and thus increase the duration of action of the drug.

[0052] Unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms, for example, the replacement of hydrogen by deuterium or tritium, or 13 C or 14 Compounds having this structure, except for the replacement of a carbon with a C-rich carbon, are within the scope of this disclosure.

[0053] The compounds of the present disclosure optionally contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the compounds may contain isotopes of, for example, deuterium ( 2 H), tritium ( 3 H), iodine-125( 125 I) or carbon-14 ( 14 It can be labeled with an isotope such as 1C. 2 H, 11 C. 13 C. 14 C. 15 C. 12 N, 13 N, 15 N, 16 N, 16 O. 17 O. 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl, 37 Cl, 79 Br, 81 Br, 125All isotopic substitutions with I are contemplated. In some embodiments, 18 Isotopic substitution with F is contemplated. All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention.

[0054] In certain embodiments, the compounds disclosed herein comprise: 4 Some or all of the H atoms 2 The deuterium-containing compounds are substituted with H atoms. Methods for synthesizing deuterium-containing compounds are known in the art and include, by way of non-limiting example only, the following synthetic methods:

[0055] Deuterium-substituted compounds are synthesized using a variety of methods, such as those described in: Dean, Dennis C.; Editor. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [Curr., Pharm. Des., 2000; 6(10)] 2000, 110 pp; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0056] Deuterated starting materials are readily available and are amenable to the synthetic methods described herein to provide for the synthesis of deuterated compounds. Numerous deuterated reagents and building blocks are commercially available from chemical vendors, such as Aldrich Chemicals.

[0057] Deuterium-transfer reagents suitable for use in nucleophilic substitution reactions, such as iodomethane-d3 (CD3I), are readily available and can be used to transfer deuterated carbon atoms to reaction substrates under nucleophilic substitution reaction conditions. The use of CD3I is illustrated, by way of example only, in the following reaction scheme.

[0058] [ka]

[0059] Deuterium transfer reagents such as lithium aluminum deuteride (LiAlD4) are used to transfer deuterium to reaction substrates under reducing conditions. The use of -1iAlD4 is illustrated, by way of example only, in the following reaction scheme.

[0060] [ka]

[0061] Deuterium gas and a palladium catalyst are used to reduce unsaturated carbon-carbon bonds and effect reductive displacement of aryl carbon-halogen bonds as illustrated in the reaction scheme below.

[0062] [ka]

[0063] In one embodiment, the compounds disclosed herein contain one deuterium atom. In another embodiment, the compounds disclosed herein contain two deuterium atoms. In another embodiment, the compounds disclosed herein contain three deuterium atoms. In another embodiment, the compounds disclosed herein contain four deuterium atoms. In another embodiment, the compounds disclosed herein contain five deuterium atoms. In another embodiment, the compounds disclosed herein contain six deuterium atoms. In another embodiment, the compounds disclosed herein contain more than six deuterium atoms. In another embodiment, the compounds disclosed herein are fully substituted with deuterium atoms and contain no non-exchangeable hydrogen atoms. In one embodiment, the level of deuterium incorporation is determined by the synthetic method in which deuterated synthetic building blocks are used as starting materials.

[0064] " Pharmaceutically acceptable salt " includes both acid addition salt and base addition salt. The pharmaceutically acceptable salt of any one of the c-KIT kinase inhibitory compounds described herein is intended to include any and all pharmaceutically suitable salt forms. The preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[0065] "Pharmaceutically acceptable acid addition salts" refer to salts which retain the biological effectiveness and properties of the free base and which are biologically or otherwise undesirable and are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, hydroiodic acid, hydrofluoric acid, phosphorous acid, etc. Also included are salts formed with organic acids such as aliphatic mono- and dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxyalkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, etc., such as acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, etc. Thus, exemplary salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, trifluoroacetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, maleate, tartrate, methanesulfonate, alginate, gluconate, galacturonate, and the like (see, e.g., Berge SM et al., "Pharmaceutical Salts," Journal of Pharmaceutical Sciences, Vol. 1, No. 1, pp. 111-114, 2003). Also contemplated are salts of amino acids such as hydroxybenzoates (see Science, 66:1-19 (1997)). Acid addition salts of basic compounds are, in some embodiments, prepared by contacting the free base form with a sufficient amount of the desired acid to produce the salt according to methods and techniques familiar to those skilled in the art.

[0066] "Pharmaceutically acceptable base addition salts" refer to salts that are biologically or otherwise undesirable and that retain the biological effectiveness and properties of the free acid. These salts are prepared from the addition of an inorganic or organic base to the free acid. Pharmaceutically acceptable base addition salts are, in some embodiments, formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N,N-dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, A-methylglucamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, polyamine resins, and the like (see Berge et al., supra).

[0067] "Pharmaceutically acceptable solvate" refers to a composition of a substance in a solvent addition form. In some embodiments, the solvate contains either a stoichiometric or non-stoichiometric amount of a solvent and is formed during the preparation process using a pharmaceutically acceptable solvent such as water, ethanol, etc. Hydrates are formed when the solvent is water, or alcoholates are formed when the solvent is alcohol. Solvates of the compounds described herein are conveniently prepared or formed during the processes described herein. The compounds provided herein exist in either unsolvated or solvated form.

[0068] The term "subject" or "patient" includes mammals. Examples of mammals include, but are not limited to, any member of the following mammalian classes: humans, non-human primates such as chimpanzees, and other ape and monkey species, farm animals such as cows, horses, sheep, goats, pigs, domestic animals such as rabbits, dogs, and cats, and laboratory animals including rodents such as rats, mice, and guinea pigs. In one aspect, the mammal is a human.

[0069] As used herein, "treatment" or "treating" or "alleviating" or "ameliorating" are used interchangeably. These terms refer to an approach to obtaining beneficial or desired results, including, but not limited to, therapeutic benefit and / or prophylactic benefit. "Therapeutic benefit" refers to the eradication or amelioration of the underlying disease being treated. A therapeutic benefit is also achieved by the eradication or amelioration of one or more physiological symptoms associated with the underlying disease, such that an improvement is observed in a patient despite the patient still suffering from the underlying disease. For prophylactic benefit, in some embodiments, the composition is administered to a patient at risk of developing a particular disease or who reports one or more physiological symptoms of the disease, even if the disease has not been diagnosed.

[0070] c-KIT kinase c-KIT is a cytokine receptor classified as a type III receptor tyrosine kinase. It is encoded by the c-kit gene and is expressed on the surface of many cell types, including melanocytes, interstitial cells of Cajal, and hematopoietic cells (e.g., stem cells, hematopoietic progenitor cells, and mast cells). The proto-oncogene c-KIT (also known as CD117, mast cell / stem cell growth factor receptor KIT, pl45 c-kit, PBT, Piebald trait protein, SFCR, v-kit Hardy Zuckerman 4 feline sarcoma viral oncogene homolog) is located on human chromosome 4q11-4q13. Factors that regulate c-KIT transcription include the transcription factors SCL (e.g., transcription factor SCL / Tall), runt-related transcription factor 1 (RUNX1), and far upstream binding protein 1 (FUBP1). It is expressed as multiple mRNA transcripts. The protein product of this gene is the receptor tyrosine kinase c-KIT.

[0071] Structurally, c-KIT is a glycosylated transmembrane protein, although the protein can be soluble. c-KIT has a molecular weight of approximately 145 kDa. c-KIT contains five immunoglobulin-like domains, a hydrophobic transmembrane domain, a juxtamembrane domain, and an N-terminal extracellular region with a C-terminal intracellular tyrosine kinase domain, separated into two domains by a hydrophilic insert sequence of approximately 80 amino acids. Four c-KIT isoforms formed by alternative RNA splicing have been identified in humans. These isoforms are distinguished by (1) the presence of a serine residue in the intracellular kinase insert sequence and (2) the presence of a four-amino acid sequence in the extracellular domain. The four isoforms exhibit different signal transduction and tumorigenesis abilities. Of the four isoforms, the isoform lacking the tetrapeptide exhibits the strongest signal transduction and tumorigenesis abilities.

[0072] Functionally, c-KIT participates in multiple signaling pathways important for cell survival, proliferation, differentiation, migration, and / or apoptosis. c-KIT is a type III receptor tyrosine kinase. Signaling by c-KIT is typical of that of other receptor tyrosine kinases. The cytokine ligand for c-KIT is called stem cell factor (SCF). Binding of SCF to c-KIT induces c-KIT dimerization. Dimerization activates c-KIT, directing it toward the phosphorylation of multiple intracellular proteins for signal transduction. Four signaling pathways involving c-KIT have been at least partially elucidated: PI3-kinase, Src family kinases, Ras-Erk, and JAK / STAT. Following activation, c-KIT is ubiquitinated, thereby marking it for destruction in the lysosome.

[0073] c-KIT is thought to be primarily involved in stem cell differentiation and maintenance, such as hematopoiesis, gametogenesis, melanogenesis, and the development, migration, and function of mast cells. c-KIT is particularly expressed in asymmetrically dividing hematopoietic stem cells. Hematopoietic stem cell division leads to self-renewal or differentiation into myeloid (e.g., monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes / platelets, and dendritic cells) and lymphoid (e.g., T cells, B cells, and NK cells) lineages. During differentiation, self-renewal and stemness decrease, and c-KIT expression can be significantly reduced or even nearly eliminated. In germ cells, c-KIT is involved in apoptosis, cell migration, and proliferation. c-KIT is also involved in the development and function of interstitial cells of Cajal and in the migration of neural stem cells (neuronal proliferative cells) to damaged areas of the brain.

[0074] SCF (also known as "bone factor"), the c-KIT cytokine ligand, is a glycosylated protein with a molecular weight of 2 to 35 kDa that stimulates cell growth and migration. SCF binds to the second and third immunoglobulin domains of c-KIT. Soluble SCF has a mass of approximately 18.5 kDa and forms a dimer. The gene encoding SCF is located at 12q21-32. SCF is found in normal human serum at a concentration of 3.3 ng / mL. SCF is primarily present in fibroblasts and bone marrow stromal cells. SCF is involved in hematopoiesis, spermatogenesis, and melanogenesis. Both soluble and transmembrane SCF must be present for normal hematopoietic function, and these heterologous forms are produced by alternative splicing of the same RNA transcript. Soluble SCF contains a proteolytic cleavage site in exon 6, a cleavage that causes release of the extracellular portion of the protein. SCF is hypothesized to direct hematopoietic stem cells to their stem cell niche (e.g., by binding to KIT) and to be involved in the maintenance of these cells. Similarly, during development, SCF helps localize melanocytes by directing melanoblasts to their final location, and during spermatogenesis, SCF directs germ cells to their appropriate location in the body. In addition to SCF, c-KIT interacts with APS, BCR, CD63, CD81, CD9, CRK, CRKL, D0K1, FES, GRB10, GRB2, KITLG-1NK-1YN, MATK, MPDZ, PIK3R1, PTPN11, PTPN6, STAT1, SOCS1, SOCS6, SRC, and TEC.

[0075] Because c-KIT is a proto-oncogene, deregulation of this gene (e.g., by gain-of-function, loss-of-function, overexpression, and point mutations) can lead to cancer. The exact role of c-KIT in cancer development and progression has not been fully elucidated. Mutations in the c-KIT proto-oncogene have been associated with myeloma, gastrointestinal stromal tumor (GIST), melanoma, systemic mastocytosis, mast cell disease, leukemia (acute myeloid, core factor-binding, and mast cell), as well as other cancers, including sinonasal natural killer / T-cell lymphoma (NKTCL), seminoma, lung adenocarcinoma, colon adenocarcinoma, conventional glioblastoma multiforme, and intracranial and ovarian dysplasia.

[0076] c-KIT is overexpressed or mutated in many types of tumors. For example, seminoma (a type of testicular germ cell tumor) often exhibits mutations, amplification, and / or overexpression of c-KIT in exon 17. While other tumors (e.g., melanoma, thyroid cancer, and breast cancer) may be associated with loss-of-function mutations in c-KIT, gain-of-function mutations are thought to be the primary events leading to cancer progression. Examples of c-KIT gain-of-function mutations include D816V, located in the juxtamembrane domain, and V560G, located in the tyrosine kinase domain. Point mutations in either of these domains can also induce c-KIT dimerization and, therefore, activation. The role of c-KIT in the aforementioned diseases has promoted the concept that inhibition of c-KIT could be a target for cancer therapy, and c-KIT inhibition has shown promising results for the treatment of GIST, acute myeloid leukemia, melanoma, and other cancers. Drugs that target c-KIT include, but are not limited to, axitinib, dasatinib, imatinib, imetelstat, midostaurin, pazopanib, sorafenib, sunitinib, and tashinga (nilotinib).Selected publications disclosing c-KIT kinase inhibitors include WO2013033167, WO2013033116, WO2013 / 033203, and US9199981.

[0077] Several challenges are associated with targeting c-KIT for cancer treatment. c-KIT mutations are not always present in tumors, even those most commonly associated with c-KIT mutations. For example, only 26% of testicular seminomas have been found to be associated with c-KIT mutations. Furthermore, for cancers most commonly associated with c-KIT mutations, these mutations do not appear to be sufficient for tumorigenesis. A major concern is the development of drug resistance. Such resistance can result from mutations that reduce c-KIT binding affinity for a given drug, overexpression of transport proteins that reduce the intracellular concentration of a given drug, or both. Resistance to imatinib in chronic myeloid leukemia is thought to result from both mutations in the kinase domain, which is also specific for drug binding, and overexpression of Ber-Abl. An additional confounding factor for the development of cancer treatments based on c-KIT inhibitors is the occurrence of c-KIT in normal, noncancerous tissues, such as breast epithelium, vascular endothelium, sweat glands, and retinal astrocytes. Therefore, targeting c-KIT is effective in treating cancer only if c-KIT mutations "drive" the cancer. Given the enormous complexity of cancer therapy, novel c-KIT inhibitors are needed to aid in cancer treatment.

[0078] c-KIT kinase inhibitor compounds In one aspect, provided herein are c-KIT kinase inhibitory compounds.

[0079] One embodiment is a compound of formula (I)

[0080] [ka] or a pharmaceutically acceptable salt or solvate thereof, During the ceremony, Ring A is an optionally substituted 5-membered nitrogen-containing heteroaryl; Ring B is an optionally substituted 9- or 10-membered bicyclic nitrogen-containing heteroaryl; R 1is optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted carbocyclylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl; R 2 is hydrogen, halo, cyano, or optionally substituted C1-C6 alkyl; R 3 is the halo, R 4 is an optionally substituted C1-C6 alkyl; R 5 is hydrogen, halo, cyano, or optionally substituted C1-C6 alkyl.

[0081] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0082] [ka] is.

[0083] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0084] [ka] is.

[0085] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0086] [ka] is.

[0087] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0088] [ka] is.

[0089] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0090] [ka] is.

[0091] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0092] [ka] is.

[0093] Another embodiment provides a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is an optionally substituted 9-membered bicyclic nitrogen-containing heteroaryl.

[0094] Another embodiment provides a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein Ring B is an optionally substituted 10-membered bicyclic nitrogen-containing heteroaryl.

[0095] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring B is

[0096] [ka] and In the formula, n is 0 to 4, and each R is hydrogen, cyano, halo, hydroxy, azido, amino, nitro, —COH, —S(O)—R 10 , -SR 10 , -S(O)2-R 10 , optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkynyl, optionally substituted carbocyclyl, optionally substituted C1-C6 alkenyl, optionally substituted heterocyclyl, -N(R 11 )2, -CO-R 10 , -CO2-R 10 , -CON(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10 , -SO2N(R 11 )2, -C(=NR 12 )-N(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10 , -NR 11 CO-N(R 10 )2, and -NR 11 SO2-N(R 10 )2 independently selected from the group consisting of: Each R 10 is independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; Each R 11 is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; R 12 is H or optionally substituted C1-C6 alkyl.

[0097] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring B is

[0098] [ka] wherein n is 0 to 4, and each R is hydrogen, cyano, halo, hydroxy, azido, amino, nitro, —COH, —S(O)—R 10 , -SR 10 , -S(O)2-R 10 , optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkynyl, optionally substituted carbocyclyl, optionally substituted C1-C6 alkenyl, optionally substituted heterocyclyl, -N(R 11 )2, -CO-R 10 , -CO2-R 10 , -CON(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10 , -SO2N(R 11 )2, -C(=NR 12 )-N(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10 , -NR 11 CO-N(R 10 )2, and -NR 11 SO2-N(R 10 )2 independently selected from the group consisting of: Each R 10 is independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; Each R 11is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; R 12 is H or optionally substituted C1-C6 alkyl. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R is hydrogen, halo, cyano, -CONH, or heterocyclyl. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R is hydrogen or halo. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R is cyano, halo, hydroxy, -COH, optionally substituted C-C alkoxy, optionally substituted C-C alkyl, optionally substituted heterocyclyl, or -CON(R 11 )2. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R is an optionally substituted heterocyclyl. Another embodiment provides a compound or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted heterocyclyl is an optionally substituted morpholinyl or piperazinyl.

[0099] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring B is

[0100] [ka] where n is 0 to 4, and each R is hydrogen, cyano, halo, hydroxy, azido, amino, nitro, -COH, -S(O)-R 10 , -SR 10 , -S(O)2-R 10, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkynyl, optionally substituted carbocyclyl, optionally substituted C1-C6 alkenyl, optionally substituted heterocyclyl, -N(R 11 )2, -CO-R 10 , -CO2-R 10 , -CON(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10 , -SO2N(R 11 )2, -C(=NR 12 )-N(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10 , -NR 11 CO-N(R 10 )2, and -NR 11 SO2-N(R 10 )2 independently selected from the group consisting of: Each R 10 is independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; Each R 11 is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; R 12 is H or optionally substituted C1-C6 alkyl. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R is hydrogen, halo, cyano, -CONH, or heterocyclyl. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R is hydrogen or halo. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 or 2 and each R is cyano, halo, hydroxy, -COH, optionally substituted C-C alkoxy, optionally substituted C-C alkyl, optionally substituted heterocyclyl, or -CON(R 11 )2. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1 and R is an optionally substituted heterocyclyl. Another embodiment provides a compound or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted heterocyclyl is an optionally substituted morpholinyl or piperazinyl.

[0101] Another embodiment provides compounds of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein the R groups are arranged to provide the regioisomers shown below:

[0102] [ka]

[0103] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring B is

[0104] [ka] where n is 0.

[0105] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring B is

[0106] [ka] where n is 0.

[0107] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is an optionally substituted carbocyclyl. Another embodiment provides a compound, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted carbocyclyl is a 3- or 4-membered optionally substituted carbocyclyl. Another embodiment provides a compound, or a pharmaceutically acceptable salt or solvate thereof, wherein the optionally substituted carbocyclyl is substituted with at least a halogen.

[0108] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is optionally substituted heterocyclyl. Another embodiment provides a compound or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is an optionally substituted azetidine or an optionally substituted oxetane. Another embodiment provides a compound or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is an optionally substituted piperazine or an optionally substituted morpholine. Another embodiment provides a compound or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is an optionally substituted pyrrolidine. Another embodiment provides a compound or a pharmaceutically acceptable salt or solvate thereof, wherein any substituent is attached to the nitrogen of the heterocyclyl group.

[0109] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is an optionally substituted azetidine, wherein the azetidine is optionally substituted alkyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, -Rb -OR a , -R b -OC(O)-R a , -R b -OC(O)-OR a , -R b -OC(O)-N(R a )2, -R b -N(R a )2, -R b -C(O)R a , -R b -C(O)OR a , -R b -C(O)N(R a )2, -R b -OR c -C(O)N(R a )2, -R b -N(R a )C(O)OR a , -R b -N(R a )C(O)R a , -R b -N(R a )S(O) t R a (wherein t is 1 or 2), -R b -S(O) t R a (wherein t is 1 or 2), -R b -S(O) t OR a where t is 1 or 2, and -R b -S(O) t N(R a )2, where t is 1 or 2, and each R aare independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a ) For two groups, both R a groups can be linked to form a nitrogen-containing heterocyclyl, and each R b are independently a direct bond or a straight or branched alkylene or alkenylene chain; R c is a linear or branched alkylene or alkenylene chain, and R a , R b , or R c Each of the substituents is unsubstituted unless otherwise indicated. Another embodiment provides a compound, or a pharmaceutically acceptable salt or solvate thereof, wherein any substituent is attached to the nitrogen of the heterocyclyl group.

[0110] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is an optionally substituted azetidine, wherein the azetidine is -R b -C(O)OR a , -Rb -C(O)N(R a )2, wherein each R a are independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally -N(R a ) For two groups, both R a groups can be linked to form a nitrogen-containing heterocyclyl, and each R b are independently a direct bond or a straight or branched alkylene or alkenylene chain; R a or R b Each of the substituents is unsubstituted unless otherwise indicated. Another embodiment provides a compound, or a pharmaceutically acceptable salt or solvate thereof, wherein any substituent is attached to the nitrogen of the heterocyclyl group.

[0111] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is an optionally substituted azetidine, wherein the azetidine is —C(O)OR a, -C(O)N(R a )2, wherein each R a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl). Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is -C(O)OR a and R is a substituted azetidine substituted with a is alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl). Another embodiment provides a compound, or a pharmaceutically acceptable salt or solvate thereof, wherein any substituent is attached to the nitrogen of the heterocyclyl group.

[0112] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 teeth,

[0113] [ka] is.

[0114] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is optionally substituted alkyl, optionally substituted carbocyclylalkyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl.

[0115] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen or halo. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen.

[0116] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 is fluoro.

[0117] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 is optionally substituted C1-C2 alkyl. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 is optionally substituted Cl alkyl. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 4 is CH.

[0118] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen or halo. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 5 is hydrogen. Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 5 is fluoro.

[0119] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0120] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0121] [ka] and R 2 is hydrogen and R3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0122] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0123] [ka] and R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0124] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0125] [ka] and R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0126] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0127] [ka] and R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0128] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0129] [ka] and R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0130] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring B is

[0131] [ka] wherein n is 0 to 4, and each R is hydrogen, cyano, halo, hydroxy, azido, amino, nitro, —COH, —S(O)—R 10 , -SR 10 , -S(O)2-R 10 , optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkynyl, optionally substituted carbocyclyl, optionally substituted C1-C6 alkenyl, optionally substituted heterocyclyl, -N(R 11 )2, -CO-R 10 , -CO2-R 10 , -CON(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10 , -SO2N(R 11 )2, -C(=NR 12 )-N(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10 , -NR 11 CO-N(R 10 )2, and -NR 11 SO2-N(R 10 )2 independently selected from the group consisting of: Each R 10is independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; Each R 11 are independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; R 12 is H or optionally substituted C1-C6 alkyl, R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0132] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring B is

[0133] [ka] wherein n is 0 to 4, and each R is hydrogen, cyano, halo, hydroxy, azido, amino, nitro, —COH, —S(O)—R 10 , -SR 10 , -S(O)2-R 10 , optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkynyl, optionally substituted carbocyclyl, optionally substituted C1-C6 alkenyl, optionally substituted heterocyclyl, -N(R 11 )2, -CO-R 10 , -CO2-R 10 , -CON(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10, -SO2N(R 11 )2, -C(=NR 12 )-N(R 11 )2, -NR 11 CO-R 10 , -NR 11 CO2-R 10 , -NR 11 CO-N(R 10 )2, and -NR 11 SO2-N(R 10 )2 independently selected from the group consisting of: Each R 10 is independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; Each R 11 is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl; R 12 is H or optionally substituted C1-C6 alkyl, R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0134] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring B is

[0135] [ka] where n is 0 and R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0136] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein the R groups are arranged to provide the regioisomers shown below:

[0137] [ka] R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0138] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is an optionally substituted azetidine or an optionally substituted oxetane, and R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0139] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is an optionally substituted azetidine, and R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0140] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0141] [ka] and R 1 is -C(O)OR a and R is a substituted azetidine substituted with ais alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), and R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro.

[0142] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0143] [ka] and R 1 is -C(O)OR a and R is a substituted azetidine substituted with a is alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), and R 2 is hydrogen and R 3 is fluoro and R 4 is CH3 and R 5 is fluoro and ring B is

[0144] [ka] where n is 0.

[0145] Another embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein ring A is

[0146] [ka] and R 1 is -C(O)OR a and R is a substituted azetidine substituted with a is alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), and R 3 is fluoro.

[0147] One embodiment is N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, 7-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, ethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, cyclopropyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(5-(1-(methylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-(4-acetylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, 6-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-(4-acetylpiperazin-1-yl)-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, 2-aminoethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, 2-methoxyethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, isopropyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(1-(ethylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-(isopropylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-((2-hydroxyethyl)carbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(1-(cyclopropylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-((2-methoxyethyl)carbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(1-((2-aminoethyl)carbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(morpholine-4-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(piperazine-1-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(4-methylpiperazine-1-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(6-isopropylimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-cyclopropylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(7-isopropylimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(7-cyclopropylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-2-methylpiperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-2-isopropylpiperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-3-methylpiperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-3-isopropylpiperazine-1-carboxylate, N-(5-(5-(4-acetylpiperazin-1-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(4-carbamoylpiperazin-1-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(4-methylpiperazin-1-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(piperazin-1-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-morpholino-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-fluoro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-chloro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-cyano-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N3-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,6-dicarboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-isopropylimidazo[1,2-a]pyridine-3-carboxamide, 6-cyclopropyl-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-fluoro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-chloro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-cyano-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N3-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,7-dicarboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-isopropylimidazo[1,2-a]pyridine-3-carboxamide, 7-cyclopropyl-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1S,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(6-fluoropyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-chloropyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-cyanopyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-carbamoylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(6-methoxypyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(6-isopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-cyclopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylpyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-methylpyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-cyclopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(5-isopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(5-fluoropyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-chloropyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-cyanopyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-carbamoylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-morpholinopyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-(piperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinopyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(3-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-5-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, isopropyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, cyclopropyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(3-(1-(methylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(1-(morpholine-4-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(1-(piperazine-1-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(5-(3-fluoro-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(6-isopropylimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-cyclopropylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(3-morpholino-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(piperazin-1-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)piperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-2-methylpiperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-2-isopropylpiperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-3-methylpiperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-3-isopropylpiperazine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,3,4-oxadiazol-2-yl)azetidine-1-carboxylate, methyl 3-(4-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-2-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-2-yl)azetidine-1-carboxylate, methyl 3-(2-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-4-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-4H-1,2,4-triazol-3-yl)azetidine-1-carboxylate, methyl (R)-3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate, N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(2-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl (R)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboxylate, methyl (R)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate, methyl (S)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboxylate, methyl (S)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-methoxyimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-3-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-3-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, methyl 3-(3-(2,5-difluoro-4-methyl-3-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-(3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl)-2,5-difluoro-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(3-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-5-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(5-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(2,5-difluoro-3-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, and Methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate or a pharmaceutically acceptable salt or solvate thereof.

[0148] The compounds used in the synthetic chemical reactions described herein are made according to organic synthesis techniques known to those skilled in the art, starting from commercially available chemicals and / or compounds described in the chemical literature."Commercially available chemicals" include Acros Organics (Pittsburgh, PA), Aldrich Chemical (Milwaukee, WI, including Sigma Chemical and Fluka), Apin Chemicals-1td. (Milton Park, UK), Avocado Research (Lancashire, UK), BDH Inc. (Toronto, Canada), Bionet (Cornwall, UK), Chemservice Inc. (Westchester, PA), Crescent Chemical Co. (Hauppauge, NY), Eastman Organic Chemicals, Eastman Kodak Company (Rochester, NY), Fisher Scientific Co. (Pittsburgh, PA), Fisons Chemicals (Leicestershire, UK), Frontier Scientific (Logan, UT), ICN Biomedicals, Inc. (Costa Mesa, CA), Key Organics (Cornwall, UK), Baycaster Synthesis (Windham, NH), Maybridge Chemical Co.-1td. (Cornwall, UK), Parish Chemical Co. (Orem, UT), Pfaltz & Bauer, Inc. (Waterbury, CT), Polyorganix (Houston, TX), Pierce Chemical Co. (Rockford, IL), Riedel de Haen AG (Hannover, Germany), Spectrum Quality Product, Inc. (New Brunswick, NJ), TCI America (Portland, OR), Trans World Chemicals, Inc. (Rockville, MD), and Wako Chemicals USA, Inc. (Richmond, VA).

[0149] Suitable references and articles detailing the synthesis of, or providing references to articles describing the preparation of, reactants useful in the preparation of the compounds described herein include, for example, "Synthetic Organic Chemistry," John Wiley & Sons, Inc., New York; S.R. Sandler, et al., "Organic Functional Group Preparations," 2nd Ed., Academic Press, New York, 1983; H.O. House, "Modern Synthetic Reactions," 2nd Ed., W.A. Benjamin, Inc. Menlo Park, Calif., 1972; T.I. Gilchrist, "Heterocyclic Chemistry," 2nd Ed., John Wiley & Sons, New York, 1992; J. March, "Advanced Organic Chemistry: Reactions, Mechanisms and Structure," 4th Ed., Wiley-Interscience, New York, 1992. Further suitable references and articles detailing the synthesis of, or providing references to articles describing the preparation of, reactants useful in the preparation of the compounds described herein include, for example, Fuhrhop, J. and Penzlin G. "Organic Synthesis: Concepts, Methods, Starting Materials", Second, Revised and Enlarged Edition (1994) John Wiley & Sons, ISBN: 3-527-29074-5; Hoffman, RV "Organic Chemistry, An Intermediate Text" (1996) Oxford University Press, ISBN 0-19-509618-5-1; and Arock, RC."Comprehensive Organic Transformations: A Guide to Functional Group Preparations" 2nd Edition (1999) Wiley-VCH, ISBN: 0-471-19031-4; March, J. "Advanced Organic Chemistry: Reactions, Mechanisms, and Structure" 4th Edition (1992) John Wiley & Sons, ISBN: 0-471-60180-2; Otera, J. (editor) "Modern Carbonyl Chemistry" (2000) Wiley-VCH, ISBN: 3-527-29871-1; Patai, S. "Patai’s 1992 Guide to the Chemistry of Functional Groups" (1992) Interscience ISBN: 0-471-93022-9; Solomons, T.W.G. "Organic Chemistry" 7th Edition (2000) John Wiley & Sons, ISBN: 0-471-19095-0; Stowell, J.C., "Intermediate Organic Chemistry" 2nd Edition (1993) Wiley-Interscience, ISBN: 0-471-57456-2; "Industrial Organic Chemicals: Starting Materials and Intermediates: An Ullmann’s Encyclopedia" (1999) John Wiley & Sons, ISBN: 3-527-29645-X, in 8 volumes; "Organic Reactions" (1942-2000) John Wiley & Sons, in over 55 volumes; and "Chemistry of Functional Groups" John Wiley & Sons, in 73 volumes.

[0150] Specific and similar reactants are optionally identified through an index of known chemicals prepared by the Chemical Abstract Service of the American Chemical Society, available in most public and university libraries, as well as through online databases (for details, contact the American Chemical Society, Washington, DC). Known but not commercially available catalog chemicals are optionally prepared by custom chemical synthesis houses, and many of the standard chemical supply houses (e.g., those listed above) offer custom synthesis services. A useful reference for the preparation and selection of pharmaceutical salts of the compounds described herein is P.H. Stahl & C.G. Wermuth, "Handbook of Pharmaceutical Salts," Verlag Helvetica Chimica Acta, Zurich, 2002.

[0151] Pharmaceutical Composition In certain embodiments, the c-KIT kinase inhibitory compounds described herein are administered as pure chemicals. In other embodiments, the c-KIT kinase inhibitory compounds described herein are combined with a pharmaceutically suitable or acceptable carrier (also referred to herein as a pharmaceutically suitable (or acceptable) excipient, a physiologically suitable (or acceptable) excipient, or a physiologically suitable (or acceptable) carrier), which is selected based on the selected route of administration and standard pharmaceutical practice, for example, as described in Remington, The Science and Practice of Pharmacy (Gennaro, 21st Ed. Mack Pub. Co., Easton, PA (2005)).

[0152] Provided herein are pharmaceutical compositions comprising at least one c-KIT kinase inhibitory compound described herein, or a stereoisomer, pharmaceutically acceptable salt, hydrate, or solvate thereof, together with one or more pharmaceutically acceptable carriers. A carrier (or excipient) is acceptable or suitable if it is compatible with the other ingredients of the composition and not deleterious to the recipient of the composition (i.e., subject or patient).

[0153] In some embodiments, the compound described herein or its pharmaceutically acceptable salt or solvate is formulated into pharmaceutical composition.In specific embodiments, pharmaceutical composition is formulated in a conventional manner using one or more physiologically acceptable carriers, including excipients and auxiliary agents that facilitate the processing of active compound into preparations that can be used as medicines.Suitable formulation depends on the route of administration selected. Any pharmaceutically acceptable technology, carrier, and excipient may be used as suitable for formulating the pharmaceutical compositions described herein, including, but not limited to, Remington: The Science and Practice of Pharmacy, Nineteenth Ed. (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975-1Iberman, H.A. and-1Achman-1., Eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams & Wilkins 1999).

[0154] Provided herein is a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable diluent, excipient, or carrier. In certain embodiments, the compound described herein or a pharmaceutically acceptable salt or solvate thereof is administered as a pharmaceutical composition in which the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is mixed with other active ingredients, such as in combination therapy. In a specific embodiment, the pharmaceutical composition comprises one or more compounds of formula (I) or a pharmaceutically acceptable salt or solvate thereof.

[0155] As used herein, a pharmaceutical composition refers to a mixture of a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof with other chemical components, such as carriers, stabilizers, diluents, dispersants, suspending agents, thickeners, and / or excipients. In certain embodiments, the pharmaceutical composition facilitates administration of the compound to an organism. In some embodiments, in practicing the methods of treatment or use provided herein, a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof provided herein is administered in a pharmaceutical composition to a mammal having the disease or disorder to be treated. In specific embodiments, the mammal is a human. In certain embodiments, the therapeutically effective amount will vary depending on the severity of the disease, the age and relative health of the subject, the potency of the compound used, and other factors. The compounds described herein are used alone or in combination with one or more therapeutic agents as components of a mixture.

[0156] In one embodiment, one or more compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof are formulated in an aqueous solution. In certain embodiments, the aqueous solution is selected from, by way of example only, a physiologically compatible buffer, such as Hank's solution, Ringer's solution, or physiological saline buffer. In other embodiments, one or more compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof are formulated for transmucosal administration. In certain embodiments, transmucosal formulations include penetrants appropriate for the barrier to be permeated. In yet other embodiments, where the compounds described herein or pharmaceutically acceptable salts or solvates thereof are formulated for other parenteral injections, suitable formulations include aqueous or non-aqueous solutions. In certain embodiments, such solutions include physiologically compatible buffers and / or excipients.

[0157] In another embodiment, the compounds described herein or their pharmaceutically acceptable salts or solvates are formulated for oral administration.The compounds described herein, including the compound of formula (I), or their pharmaceutically acceptable salts or solvates are formulated by combining the active compound with, for example, a pharmaceutically acceptable carrier or excipient.In various embodiments, the compounds described herein or their pharmaceutically acceptable salts or solvates are formulated into oral dosage forms, including, for example, tablets, powders, pills, dragees, capsules, liquids, gels, syrups, elixirs, slurries, suspensions, etc.

[0158] In certain embodiments, pharmaceutical preparations for oral use are prepared by mixing one or more solid excipients with one or more of the compounds described herein or their pharmaceutically acceptable salts or solvates, optionally grinding the resulting mixture, and optionally adding suitable excipients, and then processing the resulting granular mixture to obtain tablets or dragee cores.Suitable excipients include, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth gum, methylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose; or polyvinylpyrrolidone (PVP or povidone) or calcium phosphate.In certain embodiments, disintegrants are optionally added.Disintegrants include, by way of example only, cross-linked croscarmellose sodium, polyvinylpyrrolidone, agar, or alginic acid or its salt, such as sodium alginate.

[0159] In one embodiment, dosage forms such as dragee cores and tablets are provided with one or more suitable coatings.In certain embodiments, concentrated sugar solutions are used to coat dosage forms.The sugar solutions optionally contain additional components such as gum arabic, talc, polyvinylpyrrolidone, carbopol gel, polyethylene glycol, and / or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures, for example only.Dyes and / or pigments are also optionally added to the coating for identification purposes.Furthermore, dyes and / or pigments are optionally used to distinguish different combinations of active compound doses.

[0160] In certain embodiments, a therapeutically effective amount of at least one of the compounds described herein, or a pharmaceutically acceptable salt or solvate thereof, is formulated into other oral dosage forms. Oral dosage forms include push-fit capsules made of gelatin and soft, sealed capsules made of gelatin and a plasticizer such as glycerol or sorbitol. In certain embodiments, the push-fit capsules contain the active ingredient in a mixture with one or more fillers. Fillers include, by way of example only, binders such as lactose or starch, and / or lubricants such as talc or magnesium stearate, and optionally, stabilizers. In other embodiments, soft capsules contain one or more active compounds dissolved or suspended in a suitable liquid. Suitable liquids include, by way of example only, one or more fatty oils, liquid paraffin, or liquid polyethylene glycol. In addition, stabilizers are optionally added.

[0161] In other embodiments, a therapeutically effective amount of at least one of the compounds described herein, or a pharmaceutically acceptable salt or solvate thereof, is formulated for buccal or sublingual administration. Formulations suitable for buccal or sublingual administration include, by way of example only, tablets, lozenges, or gels. In still other embodiments, the compounds described herein, or a pharmaceutically acceptable salt or solvate thereof, are formulated for parenteral injection, including formulations suitable for bolus injection or continuous infusion. In specific embodiments, the injectable formulation is provided in a unit dosage form (e.g., an ampule) or in a multi-dose container. Optionally, a preservative is added to the injectable formulation. In still other embodiments, the pharmaceutical composition of the compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof is formulated in a form suitable for parenteral injection as a sterile suspension, solution, or emulsion in an oily or aqueous vehicle. Parenteral injection formulations optionally contain formulating agents such as suspending agents, stabilizers, and / or dispersing agents. In certain embodiments, the pharmaceutical formulation for parenteral administration comprises an aqueous solution of the active compound in water-soluble form. In another embodiment, the suspension of active compound is prepared as a suitable oily injection suspension.The lipophilic solvent or vehicle suitable for use in the pharmaceutical compositions described herein includes, for example, fatty oils such as sesame oil, or synthetic fatty acid esters such as ethyl oleate or triglycerides, or liposomes.In certain embodiments, aqueous injection suspensions contain substances that increase the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol, or dextran.Optionally, the suspension contains suitable stabilizers or agents that increase the solubility of the compound, allowing the preparation of highly concentrated solutions.Alternatively, in other embodiments, the active ingredient is in powder form, which is then reconstituted with a suitable vehicle, such as sterile pyrogen-free water, before use.

[0162] In yet another embodiment, the compound of formula (I) or its pharmaceutically acceptable salt or solvate is administered topically.The compounds described herein are formulated into various topically administrable compositions, such as solution, suspension, lotion, gel, paste, medicated stick, balm, cream or ointment.Such pharmaceutical compositions optionally contain solubilizers, stabilizers, tonicity enhancers, buffers and preservatives.

[0163] In yet other embodiments, the compound of Formula (I) or its pharmaceutically acceptable salt or solvate is formulated for transdermal administration. In certain embodiments, transdermal formulations use transdermal delivery devices and transdermal delivery patches, which may be lipophilic emulsions or buffered aqueous solutions dissolved and / or dispersed in polymers or adhesives. In various embodiments, such patches are constructed for continuous, pulsatile, or on-demand delivery of pharmaceuticals. In further embodiments, transdermal delivery of the compound of Formula (I) or its pharmaceutically acceptable salt or solvate is achieved by means such as iontophoretic patches. In certain embodiments, transdermal patches provide controlled delivery of the compound of Formula (I) or its pharmaceutically acceptable salt or solvate. In certain embodiments, the absorption rate is slowed by using rate-controlling membranes or by trapping the compound within a polymer matrix or gel. In alternative embodiments, absorption enhancers are used to increase absorption. The absorption enhancer or carrier includes absorbable pharmaceutically acceptable solvents that aid in passage through the skin. For example, in one embodiment, the transdermal device is in the form of a bandage that includes a backing member, a reservoir containing the compound, optionally with a carrier, and optionally a rate-controlling barrier for delivering the compound to the host's skin at a controlled, predetermined rate over an extended period of time, and a means for securing the device to the skin.

[0164] In other embodiments, the compound of formula (I) or its pharmaceutically acceptable salt or solvate is formulated for administration by inhalation.Various forms suitable for administration by inhalation include, but are not limited to, aerosol, mist, or powder.The pharmaceutical composition of formula (I) or its pharmaceutically acceptable salt or solvate is conveniently delivered in the form of aerosol spray presentation from a pressurized pack or nebulizer, using a suitable propellant (for example, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or other suitable gas).In certain embodiments, the dosage unit of pressurized aerosol is determined by providing a valve for delivering a metered amount.In certain embodiments, capsules and cartridges, such as gelatin, for example, for use in inhalers or insufflators are formulated to contain a powder mixture of the compound and a suitable powder base, such as lactose or starch.

[0165] In yet another embodiment, the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is formulated into a rectal composition such as an enema, rectal gel, rectal foam, rectal aerosol, suppository, jelly suppository, or retention enema containing a conventional suppository base such as cocoa butter or other glycerides, and a synthetic polymer such as polyvinylpyrrolidone, PEG, etc. For suppository forms of the composition, a low melting point wax, such as, but not limited to, a mixture of fatty acid glycerides, optionally in combination with cocoa butter, is first melted.

[0166] In certain embodiments, pharmaceutical compositions are formulated in any conventional manner, using one or more physiologically acceptable carriers, including excipients and auxiliaries that facilitate the processing of active compounds into pharmaceutical preparations.Suitable formulation depends on the route of administration selected.Any pharmaceutically acceptable technology, carrier and excipient are appropriately used as needed.The pharmaceutical composition of the compound of formula (I) or its pharmaceutically acceptable salt or solvate is prepared in a conventional manner, for example, by conventional mixing, dissolving, granulating, dragee-making, powdering, emulsifying, encapsulating, encapsulating or compressing process, for example, by way of example only.

[0167] Pharmaceutical compositions comprise at least one pharmaceutically acceptable carrier, diluent, or excipient and at least one compound of Formula (I) described herein, or a pharmaceutically acceptable salt or solvate thereof, as an active ingredient. The active ingredient may be in free acid or free base form, or in pharmaceutically acceptable salt form. Furthermore, the methods and pharmaceutical compositions described herein include the use of A-oxides, crystalline forms (also known as polymorphs), and active metabolites of these compounds having the same type of activity. All tautomers of the compounds described herein are included within the scope of the compounds presented herein. Furthermore, the compounds described herein encompass unsolvated forms as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. Solvated forms of the compounds presented herein are also considered to be disclosed herein. Additionally, pharmaceutical compositions optionally contain other medicinal or pharmaceutical agents, carriers, preservatives, stabilizers, adjuvants such as wetting agents or emulsifiers, solubility enhancers, salts for regulating osmotic pressure, buffers, and / or other therapeutically valuable substances.

[0168] Methods for preparing compositions containing the compounds described herein include formulating the compounds with one or more inert pharmaceutically acceptable excipients or carriers to form solid, semi-solid, or liquid forms. Solid compositions include, but are not limited to, powders, tablets, dispersible granules, capsules, cachets, and suppositories. Liquid compositions include solutions in which the compounds are dissolved, emulsions containing the compounds, or solutions containing liposomes, micelles, or nanoparticles containing the compounds disclosed herein. Semi-solid compositions include, but are not limited to, gels, suspensions, and creams. The pharmaceutical compositions described herein may be in the form of liquid solutions or suspensions, solid forms suitable for solution or suspension in liquid before use, or emulsions. These compositions may also optionally contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, pH buffering agents, and the like.

[0169] In some embodiments, the pharmaceutical composition comprises at least one compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, and is illustratively in the form of a liquid in which the agent is present in solution, suspension, or both. Typically, when the composition is administered as a solution or suspension, a first portion of the agent is present in solution, and a second portion of the agent is present in particulate form in suspension in a liquid matrix. In some embodiments, the liquid composition comprises a gel formulation. In other embodiments, the liquid composition is aqueous.

[0170] In certain embodiments, useful aqueous suspensions contain one or more polymers as suspending agents.Useful polymers include water-soluble polymers, such as cellulose-based polymers, such as hydroxypropylmethylcellulose, and water-insoluble polymers, such as cross-linked carboxyl-containing polymers.Some pharmaceutical compositions described herein include mucoadhesive polymers selected from, for example, carboxymethylcellulose, carbomer (acrylic acid polymer), poly(methyl methacrylate), polyacrylamide, polycarbophil, acrylic acid / butyl acrylate copolymer, sodium alginate and dextran.

[0171] Useful pharmaceutical compositions also optionally include a solubilizing agent to aid in the solubility of the compound of Formula (I) or its pharmaceutically acceptable salt or solvate. The term "solubilizing agent" generally includes agents that result in the formation of a micellar or true solution of the drug. Certain acceptable nonionic surfactants, such as polysorbate 80, are useful as solubilizing agents, as are ophthalmically acceptable glycols, polyglycols, such as polyethylene glycol 400, and glycol ethers.

[0172] In addition, useful pharmaceutical compositions optionally contain one or more pH adjusters or buffers, including acids such as acetic acid, boric acid, citric acid, lactic acid, phosphoric acid, and hydrochloric acid; bases such as sodium hydroxide, sodium phosphate, borax, sodium citrate, sodium acetate, sodium lactate, and tris-hydroxymethylaminomethane; and buffers such as citric acid / dextrose, sodium bicarbonate, and ammonium chloride. Such acids, bases, and buffers are included in amounts necessary to maintain the pH of the composition within an acceptable range.

[0173] In addition, useful compositions also optionally contain one or more salts in an amount necessary to bring the osmolality of the composition into an acceptable range.Such salts include those having sodium, potassium, or ammonium cations and chloride, citrate, ascorbic acid, borate, phosphate, bicarbonate, sulfate, thiosulfate, or bisulfite anions; suitable salts include sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfite, and ammonium sulfate.

[0174] Other useful pharmaceutical compositions optionally contain one or more preservatives to inhibit microbial activity. Suitable preservatives include mercury-containing substances, such as merfen and thiomersal; stabilized chlorine dioxide; and quaternary ammonium compounds, such as benzalkonium chloride, cetyltrimethylammonium bromide, and cetylpyridinium chloride.

[0175] Still other useful compositions contain one or more surfactants to enhance physical stability or for other purposes. Suitable nonionic surfactants include polyoxyethylene fatty acid glycerides and vegetable oils, such as polyoxyethylene (60) hydrogenated castor oil; and polyoxyethylene alkyl ethers and alkylphenyl ethers, such as Octoxynol 10 and Octoxynol 40.

[0176] Still other useful compositions include one or more antioxidants to enhance chemical stability where required. Suitable antioxidants include, by way of example only, ascorbic acid and sodium metabisulfite.

[0177] In certain embodiments, aqueous suspension compositions are packaged in single-dose non-reclosable containers. Alternatively, multi-dose reclosable containers are used, in which case it is typical to include a preservative in the composition.

[0178] In alternative embodiments, other delivery systems for hydrophobic pharmaceutical compounds are used. Liposomes and emulsions are examples of delivery vehicles or carriers useful herein. In certain embodiments, organic solvents such as A-methylpyrrolidone are also used. In further embodiments, the compounds described herein are delivered using sustained-release systems, such as semipermeable matrices of solid hydrophobic polymers containing therapeutic agents. Various sustained-release materials are useful herein. In some embodiments, sustained-release capsules release the compound for several weeks to over 100 days. Depending on the chemical nature and biological stability of the therapeutic reagent, additional strategies for protein stabilization are used.

[0179] In certain embodiments, the formulations described herein include one or more antioxidants, metal chelators, thiol-containing compounds, and / or other general stabilizers. Examples of such stabilizers include, but are not limited to, the following: (a) about 0.5% to about 2% w / v glycerol, (b) about 0.1% to about 1% w / v methionine, (c) about 0.1% to about 2% w / v monothioglycerol, (d) about 1 mM to about 10 mM EDTA, (e) about 0.01% to about 2% w / v ascorbic acid, (f) 0.003% to about 0.02% w / v polysorbate 80, (g) 0.001% to about 0.05% w / v polysorbate 20, (h) arginine, (i) heparin, (j) dextran sulfate, (k) cyclodextrin, (l) pentosan polysulfate and other heparinoids, (m) divalent cations such as magnesium and zinc, or (n) combinations thereof.

[0180] Administration route Suitable routes of administration include, but are not limited to, oral, intravenous, rectal, aerosol, parenteral, ocular, pulmonary, transmucosal, transdermal, vaginal, otic, nasal, and topical administration. Further, by way of example only, parenteral delivery includes intramuscular, subcutaneous, intravenous, intramedullary injection, as well as intrathecal, direct intraventricular, intraperitoneal, intralymphatic, and intranasal injection.

[0181] In certain embodiments, the compounds described herein are administered in a local rather than systemic manner, for example, by injecting the compound directly into an organ, often in a depot preparation or sustained-release formulation. In certain embodiments, long-acting formulations are administered by implantation (e.g., subcutaneous or intramuscular) or intramuscular injection. Furthermore, in other embodiments, the drug is delivered in a targeted drug delivery system, for example, in a liposome coated with an organ-specific antibody. In such embodiments, the liposome targets the organ and is selectively taken up by the organ. In still other embodiments, the compounds described herein are provided in the form of a rapid-release formulation, a sustained-release formulation, or an intermediate-release formulation. In still other embodiments, the compounds described herein are administered locally.

[0182] One embodiment provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the compound of formula (I) is N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, 7-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, ethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, cyclopropyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(5-(1-(methylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-(4-acetylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, 6-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-(4-acetylpiperazin-1-yl)-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, 2-aminoethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, 2-methoxyethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, isopropyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(1-(ethylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-(isopropylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-((2-hydroxyethyl)carbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(1-(cyclopropylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-((2-methoxyethyl)carbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(1-((2-aminoethyl)carbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(morpholine-4-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(piperazine-1-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(4-methylpiperazine-1-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(6-isopropylimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-cyclopropylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(7-isopropylimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(7-cyclopropylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-2-methylpiperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-2-isopropylpiperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-3-methylpiperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-3-isopropylpiperazine-1-carboxylate, N-(5-(5-(4-acetylpiperazin-1-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(4-carbamoylpiperazin-1-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(4-methylpiperazin-1-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(piperazin-1-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-morpholino-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-fluoro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-chloro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-cyano-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N3-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,6-dicarboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-isopropylimidazo[1,2-a]pyridine-3-carboxamide, 6-cyclopropyl-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-fluoro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-chloro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-cyano-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N3-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,7-dicarboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-isopropylimidazo[1,2-a]pyridine-3-carboxamide, 7-cyclopropyl-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1S,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(6-fluoropyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-chloropyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-cyanopyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-carbamoylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(6-methoxypyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(6-isopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-cyclopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylpyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-methylpyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-cyclopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(5-isopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(5-fluoropyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-chloropyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-cyanopyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-carbamoylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-morpholinopyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-(piperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinopyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(3-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-5-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, isopropyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, cyclopropyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(3-(1-(methylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(1-(morpholine-4-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(1-(piperazine-1-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(5-(3-fluoro-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(6-isopropylimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-cyclopropylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(3-morpholino-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(piperazin-1-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)piperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-2-methylpiperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-2-isopropylpiperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-3-methylpiperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-3-isopropylpiperazine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,3,4-oxadiazol-2-yl)azetidine-1-carboxylate, methyl 3-(4-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-2-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-2-yl)azetidine-1-carboxylate, methyl 3-(2-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-4-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-4H-1,2,4-triazol-3-yl)azetidine-1-carboxylate, methyl (R)-3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate, N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(2-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl (R)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboxylate, methyl (R)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate, methyl (S)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboxylate, methyl (S)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-methoxyimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-3-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-3-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, methyl 3-(3-(2,5-difluoro-4-methyl-3-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-(3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl)-2,5-difluoro-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(3-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-5-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(5-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(2,5-difluoro-3-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, and methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, or a pharmaceutically acceptable salt or solvate thereof.

[0183] One embodiment provides a method for preparing a pharmaceutical composition comprising mixing a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier.

[0184] In certain embodiments, the c-KIT kinase inhibitory compound described by Formula (I) or a pharmaceutically acceptable salt or solvate thereof is substantially pure in that it contains less than about 5%, or less than about 2%, or less than about 1%, or less than about 0.5%, or less than about 0.1% of other small organic molecules, such as unreacted intermediates or synthetic by-products produced in one or more of the steps of the synthetic method.

[0185] Suitable oral dosage forms include, for example, tablets, pills, sachets, or capsules of hard or soft gelatin, methylcellulose, or another suitable material that dissolves easily in the digestive tract. In some embodiments, suitable non-toxic solid carriers are used, including, for example, pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharin, talc, cellulose, glucose, sucrose, magnesium carbonate, and the like. (See, e.g., Remington: The Science and Practice of Pharmacy (Gennaro, 2012) st See Ed. Mack Pub. Co., Easton, PA (2005).

[0186] In some embodiments, the c-KIT kinase inhibitory compound described by formula (I) or its pharmaceutically acceptable salt or solvate is formulated for injection administration.In some examples, the injection formulation is an aqueous formulation.In some examples, the injection formulation is a non-aqueous formulation.In some examples, the injection formulation is an oil-based formulation such as sesame oil.

[0187] The dosage of the compositions comprising at least one c-KIT kinase inhibitory compound described herein varies depending on the condition of the subject or patient (e.g., human). In some embodiments, such factors include general health, age, and other factors.

[0188] Pharmaceutical compositions are administered in a manner appropriate for the disease to be treated (or prevented).Appropriate dosage and appropriate duration and frequency of administration are determined by factors such as patient's condition, the type and severity of patient's disease, the specific form of active ingredient and administration method.Generally, appropriate dosage and treatment regimen provide the composition in an amount sufficient to provide therapeutic and / or preventive benefits (for example, more frequent complete or partial remission, or longer disease-free survival and / or overall survival, or improved clinical outcome, such as alleviating the severity of symptoms).

[0189] Oral doses typically range from about 1.0 mg to about 1000 mg, one to four or more times per day.

[0190] Treatment method One embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for use in a method of treatment of the human or animal body.

[0191] One embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for use in a method of treating cancer, inflammatory, allergic, or autoimmune disease.

[0192] One embodiment provides the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for the treatment of cancer, inflammatory, allergic, or autoimmune diseases.

[0193] One embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for use in a method of treating a c-KIT mediated disease.

[0194] One embodiment provides the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for the treatment of a c-KIT mediated disease.

[0195] One embodiment provides a method of treating cancer, inflammatory, allergic, and autoimmune diseases in a patient in need thereof, comprising administering to the patient a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof.

[0196] Certain embodiments provide a method of treating cancer, inflammatory, allergic, or autoimmune disease in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable excipient.

[0197] One embodiment provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for use in a method for treating a disease selected from the group consisting of mastocytosis, asthma, chronic urticaria, rheumatoid arthritis, psoriasis, atopic dermatitis, neurofibromatosis, multiple sclerosis, and idiopathic pulmonary fibrosis.

[0198] One embodiment provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient, for use in a method for treating a disease selected from the group consisting of mastocytosis, asthma, chronic urticaria, rheumatoid arthritis, psoriasis, atopic dermatitis, neurofibromatosis, multiple sclerosis, and idiopathic pulmonary fibrosis.

[0199] One embodiment provides the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for the treatment of a disease selected from the group consisting of mastocytosis, asthma, chronic urticaria, rheumatoid arthritis, psoriasis, atopic dermatitis, neurofibromatosis, multiple sclerosis, and idiopathic pulmonary fibrosis.

[0200] One embodiment provides a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof for use in a method of treating cancer, wherein the cancer is selected from the group consisting of leukemia, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, lymphoma, germ cell tumor, hematopoietic cancer, gastrointestinal stromal tumor, uveal melanoma, colorectal cancer, breast cancer, small cell lung cancer, neuroblastoma, gynecological tumor, malignant mesothelioma, papillary renal cell carcinoma, papillary renal carcinoma, mastocytosis, mast cell leukemia, thymic carcinoma, colorectal cancer, small cell lung carcinoma, and neuroblastoma.

[0201] One embodiment provides the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for the treatment of cancer, wherein the cancer is selected from the group consisting of leukemia, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, lymphoma, germ cell tumors, hematopoietic cancers, gastrointestinal stromal tumors, uveal melanoma, colorectal cancer, breast cancer, small cell lung cancer, neuroblastoma, gynecological tumors, malignant mesothelioma, papillary renal cell carcinoma, papillary renal carcinoma, mastocytosis, mast cell leukemia, thymic carcinoma, colorectal cancer, small cell lung cancer, and neuroblastoma.

[0202]

[0010] One embodiment provides a method of treating cancer in a patient in need thereof, comprising administering to the patient a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof. One embodiment provides a method of treating cancer in a patient in need thereof, comprising administering to the patient a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable excipient. Another embodiment provides a method of treating a cancer selected from the group consisting of leukemia, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, lymphoma, germ cell tumor, hematopoietic cancer, gastrointestinal stromal tumor, uveal melanoma, colorectal cancer, breast cancer, small cell lung cancer, neuroblastoma, gynecological tumor, malignant mesothelioma, papillary renal cell carcinoma, papillary renal carcinoma, mastocytosis, mast cell leukemia, thymic carcinoma, colorectal cancer, small cell lung cancer, and neuroblastoma. Another embodiment provides a method of treating cancer, wherein the cancer is gastrointestinal stromal tumor. Another embodiment provides a method of treating cancer, wherein the cancer is acute myeloid leukemia. Another embodiment provides a method of treating cancer, wherein the cancer is melanoma.

[0203] Methods are provided herein where the pharmaceutical composition is administered orally. Methods are provided herein where the pharmaceutical composition is administered by injection. Methods are provided herein where the pharmaceutical composition is administered by inhalation.

[0204] One embodiment provides a method of inhibiting c-KIT kinase, comprising contacting the c-KIT kinase with a compound of formula (I). Another embodiment provides a method of inhibiting c-KIT kinase, wherein the c-KIT kinase is contacted in an in vivo setting. Another embodiment provides a method of inhibiting c-KIT kinase, wherein the c-KIT kinase is contacted in an in vitro setting.

[0205] In some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, 7-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, ethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, cyclopropyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(5-(1-(methylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-(4-acetylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, 6-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-(4-acetylpiperazin-1-yl)-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, 2-aminoethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, 2-methoxyethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, isopropyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(5-(1-(ethylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-(isopropylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-((2-hydroxyethyl)carbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(1-(cyclopropylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-((2-methoxyethyl)carbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(1-((2-aminoethyl)carbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(morpholine-4-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(piperazine-1-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(4-methylpiperazine-1-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(6-isopropylimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-cyclopropylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(7-isopropylimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(7-cyclopropylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-2-methylpiperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-2-isopropylpiperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-3-methylpiperazine-1-carboxylate, methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)-3-isopropylpiperazine-1-carboxylate, N-(5-(5-(4-acetylpiperazin-1-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(4-carbamoylpiperazin-1-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(4-methylpiperazin-1-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(piperazin-1-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-morpholino-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-fluoro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-chloro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-cyano-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N3-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,6-dicarboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-isopropylimidazo[1,2-a]pyridine-3-carboxamide, 6-cyclopropyl-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-fluoro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-chloro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-cyano-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N3-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,7-dicarboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-isopropylimidazo[1,2-a]pyridine-3-carboxamide, 7-cyclopropyl-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-4-methyl-5-(7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1S,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(3-fluoro-5-(6-fluoropyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-chloropyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-cyanopyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-carbamoylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(6-methoxypyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(6-isopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(6-cyclopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylpyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-methylpyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-cyclopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(5-isopropylpyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-5-(5-fluoropyrazolo[1,5-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-chloropyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-cyanopyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-(5-carbamoylpyrazolo[1,5-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-morpholinopyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-(piperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(5-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinopyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(5-(3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(3-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-5-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, isopropyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, cyclopropyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(3-(1-(methylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(1-(morpholine-4-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(1-(piperazine-1-carbonyl)azetidin-3-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(5-(3-fluoro-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(6-isopropylimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(6-cyclopropylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-4-methyl-5-(7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(3-morpholino-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(piperazin-1-yl)-1,2,4-oxadiazol-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)piperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-2-methylpiperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-2-isopropylpiperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-3-methylpiperazine-1-carboxylate, methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)-3-isopropylpiperazine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,3,4-oxadiazol-2-yl)azetidine-1-carboxylate, methyl 3-(4-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-2-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-2-yl)azetidine-1-carboxylate, methyl 3-(2-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-4-yl)azetidine-1-carboxylate, methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-4H-1,2,4-triazol-3-yl)azetidine-1-carboxylate, methyl (R)-3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate, N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(2-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)oxazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl (R)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboxylate, methyl (R)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate, methyl (S)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboxylate, methyl (S)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)-7-methoxyimidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-3-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-3-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2,5-difluoro-6-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-6-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, methyl 3-(3-(2,5-difluoro-4-methyl-3-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate, N-(3-(3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl)-2,5-difluoro-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(3-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-5-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, methyl 3-(5-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, methyl 3-(5-(2,5-difluoro-3-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate, and Methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate is selected from the group consisting of:

[0206] Other embodiments and uses will be apparent to those skilled in the art in light of the present disclosure. The following examples are provided merely as illustrations of various embodiments and should not be construed as limiting the invention in any way. [Example]

[0207] I. Chemical synthesis In some embodiments, the c-KIT kinase inhibitory compounds disclosed herein are synthesized according to the following examples. As used below, and throughout the description of the present invention, the following abbreviations shall be understood to have the following meanings, unless otherwise indicated: ℃ Celsius to degrees δ H Chemical shifts in parts per million from tetramethylsilane DCM dichloromethane (CH2Cl2) DMF Dimethylformamide DMSO dimethyl sulfoxide EA Ethyl acetate ESI electrospray ionization Et Ethyl g ~grams h ~hour HPLC High-Performance Liquid Chromatography Hz ~ Hertz J Coupling constant (NMR analysis) LCMS Liquid Chromatography Mass Spectrometry μ Micro m multiplet (spectrum), meter, millimeter M mole M + Parent molecular ion Me methyl MHz Megahertz min mol mole, molecule (as molar weight) mL milliliter MS mass spectrometry nm nanometer NMR nuclear magnetic resonance PE Petroleum Ether pH: Potential of hydrogen, a measure of the acidity or basicity of an aqueous solution RT room temperature s Singlet (spectrum) t triplet (spectrum) T temperature TFA trifluoroacetic acid THF tetrahydrofuran

[0208] Example 1 Preparation of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

[0209] [ka]

[0210] To a solution of 5-bromo-1-fluoro-2-methyl-3-nitrobenzene (50 g, 213.7 mmol, 1.0 equiv.) in DMF (1000 mL) was added Zn(CN) (37.5 g, 320.5 mmol, 1.5 equiv.) and Pd(PPh) (12.4 g, 10.6 mmol, 0.05 equiv.). The mixture was stirred at 130 °C for 5 h, and then the reaction mixture was diluted with water (2000 mL) and extracted with EtOAc (500 mL × 3). The combined organic layers were washed with brine (300 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (PE / EA = 100 / 1, v / v) to give 3-fluoro-4-methyl-5-nitrobenzonitrile as a yellow solid (25.1 g, 65.7%).

[0211] [ka]

[0212] A mixture of 3-fluoro-4-methyl-5-nitrobenzonitrile (25.1 g, 139.4 mmol, 1.0 equiv.), NHOH·HCl (14.5 g, 209.2 mmol, 1.5 equiv.), and DIEA (48.6 mL, 278.9 mmol, 2.0 equiv.) in EtOH (300 mL) was heated at 50 °C for 15 h. The solvent was concentrated in vacuo, the crude product was washed with water, and the solid was collected by vacuum filtration and dried under vacuum to give 3-fluoro-N'-hydroxy-4-methyl-5-nitrobenzimidamide as a white solid (23.2 g, 79.3%). LRMS (M+H) + ) m / z calculated 214.1, found 214.2. 1 H NMR (DMSO-d6,400MHz) δ 10.03(s,1H), 8.15(s,1H), 7.85(dd,1H), 6.09(s,2H), 2.39(d,3H).

[0213] [ka]

[0214] To a solution of 3,3-difluorocyclobutane-1-carboxylic acid (4.0 g, 29.6 mmol, 1.0 equiv) in anhydrous NMP (80 mL) was added CDI (7.2 g, 44.4 mmol, 1.5 equiv). The reaction was stirred for 15 minutes, and 3-fluoro-N'-hydroxy-4-methyl-5-nitrobenzimidamide (4.2 g, 19.7 mmol, 0.7 equiv) was added and the reaction was stirred for 25 minutes. The reaction was stirred at 130°C for 1 hour. The crude product was diluted with EtOAc (200 mL). The organic layer was washed with water (200 mL) and brine (200 mL). The mixture was concentrated under vacuum and purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give 5-(3,3-difluorocyclobutyl)-3-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazole) as a yellow solid (5.5 g, 88.7%).

[0215] [ka]

[0216] To a suspension of 5-(3,3-difluorocyclobutyl)-3-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazole (5.5 g, 17.6 mmol, 1.0 equiv.) in EtOH (90 mL) was added SnCl (10.0 g, 52.7 mmol, 3.0 equiv.). The reaction mixture was heated at 78 °C for 3 h. The reaction was cooled to room temperature, and the solvent was partially concentrated. The pH was adjusted to slightly basic with a saturated solution of sodium bicarbonate (90 mL). The resulting white suspension was filtered and washed with water (90 mL) and EtOAc (90 mL). The aqueous layer was extracted with EtOAc (150 mL × 2), and the combined organic layers were washed with brine (150 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated and purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylaniline as a white solid (2.3 g, 46.9%). LRMS (M+H + ) m / z calculated 284.1, found 284.2. 1 H NMR (DMSO-d6,400MHz) δ 7.18(d,1H), 6.88(dd,1H), 5.582(s,2H), 3.84-3.85(m,1H), 3.03-3.20(m,4H), 2.01(d,3H).

[0217] [ka]

[0218] To a solution of 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylaniline (300 mg, 1.1 mmol, 1.0 equiv.), imidazo[1,2-a]pyridine-3-carboxylic acid (196.1 mg, 1.2 mmol, 1.1 equiv.), and pyridine (0.4 mL, 5.3 mmol, 5.0 equiv.) in DCM (30 mL) was added POCl (0.3 mL, 3.2 mmol, 3.0 equiv.) on ice. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL × 2), and the combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated under vacuum and purified by reverse-phase HPLC (MeCN / HO=7 / 3, v / v) to give N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide as a white solid (72.7 mg, 15.9%). LRMS (M+H + ) m / z calculated 428.1, found 428.0. 1 H NMR(DMSO-d6,400MHz)δ 10.22(brs,1H), 9.45(d,1H), 8.60(s,1H), 7.97(s,1H), 7.79(d,1H), 7.65(d,1H), 7.51-7.56(m,1H), 7.19(t,1H), 3.87-3.97(m,1H), 3.02-3.26(m,4H), 2.25(s,3H).

[0219] Example 2 Preparation of N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (racemic, trans)

[0220] [ka]

[0221] To a solution of (1R,2S)-2-fluorocyclopropane-1-carboxylic acid and (1S,2R)-2-fluorocyclopropane-1-carboxylic acid (racemic, trans, 3.1 g, 29.6 mmol, 1.0 equiv.) in anhydrous NMP (80 mL) was added CDI (7.2 g, 44.4 mmol, 1.5 equiv.). The reaction was stirred for 15 minutes, then 3-fluoro-N'-hydroxy-4-methyl-5-nitrobenzimidamide (4.2 g, 19.7 mmol, 0.7 equiv.) was added and the reaction was stirred for 25 minutes. The reaction was then stirred at 130 °C for 1 hour. The crude product was diluted with EtOAc (200 mL). The organics were washed with water (200 mL) and brine (200 mL). The mixture was concentrated under vacuum and purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give 3-(3-fluoro-4-methyl-5-nitrophenyl)-5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole and 3-(3-fluoro-4-methyl-5-nitrophenyl)-5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole (racemic, trans) as a yellow oil (5.3 g, 96.3%).

[0222] [ka]

[0223] To a suspension of 3-(3-fluoro-4-methyl-5-nitrophenyl)-5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole and 3-(3-fluoro-4-methyl-5-nitrophenyl)-5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole) (racemic, trans, 5.3 g, 18.9 mmol, 1.0 equiv.) in EtOH (90 mL) was added SnCl (10.7 g, 56.5 mmol, 3.0 equiv.). The reaction mixture was heated at 78 °C for 3 h. The reaction was cooled to room temperature and the solvent was partially concentrated in vacuo. The pH was adjusted to slightly basic with a saturated solution of sodium bicarbonate. The resulting white suspension was filtered and washed with water and EtOAc. The aqueous layer was extracted with EtOAc (150 mL × 2) and washed with water (150 mL). The combined organic layers were washed with brine (150 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated under vacuum and purified by silica gel column chromatography (PE / EA = 5 / 1, v / v) to give 3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline and 3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline) (racemic, trans) as a white solid (1.8 g, 38.3%). LRMS (M+H + ) m / z calculated 252.1, found 252.2. 1 H NMR(DMSO-d6,400MHz)δ 7.12(d,1H), 6.82(dd,1H), 5.56(brs,2H), 5.32-5.35(m,0.5H), 5.16-5.19(m ,0.5H), 2.97-3.06(m,1H), 2.00(d,3H), 1.87-1.98(m,1H), 1.51-1.60(m,1H).

[0224] [ka]

[0225] To a solution of 3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline and 3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline) (racemic, trans, 300 mg, 1.2 mmol, 1.0 equiv), imidazo[1,2-a]pyridine-3-carboxylic acid (213.8 mg, 1.3 mmol, 1.1 equiv), and pyridine (0.5 mL, 6.0 mmol, 5.0 equiv) in DCM (30 mL) was added POCl (0.3 mL, 3.6 mmol, 3.0 equiv) in an ice bath. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL × 2), and the combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated under vacuum, and the resulting residue was purified by reverse-phase HPLC (MeCN / H2O = 7 / 3, v / v) to give N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-)3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide) (racemic) as a white solid (102.4 mg, 21.2%). LRMS (M+H + ) m / z calculated 396.1, found 396.0. 1 H NMR(DMSO-d6,400MHz)δ 10.22(brs,1H), 9.44(d,1H), 8.60(s,1H), 7.91(s,1H), 7.79(d,1H), 7.61(d,1H), 7.53(t,1H), 7.1 9(t,1H), 5.20-5.38(m,1H), 3.03-3.12(m,1H), 2.25(s,3H), 1.90-2.01(m,1H), 1.55-1.64(m,1H).

[0226] Example 3: Preparation of methyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0227] [ka]

[0228] Azetidine-3-carboxylic acid (25 g, 247.5 mmol, 1.0 equiv.) and NaHCO3 (31.2 g, 371.3 mmol, 1.5 equiv.) were dissolved in MeCN (300 mL) and water (30 mL). Methyl carbonochloridate (23.3 mmL, 297.0 mmol, 1.2 equiv.) was dissolved in MeCN (20 mL) and added dropwise to the reaction mixture in an ice bath. The reaction mixture was stirred at room temperature for 12 hours and evaporated in vacuo. Water (100 mL) was added to the residue, and the aqueous phase was extracted with EtOAc (2 × 200 mL). The aqueous phase was acidified to pH = 2 with concentrated HCl (12 M) and extracted with DCM (200 mL × 3). The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo to give 1-(methoxycarbonyl)azetidine-3-carboxylic acid as a yellow solid (20 g, 51.3%). LRMS(M+H + ) m / z calculated 160.1, found 160.2. 1 H-NMR (CD3OD) δ 4.07-4.18(m,4H), 3.65(s,3H), 3.39-3.50(m,1H).

[0229] [ka]

[0230] To a solution of 1-(methoxycarbonyl)azetidine-3-carboxylic acid (5.6 g, 35.2 mmol, 1.0 equiv) in anhydrous NMP (80 mL) was added CDI (8.6 g, 52.8 mmol, 1.5 equiv). The reaction was stirred for 15 minutes. 3-Fluoro-N'-hydroxy-4-methyl-5-nitrobenzimidamide (5.0 g, 23.5 mmol, 0.7 equiv) was added and the reaction was stirred for 25 minutes. The reaction was stirred at 130°C for 1 hour. The reaction mixture was diluted with EtOAc (200 mL). The organic layer was washed with water (200 mL) and brine (200 mL). The mixture was concentrated, and the resulting crude product was purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give methyl 3-(3-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate) as a yellow solid (5.5 g, 69.6%). LRMS (M+H + ) m / z calculated 337.1, found 337.1.

[0231] [ka]

[0232] To a suspension of methyl 3-(3-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (5.5 g, 16.4 mmol, 1.0 equiv.) in EtOH (60 mL) was added SnCl (9.3 g, 49.1 mmol, 3.0 equiv.). The reaction mixture was stirred at 78 °C for 3 h. The reaction was cooled to room temperature, and the solvent was partially concentrated in vacuo. The pH was adjusted to slightly basic with a saturated solution of sodium bicarbonate. The resulting white suspension was filtered and washed with water (60 mL) and EtOAc (60 mL). The aqueous layer was extracted with EtOAc (150 mL × 2), and the combined organic layers were washed with brine (150 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated under vacuum and purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylaniline) as a white solid (2.5 g, 50.0%). LRMS (M+H + ) m / z calculated 307.1, found 307.1. 1 H NMR (DMSO-d6,400MHz) δ 7.195(s,1H), 6.87-6.89(m,1H), 5.58(brs,2H), 4.10-4.36(m,5H), 3.60(s,3H), 2.01(d,3H).

[0233] [ka]

[0234] To a solution of methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (1.5 g, 4.9 mmol, 1.0 equiv.), imidazo[1,2-a]pyridine-3-carboxylic acid (873.5 mg, 5.4 mmol, 1.1 equiv.), and pyridine (1.9 mL, 24.5 mmol, 5.0 equiv.) in DCM (80 mL) was added POCl (1.4 mL, 14.7 mmol, 3.0 equiv.) in an ice bath. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL × 2), and the combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated, and the resulting residue was purified by reverse-phase HPLC (MeCN / HO=7 / 3, v / v) to give methyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (249.1 mg, 11.3%). LRMS (M+H + ) m / z calculated 451.1, found 451.1. 1 H NMR(DMSO-d6,400MHz)δ 10.22(s,1H), 9.45(d,1H), 8.61(s,1H), 7.99(s,1H), 7.79(d,1H), 7.67(d, 1H), 7.54(t,1H), 7.19(m,1H), 4.18-4.38(m,5H), 3.60(s,3H), 2.26(s,3H).

[0235] Example 4 Preparation of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

[0236] [ka]

[0237] To a solution of 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylaniline (349.4 mg, 1.2 mmol, 1.0 equiv.), pyrazolo[1,5-a]pyridine-3-carboxylic acid (200 mg, 1.2 mmol, 1.0 equiv.), and pyridine (0.5 mL, 6.2 mmol, 5.0 equiv.) in DCM (50 mL) was added POCl (0.3 mL, 3.7 mmol, 3.0 equiv.) on ice. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (80 mL × 2) and washed with water (50 mL). The combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated in vacuo and the resulting residue was purified by preparative HPLC to give N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (59.3 mg, 11.0%). LRMS (M+H + ) m / z calculated 428.1, found 428.1. 1 H NMR(DMSO-d6,400MHz)δ 9.95(s,1H), 8.86(d,1H), 8.79(s,1H), 8.23(d,1H), 7.99(s,1H), 7.63(d,1H) , 7.55(t,1H), 7.14(t,1H), 3.87-3.91(m,1H), 3.04-3.32(m,4H), 2.25(s,3H).

[0238] Example 5 Preparation of N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-),2,4-oxadiazol-3-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide (racemic, trans)

[0239] [ka]

[0240] To a solution of 3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline and 3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline (racemic, trans, 309.9 mg, 1.2 mmol, 1.0 equiv.), pyrazolo[1,5-a]pyridine-3-carboxylic acid (200.0 mg, 1.2 mmol, 1.1 equiv.), and pyridine (0.5 mL, 6.2 mmol, 5.0 equiv.) in DCM (30 mL) was added POCl (0.3 mL, 3.7 mmol, 3.0 equiv.) on ice. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL x 2) and washed with water (150 mL). The combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated under vacuum, and the resulting residue was purified by preparative HPLC to give N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide) (racemic, trans) as a white solid (91.0 mg, 18.7%). LRMS (M+H + ) m / z calculated 396.1, found 396.0. 1 H NMR(DMSO-d6,400MHz)δ 9.94(s,1H), 8.86(d,1H), 8.78(s,1H), 8.22(d,1H), 7.92(s,1H), 7.59(d,1H), 7.53(d,1H), 7.14 (t,1H), 5.20-5.40(m,1H), 3.03-3.11(m,1H), 2.24(s,3H), 1.90-2.01(m,1H), 1.55-1.64(m,1H).

[0241] Example 6: Preparation of methyl 3-(3-(3-fluoro-4-methyl-5-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0242] [ka]

[0243] To a solution of methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (188.9 mg, 0.62 mmol, 1.0 equiv.), pyrazolo[1,5-a]pyridine-3-carboxylic acid (100.0 mg, 0.62 mmol, 1.0 equiv.), and pyridine (0.3 mL, 3.1 mmol, 5.0 equiv.) in DCM (50 mL) was added POCl (0.2 mL, 1.9 mmol, 3.0 equiv.) on ice. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL × 2), and the combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated in vacuo and the resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-4-methyl-5-(pyrazolo[1,5-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (13.3 mg, 4.7%). LRMS (M+H + ) m / z calculated 451.1, found 451.0. 1 H NMR(DMSO-d6,400MHz)δ 9.89(s,1H), 8.86(d,1H), 8.79(s,1H), 8.24(d,1H), 8.01(s,1H), 7.63(d,1 H), 7.54(t,1H), 7.14(t,1H), 4.20-4.38(m,5H), 3.60(s,3H), 2.25(d,3H).

[0244] Example 7 Preparation of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide

[0245] [ka]

[0246] A mixture of ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate (3 g, 11.2 mmol, 1.0 equiv.), morpholine (2.9 mL, 33.6 mmol, 3.0 equiv.), CS2CO3 (7.3 g, 22.4 mmol, 2.0 equiv.), XPhos (648.1 mg, 1.1 mmol, 0.1 equiv.), and Pd2(dba)3 (512.7 mg, 0.6 mmol, 0.05 equiv.) in dioxane (100 mL) was stirred at 110 °C overnight. The reaction mixture was then concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (PE / EA = 5 / 1, v / v) to give ethyl 6-morpholinoimidazo[1,2-a]pyridine-3-carboxylate as a yellow solid (2.6 g, 83.8%). LRMS(M+H + ) m / z calculated 276.1, found 276.0.

[0247] [ka]

[0248] A solution of ethyl 6-morpholinoimidazo[1,2-a]pyridine-3-carboxylate (1 g, 3.6 mmol, 1.0 equiv.) and NaOH (218.2 mg, 5.5 mmol, 1.5 equiv.) in MeOH / HO (30 mL / 5 mL) was stirred at 30 °C for 5 h, and the solvent was partially concentrated under vacuum. The pH was adjusted to pH 5 with concentrated HCl, and the solid was then collected by vacuum filtration and dried under vacuum to give 6-morpholinoimidazo[1,2-a]pyridine-3-carboxylic acid as a white solid (780 mg, 86.6%). LRMS (M+H)+ ) m / z calculated 248.1, found 248.0.

[0249] [ka]

[0250] To a solution of 6-morpholinoimidazo[1,2-a]pyridine-3-carboxylic acid (100.0 mg, 0.40 mmol, 1.0 equiv.), 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylaniline (114.6 mg, 0.40 mmol, 1.0 equiv.), and pyridine (0.2 mL, 2.0 mmol, 5.0 equiv.) in DCM (50 mL) was added POCl (0.1 mL, 1.2 mmol, 3.0 equiv.) on ice. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL × 2), and the combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated and the resulting residue was purified by preparative HPLC to give N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide as a white solid (6.5 mg, 3.1%). LRMS (M+H + ) m / z calculated 513.2, found 513.1. 1 H NMR(DMSO-d6,400MHz)δ 8.94(s,1H), 8.51(s,1H), 7.95(s,1H), 7.64.7.71(m,2H), 7.55(d,1H), 3.86-3. 92(m,1H), 3.74-3.77(m,4H), 3.16-3.23(m,2H), 3.04-3.23(m,6H), 2.25(s,3H).

[0251] Example 8 Preparation of N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide (racemic, trans)

[0252] [ka]

[0253] To a solution of 3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline and 3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline (racemic, trans, 101.6 mg, 0.40 mmol, 1.0 equiv.), 6-morpholinoimidazo[1,2-a]pyridine-3-carboxylic acid (100.0 mg, 0.40 mmol, 1.0 equiv.), and pyridine (0.2 mL, 2.0 mmol, 5.0 equiv.) in DCM (30 mL) was added POCl (0.1 mL, 1.2 mmol, 3.0 equiv.) on ice. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL x 2), and the combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated under vacuum, and the resulting residue was purified by preparative HPLC to give N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide (racemic, trans) as a white solid (11.7 mg, 6.1%). LRMS (M+H + ) m / z calculated 481.2, found 481.1. 1 H NMR(DMSO-d6,400MHz)δ 8.94(d,1H), 8.50(s,1H), 7.90(s,1H), 7.68(d,1H), 7.60(d,1H), 7.55(d,1H), 5.35-5.23(m, 1H), 3.74-3.79(m,4H), 3.03-3.09(m,5H), 2.24(s,3H), 1.90-2.02(m,1H), 1.55-1.64(m,1H).

[0254] Example 9: Preparation of methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0255] [ka]

[0256] To a solution of 6-morpholinoimidazo[1,2-a]pyridine-3-carboxylic acid (150 mg, 0.61 mmol, 1.0 equiv.), methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (185.8 mg, 0.61 mmol, 1.0 equiv.), and pyridine (0.3 mL, 3.0 mmol, 5.0 equiv.) in DCM (50 mL) was added POCl (0.2 mL, 1.8 mmol, 3.0 equiv.) on ice. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL × 2) and washed with water (100 mL). The combined organic layers were washed with brine (50 mL) and dried over anhydrous sodium sulfate. The mixture was concentrated in vacuo and the resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (47.9 mg, 14.7%). LRMS (M+H + ) m / z calculated 536.2, found 536.1. 1 H NMR(DMSO-d6,400MHz)δ 10.13(s,1H), 8.94(d,1H), 8.51(s,1H), 7.97(s,1H), 7.65-7.70(m,2H), 7.55(d,1H) , 4.20-4.38(m,5H), 3.75-3.79(m,4H), 3.60(s,3H), 3.06-3.09(m,4H), 2.25(d,3H).

[0257] Example 10 Preparation of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide

[0258] [ka]

[0259] A mixture of ethyl 7-bromoimidazo[1,2-a]pyridine-3-carboxylate (1 g, 3.7 mmol, 1.0 equiv), tert-butyl piperazine-carboxylate (2.1 g, 11.2 mmol, 3.0 equiv), CS2CO3 (2.4 g, 7.5 mmol, 2.0 equiv), XPhos (216 mg, 0.37 mmol, 0.1 equiv), and Pd2(dba)3 (170.9 mg, 0.2 mmol, 0.05 equiv) in toluene (100 mL) was stirred at 110 °C overnight, and then the reaction mixture was concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give ethyl 7-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylate as a yellow solid (1.3 g, 92.8%). LRMS (M+H + ) m / z calculated 375.2, found 375.2.

[0260] [ka]

[0261] To a solution of ethyl 7-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylate (600 mg, 1.6 mmol, 1.0 equiv.) and 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylaniline (454.0 mg, 1.6 mmol, 1.0 equiv.) in toluene (50 mL) was added Al(Me) (2 M in toluene, 4.8 mL, 4.8 mmol, 3.0 equiv.) on ice. The reaction mixture was stirred at 90 °C for 2 hours. The reaction mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography (PE / EA=2 / 1, v / v) to give tert-butyl 4-(3-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-7-yl)piperazine-1-carboxylate) as a yellow solid (450 mg, 45.9%). LRMS (M+H + ) m / z calculated 612.2, found 612.1.

[0262] [ka]

[0263] To a solution of tert-butyl 4-(3-((5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-7-yl)piperazine-1-carboxylate (100 mg, 0.16 mmol, 1.0 equiv) in DCM (10 mL) was added 4 N HCl / dioxane (5 mL). The reaction was stirred at 30° C. for 30 minutes. The mixture was concentrated and the resulting residue was purified by preparative HPLC to give N-(5-(5-(3,3-dithiolocyclobutyl)-1,2,4-oxadiazol-3-yl-)-3-thiolo-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (35.4 mg, 42.1%) as a white solid. LRMS (M+H+ ) m / z calculated 512.2, found 512.1. 1 H NMR(CDCl3,400MHz)δ 9.25(d,1H), 8.42(s,1H), 8.06(s,1H), 7.62(d,1H), 7.48(d,1H), 6.87(d,1H), 6. 78(d,1H), 3.63-3.68(m,1H), 3.32-3.34(m,4H), 3.03-3.17(m,8H), 2.30(s,3H).

[0264] Example 11 Preparation of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide

[0265] [ka]

[0266] To a solution of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (140 mg, 0.27 mmol, 1.0 equiv.) in MeOH (15 mL) was added formaldehyde (37 wt% aqueous solution, 0.2 mL, 2.7 mmol, 10.0 equiv.) and NaBH3CN. The solution was stirred at room temperature for 2 h and then partitioned between DCM (20 mL) and saturated NaHCO3 solution (20 mL). The aqueous layer was extracted with DCM (2 × 20 mL). The organic fraction was concentrated and purified by preparative HPLC to give N-(5-(5-(3,3-dithiolocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-thiolo-2-methylphenyl)-7-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide as a white solid (9.4 mg, 6.5%). LRMS (M+H + ) m / z calculated 526.2, found 526.1. 1H NMR(CDCl3,400MHz)δ 9.30(d,1H), 8.33-8.39(m,2H), 7.63(d,1H), 6.91(s,1H), 6.79(d,1H), 3.63-3.68(m,1 H), 3.41-3.48(m,4H), 3.08-3.16(m,4H), 2.70-2.73(m,4H), 2.45(s,3H), 2.34(s,1H).

[0267] Example 12: Preparation of methyl 3-(3-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0268] [ka]

[0269] To a solution of ethyl 6-chloroimidazo[1,2-a]pyridine-3-carboxylate (250 mg, 1.1 mmol, 1.0 equiv.) and methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (341.5 mg, 1.1 mmol, 1.0 equiv.) in toluene (50 mL) was added Al(Me) (2 M in toluene, 1.6 mL, 3.3 mmol, 3.0 equiv.) on ice. The reaction mixture was stirred at 80 °C for 5 h. The reaction mixture was concentrated in vacuo. The resulting residue was partitioned between DCM (100 mL) and saturated NaHCO solution (100 mL), filtered, and the aqueous layer was extracted with DCM (2 × 100 mL). The combined organic layers were concentrated, and the resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (61.0 mg, 11.2%). LRMS (M+H + ) m / z calculated 485.1, found 485.0. 1H NMR(DMSO-d6,400MHz)δ 10.34(brs,1H), 9.53(d,1H), 8.64(s,1H), 7.99(s,1H), 7.86(d,1H), 7.68(d,1H), 7.62(d,1H), 4.21-4.41(m,5H), 3.61(s,3H), 2.25(s,3H).

[0270] Example 13 Preparation of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide)

[0271] [ka]

[0272] To a solution of ethyl 7-bromoimidazo[1,2-a]pyridine-3-carboxylate (1.00 g, 3.71 mmol, 1.0 equiv.) in dioxane (40 mL) was added morpholine (1.61 g, 18.5 mmol, 5 equiv.), Pd(dba) (169 mg, 0.185 mmol, 0.05 equiv.), X-Phos (267 mg, 0.556 mmol, 0.15 equiv.), and CSCO (2.42 g, 7.42 mmol, 2 equiv.). The reaction mixture was stirred at 120 °C for 15 h, diluted with water (100 mL), and extracted with EtOAc (80 mL × 3). The combined organic layers were washed with brine (100 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (EA) to give ethyl 7-morpholinoimidazo[1,2-a]pyridine-3-carboxylate as a yellow solid (950 mg, 92.5%). LCMS (M+H + ) m / z calculated 276.1, found 276.1.

[0273] [ka]

[0274] A solution of ethyl 7-morpholinoimidazo[1,2-a]pyridine-3-carboxylate (800 mg, 3.6 mmol, 1.0 equiv) and NaOH (218.2 mg, 5.5 mmol, 3 equiv) in MeOH / HO (15 mL / 5 mL) was stirred at 50 °C for 3 h, and the solvent was partially removed under vacuum. The pH was adjusted to 5 with dilute HCl. The precipitate was collected by filtration and dried to give 7-morpholinoimidazo[1,2-a]pyridine-3-carboxylic acid as a white solid (390 mg, 54.3%). LCMS (M+H) + ) m / z calculated 248.1, found 248.1.

[0275] [ka]

[0276] To a solution of 7-morpholinoimidazo[1,2-a]pyridine-3-carboxylic acid (100.0 mg, 0.40 mmol, 1.0 equiv), 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylaniline (114.6 mg, 0.40 mmol, 1.0 equiv), and pyridine (0.2 mL, 2.0 mmol, 5.0 equiv) in DCM (50 mL) was added POCl (0.1 mL, 1.2 mmol, 3.0 equiv) at 0 °C. The reaction mixture was stirred at room temperature for 15 h. The reaction mixture was diluted with water (50 mL) and extracted with DCM (50 mL × 2). The combined organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide) as a white solid (69.5 mg, 33.6%). LRMS (M+H + ) m / z calculated 513.2, found 513.1. 1H NMR(DMSO-d6,400MHz)δ 9.98(s,1H), 9.17(d,1H), 8.42(s,1H), 7.97(s,1H), 7.62(d,1H), 7.09(dd,1H), 6.91(s,1H) ), 3.86-3.92(m,1H), 3.74-3.77(m,4H), 3.16-3.23(m,4H), 3.04-3.23(m,4H), 2.25(s,3H).

[0277] Example 14 Preparation of N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide

[0278] [ka]

[0279] A mixture of ethyl 7-bromoimidazo[1,2-a]pyridine-3-carboxylate (2.5 g, 9.3 mmol, 1.0 equiv.), morpholine (1.6 g, 18.6 mmol, 2.0 equiv.), palladium(II) acetate (154.0 mg, 0.93 mmol, 0.1 equiv.), Xantphos (538.5 mg, 0.93 mmol, 0.1 equiv.), and CsCO (6.0 g, 18.6 mmol, 2.0 equiv.) in toluene (50 mL) was stirred at 120 °C for 15 h under N. The reaction was quenched by the addition of HO (100 mL) and extracted with EtOAc (50 mL × 3). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EtOAc = 2 / 1, v / v) to give ethyl 7-morpholinoimidazo[1,2-a]pyridine-3-carboxylate as a pale yellow solid (2.3 g, 89.8%). LCMS (M+H + ) m / z calculated 276.1, found 276.1.

[0280] [ka]

[0281] A mixture of ethyl 7-morpholinoimidazo[1,2-a]pyridine-3-carboxylate (2.3 g, 8.4 mmol, 1.0 equiv.) and NaOH (1.0 g, 25.2 mmol, 3.0 equiv.) in MeOH (30.0 mL) and HO (10 mL) was stirred at 50° C. for 2 h. The mixture was concentrated, diluted with HO, and acidified to pH 2.0 by adding 1N HCl. The precipitate was filtered and dried to give 7-morpholinoimidazo[1,2-a]pyridine-3-carboxylic acid as a pale yellow solid (1.1 g, 55.0%). LCMS (M+H + ) m / z calculated 248.1, found 248.1.

[0282] [ka]

[0283] To a solution of 7-morpholinoimidazo[1,2-a]pyridine-3-carboxylic acid (1.1 g, 4.5 mmol, 1.0 equiv.) in DCM (20.0 mL) was added 4 drops of DMF and oxalyl chloride (2.9 g, 22.5 mmol, 5.0 equiv.). The reaction mixture was stirred at room temperature for 2 hours and concentrated to give crude 7-morpholinoimidazo[1,2-a]pyridine-3-carbonyl chloride as a pale yellow solid (1.2 g, quantitative), which was used in the next step without further purification.

[0284] [ka]

[0285] A mixture of 3-fluoro-4-methyl-5-nitrobenzonitrile (2.5 g, 13.9 mmol, 1.0 equiv.) and 250 mg Pd / C in MeOH (30.0 mL) was stirred under a stream of H2 at room temperature for 12 hours. The mixture was filtered through Celite and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EtOAc = 2 / 1, v / v) to give 3-amino-5-fluoro-4-methylbenzonitrile as a yellow solid (1.2 g, 57.1%). LCMS (M+H + ) m / z calculated 151.1, found 151.1.

[0286] [ka]

[0287] To a solution of 3-amino-5-fluoro-4-methylbenzonitrile (600.0 mg, 4.0 mmol, 1.0 equiv.) and DIEA (1.5 g, 12.0 mmol, 3.0 equiv.) in THF (10.0 mL), morpholinoimidazo[1,2-a]pyridine-3-carbonyl chloride (2.1 g, 8.0 mmol, 2.0 equiv.) was added at 0° C. The resulting solution was stirred at 80° C. for 4 hours. The mixture was concentrated and purified by silica gel column chromatography (PE / EtOAc=1 / 1, v / v) to give N-(5-cyano-3-fluoro-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide as a yellow solid (200.0 mg, 13.3%). LCMS (M+H + ) m / z calculated 380.1, found 380.1.

[0288] [ka]

[0289] A mixture of N-(5-cyano-3-fluoro-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide (200.0 mg, 0.53 mmol, 1.0 equiv), hydroxylamine hydrochloride (75.9 mg, 1.1 mmol, 2.0 equiv), and N,N-diisopropylethylamine (341.9 mg, 2.7 mmol, 5.0 equiv) in EtOH (10.0 mL) was stirred at 50 °C for 3 h. The reaction was quenched with HO (50 mL) and extracted with EtOAc (50 mL × 3). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EtOAc = 1 / 1, v / v) to give (Z)-N-(3-fluoro-5-(N'-hydroxycarbamimidoyl)-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide as a pale yellow solid (250.0 mg, quantitative). LCMS (M+H + ) m / z calculated 413.2, found 413.2.

[0290] [ka]

[0291] To a mixture of (1R,2S)-2-fluorocyclopropane-1-carboxylic acid (47.3 mg, 0.45 mmol, 1.5 equiv) in NMP (5.0 mL) was added 1,1′-carbonyldiimidazole (72.9 mg, 0.45 mmol, 1.5 equiv). The mixture was stirred at 40° C. for 2.0 hours. Then, (Z)—N-(3-fluoro-5-(N′-hydroxycarbamimidoyl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (125.0 mg, 0.3 mmol, 1.0 equiv) was added, and stirring was continued at 130° C. for 3 hours. The reaction was quenched with HO (50.0 mL) and extracted with EtOAc (50 mL×3). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide) as a white solid (29.5 mg, 20.0%). LCMS (M+H + ) m / z calculated 481.2, found 481.2. 1 H NMR(DMSO-d6,400MHz)δ 9.96(s,1H), 9.14-9.16(d,1H), 8.40(s,1H), 7.90(s,1H), 7.56-7.59(m,1H), 7.08-7.10(m,1H), 6.90-6.91(d,1H), 5.20-5. 21(t,1H), 3.74-3.77(t,4H), 3.25-3.31(t,4H), 3.06-3.08(m,1H), 2.23-2.24(d,3H), 1.92-1.98(m,1H), 1.56-1.61(m,1H).

[0292] Example 15: Preparation of methyl 3-(3-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0293] [ka]

[0294] To a solution of 7-morpholinoimidazo[1,2-a]pyridine-3-carboxylic acid (120.0 mg, 0.486 mmol, 1.0 equiv), methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (148.7 mg, 0.486 mmol, 1.0 equiv), and pyridine (0.2 mL, 2.43 mmol, 5.0 equiv) in DCM (30 mL) was added POCl (0.1 mL, 1.46 mmol, 3.0 equiv) at 0 °C. The reaction mixture was stirred at room temperature for 15 h. Upon completion of the reaction, the reaction mixture was diluted with water (50 mL) and extracted with DCM (50 mL × 2). The combined organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (59.4 mg, 22.9%). LCMS (M+H + ) m / z calculated 536.2, found 536.1. 1 H NMR(DMSO-d6,400MHz)δ 9.97(s,1H), 9.17(d,1H), 8.42(s,1H), 7.99(s,1H), 7.64(d,1H), 7.09(dd,1H), 6.91(d,1H), 4.45-4.33(m, 2H), 4.33-4.24(m,1H), 4.24-4.13(m,2H), 3.81-3.70(m,4H), 3.60(s,3H), 3.26-3.32(m,4H), 2.25(d,3H).

[0295] Example 16: Preparation of methyl 3-(3-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0296] [ka]

[0297] To a stirred solution of ethyl 7-chloroimidazo[1,2-a]pyridine-3-carboxylate (250 mg, 1.1 mmol, 1.0 equiv.) and methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (341.5 mg, 1.1 mmol, 1.0 equiv.) in toluene (50 mL) was added Al(Me) (2 M in toluene, 1.6 mL, 3.3 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at 80 °C for 5 h. The reaction mixture was concentrated in vacuo. The resulting residue was partitioned between DCM (100 mL) and saturated NaHCO solution (100 mL). The aqueous layer was extracted with DCM (100 mL × 2). The combined organic layers were concentrated and the resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (58.2 mg, 10.7%). LCMS (M+H + ) m / z calculated 485.1, found 485.0. 1 H NMR(DMSO-d6,400MHz)δ 10.29(s,1H), 9.42(d,1H), 8.61(s,1H), 7.98-8.00(m,2H), 7.66(dd,1H), 7.27(dd,1H), 4.19-4.38(m,5H), 3.60(s,3H), 2.25(d,3H).

[0298] Example 17: Preparation of methyl 3-(3-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0299] [ka]

[0300] To a stirred solution of ethyl 7-bromoimidazo[1,2-a]pyridine-3-carboxylate (500 mg, 1.9 mmol, 1.0 equiv.) and Pd(PPh3)4 (214.9 mg, 0.19 mmol, 0.1 equiv.) in toluene (30 mL) was added Zn(Me)2 (1 M in toluene, 5.6 mL, 5.6 mmol, 3.0 equiv.) at 0 °C. The reaction was stirred at 120 °C for 15 h. The reaction was concentrated and purified by silica gel column chromatography (PE / EA = 2 / 1, v / v) to give ethyl 7-methylimidazo[1,2-a]pyridine-3-carboxylate as a yellow solid (190 mg, 50.0%). LCMS (M+H) + ) m / z calculated 205.1, found 205.0.

[0301] [ka]

[0302] A solution of ethyl 7-methylimidazo[1,2-a]pyridine-3-carboxylate (170 mg, 0.83 mmol, 1.0 equiv) and LiOH (40.0 mg, 1.7 mmol, 2.0 equiv) in MeOH / HO (30 mL / 5 mL) was stirred at 25° C. for 2 h. The solvent was partially removed under vacuum. The pH was adjusted to 5 with concentrated HCl. The white solid was collected by filtration and dried under vacuum to give 7-methylimidazo[1,2-a]pyridine-3-carboxylic acid as a white solid (120.0 mg, 81.6%). LCMS (M+H + ) m / z calculated 177.1, found 177.0.

[0303] [ka]

[0304] To a solution of 7-methylimidazo[1,2-a]pyridine-3-carboxylic acid (120.0 mg, 0.68 mmol, 1.0 equiv), methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (208.6 mg, 0.68 mmol, 1.0 equiv), and pyridine (0.3 mL, 3.4 mmol, 5.0 equiv) in DCM (30 mL) was added POCl (0.2 mL, 2.0 mmol, 3.0 equiv) at 0 °C. The reaction mixture was stirred at 25 °C for 15 h. The reaction mixture was diluted with water (50 mL) and extracted with DCM (50 mL × 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (16.0 mg, 5.1%). LCMS (M+H + ) m / z calculated 465.2, found 465.1. 1 H NMR(DMSO-d6,400MHz)δ 10.14(s,1H), 9.31(d,1H), 8.53(s,1H), 7.99(s,1H), 7.66(d,1H), 7.58(s, 1H), 7.04(d,1H), 4.18-4.38(m,5H), 3.60(s,3H), 2.46(s,3H), 2.25(s,3H).

[0305] Example 18 Preparation of 7-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

[0306] [ka]

[0307] To a solution of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (140 mg, 0.27 mmol, 1.0 equiv) in DCM (15 mL) was added acetic anhydride (149.7 mg, 1.4 mmol, 5.0 equiv) and TEA (277.7 mg, 2.7 mmol, 10.0 equiv). The solution was stirred at room temperature for 15 h and then partitioned between DCM (20 mL) and saturated NaHCO solution (20 mL). The aqueous layer was extracted with DCM (20 mL × 2) and concentrated. The resulting residue was purified by preparative HPLC to give 7-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide as a white solid (65.3 mg, 43.0%). LCMS (M+H + ) m / z calculated 554.2, found 554.1. 1 H NMR(DMSO-d6,400MHz)δ 10.49(s,1H), 9.22(d,1H), 8.67(s,1H), 7.95(s,1H), 7.69(d,1H), 7.37(dd,1H), 6.99(dd,1H), 3.86-3.92(m,1H), 3.64(s,6H), 3.55-3.58(m,2H), 3.05-3.24(m,4H), 2.25(s,3H), 2.07(s,3H).

[0308] Example 19: Preparation of methyl 3-(3-(3-thiolo-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate))

[0309] [ka]

[0310] To a stirred solution of ethyl 6-fluoroimidazo[1,2-a]pyridine-3-carboxylate (300 mg, 1.4 mmol, 1.0 equiv.) and methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (441.3 mg, 1.4 mmol, 1.0 equiv.) in toluene (50 mL) was added Al(Me) (2 M in toluene, 2.2 mL, 4.3 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at 80 °C for 5 h. The reaction mixture was concentrated, partitioned between DCM (100 mL) and saturated NaHCO solution (100 mL), and filtered. The aqueous layer was extracted with DCM (100 mL × 2). The combined organic phase was concentrated and the resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (203.9 mg, 30.0%). LCMS (M+H + ) m / z calculated 469.1, found 469.0. 1 H NMR(DMSO-d6,400MHz)δ 10.35(s,1H), 9.48(d,1H), 8.69(s,1H), 7.98(s,1H), 7.92(dd,1H), 7.67-7.74(m,2H), 4.20-4.39(m,5H), 3.61(s,3H), 2.26(s,3H).

[0311] Example 20: Preparation of methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0312] [ka]

[0313] A mixture of ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate (5 g, 18.6 mmol, 1.0 equiv.), tert-butyl piperazine-carboxylate (10.4 g, 55.8 mmol, 3.0 equiv.), CS2CO3 (12.1 g, 37.2 mmol, 2.0 equiv.), XantPhos (1.1 g, 1.9 mmol, 0.1 equiv.), and Pd2(dba)3 (851.3 mg, 0.9 mmol, 0.05 equiv.) in dioxane (100 mL) was stirred at 110 °C overnight. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL × 3). The combined organic layers were washed with brine (100 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give ethyl 6-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylate as a yellow solid (6.5 g, 92.8%). LCMS (M+H + ) m / z calculated 375.2, found 375.1.

[0314] [ka]

[0315] A solution of ethyl 6-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylate (5 g, 13.3 mmol, 1.0 equiv) and NaOH (802.1 mg, 20.1 mmol, 1.5 equiv) in MeOH / HO (30 mL / 5 mL) was stirred at 30 °C for 5 h, and the solvent was partially removed under vacuum. The pH was adjusted to 6 with concentrated HCl. The solid was collected by filtration and dried to give 6-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylic acid as a white solid (4.0 g, 87.0%). LCMS (M+H + ) m / z calculated 347.2, found 347.1.

[0316] [ka]

[0317] To a solution of 6-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylic acid (1 g, 2.9 mmol, 1.0 equiv.), methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (884.4 mg, 2.9 mmol, 1.0 equiv.), and pyridine (1.2 mL, 24.5 mmol, 5.0 equiv.) in DCM (50 mL) was added POCl (0.8 mL, 1.2 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at room temperature for 15 h and diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL × 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give tert-butyl 4-(3-((3-fluoro-5-(5-(1-(methoxycarbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl)piperazine-1-carboxylate as a yellow solid (1.2 g, 66.7%). LCMS (M+H + ) m / z calculated 635.3, found 635.2.

[0318] [ka]

[0319] To a stirred solution of tert-butyl 4-(3-((3-fluoro-5-(5-(1-(methoxycarbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl)piperazine-1-carboxylic acid (100 mg, 0.16 mmol, 1 equiv.) in DCM (10 mL) was added 4N HCl / Dioxane (5 mL). The reaction was stirred at 30° C. for 5 h. The mixture was concentrated and purified by preparative HPLC to give methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (24.9 mg, 29.8%). LCMS (M+H + ) m / z calculated 535.2, found 535.1. 1 H NMR(DMSO-d6,400MHz)δ 10.14(s,1H), 8.93(s,1H), 8.51(s,1H), 7.96(s,1H), 7.65-7.69(m,2H), 7. 54(d,1H), 4.20-4.38(m,5H), 3.59(s,3H), 2.98-3.09(m,8H), 2.25(s,3H).

[0320] Example 21: Preparation of methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0321] [ka]

[0322] To a stirred solution of ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate (200 mg, 0.74 mmol, 1.0 equiv.) and Pd(PPh3)4 (85.9 mg, 0.074 mmol, 0.1 equiv.) in dioxane (30 mL), Zn(Me)2 (1 M in toluene, 2.2 mL, 2.2 mmol, 3.0 equiv.) was added at 0 °C. The reaction mixture was stirred at 100 °C for 15 h. The reaction mixture was concentrated and purified by silica gel column chromatography (PE / EA = 2 / 1, v / v) to give ethyl 6-methylimidazo[1,2-a]pyridine-3-carboxylate as a yellow solid (190 mg, quantitative). LCMS (M+H) + ) m / z calculated 205.1, found 205.0.

[0323] [ka]

[0324] A solution of ethyl 6-methylimidazo[1,2-a]pyridine-3-carboxylate (190 mg, 0.93 mmol, 1.0 equiv) and NaOH (74.5 mg, 1.9 mmol, 2.0 equiv) in MeOH / HO (30 mL / 5 mL) was stirred at room temperature for 2 h, and the solvent was partially removed under vacuum. The pH was adjusted to 5 with concentrated HCl. The precipitate was collected by filtration and dried to give 6-methylimidazo[1,2-a]pyridine-3-carboxylic acid as a white solid (150.0 mg, 91.4%). LCMS (M+H + ) m / z calculated 177.1, found 177.0.

[0325] [ka]

[0326] To a solution of 6-methylimidazo[1,2-a]pyridine-3-carboxylic acid (150.0 mg, 0.85 mmol, 1.0 equiv), methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (260.8 mg, 0.85 mmol, 1.0 equiv), and pyridine (0.4 mL, 4.3 mmol, 5.0 equiv) in DCM (30 mL) was added POCl (0.24 mL, 2.0 mmol, 3.0 equiv) at 0 °C. The reaction mixture was stirred at room temperature for 15 h. The reaction mixture was diluted with water (50 mL) and extracted with DCM (50 mL × 2). The combined organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (9.7 mg, 2.5%). LCMS (M+H + ) m / z calculated 465.2, found 465.1. 1 H NMR(DMSO-d6,400MHz)δ 10.17(s,1H), 9.28(d,1H), 8.55(s,1H), 8.00(s,1H), 7.65-7.72(m,2H), 7.39(dd,1H), 4.20-4.38(m,5H), 3.60(s,3H), 2.46(s,3H), 2.25(s,3H).

[0327] Example 22 Preparation of N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (racemic, trans)

[0328] [ka]

[0329] To a stirred solution of ethyl 7-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylate (500 mg, 1.3 mmol, 1.0 equiv.), 3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline, and 3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline) (racemic, trans, 335.6 mg, 1.3 mmol, 1.0 equiv.) in toluene (50 mL) was added Al(Me) (2 M in toluene, 2.0 mL, 4.0 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at 90 °C for 2 h. The reaction mixture was concentrated and partitioned between DCM (100 mL) and saturated NaHCO3 solution (100 mL). The aqueous layer was extracted with DCM (100 mL x 2) and concentrated. The resulting residue was purified by silica gel column chromatography (DCM / MeOH=50 / 1, v / v) to give tert-butyl 4-(3-((3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-7-yl)piperazine-1-carboxylate and tert-butyl 4-(3-((3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-7-yl)piperazine-1-carboxylate (racemic, trans) as a white solid (300.0 mg, 38.7%). LCMS (M+H + ) m / z calculated 580.2, found 580.1.

[0330] [ka]

[0331] To a stirred solution of tert-butyl 4-(3-((3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-7-yl)piperazine-1-carboxylate and tert-butyl)4-(3-((3-thiolo-5-(5-((1S,2R)-2-thiolocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-7-yl)piperazine-)1-carboxylate (racemic, trans, 300 mg, 0.52 mmol, 1.0 equiv) in DCM (10 mL) was added 4N HCl / dioxane (5 mL). The reaction was stirred at 30° C. for 5 hours. The mixture was concentrated and purified by preparative HPLC to give N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (racemic, trans) as a white solid (189.5 mg, 76.4%). LCMS (M+H + ) m / z calculated 480.2, found 480.1. 1 H NMR(DMSO-d6,400MHz)δ 9.95(s,1H), 9.13(d,1H), 8.39(s,1H), 7.90(s,1H), 7.57(d,1H), 7.09(dd,1H), 6.87(d,1H), 5.20 -5.38(m,1H), 3.29(m,8H), 2.66-2.68(m,1H), 2.23(s,3H), 1.90-2.00(m,1H), 1.57-1.62(m,1H).

[0332] Example 23: Preparation of ethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0333] [ka]

[0334] To a solution of 3,3-difluorocyclobutane-1-carboxylic acid (55.0 g, 258.2 mmol, 1.0 equiv) in anhydrous NMP (180 mL) was added CDI (62.7 g, 287.3 mmol, 1.5 equiv). The reaction was stirred for 15 minutes. 1-(tert-Butoxycarbonyl)azetidine-3-carboxylic acid (51.9 g, 258.2 mmol, 1.0 equiv) was added and the reaction was stirred for 25 minutes. The reaction was stirred at 130° C. for 1 hour. The crude product was diluted with EtOAc (300 mL). The organic layer was washed with water (200 mL) and brine (200 mL). The mixture was concentrated and purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give tert-butyl 3-(3-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a yellow solid (100 g, ca. 100%).

[0335] [ka]

[0336] To a stirred suspension of tert-butyl 3-(3-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (100.0 g, 264.6 mmol, 1.0 equiv) in EtOH (190 mL) was added SnCl (150.5 g, 793.7 mmol, 3.0 equiv). The reaction mixture was heated at 78 °C for 3 h. The reaction was cooled to room temperature and the solvent was partially concentrated. The pH was adjusted to slightly basic with a saturated solution of sodium bicarbonate (190 mL). The resulting white suspension was filtered and washed with water (190 mL) and EtOAc (190 mL). The aqueous layer was extracted with EtOAc (250 mL × 2). The combined organic layers were washed with brine (250 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give tert-butyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (45.0 g, 48.9%). LCMS (M+H + ) m / z calculated 349.2, found 349.1.

[0337] [ka]

[0338] To a stirred solution of tert-butyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (45 g, 129.3 mmol, 1.0 equiv.), imidazo[1,2-a]pyridine-3-carboxylic acid (20.9 g, 129.3 mmol, 1.0 equiv.), and pyridine (52.1 mL, 646.6 mmol, 5.0 equiv.) in DCM (30 mL) was added POCl (36.0 mL, 387.9 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water (150 mL) and extracted with DCM (250 mL × 2). The combined organic layers were washed with brine (150 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (DCM / MeOH=50 / 1, v / v) to give tert-butyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (16.0 mg, 25.1%). LCMS (M+H + ) m / z calculated 493.2, found 493.1.

[0339] [ka]

[0340] To a stirred solution of tert-butyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (16 g, 32.5 mmol, 1.0 equiv) in DCM (50 mL) was added TFA (30 mL). The reaction was stirred at 30° C. for 2 h. The mixture was concentrated to give N-(5-(5-(azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide as a yellow oil (25.0 g, quantitative). LCMS (M+H) +) m / z calculated 392.2, found 392.1.

[0341] [ka]

[0342] N-(5-(5-(azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (500 mg, 1.3 mmol, 1.0 equiv) and NaHCO3 (535.7 mg, 6.4 mmol, 5.0 equiv) were dissolved in MeCN (50 mL) and water (5 mL). Ethyl carbonochloridate (165.3 mg, 1.5 mmol, 1.2 equiv) was dissolved in MeCN (20 mL) and then added dropwise to the reaction mixture at 0 °C. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated. The resulting residue was diluted with water (10 mL) and extracted with EtOAc (2 × 20 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give ethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (65.3 mg, 11.0%). LCMS (M+H + ) m / z calculated 465.2, found 465.1. 1 H NMR(CDCl3,400MHz)δ 9.53(d,1H), 8.42(s,1H), 8.23(s,1H), 7.76(d,1H), 7.62-7.69(m,2H), 7.43-7.48(m,1 H), 7.05-7.08(m,1H), 4.36-4.47(m,4H), 4.08-4.18(m,3H), 2.34(d,3H), 1.27(t,3H).

[0343] Example 24: Preparation of methyl 3-(3-(3-thiolo-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate)

[0344] [ka]

[0345] To a solution of 7-thioloimidazo[1,2-a]pyridine-3-carboxylic acid (100.0 mg, 0.56 mmol, 1.0 equiv.), methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (170.0 mg, 0.56 mmol, 1.0 equiv.), and pyridine (0.20 mL, 2.8 mmol, 5.0 equiv.) in DCM (30 mL) was added POCl (0.15 mL, 1.7 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water (50 mL) and extracted with DCM (50 mL × 2). The combined organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (33.6 mg, 13.1%). LCMS (M+H + ) m / z calculated 469.1, found 469.0. 1 H NMR(DMSO-d6,400MHz)δ 10.25(s,1H), 9.47(t,1H), 8.59(s,1H), 7.98(s,1H), 7.69(t,2H), 7.26(t,1H), 4.19-4.40(m,5H), 3.60(s,3H), 2.25(d,3H).

[0346] Example 25 Preparation of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide

[0347] [ka]

[0348] To a solution of 6-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylic acid (500.0 mg, 1.4 mmol, 1.0 equiv), 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylaniline (409.0 mg, 1.4 mmol, 1.0 equiv), and pyridine (0.60 mL, 7.2 mmol, 5.0 equiv) in DCM (30 mL) was added POCl (0.40 mL, 4.3 mmol, 3.0 equiv) at 0° C. The reaction mixture was stirred at room temperature for 2 h, diluted with water (50 mL), and extracted with DCM (50 mL × 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give tert-butyl 4-(3-((5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl)piperazine-1-carboxylate (250.0 mg, 28.3%). LCMS (M+H + ) m / z calculated 612.2, found 612.1.

[0349] [ka]

[0350] To a stirred solution of tert-butyl 4-(3-((5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl)piperazine-1-carboxylate (250 mg, 0.41 mmol, 1.0 equiv) in DCM (10 mL) was added 4N HCl / dioxane (10 mL). The reaction was stirred at 30° C. for 5 h. The mixture was concentrated and purified by preparative HPLC to give N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide as a white solid (11.0 mg, 5.3%). LCMS (M+H + ) m / z calculated 512.2, found 512.1. 1 H NMR(DMSO-d6,400MHz)δ 10.13(s,1H), 8.91(d,1H), 8.49(s,1H), 7.95(s,1H), 7.64(d,2H), 7.52(dd ,1H), 3.87-3.92(m,1H), 2.97-3.24(m,8H), 2.84-2.87(m,4H), 2.25(d,3H).

[0351] Example 26: N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (racemic, trans)

[0352] [ka]

[0353] To a solution of 6-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylic acid (1 g, 2.9 mmol, 1.0 equiv.), 3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline, 3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline (racemic, trans, 725.4 mg, 2.9 mmol, 1.0 equiv.), and pyridine (1.2 mL, 14.4 mmol, 5.0 equiv.) in DCM (50 mL) was added POCl (0.80 mL, 8.7 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred for 15 hours at 25° C. The reaction mixture was diluted with water (50 mL) and extracted with DCM (50 mL×2). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give tert-butyl 4-(3-((3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl)piperazine-1-carboxylate and tert-butyl 4-(3-((3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl)piperazine-1-carboxylate (racemic, trans, 460.0 mg, 27.1%). LCMS (M+H + ) m / z calculated 580.2, found 580.1.

[0354] [ka]

[0355] To a stirred solution of tert-butyl 4-(3-((3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl)piperazine-1-carboxylate and tert-butyl 4-(3-((3-thiolo-5-(5-((1S,2R)-2-thiolocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-6-yl)piperazine-)1-carboxylate (racemic, trans, 300 mg, 0.79 mmol, 1.0 equiv) in DCM (10 mL) was added 4N HCl in dioxane (5 mL). The reaction was stirred at 30° C. for 5 hours. The mixture was concentrated and purified by preparative HPLC to give N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-)((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (racemic, trans) as a white solid (20.2 mg, 5.3%). LCMS (M+H + ) m / z calculated 480.2, found 480.1. 1 H NMR(DMSO-d6,400MHz)δ 10.11(s,1H), 8.91(d,1H), 8.48(s,1H), 7.89(s,1H), 7.64(d,1H), 7.59(d,1H), 7.51(dd,1H), 5.20-5 .38(m,1H), 2.97-3.11(m,6H), 2.83-2.87(m,4H), 2.24(s,3H), 1.90-2.00(m,1H), 1.57-1.62(m,1H).

[0356] Example 27: Preparation of methyl 3-(3-(3-fluoro-5-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0357] [ka]

[0358] To a solution of ethyl 2-chloro-3-oxopropanoate (2.4 g, 16.1 mmol, 4.0 equiv) and 5-methoxypyridin-2-amine (500 mg, 4.0 mmol, 1.0 equiv) in EtOH (20 mL) was added concentrated H2SO4 (0.3 mL). The reaction mixture was stirred at 80 °C for 15 hours and concentrated. The pH was adjusted to slightly basic with a saturated solution of sodium bicarbonate. The resulting solution was extracted with EtOAc (80 mL x 3). The combined organic phase was washed with brine (70 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EA = 2 / 1, v / v) to give ethyl 6-methoxyimidazo[1,2-a]pyridine-3-carboxylate as a yellow solid (669 mg, 75.4%). LCMS (M+H + ) m / z calculated 221.1, found 221.0.

[0359] [ka]

[0360] A solution of ethyl 6-methoxyimidazo[1,2-a]pyridine-3-carboxylate (669 mg, 3.0 mmol, 1.0 equiv) and NaOH (243.3 mg, 6.1 mmol, 2.0 equiv) in MeOH / HO (30 mL / 5 mL) was stirred at room temperature for 2 hours. The solvent was partially removed in vacuo. The pH was adjusted to 5 with concentrated HCl. The precipitate was collected by filtration and dried to give 6-methoxyimidazo[1,2-a]pyridine-3-carboxylic acid as a white solid (386.0 mg, 66.2%). LCMS (M+H + ) m / z calculated 193.1, found 193.0.

[0361] [ka]

[0362] To a solution of 6-methoxyimidazo[1,2-a]pyridine-3-carboxylic acid (150.0 mg, 0.78 mmol, 1.0 equiv), methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (239.1 mg, 0.78 mmol, 1.0 equiv), and pyridine (0.31 mL, 3.9 mmol, 5.0 equiv) in DCM (20 mL) was added POCl (0.21 mL, 2.3 mmol, 3.0 equiv) at 0 °C. The reaction mixture was stirred at room temperature for 2 h, diluted with water (50 mL), and extracted with DCM (50 mL × 2). The combined organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-5-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (93.7 mg, 25.0%). LCMS (M+H + ) m / z calculated 481.2, found 481.1. 1H NMR(DMSO-d6,400MHz)δ 10.19(s,1H), 9.10(d,1H), 8.55(s,1H), 7.98(s,1H), 7.72(d,1H), 7.67(d,1 H), 7.32(dd,1H), 4.20-4.38(m,5H), 3.83(s,3H), 3.60(s,3H), 2.26(s,3H).

[0363] Example 28: Preparation of methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0364] [ka]

[0365] To a solution of methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (50 mg, 0.094 mmol, 1.0 equiv.) in MeOH (15 mL) was added formaldehyde (37 wt.% aqueous solution, 0.1 mL, 0.94 mmol, 10.0 equiv.) and NaBHCN (17.7 mg, 0.28 mmol, 3.0 equiv.). The solution was stirred at room temperature for 2 h and then partitioned between DCM (20 mL) and saturated NaHCO solution (20 mL). The aqueous layer was extracted with DCM (20 mL × 2). The combined organic phases were concentrated in vacuo. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazin-)1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (12.4 mg, 24.3%). LCMS (M+H + ) m / z calculated 549.2, found 549.1. 1H NMR(DMSO-d6,400MHz)δ 10.12(s,1H), 8.92(d,1H), 8.49(s,1H), 7.96(s,1H), 7.67(d,2H), 7.53(dd,1H), 4.20-4 .38(m,5H), 3.59(s,3H), 3.07-3.11(m,4H), 2.50-2.53(m,4H), 2.25(s,3H), 2.22(s,3H).

[0366] Example 29: Preparation of methyl 3-(3-(3-fluoro-5-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0367] [ka]

[0368] A solution of 4-methoxypyridin-2-amine (2.4 g, 16.1 mmol, 4.0 equiv.) and 5-methoxypyridin-2-amine (500 mg, 4.0 mmol, 1.0 equiv.) in t-BuOH (20 mL) was stirred at 140° C. for 15 hours and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (PE / EA=2 / 1, v / v) to give ethyl 7-methoxyimidazo[1,2-a]pyridine-3-carboxylate as a yellow solid (320 mg, 36.1%). LCMS (M+H) + ) m / z calculated 221.1, found 221.0.

[0369] [ka]

[0370] A solution of ethyl 7-methoxyimidazo[1,2-a]pyridine-3-carboxylate (320 mg, 1.5 mmol, 1.0 equiv) and NaOH (116.3 mg, 2.9 mmol, 2.0 equiv) in MeOH / HO (30 mL / 5 mL) was stirred at 25 °C for 2 h, and the solvent was partially removed under vacuum. The pH was adjusted to 5 with concentrated HCl. The precipitate was collected by filtration and dried to give 7-methoxyimidazo[1,2-a]pyridine-3-carboxylic acid as a white solid (250.0 mg, 89.6%). LCMS (M+H + ) m / z calculated 193.1, found 193.0.

[0371] [ka]

[0372] To a solution of 7-methoxyimidazo[1,2-a]pyridine-3-carboxylic acid (250.0 mg, 1.3 mmol, 1.0 equiv), methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (398.4 mg, 1.3 mmol, 1.0 equiv), and pyridine (0.52 mL, 6.5 mmol, 5.0 equiv) in DCM (20 mL) was added POCl (0.36 mL, 3.9 mmol, 3.0 equiv) at 0 °C. The reaction mixture was stirred at 25 °C for 2 h. The reaction mixture was diluted with water (50 mL) and extracted with DCM (50 mL × 2). The combined organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-fluoro-5-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (189.5 mg, 30.3%). LCMS (M+H + ) m / z calculated 481.2, found 481.1. 1H NMR(DMSO-d6,400MHz)δ 10.10(s,1H), 9.25(d,1H), 8.47(s,1H), 7.98(s,1H), 7.65(dd,1H), 7.17(d, 1H), 6.87(dd,1H), 4.20-4.38(m,5H), 3.90(s,3H), 3.60(s,3H), 2.25(d,3H).

[0373] Example 30: Preparation of methyl 3-(3-(3-fluoro-4-methyl-5-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0374] [ka]

[0375] To a stirred solution of ethyl 7-(4-(tert-butoxycarbonyl)piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxylate (500 mg, 1.3 mmol, 1.0 equiv.) and methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (409.1 mg, 1.3 mmol, 1.0 equiv.) in toluene (50 mL) was added Al(Me) (2 M in toluene, 2.0 mL, 4.0 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at 80 °C for 5 h. The reaction mixture was concentrated in vacuo. The resulting residue was partitioned between DCM (100 mL) and saturated NaHCO solution (100 mL). The aqueous layer was extracted with DCM (100 mL × 2). The combined organic layer was concentrated and purified by silica gel column chromatography (DCM / MeOH=50 / 1, v / v) to give tert-butyl 4-(3-((3-fluoro-5-(5-(1-(methoxycarbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-7-yl)piperazine-1-carboxylate as a yellow solid (200.6 mg, 23.6%). LCMS (M+H + ) m / z calculated 635.3, found 635.2.

[0376] [ka]

[0377] To a stirred solution of tert-butyl 4-(3-((3-fluoro-5-(5-(1-(methoxycarbonyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)carbamoyl)imidazo[1,2-a]pyridin-7-yl)piperazine-1-carboxylate (200 mg, 0.32 mmol, 1.0 equiv) in DCM (10 mL) was added 4N HCl in dioxane (5 mL). The reaction was stirred at 30° C. for 5 h. The mixture was concentrated and purified by preparative HPLC to give methyl 3-(3-(3-fluoro-4-methyl-5-(7-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (8.8 mg, 5.3%). LCMS (M+H + ) m / z calculated 535.2, found 535.1. 1 H NMR(DMSO-d6,400MHz)δ 9.94(s,1H), 9.13(d,1H), 8.39(s,1H), 7.98(s,1H), 7.62(dd,1H), 7.06(dd,1H), 6.84(d ,1H), 4.19-4.38(m,5H), 3.59(s,3H), 3.22-3.31(m,4H), 2.82-2.85(m,4H), 2.24(s,3H).

[0378] Example 31: Preparation of cyclopropyl 3-(3-(3-thiolo-5-)imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0379] [ka]

[0380] To a solution of cyclopropanol (29.6 mg, 0.51 mmol, 1.0 equiv.), TEA (515.3 mg, 5.1 mmol, 10.0 equiv.) in DCE (10 mL) was added triphosgene (151.5 mg, 0.51 mmol, 1.0 equiv.) at 0° C. The solution was warmed to room temperature, stirred for 1 h, and N-(5-(5-(azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (200.0 mg, 0.51 mmol, 1.0 equiv.) was added. The resulting solution was heated at 50° C. for 1 h. After cooling to room temperature, the solution was diluted with DCM (50 mL). The resulting solution was washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give cyclopropyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (15.2 mg, 6.3%). LCMS (M+H + ) m / z calculated 477.2, found 477.0. 1 H NMR(DMSO-d6,400MHz)δ 9.52(d,1H), 8.49(s,1H), 8.02(s,1H), 7.69-7.76(m,2H), 7.58(dd,1H), 7.18(t,1H) , 4.41-4.46(m,2H), 4.22-4.30(m,3H), 4.03(t,1H), 2.31(s,3H), 0.67-0.69(m,4H).

[0381] Example 32: Preparation of N-(3-fluoro-2-methyl-5-(5-(1-(methylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

[0382] [ka]

[0383] A solution of CDI (330.1 mg, 2.0 mmol, 4.0 equiv.) and methylamine (1 M in THF, 2.0 mL, 2.0 mmol, 4.0 equiv.) in THF (10 mL) was stirred at room temperature for 15 minutes. N-(5-(5-(azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (200.0 mg, 0.51 mmol, 1.0 equiv.) was then added, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with water (15 mL) and extracted with EtOAc (20 mL × 3). The combined organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give N-(3-fluoro-2-methyl-5-(5-(1-(methylcarbamoyl)azetidin-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide as a white solid (25.6 mg, 11.2%). LCMS (M+H + ) m / z calculated 450.2, observed 450.0. 1 H NMR(DMSO-d6,400MHz)δ 10.22(s,1H), 9.45(d,1H), 8.61(s,1H), 7.99(s,1H), 7.79(d,1H), 7.67(dd,1H), 7.54(dd,1H) ), 7.19(t,1H), 6.43(d,1H), 4.22-4.24(m,3H), 4.05-4.07(m,2H), 2.55(s,3H), 2.25(d,3H).

[0384] Example 33 Preparation of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)

[0385] [ka]

[0386] To a solution of methyl N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (40 mg, 0.078 mmol, 1.0 equiv.) in MeOH (10 mL) was added formaldehyde (37 wt.% aqueous solution, 0.1 mL, 0.78 mmol, 10.0 equiv.), NaBHCN (14.6 mg, 0.23 mmol, 3.0 equiv.), and AcOH (1 drop). The solution was stirred at room temperature for 15 h and then partitioned between DCM (20 mL) and saturated NaHCO solution (20 mL). The aqueous layer was extracted with DCM (20 mL × 2), and the combined organic phases were concentrated. The resulting residue was purified by preparative HPLC to give N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide as a white solid (5.2 mg, 12.7%). LCMS (M+H + ) m / z calculated 526.2, found 526.1. 1 H NMR(CDCl3,400MHz)δ 9.08(s,1H), 8.34(s,1H), 8.17(s,1H), 7.63-7.67(m,3H), 7.32(d,1H), 3.64-3.6 9(m,1H), 3.37(s,4H), 3.08-3.17(m,4H), 2.87(s,4H), 2.55(s,3H), 2.33(d,3H).

[0387] Example 34 Preparation of N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide) and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide) (racemic, trans)

[0388] [ka]

[0389] N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-)((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3 in MeOH (10 mL) To a solution of (-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (racemic, trans, 100 mg, 0.21 mmol, 1.0 equiv.), formaldehyde (37 wt.% solution in water, 0.3 mL, 2.1 mmol, 10.0 equiv.), NaBH3CN (39.5 mg, 0.63 mmol, 3.0 equiv.), and AcOH (2 drops) were added. The solution was stirred at room temperature for 15 h and then partitioned between DCM (20 mL) and saturated NaHCO3 solution (20 mL). The aqueous layer was extracted with DCM (20 mL × 2). The combined organic phases were concentrated. The resulting residue was purified by preparative HPLC to give N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(4-methylpiperazin-)-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (racemic, trans) as a white solid (11.7 mg, 11.7%). LCMS (M+H + ) m / z calculated 494.2, found 494.0. 1H NMR(CDCl3,400 MHz)δ 9.06(d,1H), 8.29(s,1H), 8.14(s,1H), 7.59-7.65(m,3H), 7.31(dd,1H), 4.96-5.15( m,1H), 3.31(s,4H), 2.68-2.77(m,4H), 2.50(s,3H), 2.32(d,3H), 1.58-1.90(m,3H).

[0390] Example 35: Preparation of methyl 3-(3-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0391] [ka]

[0392] To a solution of ethyl 7-bromoimidazo[1,2-a]pyridine-3-carboxylate (1 g, 3.7 mmol, 1.0 equiv.) in DMF (50 mL) was added Zn(CN) (654.9 mg, 5.6 mmol, 1.5 equiv.) and Pd(PPh) (431.3 mg, 0.37 mmol, 0.1 equiv.). The mixture was stirred at 120 °C for 15 h, and then the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL × 3). The combined organic layers were washed with brine (100 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EA = 3 / 1, v / v) to give ethyl 7-cyanoimidazo[1,2-a]pyridine-3-carboxylate as a yellow solid (600.0 g, 74.8%). LCMS (M+H + ) m / z calculated 216.1, found 216.0.

[0393] [ka]

[0394] A solution of ethyl 7-cyanoimidazo[1,2-a]pyridine-3-carboxylate (600.0 mg, 2.8 mmol, 1.0 equiv) and LiOH (134.0 mg, 5.6 mmol, 2.0 equiv) in THF / HO (30 mL / 5 mL) was stirred at room temperature for 2 h, and the solvent was partially removed under vacuum. The pH was adjusted to 5 with concentrated HCl. The precipitate was collected by vacuum filtration and dried under vacuum to give 7-cyanoimidazo[1,2-a]pyridine-3-carboxylic acid as a white solid (500.0 mg, 95.9%). LCMS (M+H + ) m / z calculated 188.0, found 187.9.

[0395] [ka]

[0396] To a solution of 7-cyanoimidazo[1,2-a]pyridine-3-carboxylic acid (500.0 mg, 2.7 mmol, 1.0 equiv), methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (818.2 mg, 2.7 mmol, 1.0 equiv), and pyridine (1.1 mL, 13.4 mmol, 5.0 equiv) in DCM (50.0 mL) was added POCl (0.75 mL, 3.9 mmol, 3.0 equiv) at 0 °C. The reaction mixture was stirred at room temperature for 15 h, diluted with water (50 mL), and extracted with DCM (50 mL × 2). The combined organic layer was washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (54.0 mg, 4.3%). LCMS (M+H + ) m / z calculated 476.1, found 476.0. 1H NMR(DMSO-d6,400MHz)δ 10.45(s,1H), 9.52(d,1H), 8.78(s,1H), 8.58(s,1H), 7.99(s,1H), 7.68(dd,1H), 7.47(dd,1H), 4.19-4.38(m,5H), 3.60(s,3H), 2.25(d,3H).

[0397] Example 36: Preparation of methyl 3-(3-(3-(6-(4-acetylpiperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0398] [ka]

[0399] To a solution of methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (40 mg, 0.075 mmol, 1.0 equiv) in MeCN / HO (15 mL / 3 mL) was added acetic anhydride (38.2 mg, 0.37 mmol, 5.0 equiv) and NaHCO (62.9 mg, 0.75 mmol, 10.0 equiv). The solution was stirred at room temperature for 15 h and then partitioned between EtOAc (20 mL) and saturated NaHCO solution (20 mL). The aqueous layer was extracted with EtOAc (2 × 20 mL). The combined organic phases were concentrated in vacuo. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-(6-(4-acetylpiperazin-1)-yl)imidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate) as a white solid (1.8 mg, 4.2%). LCMS (M+H + ) m / z calculated 577.2, found 577.1. 1H NMR(DMSO-d6,400MHz)δ 10.13(s,1H), 8.95(d,1H), 8.51(s,1H), 7.98(s,1H), 7.68(t,2H), 7.58(d,1H), 4 .19-4.38(m,5H), 3.59-3.62(m,7H), 3.04-3.12(m,4H), 2.25(s,3H), 2.04(s,3H).

[0400] Example 37: Preparation of methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate

[0401] [ka]

[0402] A mixture of 3-fluoro-4-methyl-5-nitrobenzonitrile (5.0 g, 27.8 mmol, 1.0 equiv.) in 50 mL of HSO (70% in H0) was stirred at 100° C. for 15 hours. The mixture was poured into ice water (180 mL) and adjusted to pH=5 by adding saturated aqueous NaCO. The formed precipitate was filtered and dried to give 3-fluoro-4-methyl-5-nitrobenzoic acid as a light gray solid (3.1 g, 56.3%). LCMS (M+H + ) m / z calculated 200.0, found 199.9.

[0403] [ka]

[0404] A solution of tert-butyl 3-cyanoazetidine-1-carboxylate (5.0 mg, 27.5 mmol, 1.0 equiv.), NHOH.HCl (2.9 g, 41.2 mmol, 1.5 equiv.), and TEA (17.6 mL, 54.9 mmol, 2.0 equiv.) in EtOH (30 mL) was stirred at 78 °C for 3 h, and the solvent was partially removed in vacuo. The crude product was diluted with EtOAc (200 mL). The organic layer was washed with water (200 mL) and brine (200 mL). The mixture was concentrated in vacuo to give tert-butyl 3-(N-hydroxycarbamimidoyl)azetidine-1-carboxylate) as a yellow solid (5.5 g, 93.2%). LCMS (M+H) + ) m / z calculated 216.1, found 216.0.

[0405] [ka]

[0406] To a solution of 3-fluoro-4-methyl-5-nitrobenzoic acid (2.0 g, 10.1 mmol, 1.0 equiv.) in anhydrous NMP (80 mL) was added CDI (2.5 g, 15.1 mmol, 1.5 equiv.) at room temperature. The reaction was stirred for 15 minutes, and tert-butyl 3-(N-hydroxycarbamimidoyl)azetidine-1-carboxylate (2.2 g, 10.1 mmol, 1.0 equiv.) was added. The reaction was stirred for 25 minutes, then heated at 130° C. for 1 hour. The crude product was diluted with EtOAc (200 mL). The organic layer was washed with water (200 mL), brine (200 mL), combined, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give tert-butyl 3-(5-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate as a yellow solid (1.2 g, 31.6%). LCMS (M+H + ) m / z calculated 379.1, found 379.0.

[0407] [ka]

[0408] To a stirred solution of tert-butyl 3-(5-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate (1.2 g, 3.2 mmol, 1.0 equiv) in DCM (10 mL) was added 4N HCl in dioxane (5 mL). The reaction was stirred at 30° C. for 2 h. The mixture was concentrated to give 3-(azetidin-3-yl)-5-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazole as a yellow solid (1.2 g, quantitative). LCMS (M+H) + ) m / z calculated 279.1, found 279.0.

[0409] [ka]

[0410] To a solution of 3-(azetidin-3-yl)-5-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazole (1.2 g, 4.3 mmol, 1.0 equiv.) in DCM (50 mL) was added methyl carbonochloridate (486.9 mg, 5.2 mmol, 1.2 equiv.) and TEA (3.0 mL, 21.6 mmol, 5.0 equiv.). The solution was stirred at room temperature for 2 hours and then partitioned between DCM (20 mL) and saturated NaHCO3 solution (20 mL). The aqueous layer was extracted with DCM (20 mL x 2), and the organic layer was concentrated to give methyl 3-(5-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate as a yellow solid (900.0 mg, 60.0%). LCMS (M+H) + ) m / z calculated 337.1, found 337.0.

[0411] [ka]

[0412] To a stirred suspension of methyl 3-(5-(3-fluoro-4-methyl-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate (900 mg, 2.7 mmol, 1.0 equiv) in EtOH (50 mL) was added SnCl (1.5 g, 8.1 mmol, 3.0 equiv). The reaction mixture was heated at 80 °C for 3 h. The reaction was cooled to room temperature and the solvent was partially concentrated. The pH was adjusted to slightly basic with a saturated solution of sodium bicarbonate (90 mL). The resulting white suspension was filtered and washed with water (90 mL) and EtOAc (90 mL). The aqueous layer was extracted with EtOAc (150 mL × 2). The combined organic layers were washed with brine (150 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EA=5 / 1, v / v) to give methyl 3-(5-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate as a white solid (550 mg, 63.5%). LCMS (M+H + ) m / z calculated 307.1, found 307.0.

[0413] [ka]

[0414] To a solution of methyl 3-(5-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate (200 mg, 0.65 mmol, 1.0 equiv.), imidazo[1,2-a]pyridine-3-carboxylic acid (116.5 mg, 0.72 mmol, 1.1 equiv.), and pyridine (0.3 mL, 1.3 mmol, 5.0 equiv.) in DCM (30 mL) was added POCl (0.2 mL, 2.0 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL × 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-3-yl)azetidine-1-carboxylate as a white solid (33.4 mg, 11.2%). LCMS (M+H + ) m / z calculated 451.1, found 451.1. 1 H NMR(DMSO-d6,400MHz)δ 9.45(d,1H), 8.61(s,1H), 8.12(s,1H), 7.79-7.83(m,2H), 7.54(dd,1H), 7.19(t,1H), 4.12-4.36(m,5H), 3.60(s,3H), 2.29(s,3H).

[0415] Example 38 Preparation of 6-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

[0416] [ka]

[0417] To a solution of N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide (40 mg, 0.078 mmol, 1.0 equiv) in MeCN / HO (15 mL / 3 mL) was added acetic anhydride (39.9 mg, 0.39 mmol, 5.0 equiv) and NaHCO (65.7 mg, 0.78 mmol, 10.0 equiv). The solution was stirred at room temperature for 15 h and then partitioned between EtOAc (20 mL) and saturated NaHCO solution (20 mL). The aqueous layer was extracted with EtOAc (20 mL × 2) and concentrated. The resulting residue was purified by preparative HPLC to give 6-(4-acetylpiperazin-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide as a white solid (17.6 mg, 40.6%). LCMS (M+H + ) m / z calculated 554.2, found 554.1. 1 H NMR(CDCl3,400MHz)δ 9.18(s,1H), 8.75(s,1H), 8.59(s,1H), 8.25(s,1H), 7.77(d,1H), 7.67(d,1H) , 7.44(d,1H), 3.64-3.82(m,5H), 3.08-3.19(m,8H), 2.36(s,3H), 2.15(s,3H).

[0418] Example 39 Preparation of 6-(4-acetylpiperazin-1-yl)-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide)

[0419] [ka]

[0420] N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide and N-(3-fluoro-5-(5-)((1S,2R)-2-fluorocyclopropyl)- To a solution of (1,2,4-oxadiazol-3-yl)-2-methylphenyl)-6-(piperazin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide) (racemic, trans, 100 mg, 0.21 mmol, 1.0 equiv.) was added acetic anhydride (106.5 mg, 1.0 mmol, 5.0 equiv.) and NaHCO3 (175.4 mg, 2.1 mmol, 10.0 equiv.). The solution was stirred at room temperature for 3 h and then partitioned between EtOAc (20 mL) and saturated NaHCO3 solution (20 mL). The aqueous layer was extracted with EtOAc (2 × 20 mL), and the combined organic layers were concentrated in vacuo. The resulting residue was purified by preparative HPLC to give 6-(4-acetylpiperazin-1-yl)-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide and 6-(4-acetylpiperazin-1-yl)-N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (racemic, trans) as a white solid (43.3 mg, 39.8%). LCMS (M+H + ) m / z calculated 522.2, found 522.1. 1 H NMR(CDCl3,400MHz)δ 9.06(d,1H), 8.30(s,1H), 8.15(s,1H), 7.59-7.68(m,3H), 7.33(dd,1H), 4.97-5.15(m,1H), 3.63-3.82(m, 5H), 3.12-3.17(m,4H), 2.70-2.73(m,1H), 2.32(d,3H), 2.15(s,3H), 1.82-1.89(m,1H), 1.59-1.67(m,1H).

[0421] Example 40: Preparation of methyl 3-(3-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0422] [ka]

[0423] A solution of ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate (1.0 g, 3.7 mmol, 1.0 equiv.) and LiOH (178.4 mg, 7.4 mmol, 2.0 equiv.) in MeOH / HO (30 mL / 5 mL) was stirred at 30 °C for 3 h, and the solvent was partially removed under vacuum. The pH was adjusted to 5 with concentrated HCl. The solid was then collected by vacuum filtration and dried under vacuum to give 6-bromoimidazo[1,2-a]pyridine-3-carboxylic acid as a white solid (950.0 mg, quantitative). LCMS (M+H) + ) m / z calculated 242.0, found 241.9.

[0424] [ka]

[0425] To a solution of methyl 3-(3-(3-amino-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (1.2 g, 4.0 mmol, 1.0 equiv.), 6-bromoimidazo[1,2-a]pyridine-3-carboxylic acid (950.0 mg, 4.0 mmol, 1.0 equiv.), and pyridine (1.6 mL, 19.8 mmol, 5.0 equiv.) in DCM (30 mL) was added POCl (1.1 mL, 11.9 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at room temperature for 2 h and diluted with water (50 mL). The aqueous layer was extracted with DCM (50 mL × 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (DCM / MeOH=50 / 1) to give methyl 3-(3-(3-(6-bromoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a yellow solid (800.0 mg, 38.3%). LCMS (M+H + ) m / z calculated 529.1, found 529.0.

[0426] [ka]

[0427] To a solution of methyl 3-(3-(3-(6-bromoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (300 mg, 0.57 mmol, 1.0 equiv.) in DMF (20 mL) was added Zn(CN) (100.1 mg, 0.85 mmol, 1.5 equiv.) and Pd(PPh) (65.7 mg, 0.056 mmol, 0.1 equiv.). The mixture was stirred at 130 °C for 5 h, then the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (100 mL × 3). The combined organic layers were washed with brine (100 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (54.6 mg, 20.4%). LCMS (M+H + ) m / z calculated 476.1, found 476.0.

[0428] [ka]

[0429] A mixture of methyl 3-(3-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (40.0 mg, 0.084 mmol, 1.0 equiv) in 5 mL of HSO (98% in HO) was stirred at room temperature for 3 hours. The mixture was poured into ice water (30 mL) and adjusted to pH 9 by adding saturated aqueous NaCO. The aqueous layer was extracted with EtOAc (50 mL × 2). The combined organic layers were washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (1.0 mg, 2.4%). LCMS (M+H + ) m / z calculated 494.2, found 494.0. 1 H NMR(DMSO-d6,400MHz)δ 10.31(s,1H), 9.96(s,1H), 8.66(s,1H), 8.24(s,1H), 8.01(s,1H), 7.95(d,1H), 7. 83(d,1H), 7.68(d,1H), 7.62(s,1H), 4.20-4.38(m,5H), 3.60(s,3H), 2.27(s,3H).

[0430] Example 41: Preparation of 2-aminoethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0431] [ka]

[0432] To a solution of tert-butyl (2-hydroxyethyl)carbamate (82.1 mg, 0.51 mmol, 1.0 equiv.), TEA (515.3 mg, 5.1 mmol, 10.0 equiv.) in DCE (10 mL) was added triphosgene (151.5 mg, 0.51 mmol, 1.0 equiv.) at 0° C. The solution was warmed to room temperature and stirred for 1 h, then N-(5-(5-(azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (200.0 mg, 0.51 mmol, 1.0 equiv.) was added. The resulting solution was heated at 50° C. for 2 h. After cooling to room temperature, the solution was diluted with DCM (50 mL). The resulting solution was washed with brine (30 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (DCM / MeOH=100 / 1, v / v) to give 2-((tert-butoxycarbonyl)amino)ethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a yellow solid (100.0 mg, 33.9%). LCMS (M+H + ) m / z calculated 580.2, found 580.1.

[0433] [ka]

[0434] To a stirred solution of 2-((tert-butoxycarbonyl)amino)ethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (100 mg, 0.17 mmol, 1.0 equiv) in DCM (10 mL) was added TFA (5 mL). The reaction was stirred at 30° C. for 2 h. The mixture was concentrated and purified by preparative HPLC to give 2-aminoethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (22.1 mg, 26.8%). LCMS (M+H + ) m / z calculated 480.2, observed 480.0. 1 H NMR(DMSO-d6,400MHz)δ 9.45(d,1H), 8.61(s,1H), 7.99(s,1H), 7.79(d,1H), 7.67(dd,1H), 7.51-7.56(m,1H), 7.19(t, 1H), 4.19-4.38(m,5H), 3.93-3.99(m,2H), 3.15-3.23(m,2H), 2.55-2.72(m,2H), 2.24(d,3H).

[0435] Example 42: Preparation of 2-methoxyethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0436] [ka]

[0437] To a solution of N-(5-(5-(azetidin-3-yl)-1,2,4-oxadiazol-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (100 mg, 0.26 mmol, 1.0 equiv) in MeCN / HO (15 mL / 3 mL) was added 2-methoxyethyl carbonochloridate (52.8 mg, 0.38 mmol, 1.5 equiv) and NaHCO (214.2 mg, 2.6 mmol, 10.0 equiv). The solution was stirred at room temperature for 2 h and then partitioned between EtOAc (20 mL) and saturated NaHCO solution (20 mL). The aqueous layer was extracted with EtOAc (20 mL × 2). The organic layer was concentrated and purified by preparative HPLC to give 2-methoxyethyl 3-(3-(3-thiolo-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate) as a white solid (18.1 mg, 14.4%). LCMS (M+H + ) m / z calculated 495.2, found 495.2. 1 H NMR(DMSO-d6,400MHz)δ 10.26(s,1H), 9.54(d,1H), 8.55(s,1H), 8.06(s,1H), 7.76(d,1H), 7.59(d,1H), 7.51 (t,1H), 7.15(t,1H), 4.10-4.38(m,7H), 3.49-3.52(m,2H), 3.26(s,3H), 2.25(d,3H).

[0438] Example 43: Preparation of methyl 3-(3-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

[0439] [ka]

[0440] A mixture of methyl 3-(3-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (40.0 mg, 0.084 mmol, 1.0 equiv) in 5 mL of HSO (98% in HO) was stirred at room temperature for 2 hours. The mixture was poured into ice water (30 mL) and adjusted to pH 9 by adding saturated aqueous NaCO. The aqueous layer was extracted with EtOAc (50 mL × 2). The combined organic layers were washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by preparative HPLC to give methyl 3-(3-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamido)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate as a white solid (15.4 mg, 36.5%). LCMS (M+H + ) m / z calculated 494.2, found 494.0. 1 H NMR(DMSO-d6,400MHz)δ 10.32(s,1H), 9.45(d,1H), 8.70(s,1H), 8.30-8.33(m,2H), 8.00(s,1H), 7.40-7.70(m,3H), 4.20-4.38(m,5H), 3.60(s,3H), 2.26(s,3H).

[0441] Example 44: Preparation of methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,3,4-oxadiazol-2-yl)azetidine-1-carboxylate

[0442] [ka]

[0443] To a solution of 3-fluoro-4-methyl-5-nitrobenzoic acid hydrazide (800.0 mg, 3.8 mmol, 1.0 equiv.) and NaHCO3 (957.6 mg, 11.4 mmol, 3.0 equiv.) in MeCN (9.0 mL) and HO (3.0 mL) was added benzyl 3-(quinocarbonyl)azetidine-1-carboxylate (1.9 g, 7.6 mmol, 2.0 equiv.) in MeCN (3.0 mL) at 0 °C and stirred at room temperature for 2 h. The reaction was diluted with water (50.0 mL), and the aqueous layer was extracted with DCM (50.0 mL × 3). The combined organic layers were washed with brine (50.0 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EtOAc=1 / 1, v / v) to give benzyl 3-(2-(3-fluoro-4-methyl-5-nitrobenzoyl)hydrazine-1-carbonyl)azetidine-1-carboxylate as a pale yellow solid (961.0 mg, 60.0%). LCMS (M+H + ) m / z calculated 431.1, found 431.1.

[0444] [ka]

[0445] A mixture of benzyl 3-(2-(3-fluoro-4-methyl-5-nitrobenzoyl)hydrazine-1-carbonyl)azetidine-1-carboxylate (961.0 mg, 2.2 mmol, 1.0 equiv.) in TFA (2.0 mL) was stirred at 40° C. for 15 hours. The mixture was concentrated, and the residue was obtained as crude N′-(3-fluoro-4-methyl-5-nitrobenzoyl)azetidine-3-carbohydrazide as a pale yellow solid (1.2 g, quantitative), which was used in the next step without further purification. LCMS (M+H + ) m / z calculated 297.1, found 297.1.

[0446] [ka]

[0447] To a solution of N'-(3-fluoro-4-methyl-5-nitrobenzoyl)azetidine-3-carbohydrazide (1.2 g, 4.1 mmol, 1.0 equiv.) and NaHCO (1.0 g, 12.3 mmol, 3.0 equiv.) in MeCN (15.0 mL) and HO (5.0 mL) was added a solution of methyl carbonochloridate (789.6 mg, 8.4 mmol, 2.0 equiv.) in MeCN (5.0 mL) at 0 °C and stirred at room temperature for 2.0 h. The reaction was diluted with water (30 mL), and the aqueous layer was extracted with DCM (30 mL × 3). The combined organic layers were washed with brine (30 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting residue was purified by silica gel column chromatography (PE / EtOAc=1 / 1, v / v) to give methyl 3-(2-(3-fluoro-4-methyl-5-nitrobenzoyl)hydrazine-1-carbonyl)azetidine-1-carboxylate as a pale yellow solid (370.0 mg, 26.4%). LCMS (M+H + ) m / z calculated 355.1, found 355.1.

[0448] [ka]

[0449] A mixture of methyl 3-(2-(3-fluoro-...

Claims

1. Equation (I) 【Chemistry 1】 A compound having the structure or a pharmaceutically acceptable salt or solvate thereof, During the ceremony, Ring A is an optionally substituted five-membered nitrogen-containing heteroaryl compound. Ring B is an optionally substituted 9-membered or 10-membered bicyclic nitrogen-containing heteroaryl compound. R １ This is an optionally substituted alkyl, optionally substituted carbocyrill, optionally substituted carbocyrillalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl. R ２ is a C1-C6 alkyl group that is optionally substituted with hydrogen, halo, cyano, or other hydrogen atoms. R ３ It is a halo, R ４ These are optionally substituted C1-C6 alkyl groups. R ５ is a C1-C6 alkyl group that is optionally substituted with hydrogen, halo, cyano, or other hydrogen atoms. A compound or its pharmaceutically acceptable salt or solvate.

2. Ring A is 【Chemistry 2】 And, Selectively, ring A is 【Transformation 3】 is, or Selectively, ring A is 【Chemistry 4】 is it, or Ring A is 【Transformation 5】 is it, or Ring A is 【Transformation 6】 is it, or Ring A is 【Transformation 7】 The compound according to claim 1 or a pharmaceutically acceptable salt or solvate thereof.

3. Ring B is an optionally substituted nine-membered bicyclic nitrogen-containing heteroaryl, or The compound according to claim 2, wherein ring B is an optionally substituted 10-membered bicyclic nitrogen-containing heteroaryl compound, or a pharmaceutically acceptable salt or solvate thereof.

4. Ring B is 【Transformation 8】 And, During the ceremony, n is between 0 and 4. Each R represents hydrogen, cyano, halo, hydroxy, azide, amino, nitro, -CO₂H, -S(O)-R₁₀, -S-R₁₀, -S(O)₂-R₁₀, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkynyl, optionally substituted carbocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted heterocyclyl, -N(R₁₀)₂, -CO-R₁₀, -CO₂-R₁₀, -CON(R₁₀)₂, -NR₁₀CO-R₁₀, -NR₁₀CO₂-R₁₀, -SO₂N(R₁₀)₂, -C(=NR₁₂ ) -N(R 11) 2, -NR 11 CO-R 10, -NR 11 CO 2 -R 10, -NR 11 CO-N(R 10) 2, and -NR 11 SO 2 -N(R 10) 2 are independently selected from the group, Each R 10 is independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyryl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl. Each R11 is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyrill, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl. R12 is H or an optionally substituted C1-C6 alkyl group. Selectively, ring B is 【Chemistry 9】 And, During the ceremony, n is between 0 and 4. Each R represents hydrogen, cyano, halo, hydroxy, azide, amino, nitro, -CO₂H, -S(O)-R₁₀, -S-R₁₀, -S(O)₂-R₁₀, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkynyl, optionally substituted carbocyclyl, optionally substituted C1-C6 alkenyl, optionally substituted heterocyclyl, -N(R₁₀)₂, -CO-R₁₀, -CO₂-R₁₀, -CON(R₁₀)₂, -NR₁₀CO-R₁₀, -NR₁₀CO₂-R₁₀, -SO₂N(R₁₀)₂, -C(=NR₁₂ ) -N(R 11) 2, -NR 11 CO-R 10, -NR 11 CO 2 -R 10, -NR 11 CO-N(R 10) 2, and -NR 11 SO 2 -N(R 10) 2 are independently selected from the group, Each R 10 is independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyryl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl. Each R11 is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyrill, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl. R12 is either H or an optionally substituted C1-C6 alkyl, or Selectively, ring B is 【Chemistry 10】 And, During the ceremony, n is between 0 and 4. Each R represents hydrogen, cyano, halo, hydroxy, azide, amino, nitro, -CO₂H, -S(O)-R₁₀, -S-R₁₀, -S(O)₂-R₁₀, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkynyl, optionally substituted carbocyclyl, optionally substituted C1-C6 alkenyl, optionally substituted heterocyclyl, -N(R₁₀)₂, -CO-R₁₀, -CO₂-R₁₀, -CON(R₁₀)₂, -NR₁₀CO-R₁₀, -NR₁₀CO₂-R₁₀, -SO₂N(R₁₀)₂, -C(=NR₁₂ ) -N(R 11) 2, -NR 11 CO-R 10, -NR 11 CO 2 -R 10, -NR 11 CO-N(R 10) 2, and -NR 11 SO 2 -N(R 10) 2 are independently selected from the group, Each R 10 is independently selected from the group consisting of optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyryl, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl. Each R11 is independently selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 carbocyrill, optionally substituted heterocyclyl, optionally substituted aryl, and optionally substituted heteroaryl. R12 is either H or an optionally substituted C1-C6 alkyl, or Selectively, ring B is 【Chemistry 11】 And in the formula, n is either 0 or Selectively, ring B is 【Chemistry 12】 The compound according to claim 3, wherein n is 0, and a pharmaceutically acceptable salt or solvate thereof.

5. R is hydrogen, halo, cyano, -CONH2, or heterocyclyl, Optionally, R may be hydrogen or a halo, or n is 1 or 2, and each R is independently selected from the group consisting of cyano, halo, hydroxy, -CO₂H, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 alkyl, optionally substituted heterocyclyl, or -CON(R₁₁)₂, or n is 1, and R is a heterocycline that has been selectively substituted. The optionally substituted heterocyclyl is selected from optionally substituted morpholinil or piperazinil, or The R group can be optionally selected from the following positional isomers. 【Chemistry 13】 A compound according to claim 4 or a pharmaceutically acceptable salt or solvate thereof, arranged to produce the above.

6. R1 is a carbocyclyl which is optionally substituted, Optionally, R1 may be replaced with at least a halogen, or Selectively, R1 is a three-membered or four-membered carbocyclyl that is selectively substituted, or R1 is a heterocycline that has been selectively substituted, Selectively, R1 is either a selectively substituted azetidine or a selectively substituted oxetane, or Selectively, R1 is either selectively substituted piperazine or selectively substituted morpholine, or The compound according to claim 3, wherein R1 is optionally substituted with a pyrrolidine. A pharmaceutically acceptable salt or solvate thereof.

7. R1 is an optionally substituted azetidine, The optionally substituted azetidines are optionally substituted alkyl, halo, fluoroalkyl, oxo, thioxo, cyano, nitro, -R b -OR a, -R b -OC(O)-Ra a, -R b -OC(O)-OR a, -R b -OC(O)-N(Ra a) 2, -R b -N(Ra a) 2, -R b -C(O)Ra a, -R b -C(O)OR a, -R b -C(O)N(Ra a) 2, -R b -O-R c -C(O)N(Ra a) 2, -R b -N(Ra a)C(O)OR a, -R b -N(Ra a)C(O)R a, -R b -N(Ra)S(O)t Ra a (wherein t is 1 or 2), -R b -S(O)t Ra a (wherein t is 1 or 2), -R b -S(O)t OR Ra a (wherein t is 1 or 2), and -R b -S(O)t N(Ra a) 2 (wherein t is 1 or 2), each Ra a is optionally substituted with one or more substituents selected from these, Independently, are hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally, -N(Ra)2In the group, both Ra groups may bond to form a nitrogen-containing heterocycline, each Rb independently may be directly bonded or a linear or branched alkylene or alkenylene chain, and Rc may be a linear or branched alkylene or alkenylene chain, and each of the Ra, Rb, or Rc substituents may be unsubstituted or otherwise specified. The optionally substituted azetidine is optionally substituted with one or more substituents selected from -R b -C(O)OR a and -R b -C(O)N(Ra a) 2, and each Ra a Independently, is hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), fluoroalkyl, cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), cycloalkylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), aralkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heterocyclylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), heteroaryl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or heteroarylalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or optionally, in the -N(Ra)2 group, Ra Both groups may bond to form a nitrogen-containing heterocycline, each R b independently being a directly bonded or linear or branched alkylene or alkenylene chain, and each of the R a or R b substituents is unsubstituted or otherwise indicated. The optionally substituted azetidine is optionally substituted with one or more substituents selected from -C(O)OR a, -C(O)N(Ra a) 2, where each Ra a is independently hydrogen, alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), or cycloalkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl). Optionally, an optional substituent is attached to the nitrogen of the heterocyclyl group. Optionally, R1 is 【Chemistry 14】 The compound according to claim 6 or a pharmaceutically acceptable salt or solvate thereof.

8. The compound according to claim 3 or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is an optionally substituted alkyl, optionally substituted carbocykylalkyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, or optionally substituted heteroaralkyl.

9. R2 is hydrogen or a halo, The compound according to claim 3, wherein R2 is optionally hydrogen, or a pharmaceutically acceptable salt or solvate thereof.

10. The compound according to claim 3 or a pharmaceutically acceptable salt or solvate thereof, wherein R3 is fluoro.

11. R4 is an optionally substituted C1-C2 alkyl group, Optionally, R4 is an optionally substituted C1 alkyl group. The compound according to claim 3 or a pharmaceutically acceptable salt or solvate thereof, wherein R4 is optionally CH3.

12. R5 is hydrogen or a halo, Optionally, R5 may be hydrogen, or The compound according to claim 3 or a pharmaceutically acceptable salt or solvate thereof, wherein R5 is optionally fluoro.

13. R2 is hydrogen, R3 is fluoro, R4 is CH3, R5 is fluoro, Optionally, R1 is an azetidine substituted with -C(O)OR a, and Ra is an alkyl (optionally substituted with halogen, hydroxy, methoxy, amino, or trifluoromethyl), and / or Selectively, ring B is 【Chemistry 15】 The compound according to claim 1, wherein n is 0, and a pharmaceutically acceptable salt or solvate thereof.

14. N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, Methyl 3-(3-(3-fluoro-4-methyl-5-(pyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)-6-morpholinoidamidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-6-morpholinoidamidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)-7-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)-7-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)-7-morpholinoidamidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-7-morpholinoidamidazol[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, 7-(4-acetylpiperazine-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-fluoro-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-7-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, Ethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)-6-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-6-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-fluoro-5-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-5-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(7-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Cyclopropyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(5-(1-(methylcarbamoyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)-6-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-6-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(6-(4-acetylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, 6-(4-acetylpiperazine-1-yl)-N-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-(4-acetylpiperazine-1-yl)-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, 2-aminoethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, 2-Methoxyethyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Isopropyl 3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(5-(5-(1-(ethylcarbamoyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-(isopropylcarbamoyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-((2-hydroxyethyl)carbamoyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(1-(cyclopropylcarbamoyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-(1-((2-methoxyethyl)carbamoyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(1-((2-aminoethyl)carbamoyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(morpholine-4-carbonyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(piperazine-1-carbonyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(1-(4-methylpiperazine-1-carbonyl)azetidine-3-yl)-1,2,4-oxadiazole-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-5-(6-isopropylimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(6-cyclopropylimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-5-(7-isopropylimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(7-cyclopropylimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(7-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)piperazine-1-carboxylate, Methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)-2-methylpiperazine-1-carboxylate, Methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)-2-isopropylpiperazine-1-carboxylate, Methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)-3-methylpiperazine-1-carboxylate, Methyl 4-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)-3-isopropylpiperazine-1-carboxylate, N-(5-(5-(4-acetylpiperazine-1-yl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(5-(5-(4-carbamoylpiperazine-1-yl)-1,2,4-oxadiazole-3-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(4-methylpiperazine-1-yl)-1,2,4-oxadiazole-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-(piperazin-1-yl)-1,2,4-oxadiazole-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(5-morpholino-1,2,4-oxadiazole-3-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-Fluoro-N-(3-Fluoro-5-(5-((1R,2S)-2-Fluorocyclopropyl)-1,2,4-Oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-Chloro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 6-Cyano-N-(3-Fluoro-5-(5-((1R,2S)-2-Fluorocyclopropyl)-1,2,4-Oxadiazole-3-yl)-2-Methylphenyl)Imidazo[1,2-a]Pyridine-3-Carboxamide, N3-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,6-dicarboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-6-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-6-isopropylimidazo[1,2-a]pyridine-3-carboxamide, 6-Cyclopropyl-N-(3-Fluoro-5-(5-((1R,2S)-2-Fluorocyclopropyl)-1,2,4-Oxadiazole-3-yl)-2-Methylphenyl)Imidazo[1,2-a]Pyridine-3-Carboxamide, 7-Fluoro-N-(3-Fluoro-5-(5-((1R,2S)-2-Fluorocyclopropyl)-1,2,4-Oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-Chloro-N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide, 7-Cyano-N-(3-Fluoro-5-(5-((1R,2S)-2-Fluorocyclopropyl)-1,2,4-Oxadiazole-3-yl)-2-Methylphenyl)Imidazo[1,2-a]Pyridine-3-Carboxamide, N3-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,7-dicarboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-7-isopropylimidazo[1,2-a]pyridine-3-carboxamide, 7-Cyclopropyl-N-(3-Fluoro-5-(5-((1R,2S)-2-Fluorocyclopropyl)-1,2,4-Oxadiazole-3-yl)-2-Methylphenyl)Imidazo[1,2-a]Pyridine-3-Carboxamide, N-(3-fluoro-5-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-7-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-fluoro-4-methyl-5-(7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1R,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(5-((1S,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(3-fluoro-5-(6-fluoropyrazolo[1,5-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(6-chloropyrazolo[1,5-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(6-cyanopyrazolo[1,5-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(6-carbamoylpyrazolo[1,5-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-5-(6-methoxypyrazolo[1,5-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-5-(6-isopropylpyrazolo[1,5-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(6-cyclopropylpyrazolo[1,5-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-methylpyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(5-methylpyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(5-cyclopropylpyrazolo[1,5-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-5-(5-isopropylpyrazolo[1,5-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-5-(5-fluoropyrazolo[1,5-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(5-chloropyrazolo[1,5-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(5-cyanopyrazolo[1,5-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-(5-carbamoylpyrazolo[1,5-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(5-(trifluoromethyl)pyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(5-morpholinopyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(5-(piperazine-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(5-(4-methylpiperazine-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-morpholinopyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-(piperazine-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(3-fluoro-4-methyl-5-(6-(4-methylpiperazine-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(5-(3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-5-yl)-3-fluoro-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-5-(3-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-5-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, Isopropyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Cyclopropyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(3-(1-(methylcarbamoyl)azetidine-3-yl)-1,2,4-oxadiazole-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(1-(morpholine-4-carbonyl)azetidine-3-yl)-1,2,4-oxadiazole-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(1-(piperazine-1-carbonyl)azetidine-3-yl)-1,2,4-oxadiazole-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(5-(3-fluoro-5-(6-fluoroimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-(6-chloroimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-(6-cyanoimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-(6-carbamoylimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(6-methylimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-5-(6-isopropylimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-(6-cyclopropylimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(6-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(6-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-5-(7-fluoroimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(7-methylimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-(7-chloroimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-(7-cyanoimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-(7-carbamoylimidazo[1,2-a]pyridine-3-carboxamide)-5-fluoro-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(7-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-4-methyl-5-(7-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, N-(3-fluoro-2-methyl-5-(3-morpholino-1,2,4-oxadiazole-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-fluoro-2-methyl-5-(3-(piperazin-1-yl)-1,2,4-oxadiazole-5-yl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)piperazine-1-carboxylate, Methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)-2-methylpiperazine-1-carboxylate, Methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)-2-isopropylpiperazine-1-carboxylate, Methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)-3-methylpiperazine-1-carboxylate, Methyl 4-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)-3-isopropylpiperazine-1-carboxylate, Methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,3,4-oxadiazole-2-yl)azetidine-1-carboxylate, Methyl 3-(4-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)oxazole-2-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)oxazole-2-yl)azetidine-1-carboxylate, Methyl 3-(2-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)oxazole-4-yl)azetidine-1-carboxylate, Methyl 3-(5-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-4H-1,2,4-triazole-3-yl)azetidine-1-carboxylate, Methyl(R)-3-(3-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)piperidine-1-carboxylate, N-(3-fluoro-5-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-2-methylphenyl)-7-morpholinoidamidazol[1,2-a]pyridine-3-carboxamide, Methyl 3-(2-(3-fluoro-5-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)oxazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl(R)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)pyrrolidine-1-carboxylate, Methyl(R)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)piperidine-1-carboxylate, Methyl(S)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)pyrrolidine-1-carboxylate, Methyl(S)-3-(3-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)piperidine-1-carboxylate, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-2,5-difluoro-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-2,5-difluoro-6-methylphenyl)-7-morpholinoidamidazo[1,2-a]pyridine-3-carboxamide, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-2,5-difluoro-6-methylphenyl)-7-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-6-methylphenyl)-7-morpholinoidimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-6-methylphenyl)-7-morpholinoidimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-6-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1S,2R)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-6-methylphenyl)-7-methoxyimidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-methylimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-3-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-4-methyl-3-(7-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-methylimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-3-(6-methoxyimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-morpholinoimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, Methyl 3-(3-(2,5-difluoro-4-methyl-3-(6-(4-methylpiperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(3-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-3-yl)-2,5-difluoro-6-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(5-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-3-yl)-6-methylphenyl)pyrazolo[1,5-a]pyridine-3-carboxamide, Methyl 3-(3-(2,5-difluoro-4-methyl-3-(pyrazolo[1,5-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-5-yl)azetidine-1-carboxylate, N-(3-(3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazole-5-yl)-2,5-difluoro-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, N-(2,5-difluoro-3-(3-((1R,2S)-2-fluorocyclopropyl)-1,2,4-oxadiazole-5-yl)-6-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, Methyl 3-(5-(2,5-difluoro-3-(imidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-methylimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(2,5-difluoro-3-(7-methoxyimidazo[1,2-a]pyridine-3-carboxamide)-4-methylphenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, Methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-morpholinoimidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, and Methyl 3-(5-(2,5-difluoro-4-methyl-3-(7-(piperazine-1-yl)imidazo[1,2-a]pyridine-3-carboxamide)phenyl)-1,2,4-oxadiazole-3-yl)azetidine-1-carboxylate, or a pharmaceutically acceptable salt or solvate thereof A compound according to claim 1, selected from the group consisting of the above, or a pharmaceutically acceptable salt or solvate thereof.

15. The compound according to Claim 1 or a pharmaceutically acceptable salt or solvate thereof, Pharmacologically acceptable excipients and A pharmaceutical composition containing the above.

16. The compound according to claim 14 or a pharmaceutically acceptable salt or solvate thereof, Pharmacologically acceptable excipients and A pharmaceutical composition containing the above.

17. A pharmaceutical composition for use in a method of treating a disease, comprising the compound described in Claim 1 or a pharmaceutically acceptable salt or solvate thereof, Whether the disease is cancer, inflammatory, allergic, or autoimmune, The aforementioned disease is selected from the group consisting of mastocytosis, asthma, chronic urticaria, rheumatoid arthritis, psoriasis, atopic dermatitis, neurofibromatosis, multiple sclerosis, and idiopathic pulmonary fibrosis. If the disease is cancer, The cancer is arbitrarily selected from the group consisting of leukemia, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, lymphoma, germ cell tumor, hematopoietic cancer, gastrointestinal stromal tumor, uveal melanoma, colorectal cancer, breast cancer, small cell lung cancer, neuroblastoma, gynecologic tumor, malignant mesothelioma, papillary renal cell carcinoma, papillary renal carcinoma, mastocytosis, mast cell leukemia, and thymic carcinoma. Selectively, whether the cancer is a gastrointestinal stromal tumor, Selectively, whether the cancer is acute myeloid leukemia, Selectively, the cancer is melanoma. Pharmaceutical composition.

18. A pharmaceutical composition for use in a method of treating a disease, comprising the compound described in claim 14 or a pharmaceutically acceptable salt or solvate thereof, Whether the disease is cancer, inflammatory, allergic, or autoimmune, The aforementioned disease is selected from the group consisting of mastocytosis, asthma, chronic urticaria, rheumatoid arthritis, psoriasis, atopic dermatitis, neurofibromatosis, multiple sclerosis, and idiopathic pulmonary fibrosis. If the disease is cancer, The cancer is arbitrarily selected from the group consisting of leukemia, acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, lymphoma, germ cell tumor, hematopoietic cancer, gastrointestinal stromal tumor, uveal melanoma, colorectal cancer, breast cancer, small cell lung cancer, neuroblastoma, gynecologic tumor, malignant mesothelioma, papillary renal cell carcinoma, papillary renal carcinoma, mastocytosis, mast cell leukemia, and thymic carcinoma. Selectively, whether the cancer is a gastrointestinal stromal tumor, Selectively, whether the cancer is acute myeloid leukemia, Selectively, the cancer is melanoma. Pharmaceutical composition.

Images