Novel purine-based compound and uses thereof

Abstract

The present invention provides a novel purine-based compound, an optical isomer thereof, or a pharmaceutically acceptable salt thereof. With excellent inhibitory activity against TYK2, the novel compound of the present invention is useful as a therapeutic agent for TYK2-mediated diseases such as autoimmune diseases.

Description

Novel purine compounds and their uses

[0001] The present invention relates to a novel purine compound, a pharmaceutical composition comprising the compound, and a use of the compound.

[0002] Immunity and inflammation are important areas of drug development, and Janus kinase (JAK) targets have attracted significant research attention over the past decade. The JAK / STAT signaling pathway is a cytokine-stimulated signaling pathway involved in numerous crucial biological processes, including cell proliferation, differentiation, apoptosis, and immune regulation. JAK kinases comprise four family members: JAK1, JAK2, JAK3, and TYK2. Activation of this signaling pathway is closely linked to the development and progression of various diseases, including inflammatory diseases, lymphoma, leukemia, and solid tumors.

[0003] Currently, the FDA has already approved four JAK inhibitors: Ruxolitinib, developed jointly by Incyte and Novartis, was approved in November 2011 for the treatment of polycythemia vera (PCV); Pfizer's tofacitinib, approved in November 2012 for the treatment of rheumatoid arthritis (RA), and later for the treatment of psoriatic arthritis and ulcerative colitis; Incyte and Lilly's baricitinib, developed jointly, was approved in May 2018 for the treatment of rheumatoid arthritis; and Oclacitinib, an oral formulation developed by Zoetis, was approved in May 2013 for the treatment of canine idiopathic dermatitis.

[0004] JAK inhibitors have also achieved remarkable progress in other indications, such as atopic dermatitis, psoriasis, and alopecia areata. Research has shown that the main factors related to the pathogenesis of psoriasis include changes in the functions of T cells, dendritic cells, keratinocytes, mast cells, and macrophages, and that the interactions between these cells and their associated cytokines and chemokines further mediate a series of inflammatory responses, epidermal hyperplasia, keratinocyte dysfunction, stratum spinosum hyperplasia, and vascular changes. The main targets involved in this include tumor necrosis factor-α (TNF-α), phosphodiesterase 4 (PDE4), JAK kinase, and interleukin and its receptors (IL&ILR).

[0005] TYK2 is a non-receptor tyrosine kinase member of the Janus kinase (JAK) family of protein kinases. The mammalian JAK family consists of four members: TYK2, JAK1, JAK2, and JAK3. JAK proteins, including TYK2, are essential for cytokine signaling. TYK2 binds to the cytoplasmic domains of type I and type II cytokine receptors, as well as interferon type I and type III receptors, and is activated by these receptors upon cytokine binding. Cytokines implicated in TYK2 activation include interferons (e.g., IFN-α, IFN-β, IFN-κ, IFN-δ, IFN-ε, IFN-τ, IFN-ω, and IFN-ζ (also known as limitin)) and interleukins (e.g., IL-4, IL-6, IL-10, IL-11, IL-12, IL-13, IL-22, IL-23, IL-27, IL-31, oncostatin M, ciliary neurotrophic factor, cardiotrophin 1, cardiotrophin-like cytokines, and LIF). Activated TYK2 then begins to phosphorylate additional signaling proteins, such as members of the STAT family, including STAT1, STAT2, STAT4, and STAT6.

[0006] Among the IL family, the main targets of psoriasis drug therapy are IL-12, IL-17, and IL-23, and TYK2, a downstream effector molecule targeting IL-12 / 23, is an excellent research direction. The expression of TYK2 in dendritic cells is required for the production of IL-12, IL-23, and IFN-γ, and the induction of Th1 cell differentiation (Blood, 2007). IL-23 secreted by dendritic cells can induce Th17 cells to secrete inflammatory mediators such as IL-17A, IL-17F, and IL-22. These inflammatory mediators promote the activation and hyperproliferation of epidermal keratinocytes (KC). Through the interaction of Th17 and KC cells, activated KC cells produce substances such as proinflammatory factors, chemokines, and antibacterial peptides, which can concentrate and activate immune cells at the site of inflamed skin. This triggers an expansion of the immune response, ultimately leading to the development of clinical symptoms associated with psoriasis. As can be seen from this, TYK2 plays a crucial role in the onset and progression of psoriasis, and targeting TYK2 inhibition is expected to control the disease in the early stages of inflammation.

[0007] Compounds that exhibit selectivity in inhibiting TYK2 activity are advantageous. Such compounds have the advantage of delivering a beneficial pharmacological response while minimizing the known side effects of the JAK / STAT signaling pathway. Against this backdrop, the inventors of the present invention developed novel compounds with high specificity for TYK2's JH2.

[0008] The present invention provides a novel purine compound, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

[0009] The present invention also provides a use of a novel purine compound, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

[0010] The terminology used in this application is merely used to describe specific embodiments and is not intended to limit the present invention. The singular expression includes the plural expression unless the context clearly indicates otherwise. In this application, terms such as "comprise" or "have" should be understood to indicate the presence of a feature, step, structure, or combination thereof described above, but do not preclude the presence or addition of one or more other features, steps, structures, or combinations thereof.

[0011] The meanings of terms and symbols used in this document are as follows.

[0012] In the present invention, the term “halogen” means a substituent selected from fluorine (F), chloro (Cl), bromo (Br), and iodo (I).

[0013] In the present invention, the term “unsubstituted” means a state in which no substituent is substituted and is absent or hydrogen.

[0014] In the present invention, the term "substituted" refers to a moiety having a substituent that replaces a hydrogen atom on one or more carbon atoms of the main chain. "Substituted" or "substituted with" is defined to include the implicit condition that such substitution results in a stable compound, for example, a compound that does not undergo spontaneous transformation by rearrangement, cyclization, elimination, etc., depending on the permissibility of the substituted atom and the substituent.

[0015] In the present invention, "single bond" means that two connected radicals are directly connected. For example, if L represents a single bond in ALZ, this structure is essentially AZ.

[0016] In the present invention, "C x-y" means having carbon number x or more and y or less.

[0017] As used herein, the term “C1-C6 alkyl” means a straight or branched chain saturated hydrocarbon having a carbon number of C1-C6, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, etc. Preferred alkyl groups contain about 1, 2, 3, 4, 5, or 6 carbon atoms in the chain. A branched chain means that one or more lower alkyl groups, for example, methyl, ethyl, or propyl, are attached to a linear alkyl chain. “Lower alkyl” means a group having about 1 to about 6 carbon atoms in the chain, which may be straight or branched. An “alkyl” may be unsubstituted or optionally substituted by one or more substituents, which may be the same or different. Each substituent can be halogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, cyano, hydroxy, alkoxy, alkylthio, amino, carboxy, etc. Each of these substituents can follow any of the definitions for each substituent mentioned in the present specification.

[0018] As used herein, the term “C2-C6 alkenyl” refers to a saturated monovalent hydrocarbon radical containing 2 to 6 carbon atoms with at least one carbon-carbon double bond. Alkenyl radicals include both straight-chain and branched moieties. The term “C2-C6 alkenyl” refers to an alkenyl radical containing 2 to 6 carbon atoms with a straight-chain or branched moiety. The double bond may or may not be a point of attachment to another group. Alkenyl groups include, but are not limited to, ethenyl, 1-propenyl, 2-propenyl, 2-methyl-2-propenyl, butenyl, pentenyl, 3-hexenyl, and the like.

[0019] In the present invention, the term “C1-C6 haloalkyl” means a C1-C6 straight-chain or branched-chain saturated hydrocarbon in which at least one hydrogen atom is replaced with a halogen atom (i.e., F, Cl, Br, or I). For example, and not limited thereto, it may be CH2F, CHF2, CF3, etc.

[0020] In the present invention, the term "C6-C 12 "Aryl" refers to an aromatic hydrocarbon containing 6 to 12 carbon atoms. For example, it can refer to a ring system such as monocyclic (e.g., phenyl); bicyclic (e.g., indenyl, naphthalenyl, tetrahydronaphthyl, tetrahydroindenyl). Preferably, aryl can be a phenyl group having a chemical formula of C6H5 and having 6 carbon atoms arranged in a cyclic ring structure. Phenyl group is very stable and is a type of aromatic hydrocarbon found in many organic compounds. In addition, the aryl can be substituted or unsubstituted, and when substituted, the hydrogen at the ortho, meta, or para position of the phenyl ring is replaced by halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C 2-12Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2.

[0021] In the present invention, the term "C1-C 12"Heteroaryl" refers to an optionally substituted aromatic ring containing 1 to 12 carbon atoms, wherein at least one of the ring carbon atoms is replaced by a heteroatom selected from oxygen (O), nitrogen (N) and sulfur (S), or an aromatic ring (e.g., a bicyclic or tricyclic ring system) fused to one or more rings such as a heteroaryl ring, an aryl ring, a heterocyclic ring, or a carbocyclic ring, each of which may have an optional substituent. Examples thereof include pyrrole, pyrazole, imidazole, triazole (e.g., 1,2,3-triazole, 1,2,4-triazole, 1,2,4-triazole), tetrazole, furan, isoxazole, oxazole, oxadiazole (e.g., 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole), thiophene, isothiazole, thiazole, thiadiazole (e.g., 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,3,4-thiadiazole), pyridine, pyridazine, pyrimidine, pyrazine, triazine (e.g., 1,2,4-triazine, 1,3,5-triazine) and tetrazine, and may include monocyclic heteroaryls including indole, isoindole, indazole, benzimidazole, benzotriazole, benzopyrrole, benzofuran, benzoxazole, benzoisoxazole, benzoxadiazole, benzothiophene, benzothiazole, benzoisothiazole, benzothiadiazole, 1H-Pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine, 3H-imidazo[4,5-b]pyridine, 3H-[1,2,3]triazolo[4,5-b]pyridine, 1H-pyrrolo[3,2-b]pyridine, 1H-pyrazolo[4,3-b]pyridine, 1H-imidazo[4,5-b]pyridine, 1H-[1,2,3]triazolo[4,5-b]pyridine, 1H-pyrrolo[2,3-c]pyridine, 1H-pyrazolo[3,4-c]pyridine, 3H-imidazo[4,5-c]pyridine, 3H-[1,2,3]triazolo[4,5-c]pyridine, 1H-pyrrolo[3,2-c]pyridine, 1H-pyrazolo[4,3-c]pyridine, 1H-imidazo[4,5-c]pyridine, 1H-[1,2,3]triazolo[4,5-c]pyridine, furo[2,3-b]pyridine, oxazolo[5,4-b]pyridine, isoxazolo[5,4-b]pyridine, [1,2,3]oxadiazolo[5,4-b]pyridine, furo[3,2-b]pyridine, oxazolo[4,5-b]pyridine, isoxazolo[4,5-b]pyridine, [1,2,3]oxadiazolo[4,5-b]pyridine, furo[2,3-c]pyridine, oxazolo[5,4-c]pyridine, isoxazolo[5,4-c]pyridine, [1,2,3]oxadiazolo[5,4-c]pyridine, furo[3,2-c]pyridine, oxazolo[4,5-c]pyridine, Isoxazolo[4,5-c]pyridine, [1,2,3]oxadiazolo[4,5-c]pyridine, thieno[2,3-b]pyridine, thiazolo[5,4-b]pyridine, isothiazolo[5,4-b]pyridine, [1,2,3]thiadiazolo[5,4-b]pyridine, thieno[3,2-b]pyridine, thiazolo[4,5-b]pyridine, isothiazolo[4,5-b]pyridine, [1,2,3]thiadiazolo[4,5-b]pyridine, thieno[2,3-c]pyridine, thiazolo[5,4-c]pyridine, isothiazolo[5,4-c]pyridine, [1,2,3]thiadiazolo[5,4-c]pyridine, thieno[3,2-c]pyridine, thiazolo[4,5-c]pyridine, isothiazolo[4,5-c]pyridine, [1,2,3]thiadiazolo[4,5-c]pyridine, quinoline, isoquinoline, cinnoline, quinazoline, quinoxaline, phthalazine, naphthyridine (e.g., 1,8-naphthyridine, 1,7-naphthyridine, 1,6-naphthyridine, 1,5-naphthyridine, 2,7-naphthyridine, 2,6-naphthyridine), imidazo[1,2-a]pyridine, 1H-pyrazolo[3,4-d]thiazole, Polycyclic heteroaryl such as 1H-pyrazolo[4,3-d]thiazole and imidazo[2,1-b]thiazole may be included, but are not limited thereto. In addition, the heteroaryl may be substituted or unsubstituted, and when substituted, may be halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C, 2-12Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2 may be substituted. Additionally, the polycyclic heteroaryl group may include a non-aromatic ring (e.g., cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl) fused to the heteroaryl ring, if the polycyclic heteroaryl group is attached to the parent structure via an aromatic ring.

[0022] In the present invention, the term “C3-C8 cycloalkyl” means a saturated hydrocarbon ring containing 3 to 8 carbon atoms, and the saturated hydrocarbon ring includes both monocyclic and polycyclic rings, and ring structures in which two or more rings share one or more pairs of carbon atoms (e.g., fused ring, spiro ring, bridged ring, etc.). Cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptanyl, cyclooctanyl, bicyclo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.0]hexyl, bicyclo[3.1.0]hexyl, bicyclo[2.1.1]hexyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, spiro[2.4]heptyl, spiro[3.4]octyl, etc. In addition, the cycloalkyl may be substituted or unsubstituted, and when substituted, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C 2-12Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2 may be substituted. Specific examples include cyclobutanone. Additionally, one ring of a polycyclic cycloalkyl group may be aromatic if the polycyclic cycloalkyl group is attached to the parent structure through a non-aromatic carbon.

[0023] In the present invention, “C2-C8 heterocycloalkyl” includes a saturated monocyclic or polycyclic heterocyclic ring containing 1 to 4 heteroatoms independently selected from nitrogen (N), oxygen (O), and sulfur (S), or a ring structure in which two or more rings share one or more pairs of carbon atoms (e.g., a fused ring, a spiro ring, a bridged ring, etc.). Heterocycloalkyl is oxiranyl, oxetanyl, morpholinyl, thiomorpholinyl, furyl, piperazinyl, pyranyl, 1,3-dioxanyl, 2-oxopyrrolidinyl, 2-oxopiperidinyl, thietanyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, tetrahydrothiopyranyl, hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one-yl, tetrahydro-1H-oxazolo[3,4-a]pyrazin-3(5H)-one-yl, 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin-yl, 3-Oxa-8-azabicyclo[3.2.1]octan-yl, hexahydro-2H-furo[3,2-b]pyrrole, azetidin-3-one, etc., but are not limited thereto. In addition, the heterocycloalkyl may be substituted or unsubstituted, and when substituted, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C2-C 12Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2 may be substituted. When nitrogen is present in the heterocycloalkyl ring, it may exist in an oxidized state (i.e., N+-O-) as long as the properties of adjacent atoms and groups permit. Examples include piperidinyl N-oxide and morpholinyl-N-oxide. Additionally, when sulfur is present in a heterocycloalkyl ring, it may exist in an oxidized state (i.e., S+-O- or -SO2-) as long as the properties of adjacent atoms and groups permit. Examples include thiomorpholine S-oxide and thiomorpholine S,S-dioxide. Additionally, one ring of a polycyclic heterocycloalkyl group may be aromatic (e.g., aryl or heteroaryl) if the polycyclic heterocycloalkyl group is attached to the parent structure through a non-aromatic carbon or nitrogen atom.

[0024] In the present invention, “enantiomer” refers to a case where two molecules having optical activity form a mirror-symmetric relationship. It is generally used as a synonym for mirror image isomer, and includes the R-form, S-form, or racemic compound forms, respectively.

[0025] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and will not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

[0026] A novel purine compound, an optical isomer thereof, or a pharmaceutically acceptable salt thereof

[0027] To solve the above-mentioned technical problem, the present invention provides a compound represented by the following chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof:

[0028] [Chemical Formula 1]

[0029]

[0030] In the above chemical formula 1,

[0031] A is unsubstituted or substituted phenyl, or unsubstituted or substituted C2-C 12 heteroaryl (wherein the substitution is substitution with at least one halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-C1-C3 alkyl, -O-C1-C3 haloalkyl, oxo(=O), -OH, -CN, -NO2 or -NH2);

[0032] L1 is a single bond, C1-C6 alkyl, C1-C6 haloalkyl, -O-, -C=O-, -C≡C-, C1-C3 alkyl-SO2-, or -NH-;

[0033] R1 is unsubstituted or substituted phenyl, unsubstituted or substituted C2-C8 heterocycloalkyl, unsubstituted or substituted C1-C 12 heteroaryl, unsubstituted or substituted -NH-(C1-C6alkyl), or -CN, wherein the substitution is at least one or more of halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-C1-C6haloalkyl, C2-C6alkenyl, phenyl, C2-C 12 Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2);

[0034] L2 is C1-C3 alkyl-C=O-, -C=O-, or -C=O-NH-;

[0035] R2 is unsubstituted or substituted C3-C8cycloalkyl, unsubstituted or substituted C1-C6alkyl-C3-C8cycloalkyl, unsubstituted or substituted C2-C8heterocycloalkyl, unsubstituted or substituted C1-C6alkyl-C2-C8heterocycloalkyl, unsubstituted or substituted C2-C 12 Heteroaryl, unsubstituted or substituted C1-C6 alkyl-C2-C 12 heteroaryl, unsubstituted or substituted phenyl, unsubstituted or substituted C1-C6alkyl-phenyl, C1-C3alkyl-C=OO-C1-C3alkyl or C1-C3alkyl-SO2-C1-C3alkyl, wherein substitution is with at least one halogen, C1-C3alkyl, C1-C3haloalkyl, -O-(C1-C3alkyl), oxo(=O), -OH, -CN, -NO2 or -NH2;

[0036] R3 is -NR a R b and here R a and R b are each independently -H or -C1-C3alkyl.

[0037]

[0038] Specifically, C3-C8 cycloalkyl, C2-C8 heterocycloalkyl, C6-C mentioned in the above A, L1, L2, R1 and R2 12 Aryl, C1-C 12 Heteroaryl, C1-C6 alkyl, C1-C6 haloalkyl can be selected from the specific substituents mentioned below:

[0039] The above C3-C8 cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.0]hexyl, bicyclo[3.1.0]hexyl, bicyclo[2.1.1]hexyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, spiro[2.4]heptyl, or spiro[3.4]octyl.

[0040] The above C2-C8 heterocycloalkyl may be aziridinyl, azetidinyl, morpholinyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, thietanyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, tetrahydrothiopyranyl, hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one-yl, 3-oxa-8-azabicyclo[3.2.1]octan-yl or hexahydro-2H-furo[3,2-b]pyrrole.

[0041] C1-C above 12 Heteroaryl can be thiophenyl, furanyl, thiazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, pyranyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyridonyl, pyrimidinyl, benzopyrrolyl, benzofuranyl, benzothiophenyl, isobenzofuranyl, benzoimidazolyl, benzothiazolyl, benzoisothiazolyl, benzoisooxazolyl, benzoxazolyl, isoindolyl, indolyl, indazolyl, benzothiadiazolyl, quinolyl, isoquinolyl, cinnolinyl, quinazolinyl, quinoxalinyl, carbazolyl, or benzodioxozolyl.

[0042] C6-C above 12 Aryl can be phenyl, naphthalenyl, indenyl, pentarenyl or azulenyl.

[0043] The above C1-C6 alkyl may be methyl, ethyl, propyl, butyl, pentyl or hexyl.

[0044] The above C1-C6 haloalkyl may be fluoromethyl, chloromethyl, bromomethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-fluoropropyl, 3-chloropropyl, difluoromethyl, chlorodifluoromethyl, trifluoromethyl, dichloromethyl, trichloromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, chlorodifluoromethyl, bromodifluoromethyl, pentafluoroethyl, heptafluoropropyl, heptafluoroisopropyl, 4-chlorobutyl or 4-fluorobutyl.

[0045]

[0046] Specifically, the above is any one selected from the group consisting of phenyl, piperidinyl, pyridinyl, 2-pyridonyl, thiophenyl, furanyl, thiazolyl, oxazolyl, quinolyl, benzothiazolyl and indolyl, wherein is unsubstituted or may be substituted with at least one halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-C1-C3 alkyl, -O-C1-C3 haloalkyl, oxo(=O), -OH, -CN, -NO2 or -NH2. More specifically, the above may be unsubstituted or substituted phenyl, or unsubstituted or substituted C4-C6 heteroaryl.

[0047]

[0048] Also specifically, R1 is cyclopropyl, cyclobutyl, cytlopentyl, cyclohexyl, cycloheptyl, phenyl, oxetanyl, azetidinyl, morpholinyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, thietanyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, tetrahydrothiopyranyl, pyrrolyl, thiophenyl, furanyl, thiazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, pyranyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyridonyl, pyrimidinyl, benzofuranyl, benzothiophenyl, isobenzofuranyl, benzoimidazolyl, benzothiazolyl, benzoisothiazolyl, Any one selected from the group consisting of benzoisooxazolyl, benzoxazolyl, isoindolyl, indolyl, indazolyl, benzothiadiazolyl, quinolyl, isoquinolyl, -NH-(C1-C6 alkyl) and -CN, wherein R1 is unsubstituted or at least one or more of halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C2-C 12Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2.

[0049] More specifically, the R1 may be unsubstituted or substituted phenyl, unsubstituted or substituted C3-C5 heterocycloalkyl, unsubstituted or substituted C1-C5 heteroaryl, unsubstituted or substituted -NH-(C1-C6 alkyl), or -CN. In addition, the R1 is specifically any one selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, oxazolyl, piperidinyl, piperazinyl, morpholinyl, phenyl, cyclohexyl, -NH-(C1-C6 alkyl), and -CN, wherein the R1 is unsubstituted or at least one or more of halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C2-C 12Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2.

[0050] Also, the above R1 is The carbons adjacent to each other are directly bonded and shared, so can form a fused ring. For example, if A is phenyl, L1 is a single bond, and R1 is pyrrole, the adjacent carbon atoms of phenyl and pyrrole can be directly covalently bonded to form a fused ring, i.e., indole (benzopyrrole).

[0051] More specifically, the above R1 is , , , , , , , , , , , , , , , , , , , , and Any one selected from the group consisting of, wherein R1 is unsubstituted or at least one halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C2-C 12 Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2. The above-mentioned substitutions are also applicable to the -H position mentioned above.

[0052] More specifically, the above L1-R1 , , , , , , , , , , , , , , , , , , , , , , , , , , , and Any one selected from the group consisting of, wherein R1 is unsubstituted or at least one halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C2-C 12 Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2. The above-mentioned substitutions are also applicable to the -H position mentioned above.

[0053] More specifically, L1-R1 is , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and It can be any one selected from the group consisting of .

[0054]

[0055] Also specifically, the R2 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.1.0]pentyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.0]hexyl, bicyclo[3.1.0]hexyl, bicyclo[2.1.1]hexyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, spiro[2.4]heptyl, C1-C6alkyl-cyclopropyl, C1-C6alkyl-cyclobutyl, C1-C6alkyl-cyclopentyl, C1-C6alkyl-cyclohexyl, C1-C6alkyl-cycloheptyl, tetrahydrofuranyl, tetrahydropyranyl, aziridinyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, Piperazinyl, morpholinyl, thiomorpholinyl, C1-C6 alkyl-tetrahydrofuranyl, C1-C6 alkyl-tetrahydropyranyl, C1-C6 alkyl-aziridinyl, C1-C6 alkyl-oxetanyl, C1-C6 alkyl-azetidinyl, C1-C6 alkyl-pyrrolidinyl, C1-C6 alkyl-piperidinyl, C1-C6 alkyl-piperazinyl, C1-C6 alkyl-morpholinyl, C1-C6 alkyl-thiomorpholinyl, pyrrolyl, thiophenyl, furanyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, C1-C6 alkyl-pyrrolyl, C1-C6 alkyl-thiophenyl, C1-C6 alkyl-furanyl, C1-C6 alkyl-pyrazolyl, Any one selected from the group consisting of C1-C6 alkyl-imidazolyl, C1-C6 alkyl-triazolyl, C1-C6 alkyl-thiazolyl, C1-C6 alkyl-oxazolyl, C1-C6 alkyl-isoxazolyl, phenyl, naphthalene, C1-C6 alkyl-phenyl, C1-C6 alkyl-naphthalene, C1-C3 alkyl-C=OO-C1-C3 alkyl and C1-C3 alkyl-SO2-C1-C3 alkyl, wherein R2 may be unsubstituted or substituted with at least one or more halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-(C1-C3 alkyl), oxo(=O), -OH, -CN, -NO2 or -NH2.

[0056] More specifically, R2 may be unsubstituted or substituted C3-C8cycloalkyl, unsubstituted or substituted C1-C3alkyl-C3-C8cycloalkyl, unsubstituted or substituted C2-C6heterocycloalkyl, unsubstituted or substituted C1-C3alkyl-C2-C6heterocycloalkyl, unsubstituted or substituted C2-C5heteroaryl, unsubstituted or substituted C1-C3alkyl-C2-C5heteroaryl, unsubstituted or substituted phenyl, unsubstituted or substituted C1-C3alkyl-phenyl, C1-C3alkyl-C=OO-C1-C3alkyl or C1-C3alkyl-SO2-C1-C3alkyl. In addition, the R2 is specifically one selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, spiro[3.3]heptyl, C1-C6alkyl-cyclopropyl, C1-C6alkyl-cyclobutyl, C1-C6alkyl-cyclopentyl, C1-C6alkyl-cyclohexyl, tetrahydropyranyl, aziridinyl, azetidinyl, piperidinyl, C1-C6alkyl-tetrahydropyranyl, C1-C6alkyl-aziridinyl, C1-C6alkyl-azetidinyl, C1-C6alkyl-piperidinyl, furanyl, C1-C6alkyl-furanyl, phenyl, C1-C6alkyl-phenyl, C1-C3alkyl-C=OO-C1-C3alkyl and C1-C3alkyl-SO2-C1-C3alkyl, Here, R2 may be unsubstituted or substituted with at least one halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-(C1-C3 alkyl), oxo(=O), -OH, -CN, -NO2 or -NH2.

[0057] More specifically, the above R2 is , , , , , , , , , , , , , , , , and wherein R2 is one selected from the group consisting of, wherein R2 may be unsubstituted or substituted with at least one halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-(C1-C3 alkyl), oxo(=O), -OH, -CN, -NO2 or -NH2.

[0058] More specifically, R2 is , , , , , , , , , , , , , , , , , , , , , , , , , and is one selected from the group consisting of .

[0059]

[0060] Also specifically, the above L2 may be C1-C3 alkyl-C=O-, -C=O-, or -C=O-NH-, and more specifically, methyl-C=O-, -C=O-, or -C=O-NH-.

[0061] Also specifically, the R3 is -NH-C1-C3 alkyl, and more specifically, the R3 is -NH-methyl or -NH-ethyl.

[0062]

[0063] The compound represented by the above chemical formula 1 may be a compound represented by the following chemical formula 2-1 or 2-2:

[0064] [Chemical Formula 2-1]

[0065]

[0066] In the above chemical formula 2-1, L1, R1, R2, and R3 are as described above in the above chemical formula 1,

[0067] X is carbon or nitrogen;

[0068] R4 is halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-C1-C3 alkyl, -O-C1-C3 haloalkyl, oxo(=O), -OH, -CN, -NO2 or -NH2;

[0069] a is an integer from 0 to 3.

[0070] [Chemical Formula 2-2]

[0071]

[0072] In the above chemical formula 2-2, L1, R1, R3, R4, a are as described above in the above chemical formula 1 or 2-1,

[0073] L3 is a single bond or C1-C3 alkyl;

[0074] R5 is unsubstituted or substituted C3-C5 cycloalkyl or unsubstituted or substituted C2-C5 heterocycloalkyl (wherein substitution is substitution with at least one halogen or C1-C3 alkyl).

[0075]

[0076] In addition, the compound represented by the above chemical formula 2-1 may be a compound represented by the following chemical formula 3 or 4:

[0077] [Chemical Formula 3]

[0078]

[0079] [Chemical Formula 4]

[0080]

[0081] In the above chemical formula 3 or 4, L1, R1, R2, R3, R4, a are as described above in the above chemical formula 1 or 2-1.

[0082]

[0083] According to a specific example of the present invention, the compound represented by the above chemical formula 1 may be any one selected from the group consisting of compounds described below:

[0084] N-cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0085] N-cyclopropyl-6-(methylamino)-2-((2-oxo-2H-[1,2'-bipyridin]-3-yl)amino)-9H-purine-9-carboxamide;

[0086] N-cyclopropyl-2-((3-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0087] N-cyclopropyl-2-((3-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0088] N-cyclopropyl-6-(methylamino)-2-((3-(oxazol-2-yl)phenyl)amino)-9H-purine-9-carboxamide;

[0089] N-cyclopropyl-2-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0090] N-cyclopentyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0091] N-benzyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0092] N-(furan-2-ylmethyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0093] N-cyclobutyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0094] N-cyclopropyl-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide;

[0095] N-(cyclopropylmethyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0096] N-cyclopropyl-6-(methylamino)-2-((4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)amino)-9H-purine-9-carboxamide;

[0097] N-cyclopropyl-6-(methylamino)-2-((3-(pyridin-4-yloxy)phenyl)amino)-9H-purine-9-carboxamide;

[0098] N-cyclopropyl-2-((3-(6-methoxypyridin-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0099] N-cyclopropyl-6-(methylamino)-2-((3-(pyridin-2-ylethynyl)phenyl)amino)-9H-purine-9-carboxamide;

[0100] 2-((3-(1H-imidazol-2-yl)phenyl)amino)-N-cyclopropyl-6-(methylamino)-9H-purine-9-carboxamide;

[0101] N-cyclopropyl-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide;

[0102] N-cyclopropyl-6-(methylamino)-2-((3-((4-methylpiperazin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0103] N-cyclopropyl-6-(methylamino)-2-((3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)amino)-9H-purine-9-carboxamide;

[0104] N-cyclopropyl-6-(methylamino)-2-((3-(morpholinomethyl)phenyl)amino)-9H-purine-9-carboxamide;

[0105] N-cyclopropyl-2-((3-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0106] N-cyclohexyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0107] N-cyclohexyl-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide;

[0108] N-cyclopentyl-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide;

[0109] N-(cyclopropylmethyl)-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide;

[0110] N-(cyclopropylmethyl)-2-((3-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0111] N-cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)-5-nitrophenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0112] N-cyclopropyl-2-((4'-(cyclopropylcarbamoyl)-[1,1'-biphenyl]-3-yl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0113] N-cyclopropyl-6-(methylamino)-2-((2'-vinyl-[1,1'-biphenyl]-3-yl)amino)-9H-purine-9-carboxamide;

[0114] 2-((3-amino-5-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-cyclopropyl-6-(methylamino)-9H-purine-9-carboxamide;

[0115] N-cyclopropyl-2-((3-(4,5-dichloro-1H-imidazol-2-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0116] N-cyclopropyl-2-((4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0117] N-cyclopropyl-6-(methylamino)-2-((1-((trifluoromethyl)sulfonyl)-1H-indol-5-yl)amino)-9H-purine-9-carboxamide;

[0118] N-cyclopropyl-2-((3-(1-(2-methoxyethyl)-1H-imidazol-2-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0119] N-cyclopropyl-6-(methylamino)-2-((3-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purine-9-carboxamide;

[0120] N-cyclopropyl-2-((3-fluoro-5-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0121] Butyl 1-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylate;

[0122] N-cyclopropyl-2-((3-(3-hydroxypiperidine-1-carbonyl)-5-(trifluoromethyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0123] N-cyclopropyl-2-((3-((4,4-difluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0124] N-cyclopropyl-2-((3-((4-hydroxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0125] Benzyl 4-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidine-1-carboxylate;

[0126] N-cyclopropyl-6-(methylamino)-2-((3-(piperidin-4-yloxy)phenyl)amino)-9H-purine-9-carboxamide;

[0127] N-cyclopropyl-6-(isopropylamino)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-9H-purine-9-carboxamide;

[0128] N-cyclopropyl-2-((3-(1-isopropyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0129] N-cyclopropyl-2-((3-((N-(2-(dimethylamino)ethyl)sulfamoyl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0130] N-cyclopropyl-2-((3-((1-cyclopropylpiperidin-4-yl)oxy)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0131] N-cyclopropyl-6-(methylamino)-2-((3-(4-methylpiperazine-1-carbonyl)phenyl)amino)-9H-purine-9-carboxamide;

[0132] N-cyclopropyl-6-(methylamino)-2-((3-((1-(2,2,2-trifluoroethyl)piperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide;

[0133] 1-cyclopropyl-2-(6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purin-9-yl)ethan-1-one;

[0134] 1-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid;

[0135] 6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-N-(tetrahydro-2H-pyran-4-yl)-9H-purine-9-carboxamide;

[0136] N-cyclopropyl-6-(methylamino)-2-((3-((4-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0137] N-cyclopropyl-2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0138] 2-(4-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidin-1-yl)ethyl cyclopropylcarbamate;

[0139] 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(spiro[3.3]heptan-2-yl)-9H-purine-9-carboxamide);

[0140] Ethyl (2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carbonyl)glycinate;

[0141] 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(2-(methylsulfonyl)ethyl)-9H-purine-9-carboxamide;

[0142] N-((1R,2R)-2-fluorocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0143] N-((1R,2S)-2-fluorocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0144] N-cyclobutyl-6-(methylamino)-2-((3-((4-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0145] N-cyclobutyl-6-(methylamino)-2-((3-((4-methylpiperazin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0146] N-cyclobutyl-2-((3-((4-hydroxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0147] 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(tetrahydro-2H-pyran-4-yl)-9H-purine-9-carboxamide);

[0148] N-cyclobutyl-2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0149] N-((1R,2R)-2-methoxycyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0150] N-cyclobutyl-2-((3-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0151] N-cyclobutyl-6-(methylamino)-2-((3-(morpholinomethyl)phenyl)amino)-9H-purine-9-carboxamide;

[0152] N-cyclopropyl-2-((3-(((3S,5R)-3,5-dimethylpiperazin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0153] N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide;

[0154] N-cyclopropyl-2-((3-((3-hydroxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0155] N-cyclopropyl-2-((3-(2-(4-hydroxypiperidin-1-yl)ethyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0156] 1-(3-((9-(cyclobutylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid;

[0157] 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0158] N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((4-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0159] 1-(3-((9-(((1R,2R)-2-methoxycyclobutyl)carbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid;

[0160] N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((4-methylpiperazin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0161] N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-(morpholinomethyl)phenyl)amino)-9H-purine-9-carboxamide;

[0162] 2-((3-((4-hydroxypiperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0163] N-cyclobutyl-6-(methylamino)-2-((3-(piperidin-1-ylmethyl)phenyl)amino)-9H-purine-9-carboxamide;

[0164] N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-(piperidin-1-ylmethyl)phenyl)amino)-9H-purine-9-carboxamide;

[0165] N-(2-fluorocyclopropyl)-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide;

[0166] 2-((3-(((3S,5R)-3,5-dimethylpiperazin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0167] N-cyclobutyl-6-(methylamino)-2-((3-(piperazin-1-ylmethyl)phenyl)amino)-9H-purine-9-carboxamide;

[0168] N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-(piperazin-1-ylmethyl)phenyl)amino)-9H-purine-9-carboxamide;

[0169] N-(bicyclo[1.1.1]pentan-1-yl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0170] 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(1-methylpiperidin-4-yl)-9H-purine-9-carboxamide;

[0171] N-((1S,2R)-2-fluorocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0172] 2-((3-((1H-1,2,4-triazol-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0173] 2-((3-((1H-1,2,4-triazol-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide;

[0174] N-((1R,2R)-2-fluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)- 9H-purine-9-carboxamide;

[0175] N-((1R,2S)-2-fluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0176] N-((1R,3R)-3-fluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0177] N-((1R,3S)-3-fluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0178] 2-((3-(3-(cyclopropanecarboxamido)-1H-1,2,4-triazol-1-yl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide);

[0179] N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((4-((2,2,2-trifluoroethyl)carbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0180] N-(1-cyanocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0181] 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(1-(trifluoromethyl)cyclopropyl)-9H-purine-9-carboxamide;

[0182] 2-((3-((4-(azetidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide;

[0183] N-cyclopropyl-2-((3-((3-methoxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0184] N-((1R,2R)-2-methoxycyclobutyl)-2-((3-((3-methoxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0185] 2-((3-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0186] N-cyclopropyl-2-((3-((3-((3-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0187] 2-((3-((3-(((tert-butyldimethylsilyl)oxy)piperidin-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide;

[0188] N-cyclobutyl-2-((5-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0189] N-cyclobutyl-2-((3-((3-(((dimethylamino)methyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0190] (3,3-difluoroazetidin-1-yl)(2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purin-9-yl)methanone);

[0191] N-cyclobutyl-6-(methylamino)-2-((3-((3-morpholinopiperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0192] N-(3,3-difluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0193] N-cyclobutyl-6-(methylamino)-2-((3-(pyridin-2-yl)phenyl)amino)-9H-purine-9-carboxamide;

[0194] N-cyclobutyl-6-(methylamino)-2-((3-(pyridin-4-yl)phenyl)amino)-9H-purine-9-carboxamide;

[0195] 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-(3-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0196] 2-((3-(1-(2-aminoethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide;

[0197] 2-((3-(1H-tetrazol-5-yl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide;

[0198] N-cyclobutyl-6-(methylamino)-2-((3-((4-phenylpiperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0199] N-cyclobutyl-6-(methylamino)-2-((3-((4-(pyridin-4-yl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0200] 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0201] N-cyclobutyl-2-((3-((3-methoxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0202] 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2S)-2-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0203] 2-((3-((3-(azetidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0204] N-cyclobutyl-2-((3-((3-isopropoxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0205] N-cyclobutyl-2-((3-((3-((3-(dimethylamino)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0206] 2-((3-((4-(4,4-difluoropiperidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0207] 2-((3-cyanophenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide;

[0208] N-((1R,2R)-2-methoxycyclobutyl)-2-((3-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0209] 2-((3-((3-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0210] N-cyclobutyl-6-(methylamino)-2-((3-((3-(pyridin-4-yl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0211] N-cyclobutyl-2-((3-((4,4-dimethylpiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0212] 2-((3-((4-chloropiperidin-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide;

[0213] 2-((3-((4-(3,3-difluoroazetidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide;

[0214] 1-(3-((9-(cyclobutylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-3-carboxylic acid;

[0215] N-cyclobutyl-2-((3-((3,3-dimethylpiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0216] N-cyclobutyl-6-(methylamino)-2-((3-((3-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0217] N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((3-(morpholine-4-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0218] N-cyclobutyl-2-((3-((4-fluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0219] N-cyclobutyl-2-((3-((3-fluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide;

[0220] N-cyclobutyl-6-(methylamino)-2-((3-((3-phenylpiperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0221] N-cyclobutyl-6-(methylamino)-2-((3-((3-phenoxypiperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide;

[0222] N-cyclobutyl-2-((3-((3,3-difluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide.

[0223]

[0224] In the present invention, pharmaceutically acceptable salts refer to salts commonly used in the pharmaceutical industry, and include, for example, inorganic ion salts manufactured with calcium, potassium, sodium, and magnesium; inorganic acid salts manufactured with hydrochloric acid, nitric acid, phosphoric acid, hydrobromic acid, iodic acid, perchloric acid, and sulfuric acid; organic acid salts manufactured with acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, and hydroiodic acid; sulfonic acid salts manufactured with methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and naphthalenesulfonic acid; Amino acid salts made from glycine, arginine, lysine, etc.; and amine salts made from trimethylamine, triethylamine, ammonia, pyridine, picoline, etc.; however, the types of salts meant in the present invention are not limited by these listed salts.

[0225] Pharmaceutical composition

[0226] In another aspect of the present invention, a pharmaceutical composition is provided comprising a compound represented by formula 1 as defined in any embodiment described herein, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

[0227] In another aspect of the present invention, a pharmaceutical composition is provided comprising a compound represented by formula 1 as defined in any embodiment described herein, an optical isomer thereof, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

[0228] The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier, and may be formulated in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods.

[0229] The pharmaceutically acceptable carriers include, but are not limited to, those commonly used in the art, such as lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition, the pharmaceutical composition of the present invention may include, but is not limited to, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants, and other pharmaceutically acceptable additives.

[0230] In another aspect of the present invention, a pharmaceutical composition for preventing or treating a TYK2-mediated disease is provided, comprising a compound represented by formula 1 as defined in any embodiment described herein, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

[0231] The above TYK2-mediated disease means one or more diseases or disorders associated with the activity of TYK2 or a mutant thereof, and the diseases or disorders include, but are not limited to, autoimmune diseases, inflammatory diseases, proliferative diseases, endocrine diseases, neurological diseases, and diseases associated with transplantation.

[0232] The above autoimmune disease may be any one of, but is not limited to, psoriasis, rheumatoid arthritis, vasculitis, Behcet's disease, inflammatory bowel disease, Crohn's disease, ulcerative colitis, dermatitis, osteoarthritis, asthma, inflammatory muscle disease, allergic disease, vaginitis, interstitial cystitis, scleroderma, osteoporosis, eczema, allogeneic or xenogeneic transplant rejection, graft-versus-host disease (GVHD), systemic lupus erythematosus, inflammatory disease, type I diabetes, pulmonary fibrosis, dermatomyositis, Sjogren's syndrome, thyroiditis, myasthenia gravis, autoimmune hemolytic anemia, multiple sclerosis, cystic fibrosis, chronic relapsing hepatitis, primary biliary cirrhosis, allergic conjunctivitis, or atopic dermatitis.

[0233] The above inflammatory diseases include, but are not limited to, sepsis, acute sepsis, alopecia, hair loss syndrome, gout, arthritis, rheumatoid arthritis, sclerosis, inflammatory bowel disease, ankylosing spondylitis (AS), antiphospholipid antibody syndrome (APS), myositis, scleroderma, Sjogren's syndrome, systemic lupus erythematosus, vasculitis, familial Mediterranean fever, neonatal-onset multisystem inflammatory disease, Behcet's disease, dermatitis, type 1 diabetes, autoimmune diseases, psoriasis, psoriatic arthritis, dermatitis herpetiformis, pemphigus vulgaris, vitiligo, multiple sclerosis, systemic sclerosis, Addison's disease, Graves' disease, Hashimoto's disease, myasthenia gravis, Guillain-Barré syndrome, autoimmune uveitis, autoimmune hemolytic anemia It can be any of the following: hemolytic anemia, Wegener's granulomatosis, pernicious anemia, autoimmune thrombocytopenia, temporal arteritis, celiac disease, chronic inflammation, rheumatism, encephalomyelitis, postinfectious cerebellitis, neuromyelitis optica, Devic's disease, encephalitis, metabolic encephalopathy, asthma, periodontitis, ulcerative colitis, interstitial fibrosis of the lungs, myelofibrosis, liver fibrosis, myocarditis, primary biliary cirrhosis, Crohn's disease, sinusitis, orchitis, polymyositis, dermatomyositis, autoimmune oophoritis, autoimmune adrenalitis, systemic lupus erythematosus, scleroderma, or gastric ulcer.

[0234] The proliferative disease may be, but is not limited to, any one of blood cancers, leukemias (e.g., T-cell leukemia, T-cell acute lymphoblastic leukemia (T-ALL)), polycythemia vera, myelofibrosis, or essential thrombocythemia.

[0235] The above endocrine disease may be, but is not limited to, polycystic ovary syndrome, Crouzon syndrome, or type 1 diabetes.

[0236] The above neurological diseases include, but are not limited to, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), Charcot-Marie-Tooth disease (CMT; including type 4J (CMT4J)), Yunis-Varon syndrome, autophagy, congenital brain lesions, polymicrogyria, temporo-occipital polymicrogyria, Pick's disease, Parkinson's disease, Parkinson's disease with Lewy bodies, dementia with Lewy bodies, Lewy body disease, fronto-temporal dementia, diseases of neuronal nuclear inclusions of polyglutamine and intranuclear inclusions. polyglutamine and intranuclear inclusion bodies), disease of Marinesco and Hiranobodies, tauopathy, Alzheimer's disease, neurodegeneration, spongiform neurodegeneration, peripheral neuropathy, leukoencephalopathy, motorneuropathy, sensoryneuropathy, inclusion body disease, progressive supranuclear palsy, corticobasal syndrome, chronic traumatic encephalopathy,Traumatic brain injury (TBI), cerebralischemia, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multiple sclerosis, Niemann-Pick C disease, Tay-Sachs disease, Mucolipidosis type IV, Mucolipidosis type V, neuropathy, Huntington's disease, apsychiatric disorder, ADHD, schizophrenia, mood disorder, major depressive disorder, depression, bipolar disorder I, bipolar disorder II. It could be any of FTD, chronic traumatic encephalopathy, Fabry's disorder, Gaucher's disorder, or progressive muscle atrophy.

[0237] Diseases associated with the above transplantation may include, but are not limited to, transplant rejection or graft-versus-host disease.

[0238] In the present invention, the term “prevention” means any act of inhibiting or delaying the onset of a TYK2-mediated disease by administering a composition.

[0239] In the present invention, the term “treatment” means any action by which the symptoms of the disease are improved or beneficially changed by administration of the composition.

[0240] The pharmaceutical composition of the present invention can be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically) depending on the intended method, and the dosage range varies depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and type and severity of the disease.

[0241] The route of administration of the pharmaceutical composition of the present invention may be administered to mammals such as rats, mice, livestock, and humans through any general route as long as it can reach the target tissue, but may be administered by subcutaneous injection using an osmotic pump, intradermal injection, intravein injection, intraperitoneal injection, intravitreal injection, intrathecal, inner ear, abdominal cavity, or intravenous, intramuscular, subcutaneous, intrauterine epidural, sublingual, or intracerebrovascular injection, but is not limited thereto.

[0242] The pharmaceutical composition of the present invention may contain 0.001 to 95 wt%, preferably 0.01 to 80 wt%, of the compound represented by Chemical Formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof, based on the total weight of the composition.

[0243] When the pharmaceutical composition of the present invention is formulated as an oral solid preparation, it includes tablets, pills, powders, granules, capsules, etc., and such solid preparations may include at least one excipient, for example, starch, calcium carbonate, sucrose or lactose, gelatin, etc., and include, but are not limited to, lubricants such as magnesium stearate and talc.

[0244] When the pharmaceutical composition of the present invention is formulated as an oral liquid, it includes a suspension, a solution, an emulsion, a syrup, etc., and includes, but is not limited to, a diluent such as water or liquid paraffin, a wetting agent, a sweetener, a fragrance, a preservative, etc.

[0245] When the pharmaceutical composition of the present invention is formulated for parenteral use, it includes a sterile aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a lyophilized preparation, and a suppository. Non-aqueous solvents and suspensions include, but are not limited to, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Bases for suppositories include, but are not limited to, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin.

[0246] In another aspect of the present invention, a TYK2 inhibitor is provided, comprising a compound represented by formula 1 as defined in any embodiment described herein, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

[0247] In one aspect of the present invention, a method of treating a TYK2-mediated disease is provided, comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by Formula 1 as defined in any embodiment described herein, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

[0248] In the present invention, the term “compound represented by chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof” or “TYK2-mediated disease” is as described above.

[0249] The term "subject" of the present invention refers to any animal that has developed or may develop a TYK2-mediated disease, and may typically be an animal that can exhibit a beneficial effect by treatment with a compound represented by Chemical Formula 1 of the present invention, an optical isomer thereof, or a pharmaceutically acceptable salt thereof, but includes, without limitation, any subject that has symptoms of a TYK2-mediated disease or is likely to have such symptoms. As described above, the above-described disease can be effectively prevented or treated by administering the pharmaceutical composition of the present invention to a subject. The pharmaceutical composition of the present invention can be administered as an individual therapeutic agent, or in combination with existing therapeutic agents for TYK2-mediated diseases, and can be administered sequentially or simultaneously with existing therapeutic agents.

[0250] The term "therapeutically effective amount" as used herein means an amount sufficient to prevent or treat a disease at a reasonable benefit / risk ratio applicable to medical prevention or treatment, and represents an amount of the compound represented by Chemical Formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof, which is effective in preventing or treating the disease. The effective dosage level may be determined according to factors including the severity of the disease, the activity of the drug, the age, weight, health, and sex of the patient, the patient's sensitivity to the drug, the time of administration, the route of administration, and the excretion rate of the composition of the present invention used, the duration of treatment, drugs combined with or used concurrently with the composition of the present invention used, and other factors well known in the medical field. For example, the compound represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof may be administered at 0.0001 to 100 mg / kg per day, and the administration may be administered once a day or in several divided doses.

[0251] The term "administration" in the present invention means introducing a predetermined substance into a patient by an appropriate method, and the administration route of the composition may be administered through any common route as long as it can reach the target tissue. In addition, the pharmaceutical composition of the present invention may be administered by any device that allows the active substance to move to the target tissue. For example, it may be administered by oral administration, intrathecal administration, intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, topical administration, intranasal administration, intrapulmonary administration, rectal administration, inner ear administration, intrauterine epidural administration, sublingual administration, and intracerebrovascular injection, but is not limited thereto. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories.

[0252] The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent, and may be administered sequentially or simultaneously with conventional therapeutic agents. Taking all of the above factors into account, the pharmaceutical composition may be administered in an amount that achieves maximum efficacy with minimal side effects, as can be readily determined by those skilled in the art.

[0253] The therapeutic method of the present invention includes not only treating the disease itself before the onset of symptoms, but also inhibiting or avoiding its symptoms by administering the compound represented by the above chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof. In the management of a disease, the prophylactic or therapeutic dosage of a particular active ingredient will vary depending on the nature and severity of the disease or condition, and the route by which the active ingredient is administered. The dosage and frequency of administration will vary depending on the age, weight, and response of the individual patient. An appropriate dosage regimen can be readily selected by one skilled in the art, taking these factors into account. In addition, the treatment method of the present invention may further include administration of a therapeutically effective amount of an additional active agent helpful in treating a disease together with the compound represented by the above chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof, wherein the additional active agent may exhibit a synergistic or auxiliary effect together with the compound represented by the above chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

[0254] In addition, the present invention provides a use of a compound represented by the above chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof for the manufacture of a drug for treating a TYK2-mediated disease.

[0255] In addition, the present invention provides a compound represented by the above chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof for the treatment of a TYK2-mediated disease.

[0256] In addition, the present invention provides a pharmaceutical composition comprising a compound represented by the above chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof for the treatment of a TYK2-mediated disease.

[0257] In addition, the present invention provides the use of a compound represented by the above chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof for the treatment of a TYK2-mediated disease.

[0258] The present invention is a novel compound having excellent inhibitory activity against TYK2, and thus can be usefully utilized as a therapeutic agent for TYK2-mediated diseases such as autoimmune diseases.

[0259] Hereinafter, the present invention will be described in detail using examples to aid understanding. However, the examples according to the present invention may be modified in various ways, and the scope of the present invention should not be construed as being limited to the following examples. The examples of the present invention are provided to more fully explain the present invention to those of average skill in the art.

[0260] Reagents and solvents mentioned below were purchased from Merck KGaA, TCI, BLDpharm, Enamine, Combi-Blocks, etc., unless otherwise specified, and structural analysis and purification were performed under the following conditions.

[0261] ● HPLC analysis conditions (A)

[0262] Device name: Shimadzu

[0263] Column: YMC-pack pro C18, 150x4.6mm ID, 5 νm, 40℃

[0264] Mobile phase: 5% -> 100% acetonitrile / H2O + 0.1% trifluoroacetic acid

[0265] Analysis time: 9 minutes, flow rate: 1 ml / min

[0266] UV detector: 254nm

[0267] ●HPLC analysis conditions (B)

[0268] Device name: Thermo Scientific Ultimate 3000RSLC

[0269] Column: Kinetex® 2.6 νM Biphenyl 100Å, 100x2.1mm

[0270] Mobile phase: 5% -> 100% acetonitrile / H2O + 0.1% trifluoroacetic acid

[0271] Analysis time: 8 minutes, flow rate: 0.7 ml / min

[0272] UV detector: 254nm

[0273] ● LC-MS analysis conditions

[0274] Device name: Shimadzu LCMS-2020

[0275] Column: ACE Excel2 C18, 75x2.1 mm

[0276] Mobile phase: Acetonitrile / H2O + 0.1% trifluoroacetic acid

[0277] Flow rate: 1mL / min

[0278] UV detector: 254nm

[0279] ● MPLC purification conditions

[0280] Device Name: CombiFlash®Rf +

[0281] UV detector: 254nm

[0282] ● Prep-HPLC purification conditions

[0283] Device Name: Gilson GX-281, 321 pump, UV / VIS-155

[0284] Column: Luna® 10 νM C18 (2) 100 Å, 50x21.2 m

[0285] Mobile phase: Acetonitrile / 0.1% trifluoroacetic acid H2O

[0286] Flow rate: 15mL / min

[0287] UV detector: 254nm

[0288] ● 1 H NMR analysis conditions

[0289] Device Name: Bruker Avance (400 MHz)

[0290] 1 H nuclear magnetic resonance (NMR) spectra were all consistent with the chemical structures of the compounds of the present invention. Characteristic chemical shifts (δ) are given in parts-per-million (ppm) relative to residual proton signals in deuterated solvents (CDCl3: 7.26 ppm; CD3OD: 3.31 ppm; DMSO-d6: 2.50 ppm) and are reported by the conventional abbreviations for major peak designations: e.g., s, singlet; d, doublet; t, triplet; q, quadruplet; m, multiplet; br, broad.

[0291] <Example>

[0292] <Example 1> N-Cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0293]

[0294] Step 1: Preparation of 2-chloro-N-methyl-9H-purin-6-amine

[0295]

[0296] 2,6-Dichloro-9H-purine (5 g, 26.50 mmol) was dissolved in a 40% aqueous methanamine solution (31.3 mL, 265 mmol) and stirred in a sealed tube at 100°C for 1 h. After the reaction was completed, the resulting solid was filtered and washed with cold water to produce the target compound (4.53 g, 93%, white solid). LC / MS (ESI) m / z: 184 [M+H] +

[0297] Step 2: Preparation of N6-methyl-N2-(3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-9H-purine-2,6-diamine

[0298]

[0299] 2-Chloro-N-methyl-9H-purin-6-amine (0.3 g, 1.63 mmol) and 3-(1-methyl-1H-1,2,4-triazol-3-yl)anilyl (0.37 g, 2.12 mmol) prepared in Step 1 above were dissolved in n-butanol (3 mL), and 12 M hydrochloric acid (1.3 mL, 16.34 mmol) was added. The reaction mixture was stirred at 110 °C for 48 hours. After the reaction was completed, the mixture was concentrated under reduced pressure, and the solid was stirred with a solution of dichloromethane: methanol = 9:1 for 30 minutes. Thereafter, the mixture was filtered and dried to prepare the target compound (0.46 g, 74%, white solid). LC / MS (ESI) m / z: 322 [M+H] +

[0300] Step 3: Preparation of N-cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0301]

[0302] N6-Methyl-N2-(3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-9H-purine-2,6-diamine (16 mg, 0.050 mmol), isocyanatocyclopropane (6 mg, 0.075 mmol), and DMAP (3 mg, 0.025 mmol) prepared in Step 2 above were dissolved in dimethylformamide (1 mL) and stirred at 70 °C for 0.5 h. After the reaction was completed, the mixture was diluted with ethyl acetate and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to produce the target compound (13 mg, 67%, white solid). LC / MS (ESI) m / z: 405 [M+H] +

[0303] <Examples 2 to 27>

[0304] The target compounds of Examples 2 to 27 were prepared by performing methods and procedures similar to those used in Example 1. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0305] <Example 28> Preparation of N-cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)-5-nitrophenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0306]

[0307] Step 1: Preparation of 3-(1-methyl-1H-1,2,4-triazol-3-yl)-5-nitroaniline

[0308]

[0309] (3-Amino-5-nitrophenyl)boronic acid (0.6 g, 3.30 mmol) and 3-bromo-1-methyl-1H-1,2,4-triazole (0.534 g, 3.30 mmol) were dissolved in 1,4-dioxane (6 ml), and potassium acetate (0.971 g, 9.89 mmol), tetrakis(triphenylphosphine)palladium(0) (0.381 g, 0.330 mmol), and water (1.5 ml) were added. The reaction mixture was reacted in a microwave at 150 °C for 2 h. After the reaction was completed, the mixture was concentrated under reduced pressure, and the solid was dissolved in a solution of dichloromethane: methanol = 99:1 and filtered through a Celite filter. After concentration under reduced pressure, the residue was purified by MPLC to produce the target compound (0.234 g, 32%, orange solid). LC / MS (ESI) m / z: 220 [M+H] +

[0310] Step 2: Preparation of N6-methyl-N2-(3-(1-methyl-1H-1,2,4-triazol-3-yl)-5-nitrophenyl)-9H-purine-2,6-diamine

[0311]

[0312] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 367 [M+H] +

[0313] Step 3: Preparation of N-cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)-5-nitrophenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0314]

[0315] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 450 [M+H] +

[0316] <Example 29> Preparation of N-cyclopropyl-2-((4'-(cyclopropylcarbamoyl)-[1,1'-biphenyl]-3-yl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0317]

[0318] Step 1: Preparation of N2-(3-bromophenyl)-N6-methyl-9H-purine-2,6-diamine

[0319]

[0320] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 319 [M+H] +

[0321] Step 2: Preparation of N-cyclopropyl-3'-((6-methylamino)-9H-purin-2-yl)amino)-[1,1'-biphenyl]-4-carboxamide

[0322]

[0323] To N2-(3-bromophenyl)-N6-methyl-9H-purine-2,6-diamine (100 mg, 0.313 mmol) prepared in Step 1 above, (4-(cyclopropylcarbamoyl)phenyl)boronic acid (77 mg, 0.376 mmol), sodium carbonate (100 mg, 0.940 mmol), tetrakis(triphenylphosphine)palladium(0) (36.2 mg, 0.031 mmol), 1,4-dioxane (4 ml) and water (1 ml) were added, and the mixture was stirred at 110°C overnight. After the reaction was completed, the mixture was concentrated under reduced pressure and purified by MPLC to obtain the target compound (44 mg, 35%, yellow solid). LC / MS(ESI) m / z: 400 [M+H] +

[0324] Step 3: Preparation of N-cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)-5-nitrophenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0325]

[0326] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 483 [M+H] +

[0327] <Example 30>

[0328] The target compound of Example 30 was prepared by performing a method and procedure similar to that used in Example 29. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0329] <Example 31> Preparation of 2-((3-amino-5-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino-N-cyclopropyl-6-(methylamino)-9H-purine-9-carboxamide

[0330]

[0331] Step 1: Preparation of 2-((3-amino-5-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino-N-cyclopropyl-6-(methylamino)-9H-purine-9-carboxamide

[0332]

[0333] N-Cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)-5-nitrophenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide (27 mg, 0.060 mmol) prepared in step 3 of Example 28 was added methanol (5 ml), tetrahydrofuran (5 ml) and 10% Pd / C (64 mg, 0.006 mmol), and stirred overnight under hydrogen gas. After completion of the reaction, it was concentrated under reduced pressure. The residue was diluted with dichloromethane: methanol (97:3) and filtered through a celite filter. After concentration under reduced pressure, it was purified by MPLC to prepare the target compound (11.1 mg, 44%, white solid). LC / MS(ESI) m / z: 420 [M+H] +

[0334] <Example 32> Preparation of N-cyclopropyl-2-((3-(4,5-dichloro-1H-imidazol-2-yl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0335]

[0336] Step 1: Preparation of 4,5-dichloro-2-(3-nitrophenyl)-1H-imidazole

[0337]

[0338] (3-Nitrophenyl)boronic acid (0.3 g, 1.797 mmol), 2-bromo-4,5-dichloro-1H-imidazole (0.388 g, 1.797 mmol), and PdCl2(dppf)-CH2Cl2adduct (0.147 g, 0.180 mmol) were dissolved in 1,4-dioxane (6 ml) and water (1.5 ml) and stirred for 10 min under a nitrogen atmosphere. After adding tripotassium phosphate (1.144 g, 5.39 mmol) under a nitrogen atmosphere, the mixture was stirred at 100 °C overnight. After the reaction was completed, the solvent was removed. The residue was diluted with dichloromethane:methanol (99:1) and filtered through a Celite filter. After concentration under reduced pressure, the residue was purified by MPLC to produce the target compound (0.209 g, 45%, yellow solid). LC / MS (ESI) m / z: 259 [M+H] +

[0339] Step 2: Preparation of 3-(4,5-dichloro-1H-imidazol-2-yl)aniline

[0340]

[0341] 4,5-Dichloro-2-(3-nitrophenyl)-1H-imidazole (0.209 g, 0.81 mmol), iron (159 mg, 2.43 mmol), and 37% hydrochloric acid (0.344 ml, 11.3 mmol) prepared in the above step 1 were dissolved in ethanol (5 ml), and then 80 The mixture was stirred at ℃ for 4 hours. After the reaction was completed, the solvent was removed. The residue was diluted with ethyl acetate and filtered through a Celite filter. After concentration under reduced pressure, the mixture was purified by MPLC to produce the target compound (141 mg, 76%, brown solid). LC / MS (ESI) m / z: 229 [M+H] +

[0342] Step 3: Preparation of N2-(3-(4,5-dichloro-1H-imidazol-2-yl)phenyl)-N6-methyl-9H-purine-2,6-diamine

[0343]

[0344] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 376 [M+H] +

[0345] Step 4: Preparation of N-cyclopropyl-2-((3-(4,5-dichloro-1H-imidazol-2-yl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0346]

[0347] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 459 [M+H] +

[0348] <Example 33> Preparation of N-cyclopropyl-2-((4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0349]

[0350] Step 1: Preparation of tert-butyl (4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)carbamate

[0351]

[0352] The target compound was prepared by performing similarly to step 2 of Example 29 above. LC / MS (ESI) m / z: 275 [M+H] +

[0353] Step 2: Preparation of 4-(1-methyl-1H-1,2,4-triazol-3-yl)aniline

[0354]

[0355] Tert-butyl (4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)carbamate (0.443 g, 1.615 mmol) prepared in Step 1 above was dissolved in DCM (23 ml) and trifluoroacetic acid (3.73 ml, 48.4 mmol) and stirred at room temperature for 1.5 hours. After the reaction was completed, the solvent was removed and the mixture was neutralized to pH 8-9 with ammonia water. The mixture was concentrated under reduced pressure and purified by MPLC to produce the target compound (151 mg, 54%, yellow solid). LC / MS (ESI) m / z: 175 [M+H] +

[0356] Step 3: Preparation of N6-methyl-N2-(4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-9H-purine-2,6-diamine

[0357]

[0358] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 322 [M+H] +

[0359] Step 4: Preparation of N-cyclopropyl-2-((4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0360]

[0361] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 405 [M+H] +

[0362] <Example 34> Preparation of N-cyclopropyl-6-(methylamino)-2-((1-((trifluoromethyl)sulfonyl)-1H-indol-5-yl)amino)-9H-purine-9-carboxamide

[0363]

[0364] Step 1: Preparation of 5-nitro-1-((trifluoromethyl)sulfonyl)-1H-indole

[0365]

[0366] 5-Nitro-1H-indole (500 mg, 3.08 mmol) was mixed with dimethylformamide (10 ml) and sodium hydride (247 mg, 6.17 mmol) and stirred for about 10 minutes. Trifluoromethanesulfonyl chloride (0.490 ml, 4.63 mmol) was added and stirred at room temperature overnight. After the reaction was completed, the mixture was concentrated under reduced pressure. The residue was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPL to obtain the target compound (325 mg, 36%).

[0367] Step 2: Preparation of 1-((trifluoromethyl)sulfonyl-1H-indole-5-amine

[0368]

[0369] The target compound was prepared by performing similarly to step 1 of Example 31 above. LC / MS (ESI) m / z: 265 [M+H] +

[0370] Step 3: Preparation of N6-methyl-N2-(1-((trifluoromethyl)sulfonyl)-1H-indol-5-yl)-9H-purine-2,6-diamine

[0371]

[0372] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 412 [M+H] +

[0373] Step 4: Preparation of N-cyclopropyl-6-(methylamino)-2-((1-((trifluoromethyl)sulfonyl)-1H-indol-5-yl)amino)-9H-purine-9-carboxamide

[0374]

[0375] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 495 [M+H] +

[0376] <Example 35> Preparation of N-cyclopropyl-2-((3-(1-(2-methoxyethyl)-1H-imidazol-2-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0377]

[0378] Step 1: Preparation of 2-(3-nitrophenyl)-1H-imidazole

[0379]

[0380] (3-Nitrophenyl)boronic acid (0.2 g, 1.198 mmol), 2-bromo-1H-imidazole (0.194 g, 1.318 mmol), PdCl2(dppf) (0.088 g, 0.120 mmol), and sodium bicarbonate (0.302 g, 3.59 mmol) were dissolved in 1,4-dioxane (2 ml) and water (0.5 ml) and reacted in a microwave at 150 °C for 3 h. After the reaction was completed, the solvent was removed. The residue was diluted with dichloromethane and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to produce the target compound (0.109 g, 48%, brown solid). LC / MS (ESI) m / z: 190 [M+H] +

[0381] Step 2: Preparation of 1-(2-methoxyethyl)-2-(3-nitrophenyl)-1H-imidazole

[0382]

[0383] The target compound was prepared by performing similarly to step 1 of Example 34 above. LC / MS (ESI) m / z: 248 [M+H] +

[0384] Step 3: Preparation of 3-(1-(2-methoxyethyl)-1H-imidazol-2yl)aniline

[0385]

[0386] The target compound was prepared by performing similarly to step 1 of Example 31 above. LC / MS (ESI) m / z: 218 [M+H] +

[0387] Step 4: Preparation of N2-(3-(1-(2-methoxyethyl)-1H-imidazol-2-yl)phenyl)-N6-methyl-9H-purine-2,6-diamine

[0388]

[0389] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 365 [M+H] +

[0390] Step 5: Preparation of N-cyclopropyl-2-((3-(1-(2-methoxyethyl)-1H-imidazol-2-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0391]

[0392] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 448 [M+H] +

[0393] <Example 36> Preparation of N-cyclopropyl-6-(methylamino)-2-((3-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purine-9-carboxamide

[0394]

[0395] Step 1: Preparation of 1-(3-nitrophenyl)-4-((tetrahydro-2H-pyran-4-yl)methyl)piperazine

[0396]

[0397] To 1-bromo-3-nitrobenzene (180 mg, 0.891 mmol) and 1-((tetrahydro-2H-pyran-4-yl)methyl)piperazine (181 mg, 0.980 mmol) dissolved in 1,4-dioxane (3 ml) was added cesium carbonate (1452 mg, 4.46 mmol). Palladium(II) acetate (20 mg, 0.089 mmol) and Xantphos (51.6 mg, 0.089 mmol) were added at 50 °C, and the mixture was stirred at 80 °C overnight. After completion of the reaction, the mixture was concentrated, dissolved in dichloromethane, and filtered through a celite filter. After concentration under reduced pressure, the mixture was purified by MPLC to obtain the target compound (203 mg, 75%, orange solid). LC / MS(ESI) m / z: 306 [M+H] +

[0398] Step 2: Preparation of 3-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)aniline

[0399]

[0400] The target compound was prepared by performing similarly to step 1 of Example 31 above. LC / MS (ESI) m / z: 276 [M+H] +

[0401] Step 3: Preparation of N6-methyl-N2-(3-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)phenyl)-9H-purine-2,6-diamine

[0402]

[0403] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 423 [M+H] +

[0404] Step 4: Preparation of N-cyclopropyl-6-(methylamino)-2-((3-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purine-9-carboxamide

[0405]

[0406] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 506 [M+H] +

[0407] <Example 37> Preparation of N-cyclopropyl-6-(methylamino)-2-((1-((trifluoromethyl)sulfonyl)-1H-indol-5-yl)amino)-9H-purine-9-carboxamide

[0408]

[0409] Step 1: Preparation of 4-(3-fluoro-5-nitrophenoxy)-1-methylpiperidine

[0410]

[0411] To 1,3-difluoro-5-nitrobenzene (0.355 ml, 3.14 mmol) were added dimethylformamide (2 ml) and sodium hydride (113 mg, 4.71 mmol). After stirring at room temperature for 40 minutes, 1-methylpiperidin-4-ol (0.443 ml, 3.77 mmol) was added and stirred at 65°C overnight. After completion of the reaction, the mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to give the target compound (496 mg, 62%, orange solid). LC / MS (ESI) m / z: 255 [M+H] +

[0412] Step 2: Preparation of 3-fluoro-5-((1-methylpiperidin-4-yl)oxy)aniline

[0413]

[0414] The target compound was prepared by performing similarly to step 1 of Example 31 above. LC / MS (ESI) m / z: 225 [M+H] +

[0415] Step 3: Preparation of N2-(3-fluoro-5-((1-methylpiperidin-4-yl)oxy)phenyl)-N6-methyl-9H-purine-2,6-diamine

[0416]

[0417] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 372 [M+H] +

[0418] Step 4: Preparation of N-cyclopropyl-6-(methylamino)-2-((1-((trifluoromethyl)sulfonyl)-1H-indol-5-yl)amino)-9H-purine-9-carboxamide

[0419]

[0420] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 455 [M+H] +

[0421] <Example 38> Preparation of butyl 1-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylate

[0422]

[0423] Step 1: Preparation of methyl 1-(3-nitrobenzyl)piperidine-4-carboxylate

[0424]

[0425] 1-(Chloromethyl)-3-nitrobenzene (1 g, 5.83 mmol) was added methyl piperidine-4-carboxylate (0.945 ml, 6.99 mmol), 1,2-dichloroethane (10 ml), and trimethylamine (0.975 ml, 6.99 mmol), and the mixture was refluxed overnight. After completion of the reaction, the mixture was concentrated under reduced pressure and purified by MPLC to obtain the target compound (1.537 g, 95%, beige solid). LC / MS (ESI) m / z: 279 [M+H] +

[0426] Step 2: Preparation of methyl 1-(3-aminobenzyl)piperidine-4-carboxylate

[0427]

[0428] Methyl 1-(3-nitrobenzyl)piperidine-4-carboxylate (0.696 g, 2.50 mmol) prepared in the above step 1 and SnCl22H2O (3.39 g, 15.0 mmol) were dissolved in ethyl acetate, and then 80 The mixture was stirred overnight at ℃. After the reaction was completed, ammonia water was added to neutralize the pH to 5. An excess of sodium carbonate was added and the mixture was stirred at room temperature for about 1 hour. The solution was filtered through a Celite filter. Concentration under reduced pressure produced the target compound (0.613 g, 99%, yellow liquid). LC / MS (ESI) m / z: 249 [M+H] +

[0429] Step 3: Preparation of butyl 1-(3-((6-methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylate

[0430]

[0431] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 438 [M+H] +

[0432] Step 4: Preparation of butyl 1-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylate

[0433]

[0434] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 521 [M+H] +

[0435] <Example 39> Preparation of N-cyclopropyl-2-((3-(3-hydroxypiperidine-1-carbonyl)-5-(trifluoromethyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0436]

[0437] Step 1: Preparation of 3-nitro-5-(trifluoromethyl)benzoyl chloride

[0438]

[0439] 3-Nitro-5-(trifluoromethyl)benzoic acid (0.5 g, 2.12 mmol) was dissolved in DCM (4 mL), and oxalyl chloride (0.93 mL, 10.63 mmol) was slowly added dropwise, followed by reaction at room temperature for 3 hours. After the reaction was completed, the mixture was concentrated under reduced pressure to obtain the target compound (0.54 g, 100%, orange liquid).

[0440] Step 2: Preparation of (3-hydroxypiperidin-1-yl)(3-nitro-5-(trifluoromethyl) phenyl)methanone

[0441]

[0442] Piperidin-3-ol (0.2 g, 1.97 mmol) was dissolved in THF (3 mL), and 3-nitro-5-(trifluoromethyl)benzoyl chloride (0.6 g, 2.37 mmol) and pyridine (0.48 mL, 5.93 mmol) prepared in Step 1 were added, and the mixture was stirred at room temperature for 1 h. After the reaction was completed, the mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to produce the target compound (0.36 g, 57%). LC / MS (ESI) m / z: 319 [M+H] +

[0443] Step 3: Preparation of (3-amino-5-(trifluoromethyl)phenyl)(3-hydroxypiperidin-1-yl)methanone

[0444]

[0445] (3-Hydroxypiperidin-1-yl)(3-nitro-5-(trifluoromethyl)phenyl)methanone (0.36 g, 1.13 mmol) prepared in the above step 2 was dissolved in methanol (3 ml), 10% Pd / C (0.12 g, 0.11 mmol) was added, and the mixture was stirred under hydrogen gas for 4 hours. After the reaction was completed, the mixture was filtered through a Celite filter. After concentration under reduced pressure, the mixture was purified by MPLC to produce the target compound (0.3 g, 94%, transparent liquid). LC / MS (ESI) m / z: 289 [M+H] +

[0446] Step 4: Preparation of (3-hydroxypiperidin-1-yl)(3-((6-(methylamino)-9Hpurin-2-yl)amino)-5-(trifluoromethyl)phenyl)methanone

[0447]

[0448] (3-Amino-5-(trifluoromethyl)phenyl)(3-hydroxypiperidin-1-yl)methanone (0.1 g, 0.34 mmol) and 2-fluoro-N-methyl-9H-purin-6-amine (58 mg, 0.34 mmol) prepared in Step 3 above were dissolved in 2,2,2-trifluoroethane (1 mL), and trifluoroacetic acid (0.26 mL, 3.47 mmol) was added. The mixture was stirred at 80 °C for 4 hours. After the reaction was completed, the mixture was diluted with dichloromethane and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to produce the target compound (20 mg, 13%, white solid). LC / MS(ESI) m / z: 436 [M+H] +

[0449] Step 5: Preparation of N-cyclopropyl-2-((3-(3-hydroxypiperidine-1-carbonyl)-5-(trifluoromethyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0450]

[0451] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 519 [M+H] +

[0452] <Example 40> Preparation of N-cyclopropyl-2-((3-((4,4-difluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0453]

[0454] Step 1: Preparation of 4,4-difluoro-1-(3-nitrobenzyl)piperidine

[0455]

[0456] 4,4-Difluoropiperidine (0.3 g, 2.47 mmol), 1-(bromomethyl)-3-nitrobenzene (0.64 g, 2.97 mmol), and potassium carbonate (0.68 g, 4.95 mmol) were dissolved in ACN (3 mL) and reacted at room temperature for 2 h. After the reaction was completed, the mixture was diluted with dichloromethane and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to produce the target compound (0.53 g, 84%, white solid). LC / MS (ESI) m / z: 257 [M+H] +

[0457] Step 2: Preparation of 3-((4,4-difluoropiperidin-1-yl)methyl)aniline

[0458]

[0459] 4,4-Difluoro-1-(3-nitrobenzyl)piperidine (100 mg, 0.39 mmol) prepared in Step 1 above and tin(II) chloride dihydrate (0.44 g, 1.95 mmol) were dissolved in ethanol (3 mL) and ethyl acetate (1 mL), and reacted at 80°C for 2 hours. After completion of the reaction, the mixture was diluted with dichloromethane and washed with an aqueous sodium bicarbonate solution and water. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the target compound (88 mg, 100%, white solid). LC / MS(ESI) m / z: 227 [M+H] +

[0460] Step 3: Preparation of N2-(3-((4,4-difluoropiperidin-1-yl)methyl)phenyl)-N6-methyl-9H-purine-2,6-diamine

[0461]

[0462] The target compound was prepared by performing similarly to step 4 of Example 39. LC / MS (ESI) m / z: 374 [M+H] +

[0463] Step 4: Preparation of N-cyclopropyl-2-((3-((4,4-difluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0464]

[0465] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 457 [M+H] +

[0466] <Example 41>

[0467] The target compound of Example 41 was prepared by performing a method and procedure similar to that used in Example 40. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0468] <Example 42> Preparation of benzyl 4-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidine-1-carboxylate

[0469]

[0470] Step 1: Preparation of benzyl 4-(3-nitrophenoxy)piperidine-1-carboxylate

[0471]

[0472] Benzyl 4-hydroxypiperidine-1-carboxylate (0.5 g, 2.12 mmol), 1-(fluoro)-3-nitrobenzene (0.64 g, 2.97 mmol), and sodium tert-butoxide (0.51 g, 5.31 mmol) were dissolved in dimethylformamide (3 mL) and reacted at room temperature for 8 h. After the reaction was completed, the mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to produce the target compound (0.75 g, 68%). LC / MS (ESI) m / z: 357 [M+H] +

[0473] Step 2: Preparation of benzyl 4-(3-aminophenoxy)piperidine-1-carboxylate

[0474]

[0475] The target compound was prepared by performing similarly to step 2 of the above Example 40. LC / MS (ESI) m / z: 327 [M+H] +

[0476] Step 3: Preparation of benzyl 4-(3-((6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidine-1-carboxylate

[0477]

[0478] The target compound was prepared by performing similarly to step 4 of Example 39. LC / MS (ESI) m / z: 474 [M+H]+

[0479] Step 4: Preparation of benzyl 4-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidine-1-carboxylate

[0480]

[0481] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 557 [M+H] +

[0482] <Example 43> Preparation of N-cyclopropyl-6-(methylamino)-2-((3-(piperidin-4-yloxy)phenyl)amino)-9H-purine-9-carboxamide

[0483]

[0484] The target compound was prepared using benzyl 4-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidine-1-carboxamide prepared in Example 42 above and by performing similarly to Step 3 of Example 39. LC / MS (ESI) m / z: 423 [M+H] +

[0485] <Example 44> N-Cyclopropyl-6-(isopropylamino)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-9H-purine-9-carboxamide

[0486]

[0487] Step 1: Preparation of 2-chloro-N-isopropyl-9H-purin-6-amine

[0488]

[0489] The target compound was prepared by performing similarly to step 1 of Example 1 above. LC / MS (ESI) m / z: 212 [M+H] +

[0490] Step 2: Preparation of N6-isopropyl-N2-(3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-9H-purine-2,6-diamine

[0491]

[0492] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 350 [M+H] +

[0493] Step 3: Preparation of N-cyclopropyl-6-(isopropylamino)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0494]

[0495] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 433 [M+H] +

[0496] <Example 45> N-Cyclopropyl-2-((3-(1-isopropyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0497]

[0498] Step 1: Preparation of 2-isopropyl-3-(3-nitrophenyl)-1H-1,2,4-triazole

[0499]

[0500] 3-(3-Nitrophenyl)-1H-1,2,4-triazole (0.15 g, 0.79 mmol), 2-iodopropane (0.16 g, 0.95 mmol), and potassium carbonate (0.15 g, 1.10 mmol) were dissolved in dimethylformamide (2 mL) and reacted at room temperature for 2 h. After the reaction was completed, the mixture was diluted with dichloromethane and washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to produce the target compound (0.1 g, 55%, white solid). LC / MS (ESI) m / z: 233 [M+H] +

[0501] Step 2: Preparation of 3-(1-isopropyl-1H-1,2,4-triazol-3-yl)aniline

[0502]

[0503] The target compound was prepared by performing similarly to step 2 of Example 32 above. LC / MS (ESI) m / z: 203 [M+H] +

[0504] Step 3: Preparation of N2-(3-(1-isopropyl-1H-1,2,4-triazol-3-yl)phenyl)-N6-methyl-9H-purine-2,6-diamine

[0505]

[0506] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 350 [M+H] +

[0507] Step 4: Preparation of N-cyclopropyl-2-((3-(1-isopropyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0508]

[0509] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 433 [M+H] +

[0510] <Example 46>

[0511] The target compound of Example 46 was prepared by performing a method and procedure similar to that used in Example 39. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0512] <Examples 47 to 49>

[0513] The target compounds of Examples 47 to 49 were prepared by performing methods and procedures similar to those used in Example 1. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0514] <Example 50> 1-Cyclopropyl-2-(6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purin-9-yl)ethan-1-one

[0515]

[0516] Step 1: Preparation of N6-methyl-N2-(3-((1-methylpiperidin-4-yl)oxy)phenyl)-9H-purine-2,6-diamine

[0517]

[0518] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 354 [M+H] +

[0519] Step 2: Preparation of 1-cyclopropyl-2-(6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purin-9-yl)ethan-1-one

[0520]

[0521] Sodium hydride (39.6 mg, 0.990 mmol) was added to N6-methyl-N2-(3-((1-methylpiperidin-4-yl)oxy)phenyl)-9H-purine-2,6-diamine (70 mg, 0.198 mmol) prepared in Step 1 and dissolved in dimethylformamide (1 ml), and the mixture was stirred at room temperature for about 40 minutes. 2-Bromo-1-cyclopropylethan-1-one (97 mg, 0.594 mmol) dissolved in dimethylformamide (0.5 ml) was added, and the mixture was stirred at room temperature for about 2 hours. After the reaction was completed, the mixture was concentrated under reduced pressure and purified by prep-HPLC to produce the target compound (22.1 mg, 25%). LC / MS (ESI) m / z: 436 [M+H] +

[0522] <Example 51> 1-(3-((9-(cyclopropylcarbamoyl)-6-methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid

[0523]

[0524] Step 1: Preparation of sodium 1-(3-((6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylate

[0525]

[0526] To butyl 1-(3-((6-methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylate (197 mg, 0.450 mmol) prepared in step 3 of Example 38 above, THF (5 ml) and 2 M NaOH aqueous solution (0.563 ml, 1.125 mmol) were added, and the mixture was stirred at room temperature overnight. After completion of the reaction, the mixture was concentrated under reduced pressure and then subjected to the next reaction without further purification. LC / MS (ESI) m / z: 382 [M+H] +

[0527] Step 2: Preparation of 1-(3-((9-(cyclopropylcarbamoyl)-6-methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid

[0528]

[0529] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 465 [M+H] +

[0530] <Example 52>

[0531] The target compound of Example 52 was prepared by performing a method and procedure similar to that used in Example 50 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0532] <Example 53> N-Cyclopropyl-6-(methylamino)-2-((3-((4-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide

[0533]

[0534] Step 1: Preparation of N-methyl-1-(3-((6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxamide

[0535]

[0536] To sodium 1-(3-((6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylate (170 mg, 0.446 mmol) prepared in step 1 of Example 51 above, dimethylformamide (4 ml), methylamine hydrochloride (45.1 mg, 0.669 mmol), HATU (203 mg, 0.535 mmol), and DIPEA (0.311 ml, 1.783 mmol) were added, and the mixture was stirred at 80°C overnight. After completion of the reaction, the mixture was concentrated under reduced pressure and purified by MPLC. After concentration under reduced pressure, the next reaction was carried out without further purification. LC / MS (ESI) m / z: 395 [M+H] +

[0537] Step 2: Preparation of N-cyclopropyl-6-(methylamino)-2-((3-((4-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide

[0538]

[0539] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 478 [M+H] +

[0540] <Example 54>

[0541] The target compound of Example 54 was prepared by performing a method and procedure similar to that used in Example 53. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0542] <Example 55> 2-(4-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidin-1-yl)ethyl cyclopropylcarbamate

[0543]

[0544] Step 1: Preparation of tert-butyl 4-(3-nitrophenoxy)piperidine-1-carboxylate

[0545]

[0546] The target compound was prepared by performing similarly to step 1 of Example 37 above. LC / MS (ESI) m / z: 308 [M+H] +

[0547] Step 2: Preparation of 4-(3-nitrophenoxy)piperidine hydrochloride

[0548]

[0549] 1 N hydrochloric acid (5 ml, 5.00 mmol) diluted in ethyl acetate was added to tert-butyl 4-(3-nitrophenoxy)piperidine-1-carboxylate (468 mg, 1.452 mmol) prepared in Step 1 above, and stirred for about 4 hours. 1 N hydrochloric acid (2 ml, 2.00 mmol) diluted in ethyl acetate was further added, and the mixture was stirred for about 1 hour. After the reaction was completed, the mixture was concentrated under reduced pressure to prepare the target compound (366 mg, 97%). LC / MS (ESI) m / z: 223 [M+H] +

[0550] Step 3: Preparation of 2-(4-(3-nitrophenoxy)piperidin-1-yl)ethan-1-ol

[0551]

[0552] The target compound was prepared by performing similarly to step 1 of Example 40 above. LC / MS (ESI) m / z: 267 [M+H] +

[0553] Step 4: Preparation of 2-(4-(3-aminophenoxy)piperidin-1-yl)ethan-1-ol

[0554]

[0555] The target compound was prepared by performing similarly to step 2 of Example 40 above. LC / MS (ESI) m / z: 237 [M+H] +

[0556] Step 5: Preparation of 2-(4-(3-((6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidin-1-yl)ethan-1-ol

[0557]

[0558] The target compound was prepared by performing similarly to step 4 of Example 39. LC / MS (ESI) m / z: 384 [M+H] +

[0559] Step 6: Preparation of 2-(4-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidin-1-yl)ethyl cyclopropylcarbamate

[0560]

[0561] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 550 [M+H] +

[0562] <Example 56> 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(spiro[3.3]heptan-2-yl)-9H-purine-9-carboxamide

[0563]

[0564] Step 1: Preparation of 2-isocyanatospiro[3.3]heptane

[0565]

[0566] Dichloromethane (9 ml) and pyridine (0.144 ml, 1.783 mmol) were added to spiro[3.3]heptan-2-amine hydrochloride (50 mg, 0.339 mmol) under a nitrogen atmosphere at 0 °C, and the mixture was stirred for about 30 minutes. Under the same conditions, triphosgene (90 mg, 0.303 mmol) dissolved in dichloromethane (1 ml) was slowly added over 30 seconds, and the mixture was stirred for about 2 hours. After the reaction was completed, an excess of dimethyl ether was added to wash the precipitated solid. The filtrate was concentrated under reduced pressure and then proceeded with the next reaction without further purification. LC / MS (ESI) m / z: 170 [M+H] +

[0567] Step 2: Preparation of 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(spiro[3.3]heptan-2-yl)-9H-purine-9-carboxamide

[0568]

[0569] The target compound was prepared in a similar manner to step 3 of Example 1 using 2-isocyanatospiro[3.3]heptane prepared in step 1 above. LC / MS (ESI) m / z: 459 [M+H] +

[0570] <Examples 57 to 58>

[0571] The target compounds of Examples 57 to 58 were prepared by performing methods and procedures similar to those used in Example 56 above. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0572] <Example 59> N-((1R,2R)-2-fluorocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0573]

[0574] Step 1: Preparation of N-(2-fluorocyclopropyl)-1H-imidazole-1-carboxamide

[0575]

[0576] 1,1'-Carbonyldiimidazole (436 mg, 2.690 mmol) was added to 2-fluorocyclopropan-1-amine hydrochloride (200 mg, 1.793 mmol) dissolved in acetonitrile (6 ml) and stirred at room temperature overnight. After completion of the reaction, the mixture was concentrated under reduced pressure and purified by MPLC to produce the target compound (234 mg, 77%, white solid). LC / MS (ESI) m / z: 170 [M+H] +

[0577] Step 2: Preparation of N-((1R,2R)-2-fluorocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0578]

[0579] Dimethylformamide (1 ml) and triethylamine (33 μl, 0.233 mmol) were added to N6-methyl-N2-(3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-9H-purine-2,6-diamine (50 mg, 0.156 mmol) prepared in step 2 of Example 1. After adding N-(2-fluorocyclopropyl)-1H-imidazole-1-carboxamide (52.6 mg, 0.312 mmol) prepared in step 1, the mixture was stirred at 70 °C for 2 hours. After completion of the reaction, the mixture was filtered and purified by prep-HPLC to prepare the target compound (A, 6.7 mg, 10%, white solid) and Example 62 (B, 6.6 mg, 10%, white solid). LC / MS(ESI) m / z: 423 [M+H] +

[0580] <Example 60>

[0581] The desired compound (B, 6.6 mg, 10%, white solid) was prepared using methods and procedures similar to those used in Example 59 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0582] <Example 61>

[0583] The target compound of Example 61 was prepared by performing a method and procedure similar to that used in Example 53 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0584] <Examples 62 and 63>

[0585] The target compounds of Examples 62 to 63 were prepared by performing methods and procedures similar to those used in Example 1. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0586] <Example 64>

[0587] The target compound of Example 64 was prepared by performing a method and procedure similar to that used in Example 59. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0588] <Example 65>

[0589] The target compound of Example 65 was prepared by performing a method and procedure similar to that used in Example 53 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0590] <Example 66> N-((1R,2R)-2-methoxycyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0591]

[0592] Step 1: Preparation of N-((1R,2R)-2-methoxycyclobutyl)-1H-imidazole-1-carboxamide

[0593]

[0594] To (1R,2R)-2-methoxycyclobutan-1-amine hydrochloride (200 mg, 1.453 mmol) dissolved in acetonitrile (5.8 ml) was added 1,1'-carbonyldiimidazole (354 mg, 2.180 mmol) and stirred overnight at room temperature. After completion of the reaction, the mixture was concentrated under reduced pressure and purified by MPLC to produce the target compound (262 mg, 92%, clear liquid). LC / MS (ESI) m / z: 196 [M+H] +

[0595] Step 2: Preparation of N-((1R,2R)-2-methoxycyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0596]

[0597] Dimethylformamide (1 ml) and triethylamine (43 μl, 0.311 mmol) were added to N6-methyl-N2-(3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)-9H-purine-2,6-diamine (50 mg, 0.156 mmol) prepared in step 2 of Example 1. After adding N-((1R,2R)-2-methoxycyclobutyl)-1H-imidazole-1-carboxamide (60.8 mg, 0.311 mmol) prepared in step 1, the mixture was stirred at 70°C for 2 hours. After completion of the reaction, the mixture was filtered and purified by prep-HPLC to prepare the target compound (14 mg, 20%, white solid). LC / MS(ESI) m / z: 449 [M+H] +

[0598] <Example 67>

[0599] The target compound of Example 67 was prepared by performing a method and procedure similar to that used in Example 39 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0600] <Examples 68 to 69>

[0601] The target compounds of Examples 71 and 72 were prepared by performing methods and procedures similar to those used in Example 38 above. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0602] <Example 70>

[0603] The target compound of Example 70 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0604] <Example 71> N-Cyclopropyl-2-((3-((3-hydroxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0605]

[0606] Step 1: Preparation of 1-(3-nitrobenzyl)piperidin-3-ol

[0607]

[0608] The target compound was prepared by performing similarly to step 1 of the above Example 40. LC / MS (ESI) m / z: 237 [M+H] +

[0609] Step 2: Preparation of 1-(3-aminobenzyl)piperidin-3-ol

[0610]

[0611] The target compound was prepared by performing similarly to step 2 of Example 40 above. LC / MS (ESI) m / z: 207 [M+H] +

[0612] Step 3: Preparation of 1-(3-((6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidin-3-ol

[0613]

[0614] The target compound was prepared by performing similarly to step 4 of Example 39. LC / MS (ESI) m / z: 354 [M+H] +

[0615] Step 4: Preparation of N-cyclopropyl-2-((3-((3-hydroxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0616]

[0617] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 437 [M+H] +

[0618] <Example 72>

[0619] The target compound of Example 72 was prepared by performing a method and procedure similar to that used in Example 71. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0620] <Example 73>

[0621] The target compound of Example 73 was prepared by performing a method and procedure similar to that used in Example 51 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0622] <Example 74> 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide

[0623]

[0624] Step 1: Preparation of N,N-dimethyl-1-(3-((6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxamide

[0625]

[0626] The target compound was prepared by performing similarly to step 1 of Example 53 above. LC / MS (ESI) m / z: 409 [M+H] +

[0627] Step 2: Preparation of 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide

[0628]

[0629] The target compound was prepared by performing similarly to step 2 of Example 66 above. LC / MS (ESI) m / z: 536 [M+H] +

[0630] <Example 75>

[0631] The target compound of Example 75 was prepared by performing a method and procedure similar to that used in Example 74. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0632] <Example 76> 1-(3-((9-(((1R,2R)-2-methoxycyclobutyl)carbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid

[0633]

[0634] Step 1: Preparation of 1-(3-((9-(((1R,2R)-2-methoxycyclobutyl)carbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid

[0635]

[0636] The target compound was prepared by performing similarly to step 2 of Example 66 above. LC / MS (ESI) m / z: 509 [M+H] +

[0637] <Examples 77 to 79>

[0638] The target compounds of Examples 77 to 79 were prepared by performing methods and procedures similar to those used in Example 66 above. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0639] <Example 80> N-Cyclobutyl-6-(methylamino)-2-((3-(piperidin-1-ylmethyl)phenyl)amino)-9H-purine-9-carboxamide

[0640]

[0641] The target compound of Example 80 was prepared by performing methods and procedures similar to those used in Examples 40 and 1 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0642] <Example 81>

[0643] The target compound of Example 81 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0644] <Example 82> N-(2-Fluorocyclopropyl)-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide

[0645] Step 1: Preparation of N-(2-fluorocyclopropyl)-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide

[0646]

[0647] The target compound of Example 82 was prepared by performing similarly to Step 2 of Example 66. LC / MS (ESI) m / z: 455 [M+H] +

[0648] <Example 83>

[0649] The target compound of Example 83 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0650] <Example 84>

[0651] The target compound of Example 84 was prepared by performing a method and procedure similar to that used in Example 38. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0652] <Example 85>

[0653] The target compound of Example 85 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0654] <Examples 86 to 88>

[0655] The target compounds of Examples 86 to 88 were prepared by performing methods and procedures similar to those used in Example 66 above. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0656] <Example 89>

[0657] The target compound of Example 89 was prepared by performing methods and procedures similar to those used in Examples 40 and 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0658] <Example 90>

[0659] The target compound of Example 90 was prepared by performing methods and procedures similar to those used in Examples 40 and 1 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0660] <Examples 91 to 94>

[0661] The target compounds of Examples 91 to 94 were prepared by performing methods and procedures similar to those used in Example 59 above. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0662] <Example 95>

[0663] The target compound of Example 95 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0664] <Example 96>

[0665] The target compound of Example 96 was prepared by performing methods and procedures similar to those used in Examples 53 and 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0666] <Examples 97 to 98>

[0667] The target compounds of Examples 97 to 98 were prepared by performing methods and procedures similar to those used in Example 66 above. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0668] <Example 99>

[0669] The target compound of Example 99 was prepared by performing a method and procedure similar to that used in Example 53 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0670] <Example 100>

[0671] The target compound of Example 100 was prepared by performing a method and procedure similar to those used in Example 1 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0672] <Example 101>

[0673] The target compound of Example 101 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0674] <Example 102>

[0675] The target compound of Example 102 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0676] <Example 103>

[0677] The target compound of Example 103 was prepared by performing a method and procedure similar to that used in Example 53 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0678] <Example 104> 2-((3-((3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide

[0679]

[0680] Step 1: Preparation of 1-(3-nitrobenzyl)piperidin-3-ol

[0681]

[0682] The target compound was prepared by performing similarly to step 1 of the above Example 40. LC / MS (ESI) m / z: 237 [M+H] +

[0683] Step 2: Preparation of 3-((tert-butyldimethylsilyl)oxy)-1-(3-nitrobenzyl)piperidine

[0684]

[0685] 1-(3-nitrobenzyl)piperidin-3-ol (500 mg, 2.116 mmol) and imidazole (432 mg, 6.35 mmol) prepared in Step 1 were added to tert-butylchlorodimethylsilane (478 mg, 3.17 mmol) dissolved in dimethylformamide (10.6 ml), and the mixture was stirred at room temperature overnight. After the reaction was completed, the mixture was diluted with ethyl acetate and washed with water and brine. The organic layer residue was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to produce the target compound (683 mg, 92%). LC / MS (ESI) m / z: 351 [M+H] +

[0686] Step 3: Preparation of 3-((3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)methyl)aniline

[0687]

[0688] The target compound was prepared by performing similarly to step 2 of Example 40 above. LC / MS (ESI) m / z: 321 [M+H] +

[0689] Step 4: Preparation of N2-(3-((3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)methyl)phenyl)-N6-methyl-9H-purine-2,6-diamine

[0690]

[0691] t-Butanol (15 ml) was dissolved in 2-chloro-N-methyl-9H-purin-6-amine (317 mg, 1.728 mmol) prepared in Step 1 of Example 1, and 3-((3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)methyl)aniline (554 mg, 1.728 mmol) and potassium tert-butoxide (582 mg, 5.18 mmol) prepared in Step 3 were added. After adding Pd2(dba)3 (158 mg, 0.173 mmol) and xphos (82 mg, 0.173 mmol) at 80 °C, the mixture was stirred at 80 °C for 2 hours. After completion of the reaction, the mixture was filtered and concentrated, and then purified by MPLC to prepare the target compound (407 mg, 50%). LC / MS(ESI) m / z: 468 [M+H] +

[0692] Step 4: Preparation of 2-((3-((3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide

[0693]

[0694] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 565 [M+H] +

[0695] <Example 105> N-Cyclobutyl-2-((5-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0696]

[0697] Step 1: Preparation of 5-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-amine

[0698]

[0699] 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amine (100 mg, 0.454 mmol) dissolved in toluene:ethanol (2:1) (2.3 ml) was added 3-bromo-1-methyl-1H-1,2,4-triazole (88 mg, 0.545 mmol) and 2 M sodium carbonate (0.682 ml, 1.363 mmol). PdCl2(dppf) (33.2 mg, 0.045 mmol) was added under nitrogen atmosphere, and the mixture was stirred at 110 °C for about 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, filtered through a Celite filter, and washed with dichloromethane:methanol (97:3). After concentration under reduced pressure, the residue was purified by MPLC to produce the target compound (65 mg, 82%). LC / MS (ESI) m / z: 176 [M+H] +

[0700] Step 2: Preparation of N6-methyl-N2-(5-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)-9H-purine-2,6-diamine

[0701]

[0702] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 323 [M+H] +

[0703] Step 3: Preparation of N-cyclobutyl-2-((5-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0704]

[0705] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 420 [M+H] +

[0706] <Example 106> N-Cyclobutyl-2-((3-((3-((dimethylamino)methyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0707]

[0708] Step 1: Preparation of 1-(3-nitrobenzyl)piperidine-3-carbaldehyde

[0709]

[0710] The target compound was prepared by performing similarly to step 1 of Example 40 above.

[0711] Step 2: Preparation of N,N-dimethyl-1-(1-(3-nitrobenzyl)piperidin-3-yl)methanamine

[0712]

[0713] To 1-(3-nitrobenzyl)piperidine-3-carbaldehyde (389.7 mg, 1.570 mmol) prepared in Step 1 above, methanol (5.2 ml), triethylamine (438 μl, 3.14 mmol), and dimethylamine hydrochloride (256 mg, 3.14 mmol) were added, and the mixture was stirred at room temperature for about 1 hour. Sodium borohydride (89 mg, 2.354 mmol) was added, and the mixture was stirred for about 1 hour. After the reaction was completed, the mixture was diluted with dichloromethane and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and purified by MPLC to produce the target compound (198 mg, 36%). LC / MS (ESI) m / z: 278 [M+H] +

[0714] Step 3: Preparation of 3-((3-((dimethylamino)methyl)piperidin-1-yl)methyl)aniline

[0715]

[0716] The target compound was prepared by performing similarly to step 2 of Example 40 above. LC / MS (ESI) m / z: 248 [M+H] +

[0717] Step 4: Preparation of N2-(3-((3-((dimethylamino)methyl)piperidin-1-yl)methyl)phenyl)-N6-methyl-9H-purine-2,6-diamine

[0718]

[0719] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 395 [M+H] +

[0720] Step 5: Preparation of N-cyclobutyl-2-((3-((3-((dimethylamino)methyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide

[0721]

[0722] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 492 [M+H] +

[0723] <Example 107>

[0724] The target compound of Example 107 was prepared by performing a method and procedure similar to that used in Example 59 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0725] <Example 108>

[0726] The target compound of Example 108 was prepared by performing similar methods and procedures as those used in Examples 40 and 1 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0727] <Example 109>

[0728] The target compound of Example 109 was prepared by performing a method and procedure similar to that used in Example 59 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0729] <Example 110>

[0730] The target compound of Example 110 was prepared by performing a method and procedure similar to those used in Example 1 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0731] <Example 111>

[0732] The target compound of Example 111 was prepared by performing a method and procedure similar to that used in Example 38 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0733] <Example 112> 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-(3-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide

[0734]

[0735] Step 1: Preparation of 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-(3-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide

[0736]

[0737] The target compound was prepared by performing similarly to step 2 of Example 66 above. LC / MS (ESI) m / z: 524 [M+H] +

[0738] <Example 113>2-((3-(1-(2-aminoethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide

[0739]

[0740] Step 1: Preparation of 1-(2-azidoethyl)-3-(3-nitrophenyl)-1H-1,2,4-triazole

[0741]

[0742] The target compound was prepared by performing similarly to step 1 of Example 45 above. LC / MS (ESI) m / z: 260 [M+H] +

[0743] Step 2: Preparation of 3-(1-(2-azidoethyl)-1H-1,2,4-triazol-3-yl)aniline

[0744]

[0745] 1-(2-Azidoethyl)-3-(3-nitrophenyl)-1H-1,2,4-triazole (0.92 g, 3.58 mmol) prepared in Step 1 was dissolved in tetrahydrofuran (5 mL), and then sodium dithionate (7.38 g, 35.8 mmol) dissolved in distilled water (10 mL) was added dropwise and stirred for about 15 minutes. After the reaction was completed, the mixture was diluted with ethyl acetate and washed with water and brine. The residue of the organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to produce the target compound (0.23 g, 29%). LC / MS(ESI) m / z: 230 [M+H] +

[0746] Step 3: Preparation of N2-(3-(1-(2-azidoethyl)-1H-1,2,4-triazol-3-yl)phenyl)-N6-methyl-9H-purine-2,6-diamine

[0747]

[0748] The target compound was prepared by performing similarly to step 4 of Example 39. LC / MS (ESI) m / z: 377 [M+H] +

[0749] Step 4: Preparation of 2-((3-(1-(2-azidoethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide

[0750]

[0751] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 474 [M+H] +

[0752] Step 5: Preparation of 2-((3-(1-(2-aminoethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide

[0753]

[0754] 2-((3-(1-(2-azidoethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide (0.36 g, 0.76 mmol) prepared in the above step 4 was dissolved in methanol (2 ml) and THF (2 mL), 10% Pd / C (81 mg, 0.07 mmol) was added, and the mixture was stirred under hydrogen gas for 30 minutes. After the reaction was completed, the mixture was filtered through a Celite filter. After concentration under reduced pressure, the mixture was purified by MPLC to obtain the target compound (0.21 g, 64%, white solid). LC / MS (ESI) m / z: 448 [M+H] +

[0755] <Example 114>

[0756] The target compound of Example 114 was prepared by performing a method and procedure similar to those used in Example 1. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0757] <Examples 115 to 116>

[0758] The target compounds of Examples 115 to 116 were prepared by performing methods and procedures similar to those used in Example 38 above. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0759] <Example 117> 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide

[0760]

[0761] Step 1: Preparation of 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide

[0762]

[0763] The target compound was prepared by performing similarly to step 2 of Example 59 above. LC / MS (ESI) m / z: 524 [M+H] +

[0764] <Example 118>

[0765] The target compound of Example 118 was prepared by performing a method and procedure similar to those used in Example 1. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0766] <Example 119>

[0767] The target compound of Example 119 was prepared by performing a method and procedure similar to that used in Example 59 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0768] <Example 120>

[0769] The target compound of Example 123 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0770] <Examples 121 to 122>

[0771] The target compounds of Examples 121 to 122 were prepared by performing methods and procedures similar to those used in Examples 40 and 1 above. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0772] <Example 123> 2-((3-((4-(4,4-difluoropiperidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6- (methylamino)-9H-purine-9-carboxamide

[0773]

[0774] Step 1: Preparation of (4,4-difluoropiperidin-1-yl)(1-(3-((6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidin-4-yl)methanone

[0775]

[0776] The target compound was prepared by performing a method and procedure similar to that used in step 1 of Example 53 above. LC / MS (ESI) m / z: 485 [M+H] +

[0777] Step 2: Preparation of 2-((3-((4-(4,4-difluoropiperidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide

[0778]

[0779] The target compound was prepared by performing a method and procedure similar to that used in step 2 of Example 66 above. LC / MS (ESI) m / z: 612 [M+H] +

[0780] <Example 124>

[0781] The target compound of Example 124 was prepared by performing a method and procedure similar to those used in Example 1. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0782] <Example 125>

[0783] The target compound of Example 125 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0784] <Example 126> 2-((3-((3-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide

[0785] Step 1: Preparation of N,N-dimethyl-1-(3-((6-(methylamine)-9H-purin-2-yl)amine)benzyl)piperidine-3-carboxamide

[0786]

[0787] The target compound was prepared by performing a method and procedure similar to that used in step 1 of Example 53 above. LC / MS (ESI) m / z: 409 [M+H] +

[0788] Step 2: Preparation of 2-((3-((3-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide

[0789]

[0790] The target compound was prepared by performing a method and procedure similar to that used in step 2 of Example 66 above. LC / MS (ESI) m / z: 409 [M+H] +

[0791] <Example 127> N-Cyclobutyl-6-(methylamino)-2-((3-((3-(pyridin-4-yl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide

[0792]

[0793] Step 1: Preparation of tert-butyl 5,6-dihydro-[3,4'-bipyridine]-1(2H)-carboxylate

[0794]

[0795] The target compound was prepared by performing similarly to step 1 of Example 28 above. LC / MS (ESI) m / z: 261 [M+H] +

[0796] Step 2: Preparation of 1,2,5,6-tetrahydro-3,4'-bipyridine-2,2,2-trifluoroacetate

[0797]

[0798] The compound (0.530 g, 2.04 mmol) prepared in step 1 was dissolved in dichloromethane (7 mL), trifluoroacetic acid (0.8 mL, 10.22 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was concentrated under reduced pressure to obtain the target compound, which was used in the next step without further purification. LC / MS (ESI) m / z: 161 [M+H] +

[0799] Step 3: Preparation of 1-(3-nitrobenzyl)-1,2,5,6-tetrahydro-3,4'-bipyridine

[0800]

[0801] The target compound was prepared by performing similarly to step 1 of Example 40 above. LC / MS (ESI) m / z: 275 [M+H] +

[0802] Step 4: Preparation of 3-((3-(pyridin-4-yl)piperidin-1-yl)methyl)aniline

[0803]

[0804] The target compound was prepared by performing similarly to step 1 of Example 31 above. LC / MS (ESI) m / z: 268 [M+H] +

[0805] Step 5: Preparation of N6-methyl-N2-(3-((3-(pyridin-4-yl)piperidin-1-yl)methyl)phenyl)-9H-purine-2,6-diamine

[0806]

[0807] The target compound was prepared by performing similarly to step 2 of Example 1. LC / MS (ESI) m / z: 415 [M+H] +

[0808] Step 6: Preparation of N-cyclobutyl-6-(methylamino)-2-((3-((3-(pyridin-4-yl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide

[0809]

[0810] The target compound was prepared by performing similarly to step 3 of Example 1. LC / MS (ESI) m / z: 512 [M+H] +

[0811] <Examples 128 to 129>

[0812] The target compounds of Examples 128 to 129 were prepared by performing methods and procedures similar to those used in Example 1. The names of the relevant compounds, NMR, MS, and HPLC data are summarized in Table 1.

[0813] <Example 130>

[0814] The target compound of Example 130 was prepared by performing a method and procedure similar to that used in Example 123 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0815] <Example 131>

[0816] The target compound of Example 131 was prepared by performing a method and procedure similar to that used in Example 51 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0817] <Example 132>

[0818] The target compound of Example 132 was prepared by performing a method and procedure similar to that used in Example 1. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0819] <Example 133>

[0820] The target compound of Example 133 was prepared by performing a method and procedure similar to that used in Example 53 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0821] <Example 134>

[0822] The target compound of Example 134 was prepared by performing a method and procedure similar to that used in Example 66 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0823] <Examples 135 to 137>

[0824] The target compounds of Examples 135 to 137 were prepared by performing methods and procedures similar to those used in Example 1. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0825] <Example 138>

[0826] The target compound of Example 138 was prepared by performing methods and procedures similar to those used in Examples 40 and 1 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0827] <Example 139>

[0828] The target compound of Example 139 was prepared by performing a method and procedure similar to those used in Example 1 above. The relevant compound names, NMR, MS, and HPLC data are summarized in Table 1.

[0829]

[0830] The compound structures and compound names of Examples 1 to 139 are as shown in Table 1 below.

[0831]

[0832]

[0833]

[0834]

[0835]

[0836]

[0837]

[0838]

[0839]

[0840]

[0841]

[0842]

[0843]

[0844]

[0845]

[0846]

[0847]

[0848]

[0849]

[0850]

[0851]

[0852]

[0853]

[0854]

[0855]

[0856]

[0857]

[0858]

[0859]

[0860]

[0861]

[0862]

[0863]

[0864]

[0865]

[0866]

[0867]

[0868]

[0869]

[0870]

[0871]

[0872]

[0873]

[0874]

[0875]

[0876]

[0877]

[0878]

[0879]

[0880]

[0881]

[0882]

[0883]

[0884]

[0885]

[0886]

[0887]

[0888]

[0889]

[0890]

[0891]

[0892]

[0893]

[0894]

[0895]

[0896]

[0897]

[0898]

[0899]

[0900]

[0901]

[0902]

[0903]

[0904]

[0905]

[0906]

[0907]

[0908]

[0909]

[0910]

[0911]

[0912]

[0913]

[0914]

[0915]

[0916]

[0917]

[0918]

[0919]

[0920]

[0921]

[0922]

[0923]

[0924]

[0925]

[0926]

[0927]

[0928]

[0929]

[0930]

[0931]

[0932]

[0933] <Experimental Example>

[0934] <Experimental Example 1> TYK2 JH2 Binding Assay Experimental Method

[0935] In order to evaluate the TYK2 (JH2) domain binding inhibitory ability of the compound according to the present invention, the following experiment was performed, and the results are shown in Table 2 below.

[0936] Specifically, TYK2 (JH2) domain protein was added to a black 384-well plate at a concentration of 3.5 ng / μl, and compounds diluted with DW were added at a concentration of 0.5 μM or 0.1 μM. Fluorescently labeled JH2 probe was added here at a concentration of 3 nM, and then incubated at room temperature for 1 hour. After that, the TYK2 (JH2) domain binding inhibitory ability of the compounds was measured by measuring the fluorescent polarization value using a microplate reader. The measured values ​​were classified into A if the degree of inhibition was 80% or more but less than 100%, B if 60% or more but less than 80%, C if 40% or more but less than 60%, and D if less than 40% using GraphPad Prism 7.0 (GraphPad Software Inc.), and are listed in Table 2.

[0937] Example TYK2 JH2 binding affinity%@0.5uMTYK2 JH2 binding affinity%@0.1uM Example TYK2 JH2 binding affinity%@0.5uMTYK2 JH2 binding affinity%@0.1uM1A71A2C72A3AD73A4AB74A5AB75A6AC76A7AB77A8D78A9AD79A10AB80A11AB81A12A82B13D83D14A84C15D85C16D86C17A87D18A88A19A89B20B90C21A91C22A92B23D93B24A94B25B95D26A96D27B97A28D98C29D99A30D100A31B101A32C102A33D103A34D104D35D105D36A10 6A37A107D38C108A39D109B40D110C41A111C42D112A43D113A44D114C4 5D115B46B116A47D117A48D118A49D119A50D120A51A121D52B122A53A1 23A54A124D55B125D56D126A57D127B58D128A59B129B60B130A61A131A 62A132B63A133A64B134A65A135B66A136A67D137B68A138C69A139A70C

[0938] According to Table 2 above, it was confirmed that the compounds of the present invention effectively bind to TYK2 and inhibit its function.

[0939]

[0940] The specification omits detailed descriptions of matters that would be readily apparent and inferred by those skilled in the art. Furthermore, various modifications, other than the specific examples described herein, are possible without altering the technical spirit or essential configuration of the invention. Therefore, the present invention may be practiced in ways other than those specifically described and exemplified herein, as will be readily apparent to those skilled in the art.

Claims

1. A compound represented by the following chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1] In the above chemical formula 1, A is unsubstituted or substituted phenyl, or unsubstituted or substituted C2-C 12 is heteroaryl (wherein substitution is substitution with at least one halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-C1-C3 alkyl, -O-C1-C3 haloalkyl, oxo(=O), -OH, -CN, -NO2 or -NH2); L1 is a single bond, C1-C6 alkyl, C1-C6 haloalkyl, -O-, -C=O-, -C≡C-, C1-C3 alkyl-SO2-, or -NH-; R1 is unsubstituted or substituted phenyl, unsubstituted or substituted C2-C8 heterocycloalkyl, unsubstituted or substituted C1-C 12 heteroaryl, unsubstituted or substituted -NH-(C1-C6alkyl), or -CN, wherein the substitution is at least one of halogen, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkyl-C1-C6haloalkyl, C2-C6alkenyl, phenyl, C2-C 12 Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2); L2 is C1-C3 alkyl-C=O-, -C=O-, or -C=O-NH-; R2 is unsubstituted or substituted C3-C8cycloalkyl, unsubstituted or substituted C1-C6alkyl-C3-C8cycloalkyl, unsubstituted or substituted C2-C8heterocycloalkyl, unsubstituted or substituted C1-C6alkyl-C2-C8heterocycloalkyl, unsubstituted or substituted C2-C 12 Heteroaryl, unsubstituted or substituted C1-C6 alkyl-C2-C 12 heteroaryl, unsubstituted or substituted phenyl, unsubstituted or substituted C1-C6 alkyl-phenyl, C1-C3 alkyl-C=OO-C1-C3 alkyl or C1-C3 alkyl-SO2-C1-C3 alkyl, wherein substitution is with at least one or more of halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-(C1-C3 alkyl), oxo(=O), -OH, -CN, -NO2 or -NH2; R3 is -NR a R b And here R a and R b are each independently -H or -C1-C3 alkyl.

2. In paragraph 1, Above is any one selected from the group consisting of phenyl, piperidinyl, pyridinyl, 2-pyridonyl, thiophenyl, furanyl, thiazolyl, oxazolyl, quinolyl, benzothiazolyl and indolyl, Here is the above A compound represented by formula 1, an optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein the compound is unsubstituted or substituted with at least one halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-C1-C3 alkyl, -O-C1-C3 haloalkyl, oxo(=O), -OH, -CN, -NO2 or -NH2.

3. In paragraph 1, R1 is cyclopropyl, cyclobutyl, cytlopentyl, cyclohexyl, cycloheptyl, phenyl, oxetanyl, azetidinyl, morpholinyl, thiomorpholinyl, piperazinyl, 1,3-dioxanyl, thietanyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydropyranyl, tetrahydrothiopyranyl, pyrrolyl, thiophenyl, furanyl, thiazolyl, oxazolyl, thiadiazolyl, oxadiazolyl, pyranyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, pyridinyl, pyridonyl, pyrimidinyl, benzofuranyl, benzothiophenyl, isobenzofuranyl, benzoimidazolyl, benzothiazolyl, benzoisothiazolyl, Any one selected from the group consisting of benzoisoxazolyl, benzoxazolyl, isoindolyl, indolyl, indazolyl, benzothiadiazolyl, quinolyl, isoquinolyl, -NH-(C1-C6 alkyl) and -CN, The above R1 is unsubstituted or at least one halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C2-C 12 Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, A compound represented by formula 1, an optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2.

4. In paragraph 1, The above R1 is , , , , , , , , , , , , , , , , , , , , and is one selected from the group consisting of, wherein R1 is unsubstituted or at least one halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C2-C 12 Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, A compound represented by formula 1, an optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2.

5. In paragraph 1, The above L1-R1 , , , , , , , , , , , , , , , , , , , , , , , , , , , and is one selected from the group consisting of, wherein R1 is unsubstituted or at least one halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C2-C 12 Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -O-tert-butyldimethylsilyl(TBS), -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, A compound represented by formula 1, an optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein the compound is substituted with -COO-(C1-C6 alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2.

6. In paragraph 1, L1-R1 is , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and A compound represented by the chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof, wherein the optical isomer is one selected from the group consisting of:

7. In paragraph 1, R2 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.1.0]pentyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.0]hexyl, bicyclo[3.1.0]hexyl, bicyclo[2.1.1]hexyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, spiro[2.4]heptyl, C1-C6alkyl-cyclopropyl, C1-C6alkyl-cyclobutyl, C1-C6alkyl-cyclopentyl, C1-C6alkyl-cyclohexyl, C1-C6alkyl-cycloheptyl, tetrahydrofuranyl, tetrahydropyranyl, aziridinyl, oxetanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, Morpholinyl, thiomorpholinyl, C1-C6 alkyl-tetrahydrofuranyl, C1-C6 alkyl-tetrahydropyranyl, C1-C6 alkyl-aziridinyl, C1-C6 alkyl-oxetanyl, C1-C6 alkyl-azetidinyl, C1-C6 alkyl-pyrrolidinyl, C1-C6 alkyl-piperidinyl, C1-C6 alkyl-piperazinyl, C1-C6 alkyl-morpholinyl, C1-C6 alkyl-thiomorpholinyl, pyrrolyl, thiophenyl, furanyl, pyrazolyl, imidazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, C1-C6 alkyl-pyrrolyl, C1-C6 alkyl-thiophenyl, C1-C6 alkyl-furanyl, C1-C6 alkyl-pyrazolyl, C1-C6 alkyl-imidazolyl, Any one selected from the group consisting of C1-C6 alkyl-triazolyl, C1-C6 alkyl-thiazolyl, C1-C6 alkyl-oxazolyl, C1-C6 alkyl-isoxazolyl, phenyl, naphthalene, C1-C6 alkyl-phenyl, C1-C6 alkyl-naphthalene, C1-C3 alkyl-C=OO-C1-C3 alkyl and C1-C3 alkyl-SO2-C1-C3 alkyl, A compound represented by formula 1, an optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein R2 is unsubstituted or substituted with at least one halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-(C1-C3 alkyl), oxo(=O), -OH, -CN, -NO2 or -NH2.

8. In paragraph 1, R2 is , , , , , , , , , , , , , , , , and A compound represented by chemical formula 1, an optical isomer thereof or a pharmaceutically acceptable salt thereof, wherein R2 is unsubstituted or substituted with at least one or more of halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-(C1-C3 alkyl), oxo(=O), -OH, -CN, -NO2 or -NH2.

9. In paragraph 1, A compound represented by the chemical formula 1, wherein the compound represented by the chemical formula 1 is a compound represented by the chemical formula 2-1 or 2-2, an optical isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 2-1] [Chemical Formula 2-2] In the above chemical formula 2-1 or 2-2, L1 is a single bond, C1-C6 alkyl, C1-C6 haloalkyl, -O-, -C=O-, -C≡C-, C1-C3 alkyl-SO2, or -NH-; R1 is unsubstituted or substituted phenyl, unsubstituted or substituted C2-C8 heterocycloalkyl, unsubstituted or substituted C1-C 12 Heteroaryl, unsubstituted or substituted -NH-(C1-C6 alkyl), -CN, wherein the substitution is at least one of halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkyl-C1-C6 haloalkyl, C2-C6 alkenyl, phenyl, C2-C 12 Heteroaryl, C3-C8cycloalkyl, C2-C8heterocycloalkyl, C1-C6alkyl-C2-C8heterocycloalkyl, -O-C1-C6alkyl, -O-C1-C6haloalkyl, -O-phenyl, -(C1-C6alkyl)-O-(C1-C6alkyl), oxo(=O), -C=O-C2-C8heterocycloalkyl, -C=O-NH2, -C=ON-(C1-C6alkyl)2, -C=O-NH-(C1-C6alkyl), -C=O-NH-(C1-C6alkyl-C1-C6haloalkyl), -C=O-NH-(C3-C8cycloalkyl), NH-C=O-(C3-C8cycloalkyl), -COOH, -COO-(C1-C6alkyl), -COO-(C1-C6 alkyl)-phenyl, -OC=O-NH-(C3-C8 cycloalkyl), C1-C3 alkyl-OC=O-NH-(C3-C8 cycloalkyl), -OH, C1-C6 alkyl-OH, -S(=O)2-C1-C6 alkyl, -S(=O)2-C1-C6 haloalkyl, -CN, -NO2, -N-(C1-C6 alkyl)2, C1-C6 alkyl-N-(C1-C6 alkyl)2, C1-C6 alkyl-NH2 or -NH2); R2 is unsubstituted or substituted C3-C8cycloalkyl, unsubstituted or substituted C1-C6alkyl-C3-C8cycloalkyl, unsubstituted or substituted C2-C8heterocycloalkyl, unsubstituted or substituted C1-C6alkyl-C2-C8heterocycloalkyl, unsubstituted or substituted C2-C 12 Heteroaryl, unsubstituted or substituted C1-C6 alkyl-C2-C 12 heteroaryl, unsubstituted or substituted phenyl, unsubstituted or substituted C1-C6 alkyl-phenyl, C1-C3 alkyl-C=OO-C1-C3 alkyl or C1-C3 alkyl-SO2-C1-C3 alkyl, wherein substitution is with at least one or more of halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-(C1-C3 alkyl), oxo(=O), -OH, -CN, -NO2 or -NH2; R3 is -NR a R b And here R a and R b are each independently -H or -C1-C3 alkyl; X is carbon or nitrogen; R4 is halogen, C1-C3 alkyl, C1-C3 haloalkyl, -O-C1-C3 alkyl, -O-C1-C3 haloalkyl, oxo(=O), -OH, -CN, -NO2 or -NH2; a is an integer from 0 to 3; L3 is a single bond or C1-C3 alkyl; R5 is unsubstituted or substituted C3-C5 cycloalkyl or unsubstituted or substituted C2-C5 heterocycloalkyl (wherein substitution is substitution with at least one halogen or C1-C3 alkyl).

10. In paragraph 1, The compound represented by the above chemical formula 1 is any one selected from the group consisting of the compounds described below, a compound represented by the chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof: N-Cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((2-oxo-2H-[1,2'-bipyridin]-3-yl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-(1-methyl-1H-pyrazol-4-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-(oxazol-2-yl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopentyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Benzyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-(furan-2-ylmethyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide; N-(Cyclopropylmethyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-(pyridin-4-yloxy)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-(6-methoxypyridin-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-(pyridin-2-ylethynyl)phenyl)amino)-9H-purine-9-carboxamide; 2-((3-(1H-imidazol-2-yl)phenyl)amino)-N-cyclopropyl-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-((4-methylpiperazin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-(morpholinomethyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclohexyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclohexyl-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopentyl-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide; N-(cyclopropylmethyl)-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide; N-(Cyclopropylmethyl)-2-((3-(1-(2-hydroxyethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)-5-nitrophenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((4'-(cyclopropylcarbamoyl)-[1,1'-biphenyl]-3-yl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((2'-vinyl-[1,1'-biphenyl]-3-yl)amino)-9H-purine-9-carboxamide; 2-((3-amino-5-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-cyclopropyl-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-(4,5-dichloro-1H-imidazol-2-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((4-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((1-((trifluoromethyl)sulfonyl)-1H-indol-5-yl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-(1-(2-methoxyethyl)-1H-imidazol-2-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-fluoro-5-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; Butyl 1-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylate; N-Cyclopropyl-2-((3-(3-hydroxypiperidine-1-carbonyl)-5-(trifluoromethyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-((4,4-difluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-((4-hydroxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; Benzyl 4-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidine-1-carboxylate; N-Cyclopropyl-6-(methylamino)-2-((3-(piperidin-4-yloxy)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(isopropylamino)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-(1-isopropyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-((N-(2-(dimethylamino)ethyl)sulfamoyl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-((1-cyclopropylpiperidin-4-yl)oxy)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-(4-methylpiperazine-1-carbonyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-((1-(2,2,2-trifluoroethyl)piperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide; 1-Cyclopropyl-2-(6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purin-9-yl)ethan-1-one; 1-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid; 6-(Methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-N-(tetrahydro-2H-pyran-4-yl)-9H-purine-9-carboxamide; N-Cyclopropyl-6-(methylamino)-2-((3-((4-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-(4-(3-((9-(cyclopropylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)phenoxy)piperidin-1-yl)ethyl cyclopropylcarbamate; 2-((3-(1-Methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(spiro[3.3]heptan-2-yl)-9H-purine-9-carboxamide; Ethyl (2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carbonyl)glycinate; 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(2-(methylsulfonyl)ethyl)-9H-purine-9-carboxamide; N-((1R,2R)-2-fluorocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,2S)-2-fluorocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-((4-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-((4-methylpiperazin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((4-hydroxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 1-(3-((6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidin-4-yl cyclobutylcarbamate; N-Cyclobutyl-2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-(morpholinomethyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-(((3S,5R)-3,5-dimethylpiperazin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-((3-hydroxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-(2-(4-hydroxypiperidin-1-yl)ethyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 1-(3-((9-(cyclobutylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid; 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((4-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; 1-(3-((9-(((1R,2R)-2-methoxycyclobutyl)carbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-4-carboxylic acid; N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((4-methylpiperazin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-(morpholinomethyl)phenyl)amino)-9H-purine-9-carboxamide; 2-((3-((4-hydroxypiperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-(piperidin-1-ylmethyl)phenyl)amino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-(piperidin-1-ylmethyl)phenyl)amino)-9H-purine-9-carboxamide; N-(2-Fluorocyclopropyl)-6-(methylamino)-2-((3-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-9H-purine-9-carboxamide; 2-((3-(((3S,5R)-3,5-dimethylpiperazin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-(piperazin-1-ylmethyl)phenyl)amino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-(piperazin-1-ylmethyl)phenyl)amino)-9H-purine-9-carboxamide; N-(Bicyclo[1.1.1]pentan-1-yl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(1-methylpiperidin-4-yl)-9H-purine-9-carboxamide; N-((1S,2R)-2-fluorocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((1H-1,2,4-triazol-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((1H-1,2,4-triazol-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,2R)-2-fluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,2S)-2-Fluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,3R)-3-fluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,3S)-3-fluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-(3-(cyclopropanecarboxamido)-1H-1,2,4-triazol-1-yl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((4-((2,2,2-trifluoroethyl)carbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-(1-cyanocyclopropyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-N-(1-(trifluoromethyl)cyclopropyl)-9H-purine-9-carboxamide; 2-((3-((4-(azetidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-((3-methoxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-2-((3-((3-methoxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclopropyl-2-((3-((3-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((3-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((5-(1-methyl-1H-1,2,4-triazol-3-yl)pyridin-3-yl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((3-((dimethylamino)methyl)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; (3,3-difluoroazetidin-1-yl)(2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purin-9-yl)methanone; N-Cyclobutyl-6-(methylamino)-2-((3-((3-morpholinopiperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-(3,3-difluorocyclobutyl)-2-((3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-(pyridin-2-yl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-(pyridin-4-yl)phenyl)amino)-9H-purine-9-carboxamide; 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-(3-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-(1-(2-aminoethyl)-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-(1H-tetrazol-5-yl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-((4-phenylpiperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-((4-(pyridin-4-yl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((3-methoxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((4-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2S)-2-fluorocyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((3-(azetidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((3-isopropoxypiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((3-(dimethylamino)piperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((4-(4,4-difluoropiperidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-cyanophenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-2-((3-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((3-(dimethylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-((3-(pyridin-4-yl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((4,4-dimethylpiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((4-chloropiperidin-1-yl)methyl)phenyl)amino)-N-cyclobutyl-6-(methylamino)-9H-purine-9-carboxamide; 2-((3-((4-(3,3-difluoroazetidine-1-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-9H-purine-9-carboxamide; 1-(3-((9-(cyclobutylcarbamoyl)-6-(methylamino)-9H-purin-2-yl)amino)benzyl)piperidine-3-carboxylic acid; N-Cyclobutyl-2-((3-((3,3-dimethylpiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-((3-(methylcarbamoyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-((1R,2R)-2-methoxycyclobutyl)-6-(methylamino)-2-((3-((3-(morpholine-4-carbonyl)piperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((4-fluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((3-fluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-((3-phenylpiperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclobutyl-6-(methylamino)-2-((3-((3-phenoxypiperidin-1-yl)methyl)phenyl)amino)-9H-purine-9-carboxamide; N-Cyclobutyl-2-((3-((3,3-difluoropiperidin-1-yl)methyl)phenyl)amino)-6-(methylamino)-9H-purine-9-carboxamide.

11. A pharmaceutical composition for preventing or treating a TYK2-mediated disease, comprising a compound according to any one of claims 1 to 10, an optical isomer thereof, or a pharmaceutically acceptable salt thereof.

12. In paragraph 11, A pharmaceutical composition for preventing or treating a TYK2-mediated disease, wherein the TYK2-mediated disease is any one selected from the group consisting of autoimmune diseases, inflammatory diseases, proliferative diseases, endocrine diseases, neurological diseases, and diseases associated with transplantation.

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