Pyridine carboxamide derivatives, preparation method thereof, and pharmaceutical composition for use in preventing or treating disease, containing same as active ingredient

Abstract

The present invention relates to a novel compound having PCSK9 inhibitory activity. The compound binds to PCSK9 so as to be capable of effectively inhibiting the activity of the protein, and thus can promote the absorption and metabolism of lipids and lipoproteins by hepatocytes. Therefore, the compound of the present invention or a pharmaceutically acceptable salt thereof can be effectively used for preventing, alleviating, and / or treating PCSK9-related diseases, for example, diseases related to lipid or lipoprotein metabolic disorders.

Description

Pyridine carboxamide derivative, method for preparing the same, and pharmaceutical composition for the prevention or treatment of disease containing the same as an active ingredient

[0001] Cross-citation with related application(s)

[0002] This application claims the benefit of priority based on Korean Patent Application No. 10-2025-0026957 dated February 28, 2025, and all contents disclosed in the document of said Korean patent disclosure are incorporated herein as part of the specification.

[0003] The present invention relates to a novel compound having inhibitory ability against PCSK9 (Proprotein convertase subtilisin / kexin type 9), a method for producing the same, and uses thereof.

[0004] Dyslipidemia, particularly an increase in low-density lipoprotein (LDL) cholesterol (LDL-C) levels in the blood, is known to be a major cause of hyperlipidemia, which in turn is a risk factor for atherosclerotic cardiovascular diseases including atherosclerosis, stroke, heart failure, myocardial infarction, and coronary heart disease (Prior Art 1 and 2).

[0005] Currently, treatments for reducing blood cholesterol levels are broadly divided into two types. The first is to directly reduce the amount of cholesterol produced in the liver, and the second is a method that ultimately reduces the concentration of blood LDL-C by increasing the expression of low-density lipoprotein receptors (LDLRs) to cause blood LDL cholesterol to enter cells, thereby allowing LDL-C to be metabolized in the liver and excreted.

[0006] Statins, which are representative drugs that inhibit cholesterol production in the liver, are prescribed as first-line treatments for patients with dyslipidemia, but they are known to frequently cause side effects such as muscle pain due to muscle toxicity and the development of diabetes due to increased blood sugar, and have limitations such as cholesterol levels not being controlled in some patients despite administration of the maximum dose (Prior Art 3).

[0007] Meanwhile, PCSK9 (Proprotein convertase subtilisin / kexin type 9) is a protein that regulates the number of LDLRs on the cell surface and binds to LDLRs within the cell to induce lysosomal degradation. The number of LDLRs on the surface of liver cells determines how quickly cholesterol is removed from the bloodstream; however, if LDLRs are degraded by PCSK9 before reaching the cell surface, the number of LDLRs on the cell surface decreases, ultimately resulting in more cholesterol remaining in the bloodstream. Therefore, PCSK9 inhibitors are used to treat dyslipidemia.

[0008] Recently, as it has been known that PCSK9 expression is increased by statin drugs, monoclonal antibodies and siRNA therapeutics have been developed as a method to enhance the LDL-C reduction effect by increasing the expression of LDLR in hepatocytes through the combination or monotherapy of PCSK9 inhibitors (Prior Art 4 and 5).

[0009] Currently, PCSK9-blocking antibodies such as alirocumab and evolocumab, and the siRNA therapeutic inclisiran are prescribed as injectables, but for dyslipidemia and related cardiovascular diseases requiring long-term management, there is still a need for the development of potent small molecule inhibitors with high ease of administration.

[0010] Accordingly, the inventors completed the present invention by investigating a novel compound capable of acting as a PCSK9 inhibitor and demonstrating that it can prevent diseases associated with lipid or lipoprotein metabolic disorders, such as hypercholesterolemia and atherosclerotic cardiovascular disease associated with PCSK9 activity.

[0011] [Prior Art Literature]

[0012] Prior Art Document 1. Assmann, G.; Schulte, H. The Prospective Cardiovascular Munster (PROCAM) Study: Prevalence of Hyperlipidemia in Persons with Hypertension and / or Diabetes Mellitus and the Relationship to Coronary Heart Disease. Am. Heart J. 1988, 116 (6), 1713-1724.

[0013] Prior Art Document 2. Drechsler, M.; Megens, R.T.A.; van Zandvoort, M.; Weber, C.; Soehnlein, O. Hyperlipidemia-Triggered Neutrophilia Promotes Early Atherosclerosis. Circulation 2010, 122 (18), 1837- 1845.

[0014] Prior Art Document 3. Massimiliano R.; Nicola F.; Maciej B.; Cesare R S.; Alberto C. Side effects of statins: from pathophysiology and epidemiology to diagnostic and therapeutic implications, Cardiovascular Research, 2022, 118 (17), 3288-3304.

[0015] Prior Art Document 4. Kwon, HJ; · Lagace, T.A.; · McNutt, MC Molecular basis for LDL receptor recognition by PCSK9 Proc. Natl. Acad. Sci. US A. 2008, 105, 1820-1825.

[0016] Prior Art Document 5. Bao, X.; Liang, Y.; Chang, H. Targeting proprotein convertase subtilisin / kexin type 9 (PCSK9): from bench to bedside. Sig Transduct Target Ther. 2024, 9(13).

[0017] The present invention aims to provide a novel compound capable of exhibiting efficacy in improving, preventing, and / or treating PCSK9-related diseases, such as lipid or lipoprotein metabolic disorders, more specifically, dyslipidemia, by regulating the activity of PCSK9.

[0018] Accordingly, one example of the present invention provides a compound represented by the following chemical formula 1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof (hereinafter also simply referred to as “compound, etc.”).

[0019] [Chemical Formula 1]

[0020]

[0021]

[0022] In addition, another example of the present invention provides a pharmaceutical composition for the prevention or treatment of PCSK9-related diseases, comprising the above-mentioned compound, etc., as an active ingredient.

[0023] In addition, another example of the present invention provides a food composition for the prevention or improvement of PCSK9-related diseases, comprising the above-mentioned compound, etc., as an active ingredient.

[0024] In addition, another example of the present invention provides a composition for inhibiting the activity of PCSK9, comprising the above-mentioned compound, etc., as an active ingredient.

[0025] In addition, another example of the present invention provides a composition for promoting lipid or lipoprotein metabolism, comprising the above-mentioned compound, etc., as an active ingredient.

[0026] In addition, another example of the present invention provides a method for preparing a compound represented by the above chemical formula 1.

[0027] The present disclosure is summarized as follows:

[0028] 1. A compound represented by Formula 1 of the present disclosure, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof:

[0029] [Chemical Formula 1]

[0030]

[0031] In the above chemical formula 1,

[0032] A is a mono- or bicyclic ternary to 15-membered heterocycle containing at least two Ns, and m is an integer from 0 to 5, wherein if m is 2 or more, a plurality of R1s are independent of each other, and

[0033] B is C 1-7 Hydrocarbon group, C 3-10 It is a divalent linker that is a hydrocarbon ring or a 4- to 15-membered bicyclic ring, where n is an integer from 0 to 5, and when n is 2 or greater, a plurality of R2 are independent of each other, and

[0034] X is O, S, or NH, and

[0035] C is C 5-12 Arrylene, 3 to 15-membered heteroarylene, C 3-12 Cycloalkylene, ternary to fifteenth heterocycloalkylene, C 3-12 Cycloalkenylene, 3- to 15-membered heterocycloalkenylene, C 3-12It is a divalent linker that is a cycloalkynylene, a ternary to fifteen-membered heterocycloalkynylene, or a fourary to fifteen-membered polycyclic heterocycle, where o is an integer from 0 to 5, and when o is 2 or more, a plurality of R3s are independent of each other, and

[0036] D is C 5-12 Aril, C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, C 3-12 It is a cycloalkynyl, a ternaryl to 15-membered heteroaryl, a ternaryl to 15-membered heterocycloalkyl, a ternaryl to 15-membered heterocycloalkenyl, a ternaryl to 15-membered heterocycloalkynyl, or a quaternaryl to 15-membered polycyclic heterocycle, where p is an integer from 0 to 5, and when p is 2 or more, a plurality of R4s are independent of each other, and

[0037] The above R1 to R4 are independently hydrogen, iodine, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkylthio, C 3-6 Cycloalkyl, ternary to hexavalent heterocycloalkyl, C 5-12 Aryl, 3- to 6-membered heteroaryl, C 1-6 Halogenated alkoxy, C 1-6 Alkyl thio-halogenated, acetyl, acetylamino, hydroxy, cyano, nitro, amino, C 1-3 Aminoalkyl, C 1-3 Alkylamino, thio, deuterium, C 1-6 As a deuterium alkyl, sulfonyl, sulfinyl, halogen, or -CO-R', wherein R' is C 1-3 Alkyl, C 3-6 Cycloalkyl, ternary to hexavalent heterocycloalkyl, methyl-substituted piperazine, C 1-3 Alkoxy, hydroxy, C 1-3 alkylamino, or C1-3 It is an aminoalkyl, and

[0038] The above R1 to R4 are each independently halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, iodine, acetyl, C 3-6 It is substituted or unsubstituted with one or more selected from the group consisting of cycloalkyl and ternary to hexavalent heterocycloalkyl.

[0039]

[0040] 2. In the above Paragraph 1,

[0041] The above compound is a compound represented by the following chemical formula 1-1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof:

[0042] [Chemical Formula 1-1]

[0043] .

[0044]

[0045] 3. In any one of the preceding paragraphs,

[0046] The above compound is a compound represented by any one of the following chemical formulas 1-2 to 1-6, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof:

[0047] [Chemical Formula 1-2]

[0048]

[0049] [Chemical Formula 1-3]

[0050]

[0051] [Chemical Formula 1-4]

[0052]

[0053] [Chemical Formula 1-5]

[0054]

[0055] [Chemical Formula 1-6]

[0056]

[0057] In the above chemical formulas 1-2 to 1-6, Q1 to Q3 are each independently C, O, S, or N, Z1 to Z3 are each independently C or N, Y1 to Y3 are each independently C, O, S, or N, and W1 to W3 are each independently C or N. represents a single or double bond.

[0058]

[0059] 4. In any one of the preceding paragraphs,

[0060] The above compound is a compound represented by any one of the following chemical formulas 1-7 to 1-11, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof:

[0061] [Chemical Formula 1-7]

[0062]

[0063] [Chemical Formula 1-8]

[0064]

[0065] [Chemical Formula 1-9]

[0066]

[0067] [Chemical Formula 1-10]

[0068]

[0069] [Chemical Formula 1-11]

[0070]

[0071] In the above chemical formulas 1-7 to 1-11,

[0072] Q1 to Q3 are each independently C, O, S, or N, Z1 to Z3 are each independently C or N, Y1 to Y3 are each independently C, O, S, or N, W1 to W3 are each independently C or N, V1 to V4 are each independently C or N, represents a single or double bond.

[0073]

[0074] 5. In any one of the preceding paragraphs,

[0075] A has one of the following structures:

[0076]

[0077] Here, Q1 to Q3 are each independently C, O, S, or N, Z1 to Z3 are each independently C or N, and Y1 to Y3 are each independently C, O, S, or N,

[0078] A compound, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof, wherein W1 to W3 are each independently C or N, and when m is an integer of 1 or more, a singular or mutually independent plurality of R1s are selected from the functional groups below:

[0079]

[0080]

[0081] 6. In any one of the preceding paragraphs,

[0082] B has one of the following structures:

[0083]

[0084] When n is an integer greater than or equal to 1, a compound, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof, wherein a singular or mutually independent plurality of R2 are selected from the functional groups below:

[0085]

[0086]

[0087] 7. In any one of the preceding paragraphs,

[0088] C has one of the following structures:

[0089]

[0090] When o is an integer greater than or equal to 1, a compound, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof, wherein a singular or mutually independent plurality of R3s are selected from the functional groups below:

[0091]

[0092]

[0093] 8. In any one of the preceding paragraphs,

[0094] D has one of the following structures:

[0095]

[0096]

[0097] When p is an integer greater than or equal to 1, the singular or mutually compound plural R4 is selected from the functional groups below, a compound, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof:

[0098]

[0099]

[0100] 9. In any one of the preceding paragraphs,

[0101] The above compound is a compound selected from the group consisting of compounds 1 to 231 of the present disclosure, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof.

[0102]

[0103] 10. A pharmaceutical composition for the prevention or treatment of PCSK9-related diseases, comprising as an active ingredient the compound of any one of the preceding paragraphs, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof.

[0104]

[0105] 11. A pharmaceutical composition according to claim 10 above, wherein the PCSK9-related disease is a lipid or lipoprotein metabolic disorder.

[0106]

[0107] 12. In the above Paragraph 11,

[0108] The above lipid or lipoprotein metabolic disorders include atherosclerosis, dyslipidemia, hypertriglyceridemia, hypertension, heart failure, cardiac arrhythmias, low HDL levels, high LDL levels, sudden death, stable angina, coronary heart disease, acute myocardial infarction, cardiomyopathy, endocarditis, type 2 diabetes, insulin resistance, impaired glucose tolerance, hypercholesterolemia, stroke, hyperlipidemia, hyperlipoproteinemia, chronic kidney disease, intermittent claudication, Hyperphosphatemia, carotid atherosclerosis, peripheral arterial disease, diabetic nephropathy, hypercholesterolemia in HIV infection, acute coronary syndrome (ACS), non-alcoholic fatty liver disease, arterial occlusive disease, cerebral arteriosclerosis, cerebrovascular disorder,A pharmaceutical composition comprising one or more selected from the group consisting of myocardial ischemia, nonalcoholic steatohepatitis (NASH), and diabetic autonomic neuropathy.

[0109]

[0110] 13. In any one of the preceding paragraphs,

[0111] The above pharmaceutical composition is a pharmaceutical composition that inhibits the activity of PCSK9.

[0112]

[0113] 14. A food composition for the prevention or improvement of PCSK9-related diseases, comprising as an active ingredient the compound of any one of the preceding paragraphs, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof.

[0114]

[0115] 15. A composition for inhibiting the activity of PCSK9, comprising as an active ingredient the compound of any one of the preceding claims, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, enantiomer, or diastereomer thereof.

[0116]

[0117] 16. A composition for promoting lipid or lipoprotein metabolism, comprising as an active ingredient a compound of any one of the preceding paragraphs, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, enantiomer, or diastereomer thereof.

[0118]

[0119] However, the technical problems that the present invention aims to solve are not limited to those mentioned above, and other unmentioned problems will be clearly understood by those skilled in the art to which the present invention belongs from the description below.

[0120] The present invention aims to provide novel compounds, etc., capable of exhibiting efficacy in improving, preventing, and / or treating PCSK9-related diseases, such as lipid or lipoprotein metabolic disorders, more specifically, dyslipidemia, by regulating the activity of PCSK9.

[0121] The present invention will be described in detail below.

[0122] In this specification, H bonded to other atoms may be omitted for convenience. A person skilled in the art will clearly understand the presence and number of omitted hydrogens by considering the standard valence of the atoms, etc.

[0123] Furthermore, unless otherwise defined, all technical terms used herein have the same meaning as generally understood by those skilled in the art to which the present invention pertains. Additionally, although the present invention has been described in relation to specific methods and samples, analogs or equivalents thereof must be within the scope of the present invention. Furthermore, numerical values ​​described herein are deemed to include the meaning of “about” unless explicitly stated otherwise. All publications and other references mentioned herein are incorporated herein in their entirety by reference.

[0124]

[0125] Definition of Terms

[0126] Unless otherwise stated below, the “compound represented by Chemical Formula 1” of the present invention includes all of its pharmaceutically acceptable salts, hydrates, solvates, tautomers, isotopic variants, enantiomers, and / or diastereomers, all of which should be interpreted as being included within the scope of the present invention. For convenience of explanation, the present specification may simply abbreviate the terms as “compound of Chemical Formula 1,” “compound of the present invention,” etc.

[0127] That is, unless otherwise specified, the formulas or names given in the specification and claims include not only tautomers but also all stereochemical, optical, and geometric isomers (e.g., enantiomers, diastereomers, E / Z isomers, etc.). Furthermore, the scope of the invention includes not only their racemates but also mixtures of distinct enantiomers in different proportions, mixtures of diastereomers, or any of the above forms of mixtures in which isomers and enantiomers are present, and further encompasses their pharmaceutically acceptable salts, solvates and hydrates of free compounds, or solvates of salts of said compounds.

[0128] Furthermore, the substituents described in this specification are not limited to the structures indicated or described in this specification and should be interpreted to include all possible isomers of said substituents.

[0129] As used in this specification, the term “pharmaceuticalally acceptable salt” refers to a salt form of a compound that does not cause severe irritation to the organism to which the compound is administered and does not impair the biological activity and physical properties of the compound. In the case of the present invention, it may collectively refer to any salt that possesses equivalent biological efficacy and properties of the compound of Formula 1 and is desirable in terms of pharmaceutical, biological, or other properties.

[0130] The above "pharmaceutically acceptable salt" includes acid addition salts formed by acids that form non-toxic acid addition salts containing pharmaceutically acceptable anions, such as inorganic acids like hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromide, hydroiodide, etc., organic carboxylic acids like tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, salicylic acid, etc., and sulfonic acids like methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, etc. For example, pharmaceutically acceptable carboxylic acid salts include metal salts or alkaline earth metal salts formed by lithium, sodium, potassium, calcium, magnesium, etc., amino acid salts such as lysine, arginine, guanidine, etc., and organic salts such as dicyclohexylamine, N-methyl-D-glucarmine, tris(hydroxymethyl)methylamine, diethanolamine, choline, and triethylamine, etc. The compound of Formula 1 according to the present invention may also be converted into its salt by conventional methods.

[0131] As used herein, the term “hydrate” means a compound of the present invention or a salt thereof containing stoichiometric or non-stoichiometric amounts of water bound by non-covalent intermolecular forces.

[0132] As used herein, the term “solvate” means a compound of the present invention or a salt thereof comprising stoichiometric or non-stoichiometric amounts of solvent bound by non-covalent intermolecular forces. Preferred solvents thereof include volatile, non-toxic, and / or solvents suitable for administration to humans.

[0133] As used herein, the term “tautomer” refers to a type of structural isomer having the same chemical or molecular formula but different arrangements of constituent atoms, meaning that the structure changes by continuously switching back and forth between the two isomers, such as in a keto-eno structure.

[0134] As used herein, the term “isotope variant” refers to a compound containing isotopes in a non-natural proportion in one or more atoms constituting the compound. Examples of isotopes that may be incorporated into the compound of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, fluorine, iodine, and chlorine, such as 2H (deuterium), 3H, 11C, 13C, 14C, 18F, 123I, or 125I, etc., which may be naturally occurring or non-naturally occurring isotopes.

[0135] As used herein, the terms “enantiomer” or “diastereomer” refer to isomers that have the same chemical formula or molecular formula but differ in the spatial arrangement of atoms within the molecule. The term “enantiomer” refers to an isomer that does not overlap with its mirror image, much like the relationship between a right hand and a left hand. Additionally, “diastereomer” refers to a stereoisomer that is not in a mirror image relationship, such as the trans form and the cis form; in this invention, this is limited to pharmaceutically acceptable diastereomers. All of these isomers and mixtures thereof are also included within the scope of this invention.

[0136] As used herein, the term “alkyl” refers to an aliphatic hydrocarbon group. In the present invention, “alkyl” is used as a concept encompassing both “saturated alkyl,” meaning it does not contain any alkene or alkyne groups, and “unsaturated alkyl,” meaning it contains at least one alkene or alkyne group; specifically, it may be a “saturated alkyl,” meaning it does not contain any alkene or alkyne groups. The alkyl may include branched, straight-chain, or cyclic forms, and may also include structural isomers. For example, in the case of C3 alkyl, it may mean propyl or isopropyl. In the present invention, the alkyl is C 1-20 , C 1-15 , C 1-12 , C 1-10 , C 1-8 , C 1-6 , C 1-5 , C 1-4 , C 1-3 , or C 1-2 It may be an alkyl, but is not limited thereto. For example, in the present invention, the alkyl may be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, or tert-butyl, etc.

[0137] As used herein, the term “heteroalkyl” refers to an alkyl group comprising at least one heteroatom (e.g., oxygen, nitrogen, sulfur, phosphorus, etc.) in addition to carbon and hydrogen. Like alkyls, heteroalkyls may also include branched, straight-chain, or cyclic forms and include structural isomers.

[0138] As used herein, the term "alkenyl" refers to a group in which at least two carbon atoms are connected by at least one carbon-carbon double bond, and may be a straight chain or a branched chain. The term "alkynyl" refers to a group in which at least two carbon atoms are connected by at least one carbon-carbon triple bond, and may be a straight chain or a branched chain. In the present invention, the alkenyl or alkynyl is C 2-20 , C 2-15 , C 2-12 , C 2-10 , C 2-8 , C 2-6 , C 2-5 , C 2-4 , or C 2-3 It may be an alkenyl or alkynyl, but is not limited thereto.

[0139] As used in this specification, the term "haloalkyl" refers to an alkyl group substituted with one or more halogen atoms, wherein "alkyl" is defined as above. "Halo" indicates -F, -Cl, -Br, or -I, and the term is used interchangeably with the term "halogen." The haloalkyl includes monohaloalkyl (where one hydrogen is substituted with a halogen), dihaloalkyl (where two hydrogens are substituted with a halogen), trihaloalkyl (where three hydrogens are substituted with a halogen), etc., and the substitution position may be present on any carbon atom of a straight-chain or branched alkyl. Specific examples of the haloalkyl include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, chloroethyl, bromopropyl, dichloropropyl, and trifluoroethyl.

[0140] As used in this specification, the term “oxo” refers to a functional group in which an oxygen atom exists in the form of a double bond with another atom, i.e., =O.

[0141] As used in this specification, the term “hydroxy” refers to -OH, and “hydroxyalkyl” means an alkyl bonded to -OH, wherein the alkyl is defined as above.

[0142] As used in this specification, the term “cyano” refers to -CN, and “cyanoalkyl” refers to an alkyl group substituted with -CN, wherein the alkyl is defined as above.

[0143] As used in this specification, the term “thio” refers to -SH composed of a sulfur atom and a hydrogen atom, and may also be referred to as “thiol.” “Alkylthio” refers to a substituent having a structure in which an alkyl group is connected through a sulfur atom, wherein alkyl is defined as above. Specific examples include methylthio (-SCH3) and ethylthio (-SCH2CH3), but are not limited thereto. The alkylthio may be an alkylthio halogenated by substituting one or more, two or more, three or more, or more halogen atoms, but is not limited thereto. In this specification, “alkylthio” may be used interchangeably with “thioalkyl,” “alkylsulfanyl,” etc.

[0144] As used herein, the term “alkoxy” refers to a substituent having a structure in which an alkyl group is connected through an oxygen atom, and may be a straight chain, a branched chain, or a cyclic chain. In the present invention, the alkoxy is C 1-20 , C 1-15 , C 1-12 , C 1-10 , C 1-8 , C 1-6 , C 1-5 , C 1-4 , C 1-3 , or C 1-2 It may be an alkoxy, but is not limited thereto. In addition, the alkoxy may be a halogenated alkoxy substituted with one or more, two or more, three or more, or more halogen atoms, but is not limited thereto.

[0145] As used in this specification, the term “acetyl” refers to a functional group composed of a structure in which a methyl group is bonded to a carbonyl group (C=O), namely -C(=O)CH3. “Acetylamino” refers to a substituent in which an acetyl group is bonded to the nitrogen atom of an amino group, wherein the acetyl group is defined as above.

[0146] As used in this specification, the term “amino” refers to -NH2; and “nitro” refers to -NO2. “Aminoalkyl” means an alkyl group substituted with one or more amino groups, wherein the alkyl is defined as above.

[0147] The term “deuterium (D)” as used in this specification refers to an isotope of hydrogen and is characterized by having one proton and one neutron in the atomic nucleus. “Deuterium-substituted alkyl” means an alkyl group substituted with one or more, two or more, three or more, or more deuteriums, wherein alkyl is defined as above.

[0148] The term “sulfonyl” as used in this specification refers to a divalent functional group having a structure in which a sulfur atom forms a double bond with each of two oxygen atoms, and the remaining two bonding sites are connected to other atoms or functional groups, and can be represented as -SO2-.

[0149] The term “sulfinyl” as used in this specification refers to a divalent functional group having a structure in which a sulfur atom forms a double bond with one oxygen atom and the other two bonding sites are connected to other atoms or functional groups, and may be represented as -SO-.

[0150] As used in this specification, the terms “ring,” “cycle,” and “cyclic” refer to a cyclic hydrocarbon group and encompass concepts including monocyclic, bicyclic, tricyclic, or polycyclic structures. Additionally, in this specification, a ring may be a saturated or partially unsaturated ring and encompasses concepts including both aromatic and non-aromatic rings. Furthermore, the ring of the present invention may be monovalent or polyvalent. Meanwhile, the polycyclic structure may be a spiro, fusion, linked, and / or bridged ring.

[0151] As used herein, the terms “heterocycle” or “heterocycle” refer to a ring comprising one or more heteroatoms (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom), wherein “ring” is defined as above. The heteroatoms may be selected from, for example, N, O, P, and S, but are not limited thereto. Two or more heteroatoms included in the heterocycle may be of the same or different types. The term “membered,” used in conjunction with “ring,” refers to the number of skeletal atoms constituting the ring. The scope of the heterocycle includes heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, heteroaryl, and other monocyclic or polycyclic heterocycles.

[0152] As used herein, the term “cycloalkyl” refers to a monovalent cyclic hydrocarbon group that can be substituted or unsubstituted. The cycloalkyl may include a saturated or partially unsaturated structure, but preferably refers to a saturated hydrocarbon cyclic structure. In the present invention, the cycloalkyl is C 3-20 , C 3-15 , C3-12 , C 3-10 , C 3-8 , C 3-6 , C 3-5 , C 3-4 ...or may be a C3 cycloalkyl, but is not limited thereto. For example, the cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc. The cycloalkyl may be monocyclic or polycyclic, and the polycyclic includes a spiro-type, fused-type, linked-type, or cross-linked-type ring structure.

[0153] As used herein, the term “cycloalkylene” refers to a substituted or unsubstituted divalent saturated hydrocarbon ring group and has a structure conforming to the definition of cycloalkyl described above. The cycloalkylene may be monocyclic or polycyclic, and the polycyclic may include a spiro-type, fused-type, linked-type, or cross-linked-type ring structure. The cycloalkylene is C 3-20 , C 3-15 , C 3-12 , C 3-10 , C 3-8 , C 3-6 , C 3-5 , C 3-4 , C 3-20 , C 3-15 , C 3-12 , C 3-10 , C 3-8 , C 3-6 , C 3-5 , or C 3-4 It may be a cycloalkylene, but is not limited thereto. More specific examples include cyclopropylene, cyclopentylene, cyclohexylene, etc., but are not limited thereto.

[0154] As used herein, the term "heterocycloalkyl" means a cycloalkyl comprising one or more heteroatoms (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom), wherein "cycloalkyl" is defined as above. The heteroatoms may be selected from the group consisting of N, O, P, and S, but are not limited thereto. The heterocycloalkyl may be monocyclic or polycyclic, and the polycyclic may include a spiro-type, fused-type, linked-type, or cross-linked ring structure. The above heterocycloalkyl may be 3 to 15, 3 to 14, 3 to 13, 3 to 12, 3 to 11, 3 to 10, 3 to 9, 3 to 8, 3 to 7, 3 to 6, 3 to 5, or 3 to 4 heterocycloalkyl, but is not limited thereto. Examples of non-aromatic rings include azetidinyl, oxetanil, tetrahydrothienyl, tetrahydrofuranil, pyrrolinyl, pyrrolidinyl, imidazolininyl, imidazolidinyl, oxazolininyl, oxazolidinyl, oxapiperazinyl, oxapiperidinyl, pyrazolininyl, pyrazolidinyl, thiazolininyl, thiazolidinyl, tetrahydrofuranil, tetrahydrofuryl, tetrahydroisothiazolyl, tetrahydrooxazolyl, tetrahydroisooxazolyl, piperidinyl, piperazinyl, tetrahydropyranil, dihydropyranil, tetrahydropyridinyl, dihydropyridinyl, dihydrothiopyranil, tetrahydropyrimidinyl, tetrahydropyridazinyl, dihydropyranil, tetrahydropyranil, Includes, but is not limited to, tetrahydrothiopyranyl, morpholinyl, indolinyl, indolinylmethyl, thiomophorinyl, azephanyl, diazephanyl, N-oxide, azadamantanil, diazamantanil, etc. Attachment of heterocycloalkyl substituents may occur through carbon atoms or heteroatoms, but is not limited thereto.

[0155] As used herein, the term “heterocycloalkylene” means a cycloalkylene comprising one or more heteroatoms (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom), wherein “cycloalkylene” is defined as above. The heteroatoms may be selected from the group consisting of N, O, P, and S, but are not limited thereto. The heterocycloalkylene may be monocyclic or polycyclic, and the polycyclic may include a spiro-type, fused-type, linked-type, or cross-linked ring structure.

[0156] As used herein, the term “cycloalkenyl” refers to a monovalent unsaturated hydrocarbon ring group comprising one or more carbon-carbon double bonds within a ring structure. The cycloalkenyl may be monocyclic or polycyclic, and the polycyclic may include spiro-type, fused-type, linked-type, or cross-linked ring structures. The cycloalkenyl is C 3-20 , C 3-15 , C 3-12 , C 3-10 , C 3-8 , C 3-6 , C 3-5 , C 3-4 , C 5-7 , C 5-6 , or may be a C3 cycloalkenyl, but is not limited thereto. Specific examples of cycloalkenyls include cyclopentenyl, cyclohexenyl, etc., but are not limited thereto.

[0157] As used herein, the term “cycloalkynyl” refers to a monovalent unsaturated hydrocarbon ring group comprising one or more carbon-carbon triple bonds within a ring structure. The cycloalkynyl may be monocyclic or polycyclic, and the polycyclic may include a spiro-type, fused-type, linked-type, or cross-linked ring structure. The cycloalkynyl is C 3-20 , C 3-15 , C 3-12 , C 3-10 , C 3-8 , C3-6 , C 3-5 , C 3-4 , C 5-7 , C 5-6 , or may be a C3 cycloalkinyl, but is not limited thereto.

[0158] As used in this specification, the term “heterocycloalkenyl” means a cycloalkenyl comprising one or more heteroatoms (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom), wherein “cycloalkenyl” is defined as above. The heteroatoms may be selected from the group consisting of N, O, P, and S, but are not limited thereto.

[0159] As used in this specification, the term “heterocycloalkynyl” means a cycloalkynyl comprising one or more heteroatoms (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom), wherein “cycloalkynyl” is defined as above. The heteroatoms may be selected from the group consisting of N, O, P, and S, but are not limited thereto.

[0160] As used herein, the term “aryl” refers to an aromatic hydrocarbon group having a shared pi electron system and at least one ring. In the present invention, aryl is C 5-12 , C 5-11 , C 5-10 , C 5-9 , C 5-8 , C 5-7 , C 5-6 , C 6-12 , C 6-11 , C 6-10 , C 6-9 , C 6-8 , or C 6-7It may be an aryl, but is not limited thereto. The aryl may be monocyclic or polycyclic, and the polycyclic may include a spiro-type, fused-type, linked-type, or cross-linked ring structure. Additionally, the aryl may include a structure in which an aromatic ring is fused or linked to an aromatic ring, or is partially unsaturated. Exemplary aryl groups include benzene (phenyl), substituted phenyl, biphenyl, naphthyl, toluyl, naphthalenyl, anthracenyl, indenyl, indanyl, etc., but are not limited thereto.

[0161] As used herein, the term “arylene” refers to a divalent functional group formed by the removal of two hydrogen atoms from an aromatic ring, and may be derived from an aryl. The arylene has a structure conforming to the definition of an aryl described above. In this specification, the arylene may be monocyclic or polycyclic, and the polycyclic includes spiro-type, fused-type, linked-type, or cross-linked ring structures. In the present invention, the arylene is C 5-12 , C 5-11 , C 5-10 , C 5-9 , C 5-8 , C 5-7 , C 5-6 , C 6-12 , C 6-11 , C 6-10 , C 6-9 , C 6-8 , or C 6-7 It may be an arylene, but is not limited thereto. More specific examples of arylenes include phenylene, naphthalene, anthracenediyl, etc., but are not limited thereto.

[0162] As used herein, the term “heteroaryl” means an aromatic ring group comprising one or more heteroatoms (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom). The heteroatom may be selected from the group consisting of N, O, P, and S, but is not limited thereto. The heteroaryl may be monocyclic or polycyclic, and the polycyclic may include a spiro-type, fused-type, linked-type, or cross-linked ring structure. Additionally, the heteroaryl may include a structure in which a heteroaromatic ring is fused or linked to an aromatic ring, or is partially unsaturated. The above heteroaryls may be 3 to 15, 3 to 14, 3 to 13, 3 to 12, 3 to 11, 3 to 10, 3 to 9, 3 to 8, 3 to 7, 3 to 6, 3 to 5, 3 to 4, 5 to 15, 5 to 14, 5 to 15, 5 to 12, 5 to 11, 5 to 10, 5 to 9, 5 to 8, 5 to 7, or 5 to 6 heteroaryls, but are not limited thereto. Examples of heteroaryls include, but are not limited to, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isooxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, triazolyl, tetrazolyl, triazinyl, indolyl, etc. Examples of bicyclic heteroaryls include, but are not limited to, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzisooxazolyl, benzthiazolyl, benzthiadiazolyl, quinolinyl, isoquinolinyl, furinyl, propyridinyl, octahydropyranopyridine, benzodioxolyl, and similar groups thereof.

[0163] As used herein, the term “heteroarylene” refers to a divalent aromatic ring group comprising one or more heteroatoms (e.g., 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom) and may be a divalent derivative of the previously defined heteroaryl. The heteroatoms may be selected from the group consisting of N, O, P, and S, but are not limited thereto. The heteroarylene may be monocyclic or polycyclic, and the polycyclic may include a spiro-type, fused-type, linked-type, or cross-linked ring structure. Specific examples of the above heteroarylenes include, but are not limited to, pyridylene, thiophenedil, pyrroldil, furandil, pyridindiyl, thiazinediyl, pyrandil, pyridazinediyl, pyrazinediyl, pyrimidindiyl, dithiazinediyl, and dioxazinediyl.

[0164] As described above, the polycyclic structure of this specification may include spiro, fusion, linked, and / or bridged rings. In this specification, “condensed ring” or “fused ring” refers to a polycyclic system comprising two or more rings. More specifically, it may refer to a polycyclic structure in which two or more rings are connected by sharing one or more bonds. The above polycyclic group (e.g., condensation group) may be a 4 to 15-member, 4 to 14-member, 4 to 14-member, 4 to 12-member, 4 to 11-member, 4 to 10-member, 4 to 9-member, 4 to 8-member, 4 to 7-member, 4 to 6-member, 4 to 5-member, 5 to 15-member, 5 to 14-member, 5 to 15-member, 5 to 12-member, 5 to 11-member, 5 to 10-member, 5 to 9-member, 5 to 8-member, 5 to 7-member, or 5 to 6-member polycyclic group, but is not limited thereto. In addition, the polycyclic group may be a hydrocarbon group composed of carbon and hydrogen, or a heteropolycyclic group comprising one or more heteroatoms selected from N, O, P, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1 heteroatom. In the present invention, the polycyclic group may be formed by condensation (or fusion), linkage, or crosslinking of two or more of the rings described herein. For example, in the present invention, the polycyclic group may comprise two or more, three or more, or four or more ring structures selected from the group consisting of the aforementioned cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, cycloalkynyl, heterocycloalkynyl, aryl, and heteroaryl. Furthermore, the polycyclic group may be a fully saturated, partially unsaturated ring or an aromatic ring.

[0165] In the present invention, the term "substitution" refers to the introduction of a hydrogen atom in place of another atomic group when a derivative is formed by substituting one or more hydrogen atoms in an organic compound with another atomic group, and the substituent refers to the introduced atomic group. That is, in the present invention, the substitution of any functional group means that one or more hydrogen atoms of the said functional group are replaced by another atomic group. In the present invention, each functional group may independently have one or more hydrogen atoms substituted by another atomic group. "Independently substituted" means that when the number of substitutable hydrogens is two or more, each hydrogen may be substituted with the same or different substituents. In the present invention, "substitution" includes single substitution, double substitution, triple substitution, quadruple substitution, or more substitutions.

[0166] Terms other than those described above may be interpreted in the sense commonly understood by those skilled in the art to which the present invention pertains.

[0167]

[0168] Compound of Chemical Formula 1

[0169] In the following, “loop” or “cycle” refers to a monocyclic loop unless otherwise noted.

[0170] The present invention provides a compound represented by the following chemical formula 1, and a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof:

[0171] [Chemical Formula 1]

[0172]

[0173] In the above chemical formula 1,

[0174] A may be a mono- or bicyclic ternary to 15-membered heterocycle containing at least two Ns, and m is an integer from 0 to 5, wherein if m is 2 or more, a plurality of R1s are independent of each other, and

[0175] B is C 1-7 Hydrocarbon group, C 3-10 It may be a divalent linker that is a hydrocarbon ring or a 4- to 15-membered bicyclic ring, and n is an integer from 0 to 5, and when n is 2 or greater, a plurality of R2 are independent of each other, and

[0176] X can be O, S, or NH, and

[0177] C is C 5-12 Arrylene, 3 to 15-membered heteroarylene, C 3-12 Cycloalkylene, ternary to fifteenth heterocycloalkylene, C 3-12 Cycloalkenylene, 3- to 15-membered heterocycloalkenylene, C 3-12 It may be a divalent linker that is a cycloalkynylene, a ternary to fifteen-membered heterocycloalkynylene, or a quaternary to fifteen-membered polycyclic heterocycle, and o is an integer from 0 to 5, and when o is 2 or more, a plurality of R3s are independent of each other, and

[0178] D is C 5-12 Aril, C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, C 3-12 It may be a cycloalkynyl, a ternaryl to 15-membered heteroaryl, a ternaryl to 15-membered heterocycloalkyl, a ternaryl to 15-membered heterocycloalkynyl, a ternaryl to 15-membered heterocycloalkynyl, or a quaternaryl to 15-membered polycyclic heterocycle, and p is an integer from 0 to 5, and when p is 2 or more, a plurality of R4s are independent of each other, and

[0179] The above R1 to R4 are independently hydrogen, iodine, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkylthio, C 3-6 Cycloalkyl, ternary to hexavalent heterocycloalkyl, C5-12 Aryl, 3- to 6-membered heteroaryl, C 1-6 Halogenated alkoxy, C 1-6 Alkyl thio-halogenated, acetyl, acetylamino, hydroxy, cyano, nitro, amino, C 1-3 Aminoalkyl, C 1-3 Alkylamino, thio, deuterium, C 1-6 It may be a deuteride alkyl, sulfonyl, sulfinyl, halogen, or -CO-R', and said R' is C 1-3 Alkyl, C 3-6 Cycloalkyl, ternary to hexavalent heterocycloalkyl, methyl-substituted piperazine, C 1-3 Alkoxy, hydroxy, C 1-3 alkylamino, or C 1-3 It may be an aminoalkyl (wherein the above-described heterocycle may include one or more heteroatoms selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1, but is not limited thereto),

[0180] The above R1 to R4 are each independently halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, iodine, acetyl, C 3-6 It may be substituted or unsubstituted with one or more selected from the group consisting of cycloalkyls and ternary to hexavalent heterocycloalkyls (wherein the above-mentioned heterocycle may include one or more heteroatoms selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1, but is not limited thereto).

[0181]

[0182] Each structure and substituent is explained in more detail.

[0183] The above A may be a mono- or bicyclic ternary to fifteen-membered heterocycle (group) containing at least two Ns. In one example, the above A may include one or more heteroatoms selected from N, O, and S in addition to the two essential Ns, for example, one to five, one to four, one to three, one to two, or one more. In one example, the above A may be substituted or unsubstituted with one or more substituents described herein.

[0184] When the above A is a bicyclic heterocycle, the above A may be a saturated, partially unsaturated, or aromatic ring as a whole, and may include a structure in which two rings are fused (condensed), crosslinked, or joined in a spiro form. The above bicyclic heterocycle may be a structure in which a hydrocarbon ring and a heterocycle are fused, crosslinked, or connected, or in which two heterocycles are fused, crosslinked, or connected. In one example, the above bicyclic heterocycle may be a condensed ring formed by fusing two rings selected from the group consisting of cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, and heteroaryl, etc., wherein the two rings may be of the same or different types. In this case, at least two Ns are included within the overall ring structure of the entire A.

[0185] In one example, the above A may comprise at least two Ns as a whole, as a mono- or bicyclic ternary to 15-membered heterocycloalkyl, a mono- or bicyclic ternary to 15-membered heterocycloalkenyl, a mono- or bicyclic ternary to 15-membered heterocycloalkynyl, a mono- or bicyclic ternary to 15-membered heteroaryl, a 4-membered to 15-membered condensation ring formed by fusing a cycloalkyl and a heterocyclic ring, a 4-membered to 15-membered condensation ring formed by fusing an aryl and a heterocyclic ring, or a 4-membered to 15-membered condensation ring formed by fusing two types of heterocyclic rings.

[0186] In one example, the above A may be a ternary to 15-membered heterocycloalkyl, a ternary to 15-membered heterocycloalkenyl, a ternary to 15-membered heteroaryl, or a quaternary to 15-membered bicyclic heterocycle, but is not limited thereto.

[0187] In one example, the above A may have one of the following structures:

[0188]

[0189]

[0190] Here, Q1 to Q3 can each independently be C, O, S, or N, and

[0191] Z1 to Z3 can each independently be C or N, and

[0192] Y1 to Y3 can each independently be C, O, S, or N, and

[0193] W1 to W3 can each be independently C or N.

[0194] In the above formula, “ " refers to the part that combines with other groups, and the same applies to other chemical structures below.

[0195] In the above formula, represents a single or double bond, and the same applies to other chemical structures below.

[0196] The above m may be an integer from 0 to 5.

[0197] Here, the above A In this case, Q1 to Q3 are each independently C, O, S, or N, and at least one of Q1 to Q3 may be N.

[0198] Here, the above A In this case, Z1 to Z3 are each independently C or N, and at least one of Z1 to Z3 may be N.

[0199] Here, the above A In this case, Z1 and Z2 are each independently C or N, and Y1 to Y3 are each independently C, O, S, or N, provided that at least one of Z1, Z2, and Y1 to Y3 may be N.

[0200] Here, the above A In this case, Z1 and Z2 are each independently C or N, and Y1 to Y3 are each independently C, O, S, or N, provided that at least one of Z1, Z2, and Y1 to Y3 may be N.

[0201] Here. The above A In this case, Z1 and Z2 are each independently C or N, and W1 to W3 are each independently C or N, provided that at least one of Z1, Z2, and W1 to W3 may be N.

[0202]

[0203] The above R1 may represent a hydrogen atom bonded to a skeletal atom of A, or a substituent bonded to a substitutable position of A. That is, A may be substituted by a singular or multiple R1s. For example, the above R1 may be bonded by substituting a hydrogen atom bonded to a skeletal atom of A. When m is 2 or more, the multiple R1s are independent of each other (i.e., selected independently from the aforementioned functional groups) and may be identical or different from each other. When m is 0, it means that A does not contain R1 or that A is not substituted with R1.

[0204] In one example, the above R1 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 3-6 Cycloalkyl, ternary to hexavalent heterocycloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, hydroxy, C 1-6Hydroxyalkyl, halogen, C 1-6 Haloalkyl, cyano group, C 1-6 Cyanoalkyl, acetyl group, amino group, C 1-3 Aminoalkyl, C 1-3 Alkylamino, C 1-6 Alkylthio, C 1-6 It may be an alkyl thio halide, sulfonyl, sulfinyl, or -CO-R', and said R' is C 1-3 Alkyl, C 1-3 It may be an alkoxy or a hydroxyl, but is not limited thereto. In one example, the heterocycloalkyl may include one or more heteroatoms selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1.

[0205] In one example, the above R1 is C 1-3 Alkyl, C 1-3 Alkoxy, iodine, C 3-6 One or more selected from the group consisting of cycloalkyl and ternary to hexavalent heterocycloalkyl may be substituted or unsubstituted, but are not limited thereto. The heterocycloalkyl may include one or more heteroatoms selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1.

[0206] In one example, when m is an integer greater than or equal to 1, R1 may be a singular or a plurality of independent R1s, each independently selected from the following functional groups, but is not limited thereto:

[0207]

[0208] The above B is C 1-7 Hydrocarbon group, C 3-10 It may be a hydrocarbon ring or a divalent linker (divalent ring) which is a 4- to 15-membered bicyclic ring. In one example, B may be substituted or unsubstituted with one or more substituents described herein.

[0209] Here, the hydrocarbon group may be straight-chain or branched. Here, the hydrocarbon ring and the bicyclic ring may each be saturated, partially unsaturated, or aromatic rings.

[0210] If the above B is a bicyclic ring, the above B may be a structure in which two rings are joined by fusion, cross-linking, or in a spiro form. Additionally, the above B may be a bicyclic hydrocarbon ring or a bicyclic heterocycle. In one example, the heterocycle may include one or more heteroatoms selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1.

[0211] For example, the above B may be a bicyclic ring formed by fusing or cross-linking rings selected from the group consisting of cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, and heteroaryl, wherein the two rings may be of the same or different types, but are not limited thereto.

[0212] In one example, the above B is C 1-7 Alkyl, C 1-7 Alkylene, C 1-7 Alkoxy, C 1-7 Oxyalkylene, C 3-12 Cycloalkylene, C 3-12 Cycloalkenylene, C 3-12 Cycloalkynylene, C 5-12It may be an arylene, or a 4 to 15-membered bicyclic hydrocarbon ring. Here, the bicyclic hydrocarbon ring may be formed by fusing or cross-linking rings selected from the group consisting of cycloalkyl, cycloalkenyl, cycloalkynyl, and aryl, and the two rings may be of the same or different types, but are not limited thereto. In one example, the bicyclic hydrocarbon ring may be a 4 to 15-membered cross-linked ring of cycloalkyl, a 4 to 15-membered condensation ring of cycloalkylene and benzene, or a 4 to 15-membered condensation ring of cycloalkylene and aryl, but is not limited thereto.

[0213] In one example, the above B is C 1-7 Alkyl, C 1-7 Alkylene, C 3-12 Cycloalkylene, C 3-12 Cycloalkenylene, C 5-12 It may be an arylene, a 4- to 15-membered bicyclic hydrocarbon ring, but is not limited thereto.

[0214] In one example, the above B may have one of the following structures:

[0215]

[0216] The above n may be an integer from 0 to 5.

[0217] The above R2 may represent a hydrogen atom bonded to a skeletal atom of B, or a substituent bonded to a substitutable position of B. That is, B may be substituted by a singular or multiple R2s. For example, the above R2 may be bonded by substituting a hydrogen atom bonded to a skeletal atom of B. When n is 2 or more, the multiple R2s are independent of each other (i.e., selected independently from the aforementioned functional groups) and may be identical or different from each other. When n is 0, it means that B does not contain R2 or that B is not substituted with R2.

[0218] In one example, the above R2 is hydrogen, C 1-6 Alkyl, hydroxy, C 1-6 Alkoxy, Halogen, C 1-6 Haloalkyl, C 1-6 hydroxyalkyl, or C 1-6 It may be a halogenated alkoxy, specifically hydrogen, C 1-6 Alkyl, hydroxy, C 1-6 It may be an alkoxy or a halogen, but is not limited thereto.

[0219] In one example, when n is an integer greater than or equal to 1, R2 may be a singular or a plurality of independent R2s, each independently selected from the following functional groups, but is not limited thereto:

[0220]

[0221]

[0222] The above C is C 5-12 Arrylene, 3 to 15-membered heteroarylene, C 3-12 Cycloalkylene, ternary to fifteenth heterocycloalkylene, C 3-12 Cycloalkenylene, 3- to 15-membered heterocycloalkenylene, C 3-12 It may be a divalent linker that is a cycloalkynylene, a ternary to fifteen-membered heterocycloalkynylene, or a quaternary to fifteen-membered polycyclic heterocycle. In one example, the above-described heterocycle may include one or more heteroatoms selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1. In one example, the above C may be substituted or unsubstituted with one or more substituents described herein.

[0223] In one example, when C is a polycyclic heterocycle, C may be a saturated, partially unsaturated, or aromatic ring, and may have a structure in which two or more rings are fused, cross-linked, or joined in a spiro form. For example, the polycyclic heterocycle may consist entirely of multiple saturated rings or may include at least one unsaturated ring. In one example, C may be a bicyclic heterocycle. In one example, the bicyclic heterocycle may include a 4 to 15-membered condensation ring of a cycloalkyl and heterocycle and a 4 to 15-membered condensation ring of a heterocycloalkyl and heterocycle, but is not limited thereto.

[0224] In one example, the above C is C 5-12 Arrylene, 3 to 15-membered heteroarylene, C 3-12 It may be a cycloalkylene or a 3 to 15-membered heterocycloalkylene, but is not limited thereto.

[0225] In one example, the above C may have one of the following structures:

[0226]

[0227] The above o may be an integer from 0 to 5.

[0228] The above R3 may represent a hydrogen atom bonded to the skeletal atom of the C, or a substituent bonded to a substitutable position of the C. That is, the C may be substituted by a singular or multiple R3s. For example, the R3 may be bonded by substituting a hydrogen atom bonded to the skeletal atom of the C. When o is 2 or more, the multiple R3s are independent of each other (i.e., selected independently from the aforementioned functional groups) and may be identical or different from each other. An o of 0 means that the C does not contain R3 or that the C is not substituted with R3.

[0229] In one example, the above R3 is hydrogen, C 1-6 Alkyl, C 1-6 Alkoxy, cyano, halogen, C 1-6 Haloalkyl, C 1-6 Halogenated alkoxy, or C 1-6 It may be a cyanoalkyl, specifically hydrogen, C 1-6 Alkyl, C 1-6 It may be an alkoxy, cyano, or halogen, but is not limited thereto.

[0230] In one example, when o is an integer greater than or equal to 1, R3 may be a singular or a plurality of independent R3s, each independently selected from the following functional groups, but is not limited thereto:

[0231]

[0232]

[0233] The above D is C 5-12 Aril, C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, C 3-12 It may be a cycloalkynyl, a ternaryl to 15-membered heteroaryl, a ternaryl to 15-membered heterocycloalkyl, a ternaryl to 15-membered heterocycloalkenyl, a ternaryl to 15-membered heterocycloalkynyl, or a quaternaryl to 15-membered polycyclic heterocycle. In one example, the above-described heterocycle may include one or more heteroatoms selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1. In one example, the above-described heterocycle may be substituted or unsubstituted with one or more substituents described herein. For example, the above-described heterocycle may have an oxo (=O) bonded to one or more of the skeletal atoms constituting the ring, but is not limited thereto.

[0234] In one example, if D is a polycyclic heterocycle, D may be a saturated, partially unsaturated, or aromatic ring, and may be a structure in which two or more rings are fused, cross-linked, or joined in a spiro form. For example, the polycyclic heterocycle may consist entirely of multiple saturated rings or may include at least one unsaturated ring. In one example, D may be a bicyclic or tricyclic heterocycle.

[0235] For example, the above D may be a bicyclic ring formed by fusing or cross-linking rings selected from the group consisting of cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, and heteroaryl, wherein two or more rings may be of the same or different types, but are not limited thereto.

[0236] More specifically, the polycyclic heterocycle may include, but is not limited to, polycyclic heteroaryl, polycyclic heterocycloalkyl, polycyclic heterocycloalkenyl, polycyclic heterocycloalkynyl, condensed ring of cycloalkyl and heteroaryl, condensed ring of heterocycloalkyl and heteroaryl, condensed ring of heterocycloalkyl and aryl, etc.

[0237] In one example, the above D is C 5-12 It may be an aryl, a 3 to 15-membered heteroaryl, a 3 to 15-membered heterocycloalkyl, a 3 to 15-membered heterocycloalkenyl, a 3 to 15-membered heterocycloalkinyl, a 4 to 15-membered bicyclic heterocycle, or a 4 to 15-membered tricyclic heterocycle.

[0238] In one example, the above D may have one of the following structures:

[0239]

[0240]

[0241]

[0242]

[0243] The above p may be an integer from 0 to 5.

[0244] The above R4 may represent a hydrogen atom bonded to the skeletal atom of D, or a substituent bonded to a substitutable position of D. That is, D may be substituted by a singular or multiple R4s. For example, the above R4 may be bonded by substituting a hydrogen atom bonded to the skeletal atom of D. When p is 2 or more, the multiple R4s are independent of each other (i.e., selected independently from the aforementioned functional groups) and may be identical or different from each other. A p of 0 means that C does not contain R4 or that D is not substituted with R4.

[0245] In one example, the above R4 is hydrogen, iodine, C 1-6 Alkyl, acetyl, acetylamino, halogen, C 1-6 Haloalkyl, hydroxy, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy, cyano, C 3-6 Cycloalkyl, ternary to hexavalent heterocycloalkyl, C 5-12 Aryl, 3- to 6-membered heteroaryl, C 1-3 Aminoalkyl, C 1-3 It may be an alkylamino, -CO-R', and the R' is C 1-3 Alkyl, C 3-6 Cycloalkyl, ternary to hexavalent heterocycloalkyl, methyl-substituted piperazine, C 1-3 Alkoxy, hydroxy, C 1-3 alkylamino, or C 1-3It may be an aminoalkyl, but is not limited thereto. In one example, the heterocycloalkyl or heteroaryl may include one or more heteroatoms selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1.

[0246] In addition, the above R4 is a halogen, C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 One or more selected from the group consisting of cycloalkyls and ternary to hexavalent heterocycloalkyls may be substituted or unsubstituted, but are not limited thereto. In one example, the heterocycloalkyl may include one or more heteroatoms selected from N, O, and S, for example, 1 to 5, 1 to 4, 1 to 3, 1 to 2, or 1.

[0247] In one example, when p is an integer greater than or equal to 1, R4 may be a singular or a plurality of independent R4s, each independently selected from the following functional groups, but is not limited thereto:

[0248]

[0249]

[0250] In one example, the compound may be represented by the following formula 1-1 or formula 1-1', but is not limited thereto:

[0251] [Chemical Formula 1-1]

[0252]

[0253] [Chemical Formula 1-1']

[0254]

[0255]

[0256] In the above chemical formula, A, C, D, R1 to R4, and m to p are as defined above.

[0257] In one example, the compound of Formula 1 may be represented by any one of the following Formulas 1-2 to 1-6, but is not limited thereto:

[0258] [Chemical Formula 1-2]

[0259]

[0260] [Chemical Formula 1-3]

[0261]

[0262] [Chemical Formula 1-4]

[0263]

[0264] [Chemical Formula 1-5]

[0265]

[0266] [Chemical Formula 1-6]

[0267]

[0268]

[0269] In the above chemical formulas 1-2 to 1-6,

[0270] Q1 to Q3 can each independently be C, O, S, or N, and

[0271] Z1 to Z3 can each independently be C or N, and

[0272] Y1 to Y3 can each independently be C, O, S, or N, and

[0273] W1 to W3 can each independently be C or N, and

[0274] represents a single or double bond.

[0275] In each of the above chemical formulas, C, D, X, R1 to R4, and m to p are as defined above.

[0276] Here, when the compound of the above chemical formula 1 is represented by the above chemical formula 1-2, Q1 to Q3 are each independently C, O, S, or N, and at least one of Q1 to Q3 may be N.

[0277] Here, when the compound of the above chemical formula 1 is represented by the above chemical formula 1-3, Z1 to Z3 are each independently C or N, and at least one of Z1 to Z3 may be N.

[0278] Here, when the compound of the above chemical formula 1 is represented by the above chemical formula 1-4, Z1 and Z2 are each independently C or N, and Y1 to Y3 are each independently C, O, S, or N, but at least one of Z1, Z2, and Y1 to Y3 may be N.

[0279] Here, when the compound of the above chemical formula 1 is represented by the above chemical formula 1-5, Z1 and Z2 are each independently C or N, and Y1 to Y3 are each independently C, O, S, or N, but at least one of Z1, Z2, and Y1 to Y3 may be N.

[0280] Herein, when the compound of Chemical Formula 1 is represented by Chemical Formula 1-6, Z1 and Z2 are each independently C or N, and W1 to W3 are each independently C or N, provided that at least one of Z1, Z2, and W1 to W3 may be N.

[0281]

[0282] As described above, H may be omitted for the sake of simplicity. For example, even if Y1 is denoted as C in the above Chemical Formula 1-4, those skilled in the art will clearly understand that Y1 can be represented as CH2, CHR1, or C(R1)2. In one embodiment of the present invention, the above Chemical Formula 1 may be represented as any one of the following Chemical Formulas 1-7 to 1-11, but is not limited thereto.

[0283] [Chemical Formula 1-7]

[0284]

[0285] [Chemical Formula 1-8]

[0286]

[0287] [Chemical Formula 1-9]

[0288]

[0289] [Chemical Formula 1-10]

[0290]

[0291] [Chemical Formula 1-11]

[0292]

[0293] In the above chemical formulas 1-7 to 1-11,

[0294] Q1 to Q3 can each independently be C, O, S, or N, and

[0295] Z1 to Z3 can each independently be C or N, and

[0296] Y1 to Y3 can each independently be C, O, S, or N.

[0297] W1 to W3 can each independently be C or N, and

[0298] V1 to V4 can each independently be C or N, and

[0299] represents a single or double bond.

[0300] Here, the single or multiple R1 to R4 are independent of each other. That is, this means not only that R1 to R4 are independent of each other (e.g., R2 and R4 are independent of each other), but also that R1, R2, R3, or R4 are each independent of other R1, R2, R3, or R4 (e.g., when m=2, the two R2s are independent of each other).

[0301]

[0302] In one example, the compound represented by the above chemical formula 1 may be selected from the group consisting of the following compounds 1 to 231, but is not limited thereto:

[0303] Compound 1: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0304] Compound 2: N-[(1S,3S)-3-[(5-methoxypyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0305] Compound 3: N-[(1S,3S)-3-[(5-ethoxypyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0306] Compound 4: N-[(1S,3S)-3-[(5-fluoropyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0307] Compound 5: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0308] Compound 6: 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-propane-2-ylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0309] Compound 7: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0310] Compound 8: 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0311] Compound 9: N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0312] Compound 10: N-[(1S,3S)-3-[[5-(difluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0313] Compound 11: N-[(1S,3S)-3-(6,7-dihydro-5H-cyclopenta[d]pyrimidine-2-ylamino)cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0314] Compound 12: 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(trifluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0315] Compound 13: N-[(1S,3S)-3-[(5-ethylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0316] Compound 14: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(3-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0317] Compound 15: N-[(1S,3S)-3-[[5-(difluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0318] Compound 16: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide

[0319] Compound 17: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide

[0320] Compound 18: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0321] Compound 19: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0322] Compound 20: N-[(1S,3S)-3-[(5-ethoxypyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0323] Compound 21: N-[(1S,3S)-3-[(5-methoxypyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0324] Compound 22: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0325] Compound 23: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0326] Compound 24: N-[(1S,3S)-3-[(5-fluoropyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0327] Compound 25: N-[(1S,3S)-3-[(5-cyclopropyl-4-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0328] Compound 26: 4-(6-oxopyridazine-1-yl)-N-[3-(pyrimidine-2-ylamino)cyclopentyl]pyridine-2-carboxamide

[0329] Compound 27: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0330] Compound 28: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0331] Compound 29: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]pyridine-2-carboxamide

[0332] Compound 30: N-[(1S,3S)-3-(5,7-dihydrofuro[3,4-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0333] Compound 31: N-[(1S,3S)-3-(6,7-dihydro-5H-cyclopenta[d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0334] Compound 32: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0335] Compound 33: N-[(1S,3S)-3-[(5-ethynylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0336] Compound 34: 3-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]benzamide

[0337] Compound 35: N-[(1S,3S)-3-(6,7-dihydrothieno[3,2-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0338] Compound 36: N-[(1S,3S)-3-(5,7-dihydrothieno[3,4-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0339] Compound 37: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[4-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0340] Compound 38: N-[(1S,3S)-3-[[4-methylsulfanyl-5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0341] Compound 39: N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0342] Compound 40: N-[(1S,3S)-3-[(5-cyanopyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0343] Compound 41: N-[(1S,3S)-3-[(4-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0344] Compound 42: N-[(1S,3S)-3-[[5-(difluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0345] Compound 43: N-[(1S,3S)-3-[(5-acetylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0346] Compound 44: N-[(1S,3S)-3-[[5-(1-hydroxyethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0347] Compound 45: N-[(1S,3S)-3-[[5-(2-hydroxypropane-2-yl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0348] Compound 46: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-propane-2-ylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0349] Compound 47: N-[(1S,3S)-3-[[5-(hydroxymethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0350] Compound 48: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(trifluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0351] Compound 49: N-[(1S,3S)-3-[[5-(cyclopropylmethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0352] Compound 50: N-[(1S,3S)-3-[[5-(difluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0353] Compound 51: N-[(1R,4R)-4-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-hydroxycyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0354] Compound 52: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-1-(3-methyl-2-pyridinyl)azetidine-3-carboxamide

[0355] Compound 53: 1-(3-cyano-2-pyridinyl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]azetidine-3-carboxamide

[0356] Compound 54: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(2,2,2-trifluoroethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0357] Compound 55: N-[(1S,3S)-3-[[5-(cyanomethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0358] Compound 56: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-3-(6-oxopyridazine-1-yl)benzamide

[0359] Compound 57: N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-1-bicyclo[1.1.1]fentanyl]-4-(6-oxopyridazine-1-yl)benzamide

[0360] Compound 58: N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclobutyl]-4-(6-oxopyridazine-1-yl)benzamide

[0361] Compound 59: N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]ethyl]-4-(6-oxopyridazine-1-yl)benzamide

[0362] Compound 60: N-[(1S,2S)-2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopropyl]-4-(6-oxopyridazine-1-yl)benzamide

[0363] Compound 61: N-[(1S,2S)-2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopropyl]-3-(6-oxopyridazine-1-yl)benzamide

[0364] Compound 62: N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]ethyl]-3-(6-oxopyridazine-1-yl)benzamide

[0365] Compound 63: N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclobutyl]-3-(6-oxopyridazine-1-yl)benzamide

[0366] Compound 64: N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-1-bicyclo[1.1.1]fentanyl]-3-(6-oxopyridazine-1-yl)benzamide

[0367] Compound 65: N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-methylpropyl]-3-(6-oxopyridazine-1-yl)benzamide

[0368] Compound 66: N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-methylpropyl]-4-(6-oxopyridazine-1-yl)benzamide

[0369] Compound 67: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0370] Compound 68: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide

[0371] Compound 69: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-1-yl)pyridine-2-carboxamide

[0372] Compound 70: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(1-methyl-3-oxoindazole-2-yl)pyridine-2-carboxamide

[0373] Compound 71: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-2-yl)pyridine-2-carboxamide

[0374] Compound 72: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(5-methyl-2-oxo-1,3,4-thiadiazole-3-yl)pyridine-2-carboxamide

[0375] Compound 73: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-methyl-5-oxo-4H-pyrazole-1-yl)pyridine-2-carboxamide

[0376] Compound 74: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxomorpholine-4-yl)pyridine-2-carboxamide

[0377] Compound 75: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3,4-diethyl-5-oxo-1,2,4-triazole-1-yl)pyridine-2-carboxamide

[0378] Compound 76: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide

[0379] Compound 77: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxoindazole-2-yl)pyridine-2-carboxamide

[0380] Compound 78: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-2-yl)pyridine-2-carboxamide

[0381] Compound 79: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-fluoro-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0382] Compound 80: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methyl-2-oxo-1,3,4-thiadiazole-3-yl)pyridine-2-carboxamide

[0383] Compound 81: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-ethoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0384] Compound 82: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(4-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0385] Compound 83: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-fluoro-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0386] Compound 84: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-oxo-3H-pyrrolo[3,4-c]pyridine-2-yl)pyridine-2-carboxamide

[0387] Compound 85: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-c]pyridine-2-yl)pyridine-2-carboxamide

[0388] Compound 86: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-b]pyridine-2-yl)pyridine-2-carboxamide

[0389] Compound 87: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-b]pyrazine-2-yl)pyridine-2-carboxamide

[0390] Compound 88: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-4,5,6,7-tetrahydroindazole-2-yl)pyridine-2-carboxamide

[0391] Compound 89: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-5,7-dihydro-4H-pyrano[3,4-c]pyrazole-2-yl)pyridine-2-carboxamide

[0392] Compound 90: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-6,7-dihydro-4H-pyrano[4,3-c]pyrazole-2-yl)pyridine-2-carboxamide

[0393] Compound 91: 4-(3-cyano-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0394] Compound 92: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-methyl-5-oxo-2-propane-2-ylpyrazole-1-yl)pyridine-2-carboxamide

[0395] Compound 93: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-2-(6-oxopyridazine-1-yl)pyridine-4-carboxamide

[0396] Compound 94: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0397] Compound 95: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-6-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0398] Compound 96: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0399] Compound 97: 5-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]pyridine-3-carboxamide

[0400] Compound 98: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)benzamide

[0401] Compound 99: 4-(3-methyl-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0402] Compound 100: 4-(3-methoxy-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0403] Compound 101: 4-(3-chloro-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0404] Compound 102: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0405] Compound 103: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0406] Compound 104: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide

[0407] Compound 105: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide

[0408] Compound 106: 4-(3-chloro-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0409] Compound 107: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(5-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0410] Compound 108: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(4-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0411] Compound 109: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(3-methyl-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0412] Compound 110: 4-(5-chloro-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0413] Compound 111: 4-(5-methoxy-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0414] Compound 112: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(1-oxo-2,7-naphthiridine-2-yl)pyridine-2-carboxamide

[0415] Compound 113: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(4-oxofuro[3,2-c]pyridine-5-yl)pyridine-2-carboxamide

[0416] Compound 114: N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0417] Compound 115: N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[0418] Compound 116: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0419] Compound 117: 3-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0420] Compound 118: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0421] Compound 119: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0422] Compound 120: 5-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0423] Compound 121: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)pyridine-2-carboxamide

[0424] Compound 122: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1,1-deoxydoisothiazolidine-2-yl)pyridine-2-carboxamide

[0425] Compound 123: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)pyridine-2-carboxamide

[0426] Compound 124: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2,5-dioxomidazolidine-1-yl)pyridine-2-carboxamide

[0427] Compound 125: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)thiophene-2-carboxamide

[0428] Compound 126: N-((1S,3S)-3-((5-cyclopropyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[0429] Compound 127: N-((1S,3S)-3-((5-methyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[0430] Compound 128: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0431] Compound 129: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0432] Compound 130: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-4-(6-oxopyridazine-1(6H)-yl)-1H-pyrrole-2-carboxamide

[0433] Compound 131: 3-methyl-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0434] Compound 132: 3-chloro-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0435] Compound 133: 3-methoxy-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0436] Compound 134: 3-chloro-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0437] Compound 135: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)pyridine-2-carboxamide

[0438] Compound 136: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)pyridine-2-carboxamide

[0439] Compound 137: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)furan-2-carboxamide

[0440] Compound 138: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-3-(6-oxopyridazine-1(6H)-yl)-1H-pyrazol-5-carboxamide

[0441] Compound 139: N-((1S,3S)-3-((5-cyclohexyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[0442] Compound 140: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3,4-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0443] Compound 141: 3-cyclopropyl-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0444] Compound 142: 3-acetyl-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0445] Compound 143: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1H-indazole-1-yl)pyridine-2-carboxamide

[0446] Compound 144: N-((1S,3S)-3-((5-(methylsulfonyl)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[0447] Compound 145: 3-cyclopropyl-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0448] Compound 146: 3-acetyl-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0449] Compound 147: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3,4-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0450] Compound 148: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4,5-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0451] Compound 149: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine-2-carboxamide

[0452] Compound 150: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3,5-dimethyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide

[0453] Compound 151: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-5-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0454] Compound 152: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0455] Compound 153: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(5-methyl-1H-pyrazol-1-yl)pyridine-2-carboxamide

[0456] Compound 154: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(5-methyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide

[0457] Compound 155: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-isopropyl-5-methyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide

[0458] Compound 156: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3,5-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0459] Compound 157: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-6-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0460] Compound 158: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(pyrazolo[1,5-a]pyridine-7-yl)pyridine-2-carboxamide

[0461] Compound 159: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-2-oxo-1,2-dihydro-[3,4'-bipyridine]-2'-carboxamide

[0462] Compound 160: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyrimidine-2-carboxamide

[0463] Compound 161: Methyl 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylate

[0464] Compound 162: 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylic acid

[0465] Compound 163: N-((1S,3S)-3-((5-(methylsulfinyl)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[0466] Compound 164: 4-(dibenzo[b,d]furan-4-yl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide

[0467] Compound 165: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(4-methyl-6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[0468] Compound 166: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1-oxophthalazine-2(1H)-yl)pyridine-2-carboxamide

[0469] Compound 167: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-phenyl-2H-[1,4'-bipyridine]-2'-carboxamide

[0470] Compound 168: 4-(2-cyclopropoxyphenyl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide

[0471] Compound 169: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-(dimethylamino)phenyl)pyridine-2-carboxamide

[0472] Compound 170: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-(4-methylpiperazine-1-carbonyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0473] Compound 171: 3-Bromo-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0474] Compound 172: 5-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0475] Compound 173: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-(trifluoromethyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0476] Compound 174: N2'-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-N3,N3-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2',3-dicarboxamide

[0477] Compound 175: 3-methoxy-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0478] Compound 176: 3-methoxy-2-oxo-N-((1S,3S)-3-((5-ethenylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0479] Compound 177: N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0480] Compound 178: 3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0481] Compound 179: 3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-ethenylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0482] Compound 180: 3-cyclopropyl-N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0483] Compound 181: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0484] Compound 182: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carvothioamide

[0485] Compound 183: 4-[3-chloro-5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0486] Compound 184: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-[6-oxo-5-(2,2,2-trifluoroethoxy)pyridazine-1-yl]pyridine-2-carboxamide

[0487] Compound 185: 4-[3-chloro-6-oxo-5-(2,2,2-trifluoroethoxy)pyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0488] Compound 186: 4-[5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0489] Compound 187: 4-[3-chloro-5-(3-methoxyazetidine-1-yl)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0490] Compound 188: 4-(3-chloro-6-oxo-5-pyrrolidin-1-ylpyridazine-1-yl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0491] Compound 189: 4-(3-chloro-5-morpholine-4-yl-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0492] Compound 190: 4-[3-chloro-5-(oxetane-3-ylmethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0493] Compound 191: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-[5-(3-methoxyazetidine-1-yl)-6-oxopyridazine-1-yl]pyridine-2-carboxamide

[0494] Compound 192: 4-[5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0495] Compound 193: 4-[5-(2,2-difluoroethoxy)-6-oxo-3-(1H-pyrazole-4-yl)pyrizine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0496] Compound 194: N-((1S,3S)-3-((6-cyclopropyl-1,2,4-triazine-3-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0497] Compound 195: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-3-cyclopropyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0498] Compound 196: 5-chloro-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0499] Compound 197: 5-chloro-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0500] Compound 198: 5-chloro-2-oxo-N-((1S,3S)-3-((5-vinylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0501] Compound 199: 5-chloro-N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0502] Compound 200: 3-cyano-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0503] Compound 201: 2-oxo-3-(trifluoromethyl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0504] Compound 202: 5-chloro-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0505] Compound 203: 5-chloro-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-3-cyclopropyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0506] Compound 204: 5-chloro-3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0507] Compound 205: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-(trifluoromethyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0508] Compound 206: 5-chloro-3-methoxy-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0509] Compound 207: 4-(5-methyl-6-oxopyridazine-1(6H)-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide

[0510] Compound 208: 4-(5-methoxy-6-oxopyridazine-1(6H)-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide

[0511] Compound 209: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-3-cyano-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0512] Compound 210: 3-acetyl-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0513] Compound 211: 3-acetyl-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0514] Compound 212: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-oxoisoquinoline-2(3H)-yl)picolinamide

[0515] Compound 213: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-oxo-3,4,4a,8a-tetrahydroisoquinoline-2(1H)-yl)picolinamide

[0516] Compound 214: Methyl 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-5-carboxylate

[0517] Compound 215: 5-Bromo-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0518] Compound 216: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridine-1-yl)picolinamide

[0519] Compound 217: 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-5-carboxylic acid

[0520] Compound 218: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-5-(morpholine-4-carbonyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0521] Compound 219: 5-Bromo-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[0522] Compound 220: 5-bromo-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0523] Compound 221: 5-bromo-2-oxo-N-((1S,3S)-3-((5-vinylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[0524] Compound 222: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-yl)picolinamide

[0525] Compound 223: 4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide

[0526] Compound 224: 4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-yl)-N-((1S,3S)-3-((5-vinylpyrimidine-2-yl)amino)cyclopentyl)picolinamide

[0527] Compound 225: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxo-3,4-dihydroquinoline-1(2H)-yl)picolinamide

[0528] Compound 226: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)picolinamide

[0529] Compound 227: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-4-(5-oxo-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-1-yl)picolinamide

[0530] Compound 228: 4-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-1-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide

[0531] Compound 229: 4-(5-oxo-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-1-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide

[0532] Compound 230: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-4-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-1-yl)picolinamide, and

[0533] Compound 231: 4-(2-oxoquinoline-1(2H)-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide.

[0534] The compound of the present invention has the ability to bind to PCSK9 and may have the ability to inhibit PCSK9 activity (or function). For example, the compound of the present invention may inhibit the internalization of LDLR into cells by PCSK9. More specifically, the compound of the present invention may inhibit the induction of LDLR degradation by PCSK9, thereby inhibiting the reduction of LDL (e.g., LDL-C) uptake in liver cells by PCSK9, and consequently, may increase LDL uptake in liver cells. Furthermore, the compound may have preventive, remedial, and / or therapeutic activities for PCSK9-related diseases, such as diseases that may be induced by the overactivation or overexpression of PCSK9. The PCSK9-related disease may be, for example, a disease related to lipid or lipoprotein metabolic disorders.

[0535] In addition, the compound of the present invention can promote lipid or lipoprotein metabolism by inhibiting PCSK9 activity. As described above, since the compound of the present invention can increase the uptake of lipids or lipids, such as LDL, within liver cells, it can consequently promote the metabolism of said lipids or lipoproteins by liver cells.

[0536] Meanwhile, the compound of the present invention is characterized by having excellent pharmacokinetics (PK). That is, when administered into the body, the compound of the present invention exhibits optimized absorption, distribution, metabolism, and excretion characteristics for the prevention, improvement, and / or treatment of the diseases described below, and while fully expressing the desired pharmacological effect, it has low toxicity, high bioavailability, and high convenience of administration.

[0537]

[0538] For the prevention, improvement, and / or treatment of diseases

[0539] The present invention provides a composition for the prevention, improvement, and / or treatment of PCSK9-related diseases, comprising a compound represented by the above-described Formula 1, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof. The composition may be a pharmaceutical composition and / or a food composition. The compound, etc., may be included as an active ingredient in the composition.

[0540] In addition, the present invention provides a method for the prevention, improvement, and / or treatment of a PCSK9-related disease, comprising the step of administering a compound represented by Formula 1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof, to a subject requiring prevention, improvement, and / or treatment of a PCSK9-related disease. The method may further comprise the step of identifying a subject requiring prevention, improvement, and / or treatment of a PCSK9-related disease prior to the step of administering.

[0541] In addition, the present invention provides the use of a compound represented by Formula 1, and its pharmaceutically acceptable salts, hydrates, solvates, tautomers, isotopic variants, enantiomers, or diastereomers for the prevention, improvement, and / or treatment of PCSK9-related diseases.

[0542] In addition, the present invention provides the use of a compound represented by Formula 1, its pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer for the manufacture of a drug for the prevention, improvement, and / or treatment of PCSK9-related diseases.

[0543] In this specification, "prevention" refers to any act of suppressing or delaying the onset of a disease (disease) by administering a composition according to one example, "treatment" refers to any act of improving or beneficially changing the symptoms of an individual suspected of or suffering from a disease by administering a composition according to one example, and "improvement" may refer to any act of at least reducing parameters related to the state in which the disease is treated, such as the degree of symptoms, by administering a composition according to one example. The disease may be a PCSK9-related disease.

[0544] In the present invention, “PCSK9-related disease” includes all diseases that may be caused by PCSK9 expression, activity, or function abnormalities. In one example, the disease may be a disease in which PCSK9 overactivity and / or overexpression may be a direct or indirect cause, or a disease that can be prevented, improved, and / or treated by inhibiting PCSK9 activity and / or function. More specifically, the PCSK9-related disease may be a lipid and / or lipoprotein metabolic disorder.

[0545] In the present invention, “lipid and / or lipoprotein metabolic disorder” refers to a disease in which abnormal metabolism of lipids and / or lipoproteins may be a direct or indirect cause. In particular, the said disease may be a disease that can be induced by a decrease in lipid and / or lipoprotein metabolism. The lipid and / or lipoprotein metabolic disorder includes dyslipidemia, including primary hypercholesterolemia induced by abnormal PCSK9 activity, as well as dyslipidemia-related cardiovascular disease. More specifically, the lipid and / or lipoprotein metabolic disorders mentioned above include atherosclerosis, dyslipidemia, hypertriglyceridemia, hypertension, heart failure, cardiac arrhythmias, low HDL levels, high LDL levels, sudden death, stable angina, coronary heart disease, acute myocardial infarction, cardiomyopathy, endocarditis, type 2 diabetes, insulin resistance, impaired glucose tolerance, hypercholesterolemia (including heterozygous and homozygous familial hypercholesterolemia), stroke, hyperlipidemia, and hyperlipoproteinemia. Chronic kidney disease, intermittent claudication, hyperphosphatemia, carotid atherosclerosis, peripheral arterial disease,It may be one or more selected from the group consisting of diabetic nephropathy, hypercholesterolemia in HIV infection, acute coronary syndrome (ACS), non-alcoholic fatty liver disease, arterial occlusive disease, cerebral arteriosclerosis, cerebrovascular disorder, myocardial ischemia, nonalcoholic steatohepatitis (NASH), and diabetic autonomic neuropathy, but is not limited thereto.

[0546] The pharmaceutical composition according to the present invention may further include a suitable carrier, excipient, and diluent commonly used in the manufacture of pharmaceutical compositions. The excipient may be one or more selected from the group consisting of, for example, diluents, binders, disintegrants, lubricants, adsorbents, humectants, film-coating materials, and controlled-release additives.

[0547] The pharmaceutical composition according to the present invention may be formulated and used in the form of external preparations such as powders, granules, sustained-release granules, enteric granules, liquids, eye drops, oxylic agents, emulsions, suspensions, ethanol tablets, troches, fragrances, limonene adzes, tablets, sustained-release tablets, enteric tablets, sublingual tablets, hard capsules, soft capsules, sustained-release capsules, enteric capsules, pills, tinctures, soft extracts, dry extracts, fluid extracts, injections, capsules, irrigation solutions, warning agents, lotions, pastes, sprays, inhalants, patches, sterile injectable solutions, or aerosols, according to conventional methods, and the external preparations may have formulations such as creams, gels, patches, sprays, ointments, warning agents, lotions, liniments, pastes, or cataplasms.

[0548] Carriers, excipients, and diluents that may be included in the pharmaceutical composition according to the present invention include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

[0549] When formulating, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

[0550] The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level may be determined according to factors including the type and severity of the patient's disease, drug activity, sensitivity to the drug, time of administration, route of administration and elimination rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field.

[0551] The dosage of the pharmaceutical composition of the present invention is determined by the type of active ingredient drug, along with various relevant factors such as the disease to be treated, the route of administration, the patient's age, gender, weight, and the severity of the disease. Specifically, the effective dosage of the composition according to the present invention may vary depending on the patient's age, gender, and weight, and generally, 0.001 to 150 mg, preferably 0.01 to 100 mg per kg of body weight, may be administered daily or every other day, or divided into 1 to 3 doses per day. However, since the dosage may be increased or decreased depending on the route of administration, the severity of the disease, gender, weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

[0552] In the present invention, “administration” means providing a specific compound of the present invention to an individual by any appropriate method. The pharmaceutical composition of the present invention may be administered to an individual by various routes. All modes of administration may be anticipated, for example, by oral administration, subcutaneous injection, intraperitoneal administration, intramuscular injection, intrathecal (intradural) injection, sublingual administration, buccal mucosal administration, rectal insertion, vaginal insertion, ocular administration, ear administration, nasal administration, inhalation, spray through the mouth or nose, skin administration, transdermal administration, etc.

[0553] The subjects of administration of the composition of the present invention may be one or more mammals selected from primates such as humans and monkeys, rodents such as mice and rats, livestock such as dogs, cats, pigs, cattle, horses, sheep, goats, etc., and poultry such as chickens, ducks, geese, pheasants, quails, and turkeys, or cells, tissues, or cultures derived from these.

[0554] When the compound of the present invention is used as a food additive, the compound may be added as is or used together with other foods or food ingredients, and may be used appropriately according to conventional methods. The amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health, or therapeutic treatment). Generally, when manufacturing food or beverages, the compound of the present invention may be added in an amount of 15% by weight or less, or 10% by weight or less, relative to the raw material. However, in the case of long-term consumption for the purpose of health and hygiene or health control, the amount may be less than the above range, and since there are no issues regarding safety, the active ingredient may be used in an amount greater than the above range.

[0555] There are no specific restrictions on the types of the above-mentioned foods. Examples of foods to which the above-mentioned substance may be added include meat, sausage, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and include all health functional foods in the conventional sense.

[0556] In addition to the above, the composition of the present invention may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. Furthermore, the composition of the present invention may contain fruit pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages. These ingredients may be used independently or in combination. Although the proportion of these additives is not critical, it is generally selected in the range of 0.01 to 0.20 parts by weight per 100 parts by weight of the composition of the present invention.

[0557] In this specification, the term “health functional food” is synonymous with “food for special health use (FoSHU)” and refers to a food with high medical or therapeutic effects that is processed to efficiently exhibit bio-regulatory functions in addition to nutritional supply. The food may be manufactured in various forms such as tablets, capsules, powders, granules, liquids, and pills to obtain useful effects in preventing or improving lipid or lipoprotein metabolic disorders.

[0558] The composition according to the present invention can inhibit the expression, activity, and / or function of PCSK9. Accordingly, the composition of the present invention can exhibit preventive, remedial, and / or therapeutic activity for lipid or lipoprotein metabolic disorders by inhibiting the expression, activity, and / or function of PCSK9.

[0559]

[0560] Uses of PCSK9 activity inhibitor

[0561] The present invention provides a composition for inhibiting the activity of PCSK9, comprising the compound of Formula 1 described above, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, enantiomer, or diastereomer thereof. The composition may be a pharmaceutical composition and / or a food composition. The compound, etc., may be included as an active ingredient in the composition.

[0562] In addition, the present invention provides a method for inhibiting the activity of PCSK9, comprising the step of administering a compound represented by Formula 1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof to a subject requiring inhibition of PCSK9 activity. The method may further comprise the step of identifying a subject requiring inhibition of PCSK9 activity prior to the step of administering.

[0563] In addition, the present invention provides the use of a compound represented by Formula 1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof for inhibiting the activity of PCSK9.

[0564] In addition, the present invention provides the use of a compound represented by Formula 1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof for inhibiting the activity of PCSK9.

[0565] The description of the composition and other terms is the same as that described above, so it is omitted.

[0566]

[0567] Uses for promoting lipid or lipoprotein metabolism

[0568] The present invention provides a composition for promoting lipid or lipoprotein metabolism, comprising the compound of Formula 1 described above, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, enantiomer, or diastereomer thereof. The composition may be a pharmaceutical composition and / or a food composition. The compound, etc. may be included as an active ingredient in the composition, etc.

[0569] In addition, the present invention provides a method for promoting lipid or lipoprotein metabolism, comprising the step of administering a compound represented by Formula 1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof to a subject requiring promotion of lipid or lipoprotein metabolism. The method may further comprise the step of identifying a subject requiring promotion of lipid or lipoprotein metabolism prior to the step of administering.

[0570] In addition, the present invention provides the use of a compound represented by Formula 1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof for promoting lipid or lipoprotein metabolism.

[0571] In addition, the present invention provides the use of a compound represented by Formula 1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof for promoting lipid or lipoprotein metabolism.

[0572] The description of the composition and other terms is the same as that described above, so it is omitted.

[0573]

[0574] Manufacturing method

[0575] The compound of Formula 1-1 of the present invention can be prepared according to one or more reaction schemes discussed below.

[0576] This method can be used by a skilled chemist with direct or obvious modifications to prepare the key intermediates and specific compounds of the present invention.

[0577] A suitable synthesis sequence is easily selected according to the specific structure of the present invention, but is within the scope of art known to individuals performing organic synthesis, such as methods summarized in available chemical databases including CAS Scifinder and Elesevier Reaxys. Based on these general methods, the preparation of the compounds of the present invention can be carried out simply and within general expertise. Some general synthesis methods for preparing the compounds of the present invention are exemplified in Reaction Schemes 1 to 3 below.

[0578] More specifically, the present invention provides a method for preparing a compound represented by Formula 1-1', comprising the following steps (S1) to (S4). The preparation method can be represented by the following Reaction Scheme 1:

[0579] (S1) A step of obtaining a compound of formula 5 by reacting a compound of formula 3 with a compound of formula 4 to produce an amide reaction;

[0580] (S2) The compound of Chemical Formula 5 above A step of obtaining a compound of Formula 6 by performing a Suzuki-Miyaura coupling reaction or a Ullmann coupling reaction with a compound represented by;

[0581] (S3) A step of obtaining a compound of Formula 7 by deprotecting the compound of Formula 6 with trifluoroacetic acid (CF3COOH); and

[0582] (S4) A step of obtaining a compound of formula 1-1' by performing a nucleophilic aromatic substitution reaction (SnAr) on the compound of formula 7 with the compound of formula 8,

[0583] [Chemical Formula 1-1']

[0584]

[0585] [Chemical Formula 3]

[0586]

[0587] [Chemical Formula 4]

[0588]

[0589] [Chemical Formula 5]

[0590]

[0591] [Chemical Formula 6]

[0592]

[0593] [Chemical Formula 7]

[0594]

[0595] [Chemical Formula 8]

[0596]

[0597] [Reaction Equation 1]

[0598]

[0599] In the above chemical formula and reaction scheme, A, C, D, X, R1 to R4, and m to p are as previously defined.

[0600] In one embodiment of the present invention, the step (S1) may be to prepare a compound of Formula 5 by dissolving the compound of Formula 3 and the compound of Formula 4 in dichloromethane, then adding HATU and N,N-diisopropylethylamine dropwise and stirring at room temperature for 5 hours, but is not limited thereto.

[0601] In one embodiment of the present invention, the step (S2) comprises a compound of Formula 5 and A compound represented by [formula] may be dissolved in dimethyl sulfoxide, then N,N'-dimethylcyclohexane-1,2-diamine, copper(I) iodide, and potassium carbonate are added dropwise and stirred at 120°C for 16 hours to prepare a compound of chemical formula 6, but is not limited thereto.

[0602] In one embodiment of the present invention, step (S3) may involve dissolving the compound of Formula 6 in dichloromethane, then slowly adding trifluoroacetic acid dropwise and stirring at room temperature for 16 hours to produce the compound of Formula 7, but is not limited thereto.

[0603] In one embodiment of the present invention, the step (S4) may be to dissolve the compound of Formula 7 and the compound of Formula 8 in dimethyl sulfoxide, then add N,N-diisopropylethylamine dropwise and stir at 120°C for 16 hours to prepare the compound of Formula 1-1', but is not limited thereto.

[0604] In addition, the present invention provides a method for preparing a compound represented by Formula 1-1', comprising the following steps (i) to (iv). The preparation method can be represented by Reaction Scheme 2:

[0605] (i) a step of obtaining a compound of formula 9 by performing a nucleophilic aromatic substitution reaction (SnAr) on a compound of formula 3 with a compound of formula 8;

[0606] (ii) a step of obtaining a compound of formula 10 by deprotecting the compound of formula 9 with trifluoroacetic acid (CF3COOH);

[0607] (iii) a step of obtaining a compound of Formula 11 by reacting the compound of Formula 10 with the compound of Formula 4 in an amide reaction; and

[0608] (iv) the compound of Chemical Formula 11 above A step of obtaining a compound of formula 1-1' by performing a Suzuki-Miyaura coupling reaction or a Ullmann coupling reaction with a compound represented by

[0609] [Chemical Formula 1-1']

[0610]

[0611] [Chemical Formula 3]

[0612]

[0613] [Chemical Formula 8]

[0614]

[0615] [Chemical Formula 9]

[0616]

[0617] [Chemical Formula 10]

[0618]

[0619] [Chemical Formula 11]

[0620]

[0621] [Reaction Equation 2]

[0622]

[0623] In the above chemical formula and reaction scheme, A, C, D, X, R1 to R4, and m to p are as previously defined.

[0624]

[0625] In one embodiment of the present invention, step (i) may involve dissolving the compound of Formula 3 and the compound of Formula 8 in dimethyl sulfoxide, then adding potassium carbonate dropwise and stirring at 120°C for 3 hours to prepare the compound of Formula 9, but is not limited thereto.

[0626] In one embodiment of the present invention, step (ii) may involve dissolving the compound of formula 9 in dichloromethane, then slowly adding trifluoroacetic acid dropwise and stirring at room temperature for 16 hours to prepare the compound of formula 10, but is not limited thereto.

[0627] In one embodiment of the present invention, step (iii) may involve dissolving the compound of Formula 10 and the compound of Formula 4 in dimethylformamide, then adding HATU and N,N-diisopropylethylamine dropwise and stirring at room temperature for 16 hours to prepare the compound of Formula 11, but is not limited thereto.

[0628] In one embodiment of the present invention, step (iv) comprises a compound of Formula 11 and A compound represented by [formula] may be dissolved in dimethyl sulfoxide, then N,N'-dimethylcyclohexane-1,2-diamine, copper(I) iodide, and potassium carbonate are added dropwise and stirred at 120°C for 16 hours to prepare a compound of formula 1-1', but is not limited thereto.

[0629] In addition, the present invention provides a method for preparing a compound represented by Formula 1-1', comprising the following steps (a) to (c). The preparation method can be represented by Reaction Scheme 3:

[0630] (a) A compound of chemical formula 12 A step of obtaining a compound of Formula 13 by performing a Suzuki-Miyaura coupling reaction or a Ullmann coupling reaction with a compound represented by;

[0631] (b) a step of hydrolyzing the compound of Formula 13 to obtain the compound of Formula 14; and

[0632] (c) a step of obtaining a compound of formula 1-1' by reacting the compound of formula 14 with the compound of formula 10 in an amide reaction,

[0633] [Chemical Formula 1-1']

[0634]

[0635] [Chemical Formula 12]

[0636]

[0637] [Chemical Formula 13]

[0638]

[0639] [Chemical Formula 14]

[0640]

[0641] [Chemical Formula 10]

[0642]

[0643] [Reaction Equation 3]

[0644]

[0645] In the above chemical formula and reaction scheme, A, C, D, X, R1 to R4, and m to p are as previously defined.

[0646] In one embodiment of the present invention, step (a) may involve dissolving the compound of Formula 12 in dimethyl sulfoxide, then adding N,N'-dimethylcyclohexane-1,2-diamine, copper(I) iodide, and potassium carbonate dropwise and stirring at 120°C for 16 hours to prepare the compound of Formula 13, but is not limited thereto.

[0647] In one embodiment of the present invention, step (b) may be to prepare a compound of formula 14 by dissolving the compound of formula 13 in tetrahydrofuran and methanol, then slowly adding an aqueous solution of 2N sodium hydroxide and stirring at room temperature for 16 hours, but is not limited thereto.

[0648] In one embodiment of the present invention, step (c) may involve dissolving the compound of Formula 14 and the compound of Formula 10 in dimethylformamide, then adding HATU and N,N-diisopropylethylamine dropwise and stirring at room temperature for 16 hours to prepare the compound of Formula 1-1', but is not limited thereto.

[0649] The compound of the present invention or its pharmaceutically acceptable salt, etc., can bind to PCSK9 and effectively inhibit its activity, and consequently promote the absorption and metabolism of lipids and lipoproteins by hepatocytes. Therefore, the compound of the present invention or its pharmaceutically acceptable salt, etc., can be usefully employed for the prevention, improvement, and / or treatment of PCSK9-related diseases, such as diseases related to lipid or lipoprotein metabolic disorders.

[0650] The present invention will be explained in more detail below through the following examples. However, these are merely illustrative of the invention, and the scope of the invention is not limited by these examples.

[0651]

[0652] [Preparation Examples and Examples]

[0653] When preparing the compounds of the present invention, the reaction order can be appropriately changed. That is, any reaction step may be performed first, any change in substituent may be inserted, and any reagent other than the exemplified reagent may be used as needed.

[0654] Various synthesis methods for starting materials for synthesizing the compounds of the present invention are known, and if the starting materials are commercially available, they may be purchased from suppliers. Reagent suppliers include companies such as Sigma-Aldrich, TCI, Wako, Kanto, Fluorchem, Acros, Alfa, Fluka, Combi-Blocks, and Dae-Jung, but are not limited thereto. Furthermore, unless otherwise specified, all commercially available materials were used without additional purification.

[0655] First, the compounds used in the synthesis of the compounds of the examples were prepared as in the following preparation examples. The following examples and preparation examples may be appropriately modified or changed by those skilled in the art within the scope of the present invention.

[0656]

[0657] Preparation Example 1-1) tert-butyl N-[(1S,3S)-3-[(4-iodopyridine-2-carbonyl)amino]cyclopentyl]carbamate

[0658]

[0659] Dichloromethane (50 mL) was added to 4-iodopicolinic acid (5.00 g, 19.28 mmol), HATU (8.98 g, 23.13 mmol), tert-butyl((1S,3S)-3-aminocyclopentyl)carbamate (4.78 g, 23.13 mmol), and N,N-diisopropylethylamine (3.77 g, 28.92 mmol), and stirred at room temperature for 5 hours. The reaction mixture was diluted with dichloromethane and washed with distilled water. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by MPLC to obtain tert-butyl N-[(1S,3S)-3-[(4-iodopyridine-2-carbonyl)amino]cyclopentyl]carbamate (6.41 g, 14.86 mmol, 77%) as a white solid.

[0660] ESI-MS m / z: 432.07[M+H] + .

[0661]

[0662] Preparation Example 1-2) tert-butyl N-[(1S,3S)-3-[[4-(2-oxo-1-pyridinyl)pyridin-2-carbonyl]amino]cyclopentyl]carbamate

[0663]

[0664] Dimethyl sulfoxide (60 mL) was added to tert-butyl N-[(1S,3S)-3-[(4-iodopyridine-2-carbonyl)amino]cyclopentyl]carbamate (6.41 g, 14.86 mmol), 2-hydroxypyridine (2.04 g, 20.81 mmol), N,N'-dimethylcyclohexane-1,2-diamine (0.42 g, 2.97 mmol), copper(I) iodide (0.57 g, 2.97 mmol), and potassium carbonate (4.13 g, 29.73 mmol), and stirred at 120°C for 16 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane, and washed with distilled water. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by MPLC to obtain tert-butyl N-[(1S,3S)-3-[[4-(2-oxo-1-pyridinyl)pyridine-2-carbonyl]amino]cyclopentyl]carbamate (3.77 g, 9.46 mmol, 64%) as a white solid.

[0665] ESI-MS m / z: 399.20 [M+H] + .

[0666]

[0667] Preparation Example 1-3) N-[(1S,3S)-3-aminocyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0668]

[0669] Dichloromethane (37 mL) was added to tert-butyl N-[(1S,3S)-3-[[4-(2-oxo-1-pyridinyl)pyridine-2-carbonyl]amino]cyclopentyl]carbamate (3.77 g, 9.46 mmol). Trifluoroacetic acid (21.58 g, 189.23 mmol) was slowly added to the reaction mixture and stirred at room temperature for 16 hours. An aqueous sodium hydroxide solution was slowly added to the reaction mixture to adjust the pH to 10.0. The example was extracted by adding dichloromethane, and the obtained organic layer was dried with magnesium sulfate, filtered, and then concentrated. N-[(1S,3S)-3-aminocyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide (2.53 g, 8.48 mmol, 89%) was obtained without further purification.

[0670] ESI-MS m / z: 300.14[M+H] + .

[0671]

[0672] Preparation Example 1-4) N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0673]

[0674] Dimethyl sulfoxide (2 mL) was added to N-[(1S,3S)-3-aminocyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide (50.00 mg, 0.17 mmol), 2-chloro-5-cyclopropylpyrimidine (53.42 mg, 0.34 mmol), and N,N-diisopropylethylamine (109.39 mg, 0.84 mmol), and stirred at 120°C for 16 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane, and washed with distilled water. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by PTLC to obtain N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide (8.00 mg, 0.02 mmol, 11%) as a white solid.

[0675] ESI-MS m / z: 417.20[M+H] + .

[0676] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.74 - 8.84 (m, 2 H) 8.07 (s, 3 H) 7.77 (td, J=5.66, 1.81 Hz, 2 H) 7.56 (ddd, J=9.13, 6.75, 2.00 Hz, 1 H) 7.03 (d, J=7.25 Hz, 1 H) 6.55 (d, J=9.01 Hz, 1 H) 6.40 (td, J=6.79, 1.31 Hz, 1 H) 4.48 (sxt, J=7.45 Hz, 1 H) 4.35 (dq, J=13.26, 6.75 Hz, 1 H) 2.03 - 2.16 (m, 2 H) 1.94 - 2.02 (m, 1 H) 1.84 - 1.92 (m, 1 H) 1.70 - 1.76 (m, 1 H) 1.61 - 1.69 (m, 1 H) 1.48 - 1.59 (m, 1 H) 0.80 - 0.87 (m, 2 H) 0.57 - 0.63 (m, 2 H).

[0677]

[0678] The following manufacturing examples are examples of the embodiment represented by Chemical Formula 1-1 of Reaction Scheme 2 above, and can be appropriately modified to correspond to the structure of the embodiment to be manufactured.

[0679]

[0680] Preparation Example 2-1) tert-butyl N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]carbamate

[0681]

[0682]

[0683] 2-chloro-5-(difluoromethoxy)pyrimidine (1.00 g, 5.43 mmol), tert-butyl((1S,3S)-3-aminocyclopentyl)carbamate (1.23 g, 5.97 mmol), and potassium carbonate (1.51 g, 10.86 mmol) were added to dimethyl sulfoxide (10 mL) and stirred at room temperature for 16 hours. Distilled water (30 mL) was added to the reaction mixture and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by MPLC to prepare tert-butyl N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]carbamate (1.75 g, 5.10 mmol, 94%).

[0684] ESI-MS m / z: 345.36 [M+H] + .

[0685]

[0686] Preparation Example 2-2) Trans-(1S,3S)-3-N-[5-(difluoromethoxy)pyrimidine-2-yl]cyclopentane-1,3-diamine

[0687]

[0688] tert-butyl N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]

[0689] Dichloromethane (10 mL) was added to [cyclopentyl]carbamate (1.70 g, 4.94 mmol) to dissolve it, and then trifluoroacetic acid (6.17 mL, 24.68 mmol) was added and stirred at room temperature for 16 hours. The reaction mixture was concentrated to obtain trans-(1S,3S)-3-N-[5-(difluoromethoxy)pyrimidine-2-yl]cyclopentane-1,3-diamine (1.20 g, 4.91 mmol, 99%), which was used in the next step without further purification.

[0690] ESI-MS m / z: 245.11[M+H] + .

[0691]

[0692] Preparation Example 2-3) N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-iodopyridine-2-carboxamide

[0693]

[0694] Trans-(1S,3S)-3-N-[5-(difluoromethoxy)pyrimidine-2-yl]cyclopentane-1,3-diamine (1.20 g, 4.91 mmol), 4-iodopicolinic acid (1.27 g, 4.91 mmol), HATU (2.86 g, 7.37 mmol) and N,N-diisopropylethylamine (4.32 mL, 24.57 mmol) were dissolved in dimethylformamide and stirred at room temperature for 16 hours. Distilled water (30 mL) was added to the reaction mixture and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by MPLC to prepare N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-iodopyridine-2-carboxamide (1.61 g, 3.39 mmol, 69%).

[0695] ESI-MS m / z: 476.03[M+H] + .

[0696]

[0697] Preparation Example 2-4) N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0698]

[0699] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-iodopyridine-2-carboxamide (50.00 mg, 0.10 mmol), 2-hydroxy-5-methoxypyridine (19.40 mg, 0.15 mmol), potassium carbonate (29.23 mg, 0.21 mmol), copper(I) iodide (4.01 mg, 0.02 mmol), and trans-N,N'-dimethylcyclohexane-1,2-diamine (2.99 mg, 0.02 mmol) were dissolved in dimethyl sulfoxide (2 mL) and stirred at 120°C for 16 hours. Distilled water (10 mL) was added to the reaction mixture and extracted with dichloromethane. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by prep-HPLC to prepare N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide (16.00 mg, 0.03 mmol, 32%).

[0700] ESI-MS m / z: 473.17[M+H] + .

[0701] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.66 (d, 1H, J=5.3 Hz), 8.1-8.2 (m, 3H), 8.06 (br d, 1H, J=7.8 Hz), 7.77 (br d, 1H, J=5.3 Hz), 7.3-7.3 (m, 1H), 6.82 (br s, 1H), 6.64 (d, 1H, J=9.9 Hz), 6.2-6.6 (m, 1H), 5.24 (br d, 1H, J=6.4 Hz), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 1H), 3.7-3.7 (m, 3H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 3H), 1.7-1.8 (m, 2H).

[0702]

[0703] The following manufacturing examples are examples of embodiments represented by Chemical Formula 1-1 of Reaction Scheme 3 above, and can be appropriately modified to correspond to the structure of the embodiment to be manufactured.

[0704]

[0705] Preparation Example 3-1) Methyl 3-(6-oxopyridazine-1(6H)-yl)benzoate

[0706]

[0707] Methyl 3-iodobenzoate (1.00 g, 3.81 mmol), 1H-pyridazine-6-one (561.28 mg, 5.72 mmol), potassium carbonate (1.06 g, 7.63 mmol), trans-N,N'-dimethylcyclohexane-1,2-diamine (54.28 mg, 0.38 mmol), and copper(I) iodide (145.50 mg, 0.76 mmol) were dissolved in dimethyl sulfoxide (10 mL) and stirred at room temperature for 16 hours. Distilled water (10 mL) was added to the reaction mixture and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered, and then concentrated. The residue was purified by MPLC to produce methyl 3-(6-oxopyridazine-1(6H)-yl)benzoate (450.00 mg, 1.95 mmol, 51%).

[0708] ESI-MS m / z: 231.07 [M+H] + .

[0709]

[0710] Preparation Example 3-2) 3-(6-oxopyridazine-1-yl)benzoic acid

[0711]

[0712] Methyl 3-(6-oxopyridazine-1(6H)-yl)benzoate (450.00 mg, 1.95 mmol) was dissolved in tetrahydrofuran (3 mL) and methanol (1.5 mL). A 2N aqueous sodium hydroxide solution (4.88 mmol, 2.44 mL) was slowly added to the reaction mixture, and the mixture was stirred at room temperature for 16 hours. The pH of the reaction mixture was adjusted to 4 using a 1N aqueous hydrochloric acid solution, and the resulting precipitate was filtered and dried. 3-(6-oxopyridazine-1-yl)benzoic acid (360.00 mg, 1.66 mmol) was obtained.

[0713] ESI-MS m / z: 216.05 [M+H] + .

[0714]

[0715] Preparation Example 3-3) N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-3-(6-oxopyridazine-1-yl)benzamide

[0716]

[0717] Trans-(1S,3S)-3-N-[5-(difluoromethoxy)pyrimidine-2-yl]cyclopentane-1,3-diamine (173.71 mg, 0.71 mmol), 3-(6-oxopyridazine-1-yl)benzoic acid (128.13 mg, 0.59 mmol), HATU (275.95 mg, 0.71 mmol) and N,N-diisopropylethylamine (0.15 mL, 0.88 mmol) were dissolved in dimethylformamide (2 mL) and stirred at room temperature for 16 hours. Distilled water (30 mL) was added to the reaction mixture and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by MPLC to produce N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-3-(6-oxopyridazine-1-yl)benzamide (43 mg, 0.09 mmol, 16%).

[0718] ESI-MS m / z: 443.16[M+H] + .

[0719] 1H NMR (DMSO-d6, 400 MHz) δ 8.51 (d, 1H, J=7.3 Hz), 8.24 (s, 2H), 8.10 (dd, 1H, J=1.6, 3.8 Hz), 8.0-8.0 (m, 1H), 7.92 (td, 1H, J=1.3, 8.0 Hz), 7.7-7.8 (m, 1H), 7.4-7.6 (m, 3H), 7.22 (s, 1H), 7.11 (dd, 1H, J=1.6, 9.5 Hz), 7.04 (s, 1H), 6.85 (s, 1H), 4.3-4.5 (m, 1H), 4.1-4.6 (m, 1H), 2.0-2.2 (m, 2H), 1.8-2.0 (m, 2H), 1.5-1.7 (m, 2H).

[0720]

[0721] Preparation Example 4-1) N-((1S,3S)-3-((Z)-2-hydroxyguanidino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[0722]

[0723] N-[(1S,3S)-3-aminocyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide (200.00 mg, 0.48 mmol) synthesized in Preparation Examples 1-3 was dissolved in tetrahydrofuran (5 mL), then cyanogen bromide (153.75 mg, 1.45 mmol) and sodium acetate (119.08 mg, 1.45 mmol) were added at 0 °C and stirred at room temperature for 16 hours. The reaction mixture was filtered through Celite and then concentrated.

[0724] The concentrated mixture, hydroxylamine hydrochloride (40.35 mg, 0.58 mmol), and triethylamine (97.92 mg, 0.97 mmol) were dissolved in ethanol (5 mL) and stirred at 50°C for 16 hours. The reaction mixture was concentrated to obtain N-((1S,3S)-3-((Z)-2-hydroxyguanidino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide (172.91 mg, 0.48 mmol, 99%), which was used in the next step without further purification.

[0725] ESI-MS m / z: 358.13[M+H]+.

[0726]

[0727] Preparation Example 4-2) N-((1S,3S)-3-((5-cyclopropyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[0728]

[0729] Cyclopropanecarboxylic acid (43.36 mg, 0.50 mmol) was dissolved in 1,2-dichloroethane (2 mL), then HATU (191.52 mg, 0.50 mmol) and N,N-diisopropylethylamine (97.65 mg, 0.76 mmol) were added and stirred at room temperature for 30 minutes. N-((1S,3S)-3-((Z)-2-hydroxyguanidino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide (90.00 mg, 0.25 mmol) was added to the reaction mixture and stirred at 80 °C for 3 hours. Distilled water (10 mL) was added to the reaction mixture and extracted with dichloromethane. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by MPLC to produce N-((1S,3S)-3-((5-cyclopropyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide (23.00 mg, 0.06 mmol, 22%).

[0730] ESI-MS m / z: 408.02[M+H]+.

[0731] 1H NMR (500 MHz, Chloroform-d) δ 8.62 (d, J = 5.4 Hz, 1H), 8.56 (d, J = 2.1 Hz, 1H), 8.05 - 8.00 (m, 2H), 7.96 (dd, J = 3.7, 1.7 Hz, 1H), 7.06 (dd, J = 9.5, 1.7 Hz, 1H), 4.60 (q, J = 7.0 Hz, 1H), 4.29 (d, J = 6.7 Hz, 1H), 4.10 (q, J = 6.4 Hz, 1H), 2.37 - 2.28 (m, 2H), 2.13 - 2.07 (m, 2H), 2.06 - 2.00 (m, 1H), 1.66 - 1.60 (m, 3H), 1.14 (dt, J = 8.7, 2.7 Hz, 4H).

[0732]

[0733] Preparation Example 5-1) 4-(dibenzo[b,d]furan-4-yl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide

[0734]

[0735]

[0736] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-iodopyridine-2-carboxamide (50.00 mg, 0.10 mmol) synthesized in Preparation Example 2-3 was dissolved in 1,4-dioxane (1.5 mL), then dibenzofuran-4-ylboronic acid (44.61 mg, 0.21 mmol), Pd(dppf)Cl2.CH2Cl2 (8.59 mg, 0.01 mmol), and cesium carbonate (102.84 mg, 0.32 mmol) were added, and the mixture was stirred at 100 °C for 18 hours. Distilled water (10 mL) was added to the reaction mixture, and it was extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered, and then concentrated. The residue was purified by MPLC to prepare 4-(dibenzo[b,d]furan-4-yl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide (30.00 mg, 0.06 mmol, 55%).

[0737] ESI-MS m / z: 516.13[M+H]+.

[0738] 1H NMR (500 MHz, Chloroform-d) δ 8.73 (dd, J = 1.8, 0.8 Hz, 1H), 8.69 (dd, J = 5.1, 0.8 Hz, 1H), 8.18 (d, J = 11.0 Hz, 3H), 8.11 (dd, J = 5.1, 1.9) Hz, 1H), 8.05 (dd, J = 7.6, 1.2 Hz, 1H), 8.02 - 7.99 (m, 1H), 7.77 (dd, J = 7.7, 1.2 Hz, 1H), 7.65 (d, J = 8.2 Hz, 1H), 7.53 - 7.47 (m, 2H), 7.40 (td, J = 7.4, 0.9 Hz, 1H), 6.48 (d, J = 72.9 Hz, 1H), 5.25 (d, J = 7.0 Hz, 1H), 4.67 (h, J = 7.0 Hz, 1H), 4.47 (h, J = 6.8 Hz, 1H), 2.42 - 2.36 (m, 2H), 2.18 (dt, J = 13.8, 7.0 Hz, 1H), 2.14 - 2.07 (m, 1H), 1.72 (ddd, J = 14.0, 10.4, 6.3 Hz, 1H), 1.66 - 1.60 (m, 1H).

[0739]

[0740] Examples of the compounds of the present invention are described below.

[0741] Example 1: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0742]

[0743] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 1] (11%) was prepared in the same manner as in Preparation Examples 1-4.

[0744] ESI-MS m / z: 417.20[M+H] + .

[0745] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.74 - 8.84 (m, 2 H) 8.07 (s, 3 H) 7.77 (td, J=5.66, 1.81 Hz, 2 H) 7.56 (ddd, J=9.13, 6.75, 2.00 Hz, 1 H) 7.03 (d, J=7.25 Hz, 1 H) 6.55 (d, J=9.01 Hz, 1 H) 6.40 (td, J=6.79, 1.31 Hz, 1 H) 4.48 (sxt, J=7.45 Hz, 1 H) 4.35 (dq, J=13.26, 6.75 Hz, 1 H) 2.03 - 2.16 (m, 2 H) 1.94 - 2.02 (m, 1 H) 1.84 - 1.92 (m, 1 H) 1.70 - 1.76 (m, 1 H) 1.61 - 1.69 (m, 1 H) 1.48 - 1.59 (m, 1 H) 0.80 - 0.87 (m, 2 H) 0.57 - 0.63 (m, 2 H).

[0746]

[0747] Example 2: Synthesis of N-[(1S,3S)-3-[(5-methoxypyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0748]

[0749] N-[(1S,3S)-3-[(5-methoxypyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 2] (14%) was prepared by a method similar to that of Preparation Examples 1-4.

[0750] ESI-MS m / z: 407.18[M+H] + .

[0751] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.75 - 8.82 (m, 2 H) 8.11 (s, 2 H) 8.07 (d, J=2.13 Hz, 1 H) 7.75 - 7.80 (m, 2 H) 7.56 (ddd, J=9.13, 6.75, 2.00 Hz, 1 H) 6.87 (d, J=7.13 Hz, 1 H) 6.55 (d, J=9.01 Hz, 1 H) 6.40 (td, J=6.75, 1.38 Hz, 1 H) 4.48 (sxt, J=7.48 Hz, 1 H) 4.30 (dq, J=13.24, 6.80 Hz, 1 H) 3.74 (s, 3 H) 2.04 - 2.16 (m, 2 H) 1.94 - 2.03 (m, 1 H) 1.84 - 1.92 (m, 1 H) 1.61 - 1.71 (m, 1 H) 1.50 - 1.59 (m, 1 H).

[0752]

[0753] Example 3: Synthesis of N-[(1S,3S)-3-[(5-ethoxypyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0754]

[0755] N-[(1S,3S)-3-[(5-ethoxypyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 3] (21%) was prepared by a method similar to that of Preparation Examples 1-4.

[0756] ESI-MS m / z: 421.19[M+H] + .

[0757] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.80 (d, J=5.38 Hz, 1 H) 8.77 (d, J=8.00 Hz, 1 H) 8.10 (s, 2 H) 8.08 (d, J=2.13 Hz, 1 H) 7.75 - 7.80 (m, 2 H) 7.56 (ddd, J=9.13, 6.75, 2.00 Hz, 1 H) 6.86 (d, J=7.13 Hz, 1 H) 6.55 (d, J=9.26 Hz, 1 H) 6.40 (td, J=6.75, 1.25 Hz, 1 H) 4.48 (sxt, J=7.50 Hz, 1 H) 4.30 (sxt, J=6.73 Hz, 1 H) 3.99 (q, J=6.92 Hz, 2 H) 2.04 - 2.16 (m, 2 H) 1.95 - 2.02 (m, 1 H) 1.85 - 1.92 (m, 1 H) 1.61 - 1.71 (m, 1 H) 1.49 - 1.59 (m, 1 H) 1.28 (t, J=7.00 Hz, 3 H).

[0758]

[0759] Example 4: Synthesis of N-[(1S,3S)-3-[(5-fluoropyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0760]

[0761] N-[(1S,3S)-3-[(5-fluoropyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 4] (30%) was prepared by a method similar to that of Preparation Examples 1-4.

[0762] ESI-MS m / z: 395.16[M+H] + .

[0763] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.77 - 8.83 (m, 2 H) 8.35 (d, J=0.88 Hz, 2 H) 8.08 (d, J=2.13 Hz, 1 H) 7.74 - 7.80 (m, 2 H) 7.56 (ddd, J=9.13, 6.75, 2.00 Hz, 1 H) 7.34 (d, J=7.13 Hz, 1 H) 6.55 (d, J=9.26 Hz, 1 H) 6.40 (td, J=6.72, 1.31 Hz, 1 H) 4.49 (sxt, J=7.50 Hz, 1 H) 4.31 (sxt, J=6.70 Hz, 1 H) 2.05 - 2.17 (m, 2 H) 1.95 - 2.04 (m, 1 H) 1.85 - 1.94 (m, 1 H) 1.61 - 1.72 (m, 1 H) 1.50 - 1.61 (m, 1 H).

[0764]

[0765] Example 5: Synthesis of N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0766]

[0767] N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 5] (29%) was prepared by a method similar to that of Preparation Examples 1-4.

[0768] ESI-MS m / z: 411.13[M+H] + .

[0769] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.76 - 8.84 (m, 2 H) 8.32 (s, 2 H) 8.08 (d, J=2.00 Hz, 1 H) 7.74 - 7.80 (m, 2 H) 7.52 - 7.62 (m, 2 H) 6.54 (d, J=9.26 Hz, 1 H) 6.40 (td, J=6.75, 1.25 Hz, 1 H) 4.49 (sxt, J=7.50 Hz, 1 H) 4.34 (sxt, J=6.75 Hz, 1 H) 2.05 - 2.17 (m, 2 H) 1.96 - 2.05 (m, 1 H) 1.86 - 1.95 (m, 1 H) 1.61 - 1.72 (m, 1 H) 1.51 - 1.61 (m, 1 H).

[0770]

[0771] Example 6: Synthesis of 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-propane-2-ylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[0772]

[0773] 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-propane-2-ylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [Example 6] (52%) was prepared by a method similar to that of Preparation Examples 1-4.

[0774] ESI-MS m / z: 419.21[M+H] + .

[0775] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.75 - 8.82 (m, 2 H) 8.18 (s, 2 H) 8.08 (d, J=1.63 Hz, 1 H) 7.75 - 7.80 (m, 2 H) 7.56 (ddd, J=9.10, 6.72, 2.06 Hz, 1 H) 7.04 (d, J=7.25 Hz, 1 H) 6.55 (d, J=9.01 Hz, 1 H) 6.40 (td, J=6.75, 1.25 Hz, 1 H) 4.48 (sxt, J=7.48 Hz, 1 H) 4.36 (sxt, J=6.75 Hz, 1 H) 2.68 - 2.80 (m, 1 H) 2.04 - 2.16 (m, 2 H) 1.94 - 2.03 (m, 1 H) 1.85 - 1.94 (m, 1 H) 1.61 - 1.72 (m, 1 H) 1.49 - 1.60 (m, 1 H) 1.17 (d, J=7.00 Hz, 6 H).

[0776]

[0777] Example 7: Synthesis of N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0778]

[0779] N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 7] (56%) was prepared by a method similar to that of Preparation Examples 1-4.

[0780] ESI-MS m / z: 423.15[M+H] + .

[0781] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.77 - 8.84 (m, 2 H) 8.34 (s, 2 H) 8.08 (d, J=1.75 Hz, 1 H) 7.75 - 7.80 (m, 2 H) 7.50 - 7.59 (m, 2 H) 6.55 (d, J=9.01 Hz, 1 H) 6.40 (td, J=6.79, 1.31 Hz, 1 H) 4.49 (sxt, J=7.50 Hz, 1 H) 4.38 (dq, J=13.34, 6.81 Hz, 1 H) 2.35 (s, 3 H) 2.04 - 2.17 (m, 2H) 1.96 - 2.04 (m, 1 H) 1.87 - 1.95 (m, 1 H) 1.62 - 1.72 (m, 1 H) 1.51 - 1.62 (m, 1 H).

[0782]

[0783] Example 8: Synthesis of 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0784]

[0785] 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 8] (56%) was prepared by a method similar to that of Preparation Examples 1-4.

[0786] ESI-MS m / z: 445.15[M+H] + .

[0787] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.85 (d, J=8.13 Hz, 1 H) 8.80 (d, J=5.25 Hz, 1 H) 8.62 (br d, J=17.26 Hz, 2 H) 8.21 (d, J=7.38 Hz, 1 H) 8.08 (d, J=2.13 Hz, 1 H) 7.75 - 7.80 (m, 2 H) 7.56 (ddd, J=9.13, 6.75, 2.00 Hz, 1 H) 6.53 - 6.57 (m, 1 H) 6.40 (td, J=6.75, 1.25 Hz, 1 H) 4.49 (tq, J=14.99, 7.35 Hz, 2 H) 2.08 - 2.20 (m, 2 H) 2.00 - 2.07 (m, 1 H) 1.90 - 1.98 (m, 1 H) 1.65 - 1.75 (m, 1 H) 1.54 - 1.64 (m, 1 H).

[0788]

[0789] Example 9: Synthesis of N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0790]

[0791] N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 9] (45%) was prepared by a method similar to that of Preparation Examples 1-4.

[0792] ESI-MS m / z: 403.18[M+H] + .

[0793] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.78 - 8.84 (m, 2 H) 8.43 (s, 2 H) 8.08 (d, J=1.63 Hz, 1 H) 7.75 - 7.80 (m, 2 H) 7.56 (ddd, J=9.16, 6.72, 2.00 Hz, 1 H) 7.45 (d, J=7.25 Hz, 1 H) 6.48 - 6.57 (m, 2 H) 6.40 (td, J=6.75, 1.25 Hz, 1 H) 5.70 (dd, J=17.76, 0.88 Hz, 1 H) 5.06 - 5.12 (m, 1 H) 4.45 - 4.55 (m, 1 H) 4.37 - 4.45 (m, 1 H) 2.06 - 2.16 (m, 2 H) 1.97 - 2.06 (m, 1 H) 1.87 - 1.95 (m, 1 H) 1.62 - 1.73 (m, 1 H) 1.51 - 1.62 (m, 1 H).

[0794]

[0795] Example 10: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0796]

[0797] N-[(1S,3S)-3-[[5-(difluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 10] (61%) was prepared by a method similar to that of Preparation Examples 1-4.

[0798] ESI-MS m / z: 427.16[M+H] + .

[0799] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.83 (d, J=8.13 Hz, 1 H) 8.80 (d, J=5.25 Hz, 1 H) 8.47 (br s, 2 H) 8.08 (d, J=2.13 Hz, 1 H) 7.88 (d, J=7.25 Hz, 1 H) 7.75 - 7.80 (m, 2 H) 7.56 (ddd, J=9.13, 6.75, 2.00 Hz, 1 H) 6.78 - 7.08 (m, 1 H) 6.55 (d, J=9.38 Hz, 1 H) 6.40 (td, J=6.75, 1.25 Hz, 1 H) 4.39 - 4.56 (m, 2 H) 2.06 - 2.19 (m, 2 H) 1.99 - 2.06 (m, 1 H) 1.88 - 1.97 (m, 1 H) 1.64 - 1.75 (m, 1 H) 1.53 - 1.63 (m, 1 H).

[0800]

[0801] Example 11: Synthesis of N-[(1S,3S)-3-(6,7-dihydro-5H-cyclopenta[d]pyrimidine-2-ylamino)cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0802]

[0803] N-[(1S,3S)-3-(6,7-dihydro-5H-cyclopenta[d]pyrimidine-2-ylamino)cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 11] (70%) was prepared by a method similar to that of Preparation Examples 1-4.

[0804] ESI-MS m / z: 417.20[M+H] + .

[0805] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.76 - 8.81 (m, 2 H) 8.06 - 8.09 (m, 2 H) 7.75 - 7.80 (m, 2 H) 7.56 (ddd, J=9.16, 6.72, 2.00 Hz, 1 H) 6.95 (d, J=7.38 Hz, 1 H) 6.52 - 6.57 (m, 1 H) 6.40 (td, J=6.75, 1.25 Hz, 1 H) 4.48 (sxt, J=7.48 Hz, 1 H) 4.38 (dq, J=13.35, 6.89 Hz, 1 H) 2.70 (td, J=7.47, 3.81 Hz, 4 H) 2.04 - 2.16 (m, 2 H) 1.93 - 2.02 (m, 3 H) 1.84 - 1.92 (m, 1 H) 1.61 - 1.71 (m, 1 H) 1.48 - 1.58 (m, 1 H).

[0806]

[0807] Example 12: Synthesis of 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(trifluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0808]

[0809] 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(trifluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 12] (68%) was prepared by a method similar to that of Preparation Examples 1-4.

[0810] ESI-MS m / z: 477.12[M+H] + .

[0811] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.85 (d, J=8.13 Hz, 1 H) 8.80 (d, J=5.75 Hz, 1 H) 8.45 - 8.56 (m, 2 H) 8.19 (d, J=7.38 Hz, 1 H) 8.08 (d, J=1.63 Hz, 1 H) 7.76 - 7.80 (m, 2 H) 7.56 (ddd, J=9.10, 6.72, 2.06 Hz, 1 H) 6.55 (d, J=8.88 Hz, 1 H) 6.40 (td, J=6.75, 1.25 Hz, 1 H) 4.40 - 4.56 (m, 2H) 2.07 - 2.17 (m, 2 H) 1.99 - 2.06 (m, 1 H) 1.89 - 1.97 (m, 1 H) 1.64 - 1.75 (m, 1 H) 1.54 - 1.64 (m, 1 H).

[0812]

[0813] Example 13: Synthesis of N-[(1S,3S)-3-[(5-ethylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0814]

[0815] N-[(1S,3S)-3-[(5-ethylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 13] (8%) was prepared in a manner similar to Preparation Examples 1-4.

[0816] ESI-MS m / z: 405.20[M+H] +

[0817] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.76 - 8.82 (m, 2 H) 8.15 (s, 2 H) 8.07 (d, J=2.13 Hz, 1 H) 7.75 - 7.80 (m, 2 H) 7.56 (ddd, J=9.13, 6.75, 2.00 Hz, 1 H) 7.02 (d, J=7.38 Hz, 1 H) 6.52 - 6.57 (m, 1 H) 6.40 (td, J=6.75, 1.25 Hz, 1 H) 4.48 (sxt, J=7.55 Hz, 1 H) 4.36 (dq, J=13.38, 6.84 Hz, 1 H) 2.40 (q, J=7.50 Hz, 2 H) 2.04 - 2.16 (m, 2 H) 1.95 - 2.03 (m, 1 H) 1.85 - 1.94 (m, 1 H) 1.61 - 1.72 (m, 1 H) 1.49 - 1.59 (m, 1 H) 1.12 (t, J=7.57 Hz, 3 H).

[0818]

[0819] Example 14: Synthesis of N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(3-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0820]

[0821] N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(3-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 14] (53%) was prepared by a method similar to that of Preparation Examples 1-4.

[0822] ESI-MS m / z: 442.13[M+H] + .

[0823] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.8 (m, 2H), 8.32 (s, 2H), 8.05 (d, 1H, J=2.1 Hz), 7.75 (dd, 1H, J=2.1, 5.3 Hz), 7.58 (d, 1H, J=7.3) Hz), 7.34 (dd, 1H, J=1.6, 7.1 Hz), 6.93 (dd, 1H, J=1.5, 7.5 Hz), 6.34 (t, 1H, J=7.2 Hz), 4.49 (sxt, 1H, J=7.5 Hz), 4.34 (qd, 1H, J=6.8, 13.2 Hz), 3.76 (s, 3H), 2.0-2.2 (m, 3H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[0824]

[0825] Example 15: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide

[0826]

[0827] N-[(1S,3S)-3-[[5-(difluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 15] (19%) was prepared by a method similar to that of Preparation Examples 1-4.

[0828] ESI-MS m / z: 460.13[M+H] + .

[0829] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.9 (m, 2H), 8.3-8.4 (m, 2H), 8.08 (d, 1H, J=2.1 Hz), 7.96 (d, 1H, J=7.3 Hz), 7.7-7.8 (m, 2H), 7.56 (ddd, 1H, J=2.0, 6.8, 9.1 Hz), 7.1-7.5 (m, 1H), 6.55 (d, 1H, J=9.3 Hz), 6.41 (dt, 1H, J=1.3, 6.8 Hz), 4.4-4.6 (m, 2H), 2.0-2.2 (m, 3H), 1.9-2.0 (m, 1H), 1.5-1.7 (m, 2H).

[0830]

[0831] Example 16: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide

[0832]

[0833] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide [Example 16] (36%) was prepared by a method similar to that of Preparation Examples 1-4.

[0834] ESI-MS m / z: 448.21[M+H] + .

[0835] 1H NMR (DMSO-d6, 400 MHz) δ 8.68 (d, 1H, J=8.3 Hz), 8.62 (d, 1H, J=5.6 Hz), 8.53 (d, 1H, J=1.9 Hz), 8.07 (s, 2H), 8.02 (dd, 1H, J=2.3, 5.6 Hz), 7.03 (d, 1H, J=7.3 Hz), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 3.76 (t, 2H, J=7.1 Hz), 2.87 (t, 2H, J=7.7 Hz), 2.53 (br d, 2H, J=1.9 Hz), 2.0-2.1 (m, 2H), 1.8-2.0 (m, 2H), 1.7-1.8 (m, 1H), 1.5-1.7 (m, 2H), 0.8-0.9 (m, 2H), 0.6-0.6 (m, 2H).

[0836]

[0837] Example 17: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide

[0838]

[0839] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide [Example 17] (57%) was prepared by a method similar to that of Preparation Examples 1-4.

[0840] ESI-MS m / z: 474.17[M+H] + .

[0841] 1H NMR (DMSO-d6, 400 MHz) δ 8.71 (d, 1H, J=8.1 Hz), 8.62 (d, 1H, J=5.5 Hz), 8.53 (d, 1H, J=2.1 Hz), 8.24 (s, 2H), 8.02 (dd, 1H, J=2.3, 5.6 Hz), 7.49 (d, 1H, J=7.1 Hz), 7.22 (s, 1H), 7.04 (s, 1H), 6.85 (s, 1H), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 3.76 (t, 2H, J=7.0 Hz), 2.8-2.9 (m, 2H), 2.5-2.5 (m, 2H), 2.0-2.1 (m, 2H), 1.9-2.0 (m, 2H), 1.5-1.7 (m, 2H).

[0842]

[0843] Example 18: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0844]

[0845] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide [Example 18] (44%) was prepared by a method similar to that of Preparation Examples 1-4.

[0846] ESI-MS m / z: 462.23[M+H] + .

[0847] 1H NMR (DMSO-d6, 400 MHz) δ 8.68 (d, 1H, J=8.1 Hz), 8.64 (d, 1H, J=5.6 Hz), 8.55 (d, 1H, J=2.1 Hz), 8.0-8.1 (m, 3H), 7.01 (d, 1H, J=7.3 Hz), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 3.6-3.6 (m, 2H), 2.7-2.8 (m, 2H), 2.0-2.1 (m, 2H), 1.8-1.9 (m, 6H), 1.7-1.8 (m, 1H), 1.5-1.7 (m, 2H), 0.8-0.9 (m, 2H), 0.6-0.6 (m, 2H).

[0848]

[0849] Example 19: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0850]

[0851] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide [Example 19] (68%) was prepared by a method similar to that of Preparation Examples 1-4.

[0852] ESI-MS m / z: 488.19[M+H] + .

[0853] 1H NMR (DMSO-d6, 400 MHz) δ 8.71 (d, 1H, J=8.1 Hz), 8.64 (d, 1H, J=5.6 Hz), 8.55 (d, 1H, J=1.8 Hz), 8.24 (s, 2H), 8.06 (dd, 1H, J=2.3, 5.6 Hz), 7.48 (d, 1H, J=7.1 Hz), 7.22 (s, 1H), 7.03 (s, 1H), 6.85 (s, 1H), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 3.59 (t, 2H, J=6.1 Hz), 2.7-2.8 (m, 2H), 2.0-2.1 (m, 2H), 1.9-2.0 (m, 1H), 1.8-1.9 (m, 5H), 1.5-1.7 (m, 2H).

[0854]

[0855] Example 20: Synthesis of N-[(1S,3S)-3-[(5-ethoxypyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0856]

[0857] N-[(1S,3S)-3-[(5-ethoxypyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 20] (13%) was prepared by a method similar to that of Preparation Examples 1-4.

[0858] ESI-MS m / z: 423.18[M+H] + .

[0859] 1H NMR (DMSO-d6, 400 MHz) δ 8.77 (d, 1H, J=5.6 Hz), 8.74 (d, 1H, J=8.3 Hz), 8.38 (d, 1H, J=2.1 Hz), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.09 (s, 2H), 8.00 (dd, 1H, J=2.3, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 6.85 (d, 1H, J=7.1 Hz), 4.4-4.5 (m, 1H), 4.2-4.3 (m, 1H), 3.99 (q, 2H, J=6.9 Hz), 2.0-2.1 (m, 2H), 1.9-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.6-1.7 (m, 1H), 1.5-1.6 (m, 1H).

[0860]

[0861] Example 21: Synthesis of N-[(1S,3S)-3-[(5-methoxypyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0862]

[0863] N-[(1S,3S)-3-[(5-methoxypyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 21] (8%) was prepared by a method similar to that of Preparation Examples 1-4.

[0864] ESI-MS m / z: 409.17[M+H] + .

[0865] 1H NMR (DMSO-d6, 400 MHz) δ 8.7-8.8 (m, 2H), 8.38 (d, 1H, J=2.1 Hz), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.11 (s, 2H), 8.00 (dd, 1H, J=2.3, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 6.86 (d, 1H, J=7.3 Hz), 4.48 (sxt, 1H, J=7.5 Hz), 4.30 (qd, 1H, J=6.8, 13.2 Hz), 3.74 (s, 3H), 2.0-2.2 (m, 2H), 1.99 (td, 2H, J=7.3, 19.3 Hz), 1.5-1.7 (m, 2H).

[0866]

[0867] Example 22: Synthesis of 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0868]

[0869] 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 22] (46%) was prepared by a method similar to that of Preparation Examples 1-4.

[0870] ESI-MS m / z: 446.15[M+H] + .

[0871] 1H NMR (DMSO-d6, 400 MHz) δ 8.83 (d, 1H, J=8.1 Hz), 8.78 (d, 1H, J=5.4 Hz), 8.64 (s, 1H), 8.60 (s, 1H), 8.38 (d, 1H, J=2.1 Hz), 8.2-8.2 (m, 2H), 8.00 (dd, 1H, J=2.1, 5.4 Hz), 7.55 (dd, 1H, J=3.8, 9.6 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 4.49 (dt, 2H, J=7.6, 15.3 Hz), 2.1-2.2 (m, 2H), 1.9-2.1 (m, 2H), 1.6-1.7 (m, 2H).

[0872]

[0873] Example 23: Synthesis of N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0874]

[0875] N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 23] (44%) was prepared in a manner similar to Preparation Examples 1-4.

[0876] ESI-MS m / z: 412.12[M+H] + .

[0877] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.8 (m, 2H), 8.38 (s, 1H), 8.33 (s, 2H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.00 (dd, 1H, J=2.3, 5.4 Hz), 7.59 (d, 1H, J=7.3 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 2.0-2.2 (m, 2H), 2.0-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[0878]

[0879] Example 24: Synthesis of N-[(1S,3S)-3-[(5-fluoropyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0880]

[0881] N-[(1S,3S)-3-[(5-fluoropyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 24] (43%) was prepared by a method similar to that of Preparation Examples 1-4.

[0882] ESI-MS m / z: 395.15[M+H] + .

[0883] 1H NMR (DMSO-d6, 400 MHz) δ 8.78 (d, 2H, J=5.9 Hz), 8.4-8.4 (m, 1H), 8.35 (d, 2H, J=0.9 Hz), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.08 (s, 1H), 8.0-8.0 (m, 1H), 7.55 (dd, 1H, J=3.8, 9.6 Hz), 7.34 (d, 1H, J=7.1 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 4.49 (sxt, 1H, J=7.4 Hz), 4.1-4.4 (m, 1H), 2.0-2.2 (m, 3H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[0884]

[0885] Example 25: Synthesis of N-[(1S,3S)-3-[(5-cyclopropyl-4-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0886]

[0887] N-[(1S,3S)-3-[(5-cyclopropyl-4-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 25] (24%) was prepared by a method similar to that of Preparation Examples 1-4.

[0888] ESI-MS m / z: 464.18[M+H] + .

[0889] 1H NMR (DMSO-d6, 400 MHz) δ 8.7-8.8 (m, 2H), 8.38 (d, 1H, J=1.6 Hz), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 7.99 (dd, 1H, J=2.1, 5.4 Hz), 7.73 (s, 1H), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.1-7.2 (m, 2H), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 2.5-2.5 (m, 3H), 2.0-2.2 (m, 2H), 1.9-2.0 (m, 2H), 1.5-1.7 (m, 3H), 0.8-0.9 (m, 2H), 0.5-0.6 (m, 2H).

[0890]

[0891] Example 26: Synthesis of 4-(6-oxopyridazine-1-yl)-N-[3-(pyrimidine-2-ylamino)cyclopentyl]pyridine-2-carboxamide

[0892]

[0893] 4-(6-oxopyridazine-1-yl)-N-[3-(pyrimidine-2-ylamino)cyclopentyl]pyridine-2-carboxamide [Example 26] (21%) was prepared by a method similar to that of Preparation Examples 1-4.

[0894] ESI-MS m / z: 378.16[M+H] + .

[0895] 1H NMR (DMSO-d6, 400 MHz) δ 8.79 (s, 1H), 8.77 (s, 1H), 8.38 (d, 1H, J=2.3 Hz), 8.26 (d, 2H, J=4.8 Hz), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.00 (dd, 1H, J=2.3, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.24 (d, 1H, J=7.4 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 6.54 (t, 1H, J=4.8 Hz), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 2.0-2.2 (m, 2H), 2.0-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[0896]

[0897] Example 27: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0898]

[0899] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide [Example 27] (8%) was prepared by a method similar to that of Preparation Examples 1-4.

[0900] ESI-MS m / z: 457.20 [M+H] + .

[0901] 1H NMR (DMSO-d6, 400 MHz) δ 8.7-8.8 (m, 3H), 8.24 (dd, 1H, J=2.3, 5.4 Hz), 8.08 (s, 2H), 7.98 (d, 1H, J=7.0 Hz), 7.38 (d, 2H, J=4.5 Hz), 7.37 (s, 1H),7.04 (d, 1H, J=7.3 Hz), 6.70 (ddd, 1H, J=2.6, 4.8, 7.2 Hz), 4.4-4.5 (m, 1H), 4.34 (br d, 1H, J=6.1 Hz), 2.0-2.2 (m, 2H), 1.9-2.0 (m, 2H), 1.6-1.8 (m, 2H).

[0902]

[0903] Example 28: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[0904]

[0905] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide [Example 28] (21%) was prepared by a method similar to that of Preparation Examples 1-4.

[0906] ESI-MS m / z: 483.16 [M+H] + .

[0907] 1H NMR (DMSO-d6, 400 MHz) δ 8.7-8.8 (m, 3H), 8.2-8.3 (m, 3H), 7.98 (d, 1H, J=6.7 Hz), 7.50 (d, 1H, J=7.3 Hz), 7.4-7.4 (m, 2H), 7.03 (t, 1H, J=1.0 Hz), 6.70 (ddd, 1H, J=2.5, 4.8, 7.2 Hz), 4.50 (br d, 1H, J=7.6 Hz), 4.35 (br d, 1H, J=6.1 Hz), 2.1-2.2 (m, 2H), 1.9-2.1 (m, 2H), 1.67 (br dd, 1H, J=8.2, 12.6 Hz), 1.5-1.6 (m, 1H).

[0908]

[0909] Example 29: Synthesis of 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]pyridine-2-carboxamide

[0910]

[0911] 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]pyridine-2-carboxamide [Example 29] (81%) was prepared by a method similar to that of Preparation Examples 1-4.

[0912] ESI-MS m / z: 417.17 [M+H] + .

[0913] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.8 (m, 3H), 8.39 (d, 1H, J=2.1 Hz), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.00 (dd, 1H, J=2.3, 5.4 Hz), 7.6-7.6 (m, 1H), 7.54 (dd, 1H, J=3.8, 9.5 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 6.93 (d, 1H, J=7.1 Hz), 6.68 (dd, 1H, J=1.5, 4.5 Hz), 6.60 (dd, 1H, J=2.4, 4.5 Hz), 4.50 (sxt, 1H, J=7.5 Hz), 4.2-4.3 (m, 1H), 2.0-2.2 (m, 2H), 1.9-2.0 (m, 2H), 1.5-1.7 (m, 2H).

[0914]

[0915] Example 30: Synthesis of N-[(1S,3S)-3-(5,7-dihydrofuro[3,4-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0916]

[0917] N-[(1S,3S)-3-(5,7-dihydrofuro[3,4-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 30] (67%) was prepared by a method similar to that of Preparation Examples 1-4.

[0918] ESI-MS m / z: 420.17 [M+H] + .

[0919] 1H NMR (DMSO-d6, 400 MHz) δ 8.7-8.8 (m, 2H), 8.4-8.4 (m, 1H), 8.24 (s, 1H), 8.18 (dd, 1H, J=1.8, 3.8 Hz), 8.00 (dd, 1H, J=2.1, 5.4 Hz), 7.55 (dd, 1H, J=3.8, 9.5 Hz), 7.33 (br d, 1H, J=7.3 Hz), 7.15 (dd, 1H, J=1.5, 9.5 Hz), 4.92 (s, 2H), 4.72 (s, 2H), 4.4-4.6 (m, 2H), 2.1-2.2 (m, 2H), 2.0-2.1 (m, 1H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[0920]

[0921] Example 31: Synthesis of N-[(1S,3S)-3-(6,7-dihydro-5H-cyclopenta[d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0922]

[0923] N-[(1S,3S)-3-(6,7-dihydro-5H-cyclopenta[d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 31] (6%) was prepared by a method similar to that of Preparation Examples 1-4.

[0924] ESI-MS m / z: 418.19 [M+H] + .

[0925] 1H NMR (DMSO-d6, 400 MHz) δ 8.7-8.8 (m, 2H), 8.38 (d, 1H, J=2.0 Hz), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.08 (s, 1H), 8.00 (dd, 1H, J=2.1, 5.4 Hz), 7.55 (dd, 1H, J=3.8, 9.5 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 6.95 (d, 1H, J=7.5 Hz), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 2.70 (dt, 6H, J=3.6, 7.4 Hz), 2.0-2.1 (m, 3H), 1.65 (td, 1H, J=7.6, 12.4 Hz), 1.4-1.6 (m, 2H).

[0926]

[0927] Example 32: Synthesis of N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0928]

[0929] N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 32] (59%) was prepared by a method similar to that of Preparation Examples 1-4.

[0930] ESI-MS m / z: 424.15 [M+H] + .

[0931] 1H NMR (DMSO-d6, 400 MHz) δ 8.76 (d, 1H, J=5.4 Hz), 8.66 (d, 1H, J=8.3 Hz), 8.4-8.4 (m, 1H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 7.98 (dd, 1H, J=2.1, 5.4 Hz),7.54 (dd, 1H, J=3.8, 9.5 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 4.4-4.6 (m, 1H), 3.4-3.5 (m, 2H), 2.0-2.1 (m, 1H), 1.9-2.0 (m, 1H), 1.7-1.8 (m, 1H), 1.6-1.7 (m, 1H), 1.5-1.6 (m, 1H), 1.2-1.3 (m, 1H).

[0932]

[0933] Example 33: Synthesis of N-[(1S,3S)-3-[(5-ethynylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0934]

[0935] N-[(1S,3S)-3-[(5-ethynylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 33] (70%) was prepared in a manner similar to Preparation Examples 1-4.

[0936] ESI-MS m / z: 402.16 [M+H] + .

[0937] 1H NMR (DMSO-d6, 400 MHz) δ 8.76 (d, 1H, J=5.4 Hz), 8.66 (d, 1H, J=8.3 Hz), 8.4-8.4 (m, 1H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 7.98 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.5 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 4.4-4.6 (m, 1H), 3.4-3.5 (m, 2H), 2.0-2.1 (m, 1H), 1.9-2.0 (m, 1H), 1.7-1.8 (m, 1H), 1.6-1.7 (m, 1H), 1.5-1.6 (m, 1H), 1.2-1.3 (m, 1H).

[0938]

[0939] Example 34: Synthesis of 3-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]benzamide

[0940]

[0941] 3-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]benzamide [Example 34] (31%) was prepared in a manner similar to that of Preparation Examples 1-4.

[0942] ESI-MS m / z: 416.18 [M+H] + .

[0943] 1H NMR (DMSO-d6, 400 MHz) Shift 8.78 (s, 1H), 8.53 (d, 1H, J=7.3 Hz), 8.11 (dd, 1H, J=1.6, 3.8 Hz), 8.03 (t, 1H, J=1.7 Hz), 7.9-7.9 (m, 1H), 7.7-7.7 (m, 1H), 7.6-7.6 (m, 2H), 7.5-7.6 (m, 1H), 7.1-7.1 (m, 1H), 6.94 (d, 1H, J=7.1 Hz), 6.68 (dd, 1H, J=1.5, 4.5 Hz), 6.60 (dd, 1H, J=2.4, 4.5 Hz), 4.46 (br d, 1H, J=7.1 Hz), 4.21 (br d, 1H, J=6.9 Hz), 2.1-2.2 (m, 2H), 1.97 (t, 2H, J=7.0 Hz), 1.58 (br d, 2H, J=5.1 Hz).

[0944]

[0945] Example 35: Synthesis of N-[(1S,3S)-3-(6,7-dihydrothieno[3,2-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0946]

[0947] N-[(1S,3S)-3-(6,7-dihydrothieno[3,2-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 35] (20%) was prepared in a manner similar to Preparation Examples 1-4.

[0948] ESI-MS m / z: 436.15 [M+H] + .

[0949] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.8 (m, 2H), 8.7-8.8 (m, 1H), 8.6-8.9 (m, 1H), 8.37 (d, 1H, J=2.3 Hz), 8.17 (dd, 1H, J=1.6, 3.8 Hz), 8.08 (s, 1H), 8.0-8.1 (m, 1H), 7.98 (dd, 1H, J=2.1, 5.4 Hz), 7.53 (dd, 1H, J=3.8, 9.5 Hz), 7.14 (dd, 1H, J=1.6, 9.5 Hz), 7.06 (d, 1H, J=7.3 Hz), 7.0-7.2 (m, 1H), 4.2-4.6 (m, 1H), 3.55 (s, 1H), 3.3-3.3 (m, 2H), 3.1-3.1 (m, 2H), 2.0-2.1 (m, 1H), 2.0-2.2 (m, 1H), 1.96 (br d, 2H, J=6.9 Hz), 1.5-1.7 (m, 1H), 1.4-1.8 (m, 2H).

[0950]

[0951] Example 36: Synthesis of N-[(1S,3S)-3-(5,7-dihydrothieno[3,4-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0952]

[0953] N-[(1S,3S)-3-(5,7-dihydrothieno[3,4-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 36] (17%) was prepared by a method similar to that of Preparation Examples 1-4.

[0954] ESI-MS m / z: 436.15 [M+H] + .

[0955] 1H NMR (DMSO-d6, 400 MHz) Shift 8.8-8.8 (m, 1H), 8.77 (s, 1H), 8.38 (d, 1H, J=2.3 Hz), 8.24 (s, 1H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 7.99 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.29 (d, 1H, J=7.4 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 4.4-4.5 (m, 1H), 4.39 (br d, 1H, J=6.3 Hz), 4.02 (br d, 3H, J=2.9 Hz), 4.0-4.1 (m, 1H), 2.0-2.2 (m, 2H), 1.9-2.0 (m, 2H), 1.66 (br dd, 1H, J=8.2, 12.7 Hz), 1.4-1.6 (m, 1H).

[0956]

[0957] Example 37: Synthesis of 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[4-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[0958]

[0959] 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[4-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 37] (61%) was prepared by a method similar to that of Preparation Examples 1-4.

[0960] ESI-MS m / z: 446.15 [M+H] + .

[0961] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.9 (m, 2H), 8.60 (br s, 1H), 8.37 (d, 1H, J=2.1 Hz), 8.17 (dd, 1H, J=1.6, 3.8 Hz), 7.98 (dd, 2H, J=2.1, 5.4 Hz), 7.53 (dd, 1H, J=3.8, 9.6 Hz), 7.14 (dd, 1H, J=1.6, 9.5 Hz), 6.95 (d, 1H, J=4.9 Hz), 4.49 (br d, 2H, J=7.5 Hz), 1.9-2.2 (m, 4H), 1.67 (br d, 1H, J=12.5 Hz), 1.5-1.6 (m, 1H).

[0962]

[0963] Example 38: Synthesis of N-[(1S,3S)-3-[[4-methylsulfanyl-5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0964]

[0965] N-[(1S,3S)-3-[[4-methylsulfanyl-5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 38] (64%) was prepared by a method similar to that of Preparation Examples 1-4.

[0966] ESI-MS m / z: 492.14 [M+H] + .

[0967] 1H NMR (DMSO-d6, 400 MHz) Shift 8.8-8.9 (m, 2H), 8.37 (d, 1H, J=1.8 Hz), 8.32 (s, 1H), 8.27 (s, 1H), 8.3-8.3 (m, 1H), 8.17 (dd, 1H, J=1.6, 3.8 Hz), 8.1-8.2 (m, 1H), 7.99 (dd, 1H, J=2.1, 5.4 Hz), 7.53 (dd, 1H, J=3.8, 9.6 Hz), 7.14 (dd, 1H, J=1.6, 9.6 Hz), 4.4-4.6 (m, 2H), 2.53 (s, 3H), 2.1-2.2 (m, 2H), 1.9-2.1 (m, 2H), 1.5-1.8 (m, 2H).

[0968]

[0969] Example 39: Synthesis of N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0970]

[0971] N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 39] (4%) was prepared in a manner similar to Preparation Examples 1-4.

[0972] ESI-MS m / z: 404.18 [M+H] + .

[0973] 1H NMR (DMSO-d6, 400 MHz) Shift 8.79 (s, 1H), 8.8-8.8 (m, 1H), 8.4-8.4 (m, 3H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.00 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.44 (d, 1H, J=7.3 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 6.53 (dd, 1H, J=11.3, 17.8 Hz), 5.70 (dd, 1H, J=0.9, 17.8 Hz), 5.33 (t, 1H, J=4.6 Hz), 5.1-5.1 (m, 1H), 4.4-4.5 (m, 2H), 2.1-2.2 (m, 2H), 2.01 (br d, 2H, J=7.6 Hz), 1.5-1.7 (m, 2H).

[0974]

[0975] Example 40: Synthesis of N-[(1S,3S)-3-[(5-cyanopyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0976]

[0977] N-[(1S,3S)-3-[(5-cyanopyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 40] (62%) was prepared by a method similar to that of Preparation Examples 1-4.

[0978] ESI-MS m / z: 403.16 [M+H] + .

[0979] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.8 (m, 2H), 8.70 (d, 1H, J=2.9 Hz), 8.63 (d, 1H, J=2.9 Hz), 8.4-8.4 (m, 2H), 8.17 (dd, 1H, J=1.6, 3.8 Hz), 7.98 (dd, 1H, J=2.3, 5.4 Hz), 7.53 (dd, 1H, J=3.8, 9.5 Hz), 7.14 (dd, 1H, J=1.6, 9.6 Hz), 4.4-4.6 (m, 2H), 1.9-2.2 (m, 4H), 1.5-1.7 (m, 2H).

[0980]

[0981] Example 41: Synthesis of N-[(1S,3S)-3-[(4-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0982]

[0983] N-[(1S,3S)-3-[(4-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 41] (36%) was prepared by a method similar to that of Preparation Examples 1-4.

[0984] ESI-MS m / z: 424.15 [M+H] + .

[0985] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.8 (m, 2H), 8.36 (d, 1H, J=2.1 Hz), 8.17 (dd, 1H, J=1.6, 3.8 Hz), 7.97 (t, 2H, J=6.3 Hz), 7.53 (dd, 1H, J=3.8, 9.6 Hz), 7.22 (d, 1H, J=7.1 Hz), 7.14 (dd, 1H, J=1.6, 9.6 Hz), 6.48 (d, 1H, J=5.4 Hz), 4.3-4.5 (m, 2H), 2.44 (s, 3H), 2.1-2.2 (m, 2H), 1.9-2.0 (m, 2H), 1.5-1.7 (m, 2H).

[0986]

[0987] Example 42: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0988]

[0989] N-[(1S,3S)-3-[[5-(difluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 42] (54%) was prepared by a method similar to that of Preparation Examples 1-4.

[0990] ESI-MS m / z: 428.16 [M+H] + .

[0991] 1H NMR (DMSO-d6, 400 MHz) Shift 8.8-8.8 (m, 2H), 8.47 (br s, 2H), 8.39 (d, 1H, J=2.1 Hz), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.00 (dd, 1H, J=2.3, 5.4 Hz), 7.87 (d, 1H, J=7.3 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 7.06 (s, 1H), 6.92 (s, 1H), 6.79 (s, 1H), 6.7-7.1 (m, 1H), 4.4-4.6 (m, 2H), 2.1-2.2 (m, 2H), 1.9-2.0 (m, 2H), 1.67 (br d, 1H, J=12.5 Hz), 1.4-1.6 (m, 1H).

[0992]

[0993] Example 43: Synthesis of N-[(1S,3S)-3-[(5-acetylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[0994]

[0995] N-[(1S,3S)-3-[(5-acetylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 43] (74%) was prepared in a manner similar to Preparation Examples 1-4.

[0996] ESI-MS m / z: 420.17 [M+H] + .

[0997] 1H NMR (DMSO-d6, 400 MHz) Shift 8.8-8.9 (m, 4H), 8.39 (d, 1H, J=2.1 Hz), 8.27 (d, 1H, J=7.5 Hz), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.00 (dd, 1H, J=2.1, 5.4 Hz), 7.55 (dd, 1H, J=3.8, 9.6 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 4.5-4.6 (m, 2H), 1.9-2.2 (m, 4H), 1.6-1.8 (m, 2H).

[0998]

[0999] Example 44: Synthesis of N-[(1S,3S)-3-[[5-(1-hydroxyethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1000]

[1001] N-[(1S,3S)-3-[[5-(1-hydroxyethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 44] (8%) was prepared in a manner similar to Preparation Examples 1-4.

[1002] ESI-MS m / z: 422.19 [M+H] + .

[1003] 1H NMR (DMSO-d6, 400 MHz) Shift 8.79 (s, 1H), 8.8-8.8 (m, 1H), 8.38 (d, 1H, J=2.3 Hz), 8.2-8.2 (m, 3H), 8.00 (dd, 1H, J=2.3, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.1-7.2 (m, 1H), 7.14 (s, 1H), 5.08 (d, 1H, J=4.1 Hz), 4.59 (br dd, 1H, J=3.5, 6.4 Hz), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 1.9-2.1 (m, 4H), 1.5-1.7 (m, 2H), 1.33 (d, 3H, J=6.5 Hz).

[1004]

[1005] Example 45: Synthesis of N-[(1S,3S)-3-[[5-(2-hydroxypropane-2-yl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1006]

[1007] N-[(1S,3S)-3-[[5-(2-hydroxypropane-2-yl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 45] (16%) was prepared by a method similar to that of Preparation Examples 1-4.

[1008] ESI-MS m / z: 436.20 [M+H] + .

[1009] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.8 (m, 2H), 8.3-8.4 (m, 3H), 8.18 (dd, 1H, J=1.6, 3.9 Hz), 7.99 (dd, 1H, J=2.2, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 7.09 (d, 1H, J=7.3 Hz), 5.01 (s, 1H), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 1.9-2.2 (m, 4H), 1.5-1.7 (m, 2H), 1.40 (s, 6H).

[1010]

[1011] Example 46: Synthesis of 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-propane-2-ylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[1012]

[1013] 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-propane-2-ylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [Example 46] (15%) was prepared by a method similar to that of Preparation Examples 1-4.

[1014] ESI-MS m / z: 420.21 [M+H] + .

[1015] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.8 (m, 2H), 8.38 (d, 1H, J=2.1 Hz), 8.2-8.2 (m, 3H), 7.99 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.5 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 7.03 (d, 1H, J=7.3 Hz), 4.48 (br d, 1H, J=7.5 Hz), 4.35 (br d, 1H, J=6.4 Hz), 2.7-2.8 (m, 1H), 2.0-2.2 (m, 2H), 1.9-2.0 (m, 2H), 1.5-1.7 (m, 2H), 1.18 (s, 1H), 1.2-1.2 (m, 1H), 1.16 (s, 3H).

[1016]

[1017] Example 47: Synthesis of N-[(1S,3S)-3-[[5-(hydroxymethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1018]

[1019] N-[(1S,3S)-3-[[5-(hydroxymethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 47] (54%) was prepared by a method similar to that of Preparation Examples 1-4.

[1020] ESI-MS m / z: 408.17 [M+H] + .

[1021] 1H NMR (DMSO-d6, 400 MHz) Shift 8.78 (d, 2H, J=5.8 Hz), 8.38 (d, 1H, J=2.0 Hz), 8.2-8.2 (m, 3H), 7.99 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.5 Hz), 7.1-7.2 (m, 2H), 5.01 (t, 1H, J=5.4 Hz), 4.49 (br d, 1H, J=7.5 Hz), 4.39 (br d, 1H, J=6.3 Hz), 4.29 (d, 2H, J=5.0 Hz), 2.1-2.2 (m, 2H), 1.9-2.0 (m, 2H), 1.5-1.7 (m, 2H).

[1022]

[1023] Example 48: Synthesis of 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(trifluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1024]

[1025] 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(trifluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 48] (38%) was prepared by a method similar to that of Preparation Examples 1-4.

[1026] ESI-MS m / z: 478.12 [M+H] + .

[1027] 1H NMR (DMSO-d6, 400 MHz) Shift 8.83 (d, 1H, J=8.1 Hz), 8.78 (d, 1H, J=5.4 Hz), 8.53 (br s, 1H), 8.48 (br s, 1H), 8.38 (d, 1H, J=2.1 Hz), 8.2-8.2 (m, 2H), 8.00 (dd, 1H, J=2.1, 5.4 Hz), 7.55 (dd, 1H, J=3.8, 9.5 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 4.4-4.6 (m, 2H), 1.9-2.2 (m, 4H), 1.5-1.7 (m, 2H).

[1028]

[1029] Example 49: Synthesis of N-[(1S,3S)-3-[[5-(cyclopropylmethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1030]

[1031] N-[(1S,3S)-3-[[5-(cyclopropylmethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 49] (2%) was prepared by a method similar to that of Preparation Examples 1-4.

[1032] ESI-MS m / z: 432.21 [M+H] + .

[1033] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.8 (m, 2H), 8.38 (d, 1H, J=2.1 Hz), 8.2-8.2 (m, 3H), 8.00 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 7.05 (d, 1H, J=7.3 Hz), 4.49 (d, 1H, J=7.5 Hz), 4.36 (br d, 1H, J=6.4 Hz), 2.30 (d, 2H, J=6.9 Hz), 1.9-2.2 (m, 4H), 1.5-1.7 (m, 2H), 0.9-0.9 (m, 1H), 0.4-0.5 (m, 2H), 0.1-0.2 (m, 2H).

[1034]

[1035] Example 50: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1036]

[1037] N-[(1S,3S)-3-[[5-(difluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 50] (6%) was prepared by a method similar to that of Preparation Examples 1-4.

[1038] ESI-MS m / z: 460.13 [M+H] + .

[1039] 1H NMR (DMSO-d6, 400 MHz) Shift 8.8-8.8 (m, 2H), 8.3-8.4 (m, 3H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 7.9-8.0 (m, 2H), 7.54 (dd, 1H, J=3.8, 9.5 Hz), 7.44 (s, 1H), 7.30 (s, 1H), 7.1-7.2 (m, 1H), 4.4-4.6 (m, 2H), 1.9-2.2 (m, 4H), 1.5-1.7 (m, 2H).

[1040]

[1041] Example 51: Synthesis of N-[(1R,4R)-4-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-hydroxycyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1042]

[1043] N-[(1R,4R)-4-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-hydroxycyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 51] (10%) was prepared by a method similar to that of Preparation Examples 1-4.

[1044] ESI-MS m / z: 460.15 [M+H] + .

[1045] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.9 (m, 2H), 8.39 (d, 1H, J=2.3 Hz), 8.2-8.3 (m, 1H), 8.24 (s, 1H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.00 (dd, 1H, J=2.2, 5.4 Hz), 7.55 (dd, 1H, J=3.8, 9.6 Hz), 7.45 (d, 1H, J=7.4 Hz), 7.22 (s, 1H), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 7.04 (s, 1H), 6.85 (s, 1H), 4.9-5.1 (m, 1H), 4.2-4.4 (m, 2H), 4.11 (br d, 1H, J=7.3 Hz), 2.3-2.4 (m, 1H), 1.9-2.1 (m, 2H), 1.57 (br d, 1H, J=12.8 Hz).

[1046]

[1047] Example 52: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-1-(3-methyl-2-pyridinyl)azetidine-3-carboxamide

[1048]

[1049] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-1-(3-methyl-2-pyridinyl)azetidine-3-carboxamide [Example 52] (4%) was prepared by a method similar to that of Preparation Examples 1-4.

[1050] ESI-MS m / z: 419.19 [M+H] + .

[1051] 1H NMR (DMSO-d6, 400 MHz) Shift 8.23 ​​(s, 2H), 8.03 (d, 1H, J=7.4 Hz), 7.95 (dd, 1H, J=1.3, 4.9 Hz), 7.45 (d, 1H, J=7.1 Hz), 7.30 (td, 1H, J=0.8, 7.2 Hz), 7.22 (s, 1H), 7.04 (s, 1H), 6.85 (s, 1H), 6.65 (dd, 1H, J=4.9, 7.1 Hz), 4.2-4.3 (m, 2H), 4.0-4.1 (m, 4H), 2.13 (s, 3H), 2.0-2.1 (m, 2H), 1.79 (td, 2H, J=6.7, 11.5 Hz), 1.3-1.5 (m, 2H).

[1052]

[1053] Example 53: Synthesis of 1-(3-cyano-2-pyridinyl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]azetidine-3-carboxamide

[1054]

[1055] 1-(3-cyano-2-pyridinyl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]azetidine-3-carboxamide [Example 53] (50%) was prepared by a method similar to that of Preparation Examples 1-4.

[1056] ESI-MS m / z: 430.17 [M+H] + .

[1057] 1H NMR (DMSO-d6, 400 MHz) Shift 8.33 (dd, 1H, J=1.8, 4.8 Hz), 8.23 ​​(s, 2H), 8.12 (d, 1H, J=7.3 Hz), 7.95 (dd, 1H, J=1.9, 7.6 Hz), 7.46 (d, 1H, J=7.3 Hz), 7.22 (s, 1H), 7.04 (s, 1H), 6.85 (s, 1H), 6.77 (dd, 1H, J=4.9, 7.6 Hz), 4.2-4.4 (m, 6H), 3.44 (s, 1H), 2.0-2.1 (m, 2H), 1.7-1.9 (m, 2H).

[1058]

[1059] Example 54: Synthesis of 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(2,2,2-trifluoroethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1060]

[1061] 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(2,2,2-trifluoroethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 54] (20%) was prepared by a method similar to that of Preparation Examples 1-4.

[1062] ESI-MS m / z: 460.16 [M+H] + .

[1063] 1H NMR (DMSO-d6, 400 MHz) Shift 8.8-8.8 (m, 3H), 8.38 (d, 1H, J=2.1 Hz), 8.25 (s, 2H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 8.00 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.43 (d, 1H, J=7.4 Hz), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 2.0-2.2 (m, 3H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[1064]

[1065] Example 55: Synthesis of N-[(1S,3S)-3-[[5-(cyanomethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1066]

[1067] N-[(1S,3S)-3-[[5-(cyanomethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 55] (49%) was prepared by a method similar to that of Preparation Examples 1-4.

[1068] ESI-MS m / z: 417.17 [M+H] + .

[1069] 1H NMR (DMSO-d6, 400 MHz) Shift 8.8-8.8 (m, 2H), 8.38 (s, 1H), 8.26 (s, 2H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 7.99 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.42 (d, 1H, J=7.3 Hz), 7.15 (dd, 1H, J=1.6, 9.5 Hz), 3.81 (s, 2H), 2.0-2.2 (m, 2H), 1.99 (s, 2H).

[1070]

[1071] Example 56: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-3-(6-oxopyridazine-1-yl)benzamide

[1072]

[1073] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-3-(6-oxopyridazine-1-yl)benzamide [Example 56] (16%) was prepared in the same manner as in Preparation Example 3-3.

[1074] ESI-MS m / z: 443.16[M+H] + .

[1075] 1H NMR (DMSO-d6, 400 MHz) δ 8.51 (d, 1H, J=7.3 Hz), 8.24 (s, 2H), 8.10 (dd, 1H, J=1.6, 3.8 Hz), 8.0-8.0 (m, 1H), 7.92 (td, 1H, J=1.3, 8.0 Hz), 7.7-7.8 (m, 1H), 7.4-7.6 (m, 3H), 7.22 (s, 1H), 7.11 (dd, 1H, J=1.6, 9.5 Hz), 7.04 (s, 1H), 6.85 (s, 1H), 4.3-4.5 (m, 1H), 4.1-4.6 (m, 1H), 2.0-2.2 (m, 2H), 1.8-2.0 (m, 2H), 1.5-1.7 (m, 2H).

[1076]

[1077] Example 57: Synthesis of N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-1-bicyclo[1.1.1]fentanyl]-4-(6-oxopyridazine-1-yl)benzamide

[1078]

[1079] N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-1-bicyclo[1.1.1]fentanyl]-4-(6-oxopyridazine-1-yl)benzamide [Example 57] (36%) was prepared by a method similar to that of Preparation Example 3-3.

[1080] ESI-MS m / z: 441.14[M+H] + .

[1081] 1H NMR (DMSO-d6, 400 MHz) δ 9.14 (s, 1H), 8.30 (s, 2H), 8.12 (s, 1H), 8.10 (dd, 1H, J=1.6, 3.8 Hz), 7.9-8.0 (m, 2H), 7.7-7.7 (m, 2H), 7.52 (dd, 1H, J=3.8, 9.6 Hz), 7.24 (s, 1H), 7.10 (dd, 1H, J=1.6, 9.6 Hz), 7.07 (s, 1H), 6.88 (s, 1H), 2.39 (s, 6H).

[1082]

[1083] Example 58: Synthesis of N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclobutyl]-4-(6-oxopyridazine-1-yl)benzamide

[1084]

[1085] N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclobutyl]-4-(6-oxopyridazine-1-yl)benzamide [Example 58] (75%) was prepared in a manner similar to Preparation Example 3-3.

[1086] ESI-MS m / z: 429.14[M+H] + .

[1087] 1H NMR (DMSO-d6, 400 MHz) δ 8.85 (d, 1H, J=7.0 Hz), 8.26 (s, 2H), 8.10 (dd, 1H, J=1.5, 3.8 Hz), 8.0-8.0 (m, 2H), 7.83 (d, 1H, J=6.8 Hz), 7.7-7.7 (m, 2H), 7.52 (dd, 1H, J=4.0, 9.5 Hz), 7.23 (s, 1H), 7.10 (dd, 1H, J=1.5, 9.5 Hz), 7.05 (s, 1H), 6.86 (s, 1H), 4.3-4.6 (m, 2H), 2.3-2.5 (m, 4H).

[1088]

[1089] Example 59: Synthesis of N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]ethyl]-4-(6-oxopyridazine-1-yl)benzamide

[1090]

[1091] N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]ethyl]-4-(6-oxopyridazine-1-yl)benzamide [Example 59] (67%) was prepared in a manner similar to that of Preparation Example 3-3.

[1092] ESI-MS m / z: 403.13[M+H] + .

[1093] 1H NMR (DMSO-d6, 400 MHz) δ 8.66 (s, 4H), 8.2-8.3 (m, 8H), 8.10 (dd, 4H, J=1.6, 3.8 Hz), 7.9-8.0 (m, 8H), 7.7-7.7 (m, 8H), 7.5-7.6 (m, 8H), 7.23 (s, 1H), 7.0-7.1 (m, 6H), 6.86 (s, 1H), 3.4-3.5 (m, 21H), 3.2-3.3 (m, 4H), 2.5-2.6 (m, 3H), 2.4-2.5 (m, 2H).

[1094]

[1095] Example 60: Synthesis of N-[(1S,2S)-2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopropyl]-4-(6-oxopyridazine-1-yl)benzamide

[1096]

[1097] N-[(1S,2S)-2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopropyl]-4-(6-oxopyridazine-1-yl)benzamide [Example 60] (65%) was prepared in a manner similar to Preparation Example 3-3.

[1098] ESI-MS m / z: 415.13[M+H] + .

[1099] 1H NMR (DMSO-d6, 400 MHz) δ 8.63 (d, 1H, J=5.1 Hz), 8.29 (s, 2H), 8.10 (dd, 1H, J=1.6, 3.8 Hz), 7.9-8.0 (m, 2H), 7.6-7.7 (m, 3H), 7.52 (dd, 1H, J=3.9, 9.5 Hz), 6.9-7.3 (m, 2H), 3.1-3.2 (m, 2H), 1.0-1.1 (m, 2H).

[1100]

[1101] Example 61: Synthesis of N-[(1S,2S)-2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopropyl]-3-(6-oxopyridazine-1-yl)benzamide

[1102]

[1103] N-[(1S,2S)-2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopropyl]-3-(6-oxopyridazine-1-yl)benzamide [Example 61] (78%) was prepared in a manner similar to Preparation Example 3-3.

[1104] ESI-MS m / z: 415.13[M+H] + .

[1105] 1H NMR (DMSO-d6, 400 MHz) δ 8.64 (d, 1H, J=5.3 Hz), 8.29 (s, 2H), 8.10 (dd, 1H, J=1.6, 3.8 Hz), 8.02 (t, 1H, J=1.8 Hz), 7.91 (td, 1H, J=1.3, 7.9 Hz), 7.7-7.8 (m, 1H), 7.5-7.7 (m, 3H), 7.25 (s, 1H), 7.1-7.1 (m, 1H), 6.88 (s, 1H), 3.0-3.2 (m, 2H), 1.0-1.1 (m, 2H).

[1106]

[1107] Example 62: Synthesis of N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]ethyl]-3-(6-oxopyridazine-1-yl)benzamide

[1108]

[1109] N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]ethyl]-3-(6-oxopyridazine-1-yl)benzamide [Example 62] (85%) was prepared in a manner similar to Preparation Example 3-3.

[1110] ESI-MS m / z: 403.13[M+H] + .

[1111] 1H NMR (DMSO-d6, 400 MHz) δ 8.70 (s, 1H), 8.25 (s, 2H), 8.10 (dd, 1H, J=1.6, 3.8 Hz), 8.02 (t, 1H, J=1.8 Hz), 7.90 (td, 1H, J=1.3, 7.8 Hz), 7.73 (d, 1H, J=7.9 Hz), 7.5-7.6 (m, 3H), 7.23 (s, 1H), 7.12 (dd, 1H, J=1.6, 9.5 Hz), 7.05 (s, 1H), 6.86 (s, 1H), 3.45 (br s, 4H).

[1112]

[1113] Example 63: Synthesis of N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclobutyl]-3-(6-oxopyridazine-1-yl)benzamide

[1114]

[1115] N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclobutyl]-3-(6-oxopyridazine-1-yl)benzamide [Example 63] (63%) was prepared in a manner similar to Preparation Example 3-3.

[1116] ESI-MS m / z: 429.14[M+H] + .

[1117] 1H NMR (DMSO-d6, 400 MHz) δ 8.88 (d, 1H, J=6.9 Hz), 8.26 (s, 2H), 8.11 (dd, 1H, J=1.6, 3.8 Hz), 8.06 (t, 1H, J=1.8 Hz), 7.94 (td, 1H, J=1.3, 7.9 Hz), 7.85 (d, 1H, J=6.6 Hz), 7.7-7.7 (m, 1H), 7.5-7.6 (m, 2H), 7.24 (s, 1H), 7.12 (dd, 1H, J=1.6, 9.5 Hz), 7.05 (s, 1H), 6.87 (s, 1H), 4.4-4.5 (m, 2H), 2.3-2.4 (m, 4H).

[1118]

[1119] Example 64: Synthesis of N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-1-bicyclo[1.1.1]fentanyl]-3-(6-oxopyridazine-1-yl)benzamide

[1120]

[1121] N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-1-bicyclo[1.1.1]fentanyl]-3-(6-oxopyridazine-1-yl)benzamide [Example 64] (78%) was prepared by a method similar to that of Preparation Example 3-3.

[1122] ESI-MS m / z: 441.14[M+H] + .

[1123] 1H NMR (DMSO-d6, 400 MHz) δ 9.17 (s, 1H), 8.31 (s, 2H), 8.14 (s, 1H), 8.11 (dd, 1H, J=1.6, 3.8 Hz), 8.04 (t, 1H, J=1.8 Hz), 7.91 (d, 1H, J=8.0 Hz), 7.7-7.7 (m, 1H), 7.6-7.6 (m, 1H), 7.54 (dd, 1H, J=3.8, 9.6 Hz), 7.26 (s, 1H), 7.12 (dd, 1H, J=1.6, 9.5 Hz), 7.07 (s, 1H), 6.89 (s, 1H), 2.38 (s, 6H).

[1124]

[1125] Example 65: Synthesis of N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-methylpropyl]-3-(6-oxopyridazine-1-yl)benzamide

[1126]

[1127] N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-methylpropyl]-3-(6-oxopyridazine-1-yl)benzamide [Example 65] (30%) was prepared in a manner similar to Preparation Example 3-3.

[1128] ESI-MS m / z: 431.16[M+H] + .

[1129] 1H NMR (DMSO-d6, 400 MHz) Shift 8.76 (t, 1H, J=6.2 Hz), 8.25 (s, 2H), 8.10 (dd, 1H, J=1.6, 3.8 Hz), 8.03 (t, 1H, J=1.8 Hz), 7.93 (td, 1H, J=1.3, 7.8 Hz), 7.7-7.8 (m, 1H), 7.5-7.6 (m, 2H), 7.24 (s, 1H), 7.18 (s, 1H), 7.0-7.1 (m, 1H), 6.87 (s, 1H), 6.8-7.3 (m, 1H), 3.5-3.6 (m, 2H), 1.39 (s, 6H).

[1130]

[1131] Example 66: Synthesis of N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-methylpropyl]-4-(6-oxopyridazine-1-yl)benzamide

[1132]

[1133] N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-methylpropyl]-4-(6-oxopyridazine-1-yl)benzamide [Example 66] (21%) was prepared by a method similar to that of Preparation Example 3-3.

[1134] ESI-MS m / z: 431.16[M+H] + .

[1135] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.8 (m, 1H), 8.25 (s, 2H), 8.10 (dd, 1H, J=1.6, 3.8 Hz), 7.9-8.0 (m, 2H), 7.7-7.7 (m, 2H), 7.52 (dd, 1H, J=3.9, 9.5 Hz), 7.24 (s, 1H), 7.0-7.2 (m, 1H), 6.87 (s, 1H), 6.8-7.3 (m, 1H), 3.60 (d, 2H, J=6.3 Hz), 1.41 (s, 6H).

[1136]

[1137] Example 67: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[1138]

[1139] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 67] (32%) was prepared as in Preparation Examples 2-4.

[1140] ESI-MS m / z: 473.17[M+H] + .

[1141] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.66 (d, 1H, J=5.3 Hz), 8.1-8.2 (m, 3H), 8.06 (br d, 1H, J=7.8 Hz), 7.77 (br d, 1H, J=5.3 Hz), 7.3-7.3 (m, 1H), 6.82 (br s, 1H), 6.64 (d, 1H, J=9.9 Hz), 6.2-6.6 (m, 1H), 5.24 (br d, 1H, J=6.4 Hz), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 1H), 3.7-3.7 (m, 3H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 3H), 1.7-1.8 (m, 2H).

[1142]

[1143] Example 68: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide

[1144]

[1145] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide [Example 68] (50%) was prepared by a method similar to that of Preparation Examples 2-4.

[1146] ESI-MS m / z: 463.21[M+H] + .

[1147] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.63 (s, 1H), 8.52 (d, 1H, J=5.5 Hz), 8.20 (br d, 1H, J=5.4 Hz), 8.09 (s, 3H), 5.06 (br d, 1H, J=6.6 Hz), 4.75 (s, 2H), 4.61 (qd, 1H, J=6.9, 13.9 Hz), 4.4-4.5 (m, 1H), 4.06 (t, 2H, J=5.3 Hz), 3.79 (t, 2H, J=5.2 Hz), 2.3-2.4 (m, 2H), 1.9-2.2 (m, 3H), 1.5-1.8 (m, 7H).

[1148]

[1149] Example 69: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-1-yl)pyridine-2-carboxamide

[1150]

[1151] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-1-yl)pyridine-2-carboxamide [Example 69] (34%) was prepared by a method similar to that of Preparation Examples 2-4.

[1152] ESI-MS m / z: 460.24[M+H] + .

[1153] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.54 (d, 1H, J=5.4 Hz), 8.09 (br s, 3H), 7.96 (s, 1H), 7.88 (d, 1H, J=5.6 Hz), 5.44 (s, 1H), 5.04 (br d, 1H, J=6.0 Hz), 4.5-4.6 (m, 1H), 4.4-4.5 (m, 1H), 3.29 (br t, 2H, J=5.3 Hz), 2.71 (br t, 2H, J=6.3 Hz), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 4H), 1.8-1.9 (m, 2H), 1.7-1.8 (m, 1H), 1.4-1.6 (m, 2H).

[1154]

[1155] Example 70: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(1-methyl-3-oxoindazole-2-yl)pyridine-2-carboxamide

[1156]

[1157] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(1-methyl-3-oxoindazole-2-yl)pyridine-2-carboxamide [Example 70] (29%) was prepared by a method similar to that of Preparation Examples 2-4.

[1158] ESI-MS m / z: 470.22[M+H] + .

[1159] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.60 (d, 1H, J=5.4 Hz), 8.22 (s, 1H), 8.0-8.2 (m, 4H), 7.91 (d, 1H, J=7.8 Hz), 7.68 (t, 1H, J=7.8 Hz), 7.3-7.4 (m, 2H), 5.04 (br s, 1H), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 1H), 3.21 (s, 3H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 3H), 1.7-1.9 (m, 3H), 1.4-1.6 (m, 1H).

[1160]

[1161] Example 71: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-2-yl)pyridine-2-carboxamide

[1162]

[1163] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-2-yl)pyridine-2-carboxamide [Example 71] (42%) was prepared by a method similar to that of Preparation Examples 2-4.

[1164] ESI-MS m / z: 475.25[M+H] + .

[1165] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.66 (s, 1H), 8.50 (d, 1H, J=5.5 Hz), 8.2-8.3 (m, 1H), 8.08 (s, 3H), 5.09 (br d, 1H, J=6.6 Hz), 4.6-4.7 (m, 1H),

[1166] 4.4-4.5 (m, 1H), 3.83 (br s, 2H), 3.5-3.8 (m, 1H), 2.8-2.8 (m, 3H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 3H), 1.8-1.9 (m, 3H), 1.8-1.8 (m, 5H), 1.4-1.6 (m, 3H).

[1167]

[1168] Example 72: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(5-methyl-2-oxo-1,3,4-thiadiazole-3-yl)pyridine-2-carboxamide

[1169]

[1170] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(5-methyl-2-oxo-1,3,4-thiadiazole-3-yl)pyridine-2-carboxamide

[1171] [Example 72] (5%) was prepared in a manner similar to Preparation Examples 2-4.

[1172] ESI-MS m / z: 438.52[M+H] + .

[1173] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.64 (s, 1H), 8.55 (br d, 1H, J=5.4 Hz), 8.0-8.2 (m, 4H), 5.05 (br s, 1H), 4.5-4.7 (m, 1H), 4.4-4.5 (m, 1H), 2.52 (s,3H), 2.3-2.4 (m, 2H), 2.2-2.3 (m, 1H), 2.0-2.2 (m, 3H), 1.89 (br s, 1H), 1.7-1.8 (m, 3H).

[1174]

[1175] Example 73: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-methyl-5-oxo-4H-pyrazole-1-yl)pyridine-2-carboxamide

[1176]

[1177] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-methyl-5-oxo-4H-pyrazole-1-yl)pyridine-2-carboxamide [Example 73] (7%) was prepared by a method similar to that of Preparation Examples 2-4.

[1178] ESI-MS m / z: 420.21[M+H] + .

[1179] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.51 (d, 1H, J=5.4 Hz), 8.2-8.2 (m, 1H), 8.10 (s, 2H), 7.83 (br d, 1H, J=7.9 Hz), 7.6-7.6 (m, 1H), 6.28 (br d, 1H, J=6.1 Hz), 5.76 (s, 1H), 4.3-4.5 (m, 2H), 2.50 (s, 3H), 2.1-2.4 (m, 3H), 2.0-2.1 (m, 1H), 1.8-1.9 (m, 4H), 1.6-1.8 (m, 3H), 1.4-1.6 (m, 4H).

[1180]

[1181] Example 74: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxomorpholine-4-yl)pyridine-2-carboxamide

[1182]

[1183] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxomorpholine-4-yl)pyridine-2-carboxamide [Example 74] (18%) was prepared by a method similar to that of Preparation Examples 2-4.

[1184] ESI-MS m / z: 423.21[M+H] + .

[1185] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.51 (d, 1H, J=5.5 Hz), 8.0-8.1 (m, 4H), 7.96 (br d, 1H, J=5.5 Hz), 5.06 (br d, 1H, J=6.8 Hz), 4.5-4.6 (m, 1H), 4.3-4.5 (m, 3H), 4.07 (t, 2H, J=4.9 Hz), 3.89 (t, 2H, J=4.9 Hz), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 2H), 1.7-1.9 (m, 1H), 1.4-1.7 (m, 2H).

[1186]

[1187] Example 75: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3,4-diethyl-5-oxo-1,2,4-triazole-1-yl)pyridine-2-carboxamide

[1188]

[1189] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3,4-diethyl-5-oxo-1,2,4-triazole-1-yl)pyridine-2-carboxamide [Example 75] (55%) was prepared by a method similar to that of Preparation Examples 2-4.

[1190] ESI-MS m / z: 463.25[M+H] + .

[1191] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.66 (s, 1H), 8.50 (d, 1H, J=5.5 Hz), 8.2-8.3 (m, 1H), 8.1-8.1 (m, 3H), 5.04 (br d, 1H, J=6.9 Hz), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 1H), 3.74 (q, 2H, J=7.2 Hz), 2.63 (q, 2H, J=7.4 Hz), 2.3-2.4 (m, 3H), 2.0-2.2 (m, 3H), 1.7-1.8 (m, 1H), 1.5-1.6 (m, 2H), 1.38 (br t, 3H, J=7.6 Hz), 1.34 (br t, 4H, J=7.3 Hz).

[1192]

[1193] Example 76: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide

[1194]

[1195] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide [Example 76] (40%) was prepared by a method similar to that of Preparation Examples 2-4.

[1196] ESI-MS m / z: 489.17[M+H] + .

[1197] 1H NMR (DMSO-d6, 400 MHz) δ 8.73 (d, 1H, J=8.1 Hz), 8.65 (d, 1H, J=5.5 Hz), 8.52 (d, 1H, J=2.0 Hz), 8.22 (s, 2H), 8.03 (dd, 1H, J=2.3, 5.5 Hz), 7.43 (d, 1H, J=7.3 Hz), 6.8-7.2 (m, 1H), 4.76 (s, 2H), 4.45 (sxt, 1H, J=7.4 Hz), 4.31 (qd, 1H, J=6.8, 13.4 Hz), 4.01 (t, 2H, J=5.3 Hz), 2.0-2.1 (m, 2H), 1.9-2.0 (m, 2H), 1.4-1.7 (m, 2H).

[1198]

[1199] Example 77: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxoindazole-2-yl)pyridine-2-carboxamide

[1200]

[1201]

[1202] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxoindazole-2-yl)pyridine-2-carboxamide [Example 77] (44%) was prepared by a method similar to that of Preparation Examples 2-4.

[1203] ESI-MS m / z: 496.18[M+H] + .

[1204] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.61 (d, 1H, J=5.5 Hz), 8.23 ​​(d, 1H, J=2.0 Hz), 8.18 (s, 2H), 8.0-8.2 (m, 2H), 7.91 (d, 1H, J=7.8 Hz), 7.68 (t, 1H,

[1205] J=7.7 Hz), 7.2-7.4 (m, 3H), 6.2-6.6 (m, 1H), 5.2-5.3 (m, 1H), 4.63 (sxt, 1H, J=7.1 Hz), 4.45 (sxt, 1H, J=6.8 Hz), 3.21 (s, 3H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 2H), 1.7-1.8 (m, 1H), 1.5-1.6 (m, 2H).

[1206]

[1207] Example 78: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-2-yl)pyridine-2-carboxamide

[1208]

[1209]

[1210] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-2-yl)pyridine-2-carboxamide [Example 78] (66%) was prepared by a method similar to that of Preparation Examples 2-4.

[1211] ESI-MS m / z: 501.21[M+H] + .

[1212] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.66 (d, 1H, J=1.9 Hz), 8.50 (d, 1H, J=5.5 Hz), 8.23 ​​(dd, 1H, J=2.1, 5.5 Hz), 8.18 (s, 2H), 8.08 (br d, 1H, J=7.8 Hz), 6.2-6.6 (m, 1H), 5.2-5.4 (m, 1H), 4.62 (sxt, 1H, J=7.1 Hz), 4.44 (sxt, 1H, J=6.8 Hz), 3.8-3.9 (m, 2H), 2.7-2.8 (m, 2H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 3H), 1.88 (br d, 2H, J=4.4 Hz), 1.7-1.8 (m, 7H), 1.5-1.7 (m, 2H).

[1213]

[1214] Example 79: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-fluoro-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[1215]

[1216]

[1217] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-fluoro-2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 79] (17%) was prepared by a method similar to that of Preparation Examples 2-4.

[1218] ESI-MS m / z: 464.12[M+H] + .

[1219] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.65 (d, 1H, J=1.6 Hz), 8.56 (d, 1H, J=5.5 Hz), 8.1-8.2 (m, 3H), 8.07 (br d, 1H, J=7.4 Hz), 6.2-6.6 (m, 1H), 5.2-5.3 (m, 2H), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 1H), 2.52 (s, 3H), 2.3-2.4 (m, 3H), 2.0-2.3 (m, 3H), 1.7-1.8 (m, 2H).

[1220]

[1221] Example 80: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methyl-2-oxo-1,3,4-thiadiazole-3-yl)pyridine-2-carboxamide

[1222]

[1223]

[1224] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methyl-2-oxo-1,3,4-thiadiazole-3-yl)pyridine-2-carboxamide [Example 80] (10%) was prepared by a method similar to that of Preparation Examples 2-4.

[1225] ESI-MS m / z: 461.15[M+H] + .

[1226] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.69 (d, 1H, J=5.3 Hz), 8.18 (s, 3H), 8.0-8.1 (m, 1H), 7.7-7.8 (m, 1H), 7.2-7.2 (m, 2H), 6.2-6.6 (m, 2H), 5.23 (br d, 1H, J=6.9 Hz), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 1H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 3H), 1.6-1.8 (m, 2H).

[1227]

[1228] Example 81: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-ethoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[1229]

[1230] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-ethoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 81] (39%) was prepared by a method similar to that of Preparation Examples 2-4.

[1231] ESI-MS m / z: 487.18[M+H] + .

[1232] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.65 (d, 1H, J=5.3 Hz), 8.18 (s, 3H), 8.05 (br d, 1H, J=7.8 Hz), 7.75 (br d, 1H, J=5.3 Hz), 7.00 (d, 1H, J=7.0 Hz), 6.66 (d, 1H, J=7.4 Hz), 6.2-6.6 (m, 2H), 5.26 (br d, 1H, J=6.5 Hz), 4.62 (sxt, 1H, J=7.0 Hz), 4.4-4.5 (m, 1H), 4.0-4.1 (m, 2H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 2H), 1.7-1.7 (m, 1H), 1.4-1.6 (m, 5H).

[1233]

[1234] Example 82: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(4-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[1235]

[1236] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(4-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 82] (32%) was prepared by a method similar to that of Preparation Examples 2-4.

[1237] ESI-MS m / z: 473.17[M+H] + .

[1238] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.64 (d, 1H, J=5.3 Hz), 8.1-8.2 (m, 3H), 8.04 (br d, 1H, J=7.8 Hz), 7.7-7.8 (m, 1H), 7.3-7.3 (m, 1H), 6.2-6.6 (m, 1H), 6.0-6.1 (m, 1H), 5.96 (d, 1H, J=2.4 Hz), 5.23 (br d, 1H, J=6.8 Hz), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 1H), 3.8-3.9 (m, 3H), 2.3-2.4 (m, 2H), 2.10 (tt, 2H,J=6.9, 13.9 Hz), 1.6-1.7 (m, 2H).

[1239]

[1240] Example 83: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-fluoro-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[1241]

[1242] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-fluoro-2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 83] (14%) was prepared by a method similar to that of Preparation Examples 2-4.

[1243] ESI-MS m / z: 461.15[M+H] + .

[1244] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.70 (d, 2H, J=5.3 Hz), 8.2-8.3 (m, 6H), 8.05 (br d, 2H, J=7.6 Hz), 7.7-7.8 (m, 2H), 7.3-7.5 (m, 4H), 6.2-6.7 (m, 4H), 5.27 (br d, 2H, J=6.8 Hz), 4.6-4.7 (m, 2H), 4.4-4.5 (m, 2H), 2.3-2.4 (m, 4H), 2.0-2.3 (m, 6H), 1.6-1.9 (m, 6H).

[1245]

[1246] Example 84: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-oxo-3H-pyrrolo[3,4-c]pyridine-2-yl)pyridine-2-carboxamide

[1247]

[1248] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-oxo-3H-pyrrolo[3,4-c]pyridine-2-yl)pyridine-2-carboxamide [Example 84] (9%) was prepared by a method similar to that of Preparation Examples 2-4.

[1249] ESI-MS m / z: 482.17[M+H] + .

[1250] 1H NMR (CHLOROFORM-d, 400 MHz) δ 9.21 (s, 1H), 8.88 (d, 1H, J=5.1 Hz), 8.71 (dd, 1H, J=2.3, 5.7 Hz), 8.55 (d, 1H, J=5.8 Hz), 8.1-8.2 (m, 3H), 8.02 (d,

[1251] 1H, J=2.1 Hz), 7.57 (d, 1H, J=5.0 Hz), 6.2-6.6 (m, 1H), 5.23 (br d, 1H, J=6.8 Hz), 5.00 (s, 2H), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 1H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 3H), 1.6-1.7 (m, 2H).

[1252]

[1253] Example 85: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-c]pyridine-2-yl)pyridine-2-carboxamide

[1254]

[1255] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-c]pyridine-2-yl)pyridine-2-carboxamide [Example 85] (35%) was prepared by a method similar to that of Preparation Examples 2-4.

[1256] ESI-MS m / z: 497.18[M+H] + .

[1257] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.91 (s, 1H), 8.6-8.7 (m, 2H), 8.25 (d, 1H, J=2.0 Hz), 8.18 (s, 2H), 8.10 (br d, 1H, J=7.9 Hz), 8.01 (dd, 1H, J=2.1,

[1258] 5.4 Hz), 7.80 (d, 1H, J=4.9 Hz), 6.2-6.6 (m, 1H), 5.2-5.4 (m, 1H), 4.63 (sxt, 1H, J=7.2 Hz), 4.45 (sxt, 1H, J=6.7 Hz), 3.30 (s, 3H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 2H), 1.7-1.8 (m, 1H), 1.5-1.6 (m, 1H).

[1259]

[1260] Example 86: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-b]pyridine-2-yl)pyridine-2-carboxamide

[1261]

[1262] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-b]pyridine-2-yl)pyridine-2-carboxamide [Example 86] (42%) was prepared by a method similar to that of Preparation Examples 2-4.

[1263] ESI-MS m / z: 497.18[M+H] + .

[1264] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.72 (dd, 1H, J=1.6, 4.8 Hz), 8.63 (d, 1H, J=5.4 Hz), 8.2-8.3 (m, 4H), 8.10 (br d, 1H, J=7.9 Hz), 7.93 (dd, 1H, J=2.1, 5.4 Hz), 7.2-7.3 (m, 1H), 6.2-6.6 (m, 1H), 5.24 (br d, 1H, J=7.0 Hz), 4.63 (sxt, 1H, J=7.1 Hz), 4.45 (sxt, 1H, J=6.8 Hz), 3.41 (s, 3H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 2H), 1.6-1.7 (m, 2H).

[1265]

[1266] Example 87: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-b]pyrazine-2-yl)pyridine-2-carboxamide

[1267]

[1268] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-b]pyrazine-2-yl)pyridine-2-carboxamide [Example 87] (7%) was prepared by a method similar to that of Preparation Examples 2-4.

[1269] ESI-MS m / z: 498.17[M+H] + .

[1270] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.6-8.7 (m, 2H), 8.1-8.2 (m, 3H), 8.10 (br d, 1H, J=8.0 Hz), 8.02 (dd, 1H, J=2.1, 5.4 Hz), 6.2-6.6 (m, 1H), 5.24 (br d, 1H, J=5.3 Hz), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 1H), 3.45 (s, 2H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 3H), 1.6-1.8 (m, 3H).

[1271]

[1272] Example 88: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-4,5,6,7-tetrahydroindazole-2-yl)pyridine-2-carboxamide

[1273]

[1274] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-4,5,6,7-tetrahydroindazole-2-yl)pyridine-2-carboxamide [Example 88] (71%) was prepared by a method similar to that of Preparation Examples 2-4.

[1275] ESI-MS m / z: 500.21[M+H] + .

[1276] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.54 (d, 1H, J=5.4 Hz), 8.18 (s, 2H), 8.10 (br d, 1H, J=7.8 Hz), 7.98 (s, 1H), 7.91 (dd, 1H, J=1.4, 5.3 Hz), 6.2-6.6 (m, 1H), 5.33 (br d, 1H, J=6.8 Hz), 4.61 (sxt, 1H, J=7.1 Hz), 4.4-4.5 (m, 1H), 3.00 (s, 3H), 2.48 (br t, 2H, J=5.9 Hz), 2.3-2.4 (m, 4H), 2.0-2.2 (m, 2H), 1.8-1.9 (m, 5H), 1.7-1.8 (m, 2H), 1.5-1.7 (m, 2H).

[1277]

[1278] Example 89: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-5,7-dihydro-4H-pyrano[3,4-c]pyrazol-2-yl)pyridine-2-carboxamide

[1279]

[1280] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-5,7-dihydro-4H-pyrano[3,4-c]pyrazol-2-yl)pyridine-2-carboxamide [Example 89] (11%) was prepared by a method similar to that of Preparation Examples 2-4.

[1281] ESI-MS m / z: 502.19[M+H] + .

[1282] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.57 (d, 1H, J=5.4 Hz), 8.18 (s, 2H), 8.09 (br d, 1H, J=7.8 Hz), 7.99 (d, 1H, J=1.9 Hz), 7.90 (dd, 1H, J=2.1, 5.5 Hz), 6.2-6.6 (m, 1H), 5.2-5.4 (m, 1H), 4.6-4.7 (m, 3H), 4.44 (sxt, 1H, J=6.8 Hz), 3.90 (t, 2H, J=5.4 Hz), 3.00 (s, 3H), 2.48 (br t, 2H, J=5.3 Hz), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 2H), 1.7-1.8 (m, 1H).

[1283]

[1284] Example 90: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-6,7-dihydro-4H-pyrano[4,3-c]pyrazol-2-yl)pyridine-2-carboxamide

[1285]

[1286] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-6,7-dihydro-4H-pyrano[4,3-c]pyrazol-2-yl)pyridine-2-carboxamide [Example 90] (81%) was prepared by a method similar to that of Preparation Examples 2-4.

[1287] ESI-MS m / z: 502.19[M+H] + .

[1288] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.57 (d, 1H, J=5.4 Hz), 8.18 (s, 2H), 8.10 (br d, 1H, J=7.6 Hz), 7.99 (s, 1H), 7.87 (br d, 1H, J=5.3 Hz), 6.2-6.6 (m, 1H), 5.32 (br d, 1H, J=6.8 Hz), 4.61 (qd, 1H, J=7.2, 14.1 Hz), 4.4-4.5 (m, 3H), 4.00 (t, 2H, J=5.3 Hz), 3.07 (s, 3H), 2.64 (br s, 2H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 2H), 1.5-1.7 (m, 2H).

[1289]

[1290] Example 91: Synthesis of 4-(3-cyano-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1291]

[1292] 4-(3-cyano-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidin-2-yl]amino]cyclopentyl]pyridin-2-carboxamide [Example 91] (6%) was prepared by a method similar to that of Preparation Examples 2-4.

[1293] ESI-MS m / z: 468.15[M+H] + .

[1294] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.72 (d, 1H, J=5.3 Hz), 8.1-8.3 (m, 3H), 8.03 (br d, 1H, J=8.0 Hz), 7.94 (dd, 1H, J=1.7, 6.9 Hz), 7.5-7.8 (m, 2H), 6.2-6.6 (m, 2H), 5.22 (br d, 1H, J=5.8 Hz), 4.5-4.7 (m, 1H), 4.4-4.5 (m, 1H), 2.3-2.4 (m, 2H), 2.0-2.2 (m, 4H), 1.6-1.8 (m, 2H).

[1295]

[1296] Example 92: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-methyl-5-oxo-2-propane-2-ylpyrazole-1-yl)pyridine-2-carboxamide

[1297]

[1298] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-methyl-5-oxo-2-propane-2-ylpyrazole-1-yl)pyridine-2-carboxamide [Example 92] (21%) was prepared by a method similar to that of Preparation Examples 2-4.

[1299] ESI-MS m / z: 488.21[M+H] + .

[1300] 1H NMR (CHLOROFORM-d, 400 MHz) δ 8.37 (d, 1H, J=5.5 Hz), 8.17 (s, 2H), 8.05 (br d, 1H, J=7.6 Hz), 7.84 (d, 1H, J=2.3 Hz), 7.12 (dd, 1H, J=2.4, 5.5 Hz), 6.2-6.6 (m, 1H), 5.66 (s, 1H), 5.21 (br d, 1H, J=6.8 Hz), 4.56 (sxt, 1H, J=7.1 Hz), 4.3-4.5 (m, 2H), 2.2-2.4 (m, 5H), 2.0-2.2 (m, 2H), 1.6-1.8 (m, 1H), 1.5-1.6 (m, 1H), 1.46 (d, 6H, J=6.5 Hz).

[1301]

[1302] Example 93: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-2-(6-oxopyridazine-1-yl)pyridine-4-carboxamide

[1303]

[1304]

[1305] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-2-(6-oxopyridazine-1-yl)pyridine-4-carboxamide [Example 93] (20%) was prepared by a method similar to that of Preparation Examples 2-4.

[1306] ESI-MS m / z: 418.19[M+H] + .

[1307] 1H NMR (DMSO-d6, 400 MHz) δ 8.51 (d, 1H, J=8.1 Hz), 8.20 (t, 1H, J=1.0 Hz), 8.1-8.2 (m, 2H), 8.06 (s, 2H), 7.79 (dd, 1H, J=1.0, 7.8 Hz), 7.57 (dd, 1H, J=3.8, 9.6 Hz), 7.14 (dd, 1H, J=1.6, 9.6 Hz), 7.01 (d, 1H, J=7.4 Hz), 4.47 (qd, 1H, J=7.7, 15.3 Hz), 4.31 (qd, 1H, J=6.7, 13.4 Hz), 2.0-2.1 (m, 2H), 1.9-2.0 (m, 1H), 1.8-1.9 (m, 1H), 1.7-1.8 (m, 1H), 1.6-1.6 (m, 1H), 1.4-1.6 (m, 1H), 0.8-0.9 (m, 2H), 0.6-0.6 (m, 2H).

[1308]

[1309] Example 94: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1310]

[1311] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 94] (76%) was prepared by a method similar to that of Preparation Examples 2-4.

[1312] ESI-MS m / z: 418.19[M+H] + .

[1313] 1H NMR (DMSO-d6, 400 MHz) δ 8.51 (d, 1H, J=8.1 Hz), 8.20 (t, 1H, J=1.0 Hz), 8.1-8.2 (m, 2H), 8.06 (s, 2H), 7.79 (dd, 1H, J=1.0, 7.8 Hz), 7.57 (dd, 1H, J=3.8, 9.6 Hz), 7.14 (dd, 1H, J=1.6, 9.6 Hz), 7.01 (d, 1H, J=7.4 Hz), 4.47 (qd, 1H, J=7.7, 15.3 Hz), 4.31 (qd, 1H, J=6.7, 13.4 Hz), 2.0-2.1 (m, 2H), 1.9-2.0 (m, 1H), 1.8-1.9 (m, 1H), 1.7-1.8 (m, 1H), 1.6-1.6 (m, 1H), 1.4-1.6 (m, 1H), 0.8-0.9 (m, 2H), 0.6-0.6 (m, 2H).

[1314]

[1315] Example 95: Synthesis of N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-6-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1316]

[1317] N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-6-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 95] (58%) was prepared by a method similar to that of Preparation Examples 2-4.

[1318] ESI-MS m / z: 418.19[M+H] + .

[1319] 1H NMR (DMSO-d6, 400 MHz) δ 8.51 (d, 1H, J=8.1 Hz), 8.20 (t, 1H, J=1.0 Hz), 8.1-8.2 (m, 2H), 8.06 (s, 2H), 7.79 (dd, 1H, J=1.0, 7.8 Hz), 7.57 (dd, 1H, J=3.8, 9.6 Hz), 7.14 (dd, 1H, J=1.6, 9.6 Hz), 7.01 (d, 1H, J=7.4 Hz), 4.47 (qd, 1H, J=7.7, 15.3 Hz), 4.31 (qd, 1H, J=6.7, 13.4 Hz), 2.0-2.1 (m, 2H), 1.9-2.0 (m, 1H), 1.8-1.9 (m, 1H), 1.7-1.8 (m, 1H), 1.6-1.6 (m, 1H), 1.4-1.6 (m, 1H), 0.8-0.9 (m, 2H), 0.6-0.6 (m, 2H).

[1320]

[1321] Example 96: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1322]

[1323] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 96] (53%) was prepared by a method similar to that of Preparation Examples 2-4.

[1324] ESI-MS m / z: 444.15[M+H] + .

[1325] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.8 (m, 2H), 8.38 (d, 1H, J=2.1 Hz), 8.24 (s, 2H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 7.99 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.5 Hz), 7.49 (d, 1H, J=7.1 Hz), 7.22 (s, 1H), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 7.03 (s, 1H), 6.85 (s, 1H), 4.49 (qd, 1H, J=7.5, 15.1 Hz), 4.3-4.4 (m, 1H), 2.0-2.1 (m, 2H), 2.0-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[1326]

[1327] Example 97: Synthesis of 5-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]pyridine-3-carboxamide

[1328]

[1329] 5-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]pyridine-3-carboxamide [Example 97] (53%) was prepared by a method similar to that of Preparation Examples 2-4.

[1330] ESI-MS m / z: 417.17[M+H] + .

[1331] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.8 (m, 2H), 8.38 (d, 1H, J=2.1 Hz), 8.24 (s, 2H), 8.18 (dd, 1H, J=1.6, 3.8 Hz), 7.99 (dd, 1H, J=2.1, 5.4 Hz), 7.54 (dd, 1H, J=3.8, 9.5 Hz), 7.49 (d, 1H, J=7.1 Hz), 7.22 (s, 1H), 7.15 (dd, 1H, J=1.6, 9.6 Hz), 7.03 (s, 1H), 6.85 (s, 1H), 4.49 (qd, 1H, J=7.5, 15.1 Hz), 4.3-4.4 (m, 1H), 2.0-2.1 (m, 2H), 2.0-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[1332]

[1333] Example 98: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)benzamide

[1334]

[1335] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)benzamide [Example 98] (45%) was prepared by a method similar to that of Preparation Examples 2-4.

[1336] ESI-MS m / z: 443.16[M+H] + .

[1337] 1H NMR (DMSO-d6, 400 MHz) δ 8.50 (d, 1H, J=7.3 Hz), 8.25 (s, 2H), 8.10 (dd, 1H, J=1.6, 3.9 Hz), 7.9-8.0 (m, 2H), 7.6-7.7 (m, 2H), 7.5-7.5 (m, 2H), 7.23 (s, 1H), 7.10 (dd, 1H, J=1.6, 9.5 Hz), 7.04 (s, 1H), 6.86 (s, 1H), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 2.1-2.2 (m, 2H), 1.9-2.0 (m, 2H), 1.5-1.7 (m, 2H).

[1338]

[1339] Example 99: Synthesis of 4-(3-methyl-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[1340]

[1341] 4-(3-methyl-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [Example 99] (47%) was prepared by a method similar to that of Preparation Examples 2-4.

[1342] ESI-MS m / z: 405.20[M+H] + .

[1343] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.78 - 8.83 (m, 2 H) 8.34 (s, 2 H) 8.07 (d, J=2.13 Hz, 1 H) 7.76 (dd, J=5.25, 2.13 Hz, 1 H) 7.63 (dt, J=6.88, 0.94 Hz, 1 H) 7.52 (d, J=7.25 Hz, 1 H) 7.42 - 7.46 (m, 1 H) 6.33 (t, J=6.82 Hz, 1 H) 4.49 (sxt, J=7.48 Hz, 1 H) 4.38 (sxt, J=6.83 Hz, 1 H) 2.35 (s, 3 H) 2.07 - 2.18 (m, 2 H) 2.06 (s, 3 H) 1.96 - 2.03 (m, 1 H) 1.87 - 1.95 (m, 1 H) 1.62 - 1.72 (m, 1 H) 1.51 - 1.61 (m, 1 H).

[1344]

[1345] Example 100: Synthesis of 4-(3-methoxy-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[1346]

[1347] 4-(3-methoxy-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [Example 100] (34%) was prepared by a method similar to that of Preparation Examples 2-4.

[1348] ESI-MS m / z: 453.16[M+H] + .

[1349] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.77 - 8.85 (m, 2 H) 8.34 (s, 2 H) 8.06 (d, J=2.13 Hz, 1 H) 7.75 (dd, J=5.25, 2.25 Hz, 1 H) 7.52 (d, J=7.25 Hz, 1 H) 7.35 (dd, J=7.00, 1.63 Hz, 1 H) 6.93 (dd, J=7.50, 1.63 Hz, 1 H) 6.34 (t, J=7.19 Hz, 1 H) 4.49 (sxt, J=7.50 Hz, 1 H) 4.38 (sxt, J=6.80 Hz, 1 H) 3.77 (s, 3 H) 2.35 (s, 3 H) 2.03 - 2.16 (m, 2 H) 1.95 - 2.03 (m, 1 H) 1.86 - 1.95 (m, 1 H) 1.62 - 1.74 (m, 1 H) 1.51 - 1.62 (m, 1 H).

[1350]

[1351] Example 101: Synthesis of 4-(3-chloro-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[1352]

[1353] 4-(3-chloro-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [Example 101] (27%) was prepared by a method similar to that of Preparation Examples 2-4.

[1354] ESI-MS m / z: 457.11[M+H] + .

[1355] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.80 - 8.85 (m, 2 H) 8.35 (s, 2 H) 8.11 (d, J=2.13 Hz, 1 H) 7.89 (dd, J=7.32, 1.81 Hz, 1 H) 7.79 - 7.83 (m, 2 H) 7.52 (d, J=7.25 Hz, 1 H) 6.43 (t, J=7.13 Hz, 1 H) 4.49 (sxt, J=7.53 Hz, 1 H) 4.38 (sxt, J=6.78 Hz, 1 H) 2.35 (s, 3 H) 2.05 - 2.17 (m, 2 H) 1.97 - 2.04 (m, 1 H) 1.87 - 1.95 (m, 1 H) 1.62 - 1.73 (m, 1 H) 1.50 - 1.61 (m, 1 H).

[1356]

[1357] Example 102: Synthesis of N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[1358]

[1359] N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide [Example 102] (63%) was prepared by a method similar to that of Preparation Examples 2-4.

[1360] ESI-MS m / z: 463.16[M+H] + .

[1361] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.71 - 8.80 (m, 3 H) 8.35 (s, 2 H) 8.24 (dd, J=5.50, 2.25 Hz, 1 H) 7.98 (d, J=7.13 Hz, 1 H) 7.52 (d, J=7.25 Hz, 1 H) 7.33 - 7.42 (m, 2 H) 6.69 (ddd, J=7.13, 4.88, 2.38 Hz, 1 H) 4.50 (sxt, J=7.50 Hz, 1 H) 4.33 - 4.43 (m, 1 H) 2.35 (s, 3 H) 2.05 - 2.18 (m, 2H) 1.96 - 2.04 (m, 1 H) 1.86 - 1.96 (m, 1 H) 1.62 - 1.72 (m, 1 H) 1.51 - 1.61 (m, 1 H).

[1362]

[1363] Example 103: Synthesis of N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide

[1364]

[1365] N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide [Example 103] (40%) was prepared by a method similar to that of Preparation Examples 2-4.

[1366] ESI-MS m / z: 467.19[M+H] + .

[1367] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.72 (d, J=8.13 Hz, 1 H) 8.64 (d, J=5.63 Hz, 1 H) 8.55 (d, J=2.13 Hz, 1 H) 8.34 (s, 2 H) 8.06 (dd, J=5.50, 2.25 Hz, 1 H) 7.52 (d, J=7.25 Hz, 1 H) 4.48 (sxt, J=7.53 Hz, 1 H) 4.37 (sxt, J=6.78 Hz, 1 H) 3.59 (t, J=6.00 Hz, 2 H) 2.74 (t, J=6.32 Hz, 2 H) 2.35 (s, 3 H) 2.03 - 2.16 (m, 2 H) 1.94 - 2.02 (m, 1 H) 1.85 - 1.93 (m, 3 H) 1.77 - 1.85 (m, 2 H) 1.60 - 1.70 (m, 1 H) 1.50 - 1.60 (m, 1 H).

[1368]

[1369] Example 104: Synthesis of N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide

[1370]

[1371] N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide [Example 104] (38%) was prepared by a method similar to that of Preparation Examples 2-4.

[1372] ESI-MS m / z: 453.17[M+H] + .

[1373] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.71 (d, J=8.26 Hz, 1 H) 8.62 (d, J=5.63 Hz, 1 H) 8.53 (d, J=1.88 Hz, 1 H) 8.34 (s, 2 H) 8.02 (dd, J=5.63, 2.25 Hz, 1 H) 7.51 (d, J=7.25 Hz, 1 H) 4.47 (sxt, J=7.48 Hz, 1 H) 4.32 - 4.41 (m, 1 H) 3.76 (t, J=7.07 Hz, 2 H) 2.87 (t, J=7.75 Hz, 2 H) 2.53 (br s, 2 H) 2.35 (s, 3 H) 2.03 - 2.16 (m, 2 H) 1.94 - 2.02 (m, 1 H) 1.85 - 1.94 (m, 1 H) 1.60 - 1.71 (m, 1 H) 1.49 - 1.60 (m, 1 H).

[1374]

[1375] Example 105: Synthesis of N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide

[1376]

[1377] N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide [Example 105] (27%) was prepared by a method similar to that of Preparation Examples 2-4.

[1378] ESI-MS m / z: 469.17[M+H] + .

[1379] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.74 (d, J=8.25 Hz, 1 H) 8.66 (d, J=5.50 Hz, 1 H) 8.54 (d, J=2.25 Hz, 1 H) 8.34 (s, 2 H) 8.06 (dd, J=5.50, 2.25 Hz, 1 H) 7.51 (d, J=7.25 Hz, 1 H) 4.78 (s, 2 H) 4.48 (sxt, J=7.55 Hz, 1 H) 4.37 (dq, J=13.46, 6.85 Hz, 1 H) 4.03 (t, J=5.32 Hz, 2 H) 3.69 (t, J=5.32 Hz, 2 H) 2.35 (s, 3 H) 2.02 - 2.15 (m, 2 H) 1.94 - 2.02 (m, 1 H) 1.85 - 1.94 (m, 1 H) 1.60 - 1.70 (m, 1 H) 1.50 - 1.60 (m, 1 H).

[1380]

[1381] Example 106: Synthesis of 4-(3-chloro-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[1382]

[1383] 4-(3-chloro-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [Example 106] (19%) was prepared by a method similar to that of Preparation Examples 2-4.

[1384] ESI-MS m / z: 455.09[M+H] + .

[1385] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.80 - 8.86 (m, 2 H) 8.33 (s, 2 H) 8.09 - 8.13 (m, 1 H) 7.89 (dd, J=7.32, 1.81 Hz, 1 H) 7.77 - 7.83 (m, 2 H) 7.59 (d, J=7.25 Hz, 1 H) 6.43 (t, J=7.13 Hz, 1 H) 4.50 (sxt, J=7.48 Hz, 1 H) 4.34 (sxt, J=6.68 Hz, 1 H) 2.06 - 2.17 (m, 2 H) 1.97 - 2.05 (m, 1 H) 1.86 - 1.94 (m, 1 H) 1.62 - 1.72 (m, 1 H) 1.53 - 1.61 (m, 1 H).

[1386]

[1387] Example 107: Synthesis of N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(5-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1388]

[1389] N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(5-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 107] (25%) was prepared by a method similar to that of Preparation Examples 2-4.

[1390] ESI-MS m / z: 426.14[M+H] + .

[1391] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.74 - 8.82 (m, 2 H) 8.36 - 8.40 (m, 1 H) 8.33 (s, 2 H) 8.06 (d, J=4.00 Hz, 1 H) 7.99 (dd, J=5.38, 2.13 Hz, 1 H) 7.59 (d, J=7.25 Hz, 1 H) 7.41 - 7.44 (m, 1 H) 4.49 (sxt, J=7.53 Hz, 1 H) 4.29 - 4.38 (m, 1 H) 2.18 (d, J=1.25 Hz, 3 H) 2.04 - 2.15 (m, 2 H) 1.95 - 2.03 (m, 1 H) 1.86 - 1.95 (m, 1 H) 1.61 - 1.73 (m, 1 H) 1.51 - 1.61 (m, 1 H).

[1392]

[1393] Example 108: Synthesis of N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(4-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1394]

[1395] N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(4-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 108] (28%) was prepared by a method similar to that of Preparation Examples 2-4.

[1396] ESI-MS m / z: 426.14[M+H] + .

[1397] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.74 - 8.81 (m, 2 H) 8.38 (d, J=2.13 Hz, 1 H) 8.32 (s, 2 H) 8.09 (d, J=2.13 Hz, 1 H) 8.00 (dd, J=5.38, 2.25 Hz, 1 H) 7.59 (d, J=7.25 Hz, 1 H) 6.95 (dd, J=2.00, 1.38 Hz, 1 H) 4.49 (sxt, J=7.53 Hz, 1 H) 4.29 - 4.39 (m, 1 H) 2.26 (d, J=1.25 Hz, 3 H) 2.05 - 2.15 (m, 2 H) 1.96 - 2.03 (m, 1 H) 1.86 - 1.94 (m, 1 H) 1.61 - 1.71 (m, 1 H) 1.51 - 1.61 (m, 1 H).

[1398]

[1399] Example 109: Synthesis of N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(3-methyl-2-oxo-1-pyridinyl)pyridine-2-carboxamide

[1400]

[1401] N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(3-methyl-2-oxo-1-pyridinyl)pyridine-2-carboxamide [Example 109] (49%) was prepared by a method similar to that of Preparation Examples 2-4.

[1402] ESI-MS m / z: 425.14[M+H] + .

[1403] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.77 - 8.84 (m, 2 H) 8.33 (s, 2 H) 8.07 (d, J=2.13 Hz, 1 H) 7.76 (dd, J=5.25, 2.25 Hz, 1 H) 7.61 - 7.65 (m, 1 H) 7.59 (d, J=7.25 Hz, 1 H) 7.42 - 7.47 (m, 1 H) 6.33 (t, J=6.82 Hz, 1 H) 4.49 (sxt, J=7.50 Hz, 1 H) 4.29 - 4.39 (m, 1 H) 2.04 - 2.17 (m, 5 H) 1.96 - 2.03 (m, 1 H) 1.86 - 1.95 (m, 1 H) 1.62 - 1.72 (m, 1 H) 1.51 - 1.61 (m, 1 H).

[1404]

[1405] Example 110: Synthesis of 4-(5-chloro-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[1406]

[1407] 4-(5-chloro-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [Example 110] (59%) was prepared by a method similar to that of Preparation Examples 2-4.

[1408] ESI-MS m / z: 446.08[M+H] + .

[1409] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.78 - 8.84 (m, 2 H) 8.34 - 8.36 (m, 1 H) 8.32 (s, 2 H) 8.14 (d, J=4.50 Hz, 1 H) 7.96 (dd, J=5.32, 2.19 Hz, 1 H) 7.91 (d, J=4.50 Hz, 1 H) 7.59 (d, J=7.25 Hz, 1 H) 4.49 (sxt, J=7.53 Hz, 1 H) 4.28 - 4.39 (m, 1 H) 2.03 - 2.16 (m, 2 H) 1.96 - 2.03 (m, 1 H) 1.86 - 1.94 (m, 1 H) 1.62 - 1.73 (m, 1 H) 1.50 - 1.61 (m, 1 H).

[1410]

[1411] Example 111: Synthesis of 4-(5-methoxy-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[1412]

[1413] 4-(5-methoxy-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [Example 111] (54%) was prepared by a method similar to that of Preparation Examples 2-4.

[1414] ESI-MS m / z: 442.13[M+H] + .

[1415] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.74 - 8.82 (m, 2 H) 8.36 (d, J=2.13 Hz, 1 H) 8.32 (s, 2 H) 8.07 (d, J=4.88 Hz, 1 H) 7.98 (dd, J=5.38, 2.25 Hz, 1 H) 7.59 (d, J=7.25 Hz, 1 H) 6.87 (d, J=5.00 Hz, 1 H) 4.49 (sxt, J=7.48 Hz, 1 H) 4.28 - 4.39 (m, 1 H) 3.90 (s, 3 H) 2.04 - 2.15 (m, 2 H) 1.96 - 2.04 (m, 1 H) 1.86 - 1.95 (m, 1 H) 1.61 - 1.73 (m, 1 H) 1.52 - 1.61 (m, 1 H).

[1416]

[1417] Example 112: Synthesis of N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(1-oxo-2,7-naphthiridine-2-yl)pyridine-2-carboxamide

[1418]

[1419] N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(1-oxo-2,7-naphthiridin-2-yl)pyridine-2-carboxamide [Example 112] (61%) was prepared by a method similar to that of Preparation Examples 2-4.

[1420] ESI-MS m / z: 462.14[M+H] + .

[1421] 1H NMR (DMSO-d6, 400 MHz) δ ppm 9.40 (s, 1 H) 8.82 (dd, J=9.63, 5.63 Hz, 3 H) 8.33 (s, 2 H) 8.19 (d, J=2.13 Hz, 1 H) 7.83 - 7.89 (m, 2 H) 7.70 (dd, J=5.50, 0.75 Hz, 1 H) 7.60 (d, J=7.25 Hz, 1 H) 6.83 (d, J=7.25 Hz, 1 H) 4.50 (sxt, J=7.48 Hz, 1 H) 4.35 (sxt, J=6.73 Hz, 1 H) 2.07 - 2.18 (m, 2H) 1.97 - 2.06 (m, 1 H) 1.87 - 1.95 (m, 1 H) 1.63 - 1.74 (m, 1 H) 1.51 - 1.62 (m, 1 H).

[1422]

[1423] Example 113: Synthesis of N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(4-oxofuro[3,2-c]pyridine-5-yl)pyridine-2-carboxamide

[1424]

[1425] N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(4-oxofuro[3,2-c]pyridine-5-yl)pyridine-2-carboxamide [Example 113] (57%) was prepared by a method similar to that of Preparation Examples 2-4.

[1426] ESI-MS m / z: 451.12[M+H] + .

[1427] 1H NMR (DMSO-d6, 400 MHz) δ ppm 8.80 - 8.86 (m, 2 H) 8.33 (s, 2 H) 8.09 - 8.12 (m, 1 H) 8.00 (d, J=2.13 Hz, 1 H) 7.79 (dd, J=5.25, 2.13 Hz, 1 H) 7.75 (d, J=7.63 Hz, 1 H) 7.59 (d, J=7.25 Hz, 1 H) 7.06 (dd, J=2.13, 0.75 Hz, 1 H) 6.96 (dd, J=7.50, 0.88 Hz, 1 H) 4.50 (sxt, J=7.53 Hz, 1 H) 4.30 - 4.40 (m, 1 H) 2.06 - 2.17 (m, 2 H) 1.96 - 2.06 (m, 1 H) 1.86 - 1.94 (m, 1 H) 1.63 - 1.72 (m, 1 H) 1.51 - 1.62 (m, 1 H).

[1428]

[1429] Example 114: Synthesis of N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1430]

[1431] N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 114] (14%) was prepared by a method similar to that of Preparation Examples 2-4.

[1432] ESI-MS m / z: 391.08[M+H] + .

[1433] 1H NMR (500 MHz, DMSO) δ 8.79 (t, J = 6.2 Hz, 2H), 8.12 (s, 2H), 8.07 (d, J = 2.1 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.59 - 7.52 (m, 1H), 6.99 (d, J = 7.3 Hz, 1H), 6.54 (dd, 1H), 6.40 (t, 1H), 4.52 - 4.43 (m, 1H), 4.38 - 4.30 (m, 1H), 2.14 - 2.06 (m, 2H), 2.04 (s, 3H), 2.02 - 1.94 (m, 1H), 1.92 - 1.85 (m, 1H), 1.69 - 1.61 (m, 1H), 1.58 - 1.50 (m, 1H).

[1434]

[1435] Example 115: Synthesis of N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[1436]

[1437] N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide [Example 115] (28%) was prepared in a manner similar to that of Preparation Examples 2-4.

[1438] ESI-MS m / z: 392.16[M+H] + .

[1439] 1H NMR (500 MHz, DMSO) δ 8.77 (t, J = 6.6 Hz, 2H), 8.37 (d, J = 2.2 Hz, 1H), 8.18 (dd, J = 3.9, 1.6 Hz, 1H), 8.12 (s, 2H), 7.99 (dd, J = 5.4, 2.2 Hz, 1H), 7.54 (dd, J = 9.6, 3.8 Hz, 1H), 7.15 (dd, J = 9.6, 1.6 Hz, 1H), 6.98 (d, J = 7.3 Hz, 1H), 4.53 - 4.42 (m, 1H), 4.39 - 4.29 (m, 1H), 2.16 - 2.05 (m, 2H), 2.04 (s, 3H), 2.02 - 1.93 (m, 1H), 1.92 - 1.83 (m, 1H), 1.71 - 1.59 (m, 1H), 1.58 - 1.43 (m, 1H).

[1440]

[1441] Example 116: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1442]

[1443] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 116] (31%) was prepared by a method similar to that of Preparation Examples 2-4.

[1444] ESI-MS m / z: 457.19[M+H] + .

[1445] 1H NMR (500 MHz, Chloroform-d) δ 8.64 (d, J = 5.2 Hz, 1H), 8.17 (d, J = 3.0 Hz, 2H), 8.05 (d, J = 7.9 Hz, 1H), 7.72 (dd, J = 5.3, 2.1 Hz, 1H), 7.29 (dt, J = 6.7, 1.6 Hz, 1H), 7.24 (d, J = 2.0 Hz, 1H), 6.56 - 6.23 (m, 2H), 5.28 (d, J = 7.0 Hz, 1H), 4.62 (p, J = 7.1 Hz, 1H), 4.44 (h, J = 6.8 Hz, 1H), 2.35 (dtt, J = 14.9, 7.6, 3.8 Hz, 2H), 2.19 (s, 3H), 2.14 - 2.03 (m, 2H), 1.68 - 1.57 (m, 2H).

[1446]

[1447] Example 117: Synthesis of 3-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1448]

[1449] 3-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 117] (29%) was prepared by a method similar to that of Preparation Examples 2-4.

[1450] ESI-MS m / z: 477.02[M+H] + .

[1451] 1H NMR (500 MHz, Chloroform-d) δ 8.67 (d, J = 5.2 Hz, 1H), 8.17 (d, J = 2.1 Hz, 3H), 8.05 (d, J = 7.9 Hz, 1H), 7.71 (dd, J = 5.3, 2.2 Hz, 1H), 7.64 - 7.62 (m, 1H), 7.34 (dd, J = 7.0, 1.9 Hz, 1H), 6.48 (d, J = 72.8 Hz, 1H), 5.45 (d, J = 7.1 Hz, 1H), 4.61 (h, J = 7.1 Hz, 1H), 4.44 (p, J = 6.8 Hz, 1H), 2.34 (tdd, J = 10.8, 6.7, 4.1 Hz, 2H), 2.14 - 2.06 (m, 2H), 1.69 - 1.57 (m, 3H).

[1452]

[1453] Example 118: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1454]

[1455] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 118] (29%) was prepared by a method similar to that of Preparation Examples 2-4.

[1456] ESI-MS m / z: 473.20[M+H] + .

[1457] 1H NMR (500 MHz, Chloroform-d) δ 8.66 (d, J = 5.3 Hz, 1H), 8.18 (d, J = 3.6 Hz, 3H), 8.05 (d, J = 7.9 Hz, 1H), 7.73 (dd, J = 5.2, 2.1 Hz, 1H), 7.01 (dd, J = 7.1, 1.6 Hz, 1H), 6.67 (dd, J = 7.5, 1.6 Hz, 1H), 6.56 - 6.28 (m, 1H), 6.28 - 6.25 (m, 1H), 5.29 (d, J = 7.1 Hz, 1H), 4.61 (q, J = 7.2 Hz, 1H), 4.44 (q, J = 6.8 Hz, 1H), 3.86 (s, 3H), 2.35 (qd, J = 7.6, 3.6 Hz, 2H), 2.16 - 2.05 (m, 2H), 1.70 - 1.53 (m, 4H).

[1458]

[1459] Example 119: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1460]

[1461] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 119] (11%) was prepared by a method similar to that of Preparation Examples 2-4.

[1462] ESI-MS m / z: 443.12[M+H] + .

[1463] 1H NMR (500 MHz, Chloroform-d) δ 8.66 (d, J = 5.3 Hz, 1H), 8.17 (d, J = 2.8 Hz, 3H), 8.05 (d, J = 8.0 Hz, 1H), 7.72 (dd, J = 5.3, 2.1 Hz, 1H), 7.43 (ddd, J = 8.9, 6.5, 2.0 Hz, 1H), 7.38 - 7.35 (m, 1H), 6.67 (d, J = 9.3 Hz, 1H), 6.56 - 6.31 (m, 2H), 5.25 (d, J = 7.1 Hz, 1H), 4.61 (q, J = 7.2 Hz, 1H), 4.44 (q, J = 6.8 Hz, 1H), 2.36 (tt, J = 8.0, 3.6 Hz, 2H), 2.12 (ddd, J = 19.3, 13.1, 7.1 Hz, 2H), 2.07 - 1.99 (m, 3H), 1.71 - 1.64 (m, 3H).

[1464]

[1465] Example 120: Synthesis of 5-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1466]

[1467] 5-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 120] (9%) was prepared by a method similar to that of Preparation Examples 2-4.

[1468] ESI-MS m / z: 477.08[M+H] + .

[1469] 1H NMR (500 MHz, CDCl3) δ 8.68 (d, J = 5.2 Hz, 1H), 8.20 - 8.16 (m, 3H), 8.04 (d, J = 8.0 Hz, 1H), 7.69 (dd, J = 5.3, 2.2 Hz, 1H), 7.44 (d, J) = 2.9 Hz, 1H), 7.38 (dd, J = 9.8, 2.8 Hz, 1H), 6.65 (d, J = 9.9 Hz, 1H), 6.41 (s, 1H), 5.31 (s, 1H), 4.64 - 4.58 (m, 1H), 4.47 - 4.42 (m, 1H), 2.39 - 2.34 (m, 2H), 2.13 - 2.05 (m, 2H), 1.61 - 1.58 (m, 1H), 1.25 (s, 1H).

[1470]

[1471] Example 121: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)pyridine-2-carboxamide

[1472]

[1473] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)pyridine-2-carboxamide [Example 121] (14%) was prepared by a method similar to that of Preparation Examples 2-4.

[1474] ESI-MS m / z: 493.16[M+H] + .

[1475] 1H NMR (500 MHz, CDCl3) δ 8.81 (d, J = 5.1 Hz, 1H), 8.19 - 8.16 (m, 3H), 8.10 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 9.6 Hz, 1H), 7.62 (dd, J = 7.7, 1.5 Hz, 1H), 7.45 (dd, J = 5.1, 2.0 Hz, 1H), 7.38 - 7.32 (m, 1H), 7.24 (d, J = 7.5 Hz, 1H), 6.76 (d, J = 9.6 Hz, 1H), 6.58 (d, 1H), 6.41 (s, 1H), 5.30 - 5.22 (m, 1H), 4.67 - 4.59 (m, 1H), 4.51 - 4.42 (m, 1H), 2.39 - 2.32 (m, 2H), 2.16 - 2.11 (m, 1H), 2.11 - 2.06 (m, 1H), 1.61 - 1.59 (m, 1H), 1.30 - 1.24 (m, 1H).

[1476]

[1477] Example 122: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1,1-deoxydoisothiazolidine-2-yl)pyridine-2-carboxamide

[1478]

[1479] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1,1-deoxydoisothiazolidin-2-yl)pyridine-2-carboxamide [Example 122] (14%) was prepared by a method similar to that of Preparation Examples 2-4.

[1480] ESI-MS m / z: 469.04[M+H] + .

[1481] 1H NMR (500 MHz, DMSO) δ 8.68 (d, J = 8.2 Hz, 1H), 8.50 (d, J = 5.6 Hz, 1H), 8.24 (s, 2H), 7.78 (d, J = 2.5 Hz, 1H), 7.49 (d, J = 7.2 Hz, 1H), 7.22 (dd, J = 5.6, 2.5 Hz, 1H), 7.03 (s, 1H), 4.50 - 4.39 (m, 1H), 4.36 - 4.26 (m, 1H), 3.87 (t, J = 6.5 Hz, 2H), 3.64 (t, J = 7.2 Hz, 2H), 2.49 - 2.40 (m, 2H), 2.19 - 1.98 (m, 2H), 2.03 - 1.78 (m, 2H), 1.71 - 1.43 (m, 2H).

[1482]

[1483] Example 123: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)pyridine-2-carboxamide

[1484]

[1485] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)pyridine-2-carboxamide [Example 123] (19%) was prepared by a method similar to that of Preparation Examples 2-4.

[1486] ESI-MS m / z: 496.30[M+H] + .

[1487] 1H NMR (500 MHz, DMSO) δ 8.94 - 8.72 (m, 2H), 8.29 (d, J = 2.2 Hz, 1H), 8.24 (s, 2H), 7.90 (dd, J = 5.4, 2.2 Hz, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.34 (dd, J = 20.5, 7.9 Hz, 2H), 7.24 (t, J = 7.7 Hz, 1H), 7.19 - 7.12 (m, 1H), 7.03 (s, 1H), 4.54 - 4.46 (m, 1H), 4.39 - 4.31 (m, 1H), 3.42 (s, 3H), 2.18 - 1.97 (m, 3H), 1.96 - 1.87 (m, 1H), 1.72 - 1.62 (m, 1H), 1.62 - 1.53 (m, 1H).

[1488]

[1489] Example 124: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2,5-dioxomidazolidine-1-yl)pyridine-2-carboxamide

[1490]

[1491] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2,5-dioxomidazolidine-1-yl)pyridine-2-carboxamide [Example 124] (23%) was prepared by a method similar to that of Preparation Examples 2-4.

[1492] ESI-MS m / z: 462.15[M+H] + .

[1493] 1H NMR (500 MHz, CDCl3) δ 8.62 (d, J = 5.3 Hz, 1H), 8.46 - 8.43 (m, 1H), 8.18 (s, 2H), 8.05 - 8.02 (m, 1H), 7.71 (dd, J = 5.3, 2.1 Hz, 1H), 6.56 (s, 1H), 6.41 (s, 1H), 5.28 (d, J = 7.1 Hz, 1H), 4.66 - 4.58 (m, 1H), 4.46 - 4.40 (m, 1H), 4.08 (s, 2H), 3.12 (s, 3H), 2.37 - 2.31 (m, 2H), 2.13 - 2.04 (m, 2H), 1.67 - 1.63 (m, 2H).

[1494]

[1495] Example 125: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)thiophene-2-carboxamide

[1496]

[1497]

[1498] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)thiophene-2-carboxamide [Example 125] (9%) was prepared by a method similar to that of Preparation Examples 2-4.

[1499] ESI-MS m / z: 449.09[M+H] + .

[1500] 1H NMR (500 MHz, CDCl3) δ 8.23 ​​(d, J = 1.4 Hz, 1H), 8.20 (s, 2H), 8.08 (d, J = 1.5 Hz, 1H), 7.94 (dd, J = 3.7, 1.7 Hz, 1H), 7.26 (dd, J = 9.5, 3.8 Hz, 1H), 7.10 (dd, J = 9.5, 1.7 Hz, 1H), 6.43 (t, J = 72.8 Hz, 1H), 6.17 (d, J = 7.3 Hz, 1H), 5.24 (d, J = 7.0 Hz, 1H), 4.60 (q, J = 7.0 Hz, 1H), 4.44 (p, J = 7.1 Hz, 1H), 2.44 - 2.29 (m, 3H), 2.16 - 2.01 (m, 3H).

[1501]

[1502] Example 126: Synthesis of N-((1S,3S)-3-((5-cyclopropyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[1503]

[1504] N-((1S,3S)-3-((5-cyclopropyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide [Example 126] (22%) was prepared in the same manner as in Preparation Example 4-2.

[1505] ESI-MS m / z: 408.02[M+H]+.

[1506] 1H NMR (500 MHz, Chloroform-d) δ 8.62 (d, J = 5.4 Hz, 1H), 8.56 (d, J = 2.1 Hz, 1H), 8.05 - 8.00 (m, 2H), 7.96 (dd, J = 3.7, 1.7 Hz, 1H), 7.06 (dd, J = 9.5, 1.7 Hz, 1H), 4.60 (q, J = 7.0 Hz, 1H), 4.29 (d, J = 6.7 Hz, 1H), 4.10 (q, J = 6.4 Hz, 1H), 2.37 - 2.28 (m, 2H), 2.13 - 2.07 (m, 2H), 2.06 - 2.00 (m, 1H), 1.66 - 1.60 (m, 3H), 1.14 (dt, J = 8.7, 2.7 Hz, 4H).

[1507]

[1508] Example 127: Synthesis of N-((1S,3S)-3-((5-methyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[1509]

[1510] N-((1S,3S)-3-((5-methyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide [Example 127] (31%) was prepared by a method similar to that of Preparation Example 4-2.

[1511] ESI-MS m / z: 382.04[M+H] + .

[1512] 1H NMR (500 MHz, Chloroform-d) δ 8.63 (d, J = 5.4 Hz, 1H), 8.56 (d, J = 2.1 Hz, 1H), 8.06 - 8.01 (m, 2H), 7.97 (dd, J = 3.8, 1.7 Hz, 1H), 7.06 (dd, J = 9.5, 1.7 Hz, 1H), 4.61 (q, J = 7.1 Hz, 1H), 4.34 (d, J = 6.8 Hz, 1H), 4.12 (q, J = 6.5 Hz, 1H), 2.44 (s, 3H), 2.36 - 2.30 (m, 2H), 2.14 - 2.05 (m, 2H), 1.65 (s, 3H).

[1513]

[1514] Example 128: Synthesis of N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1515]

[1516] N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 128] (13%) was prepared by a method similar to that of Preparation Examples 2-4.

[1517] ESI-MS m / z: 431.34[M+H] + .

[1518] 1H NMR (500 MHz, DMSO) δ 8.82 - 8.77 (m, 2H), 8.09 - 8.04 (m, 3H), 7.75 (dd, J = 5.2, 2.1 Hz, 1H), 7.63 (d, J = 7.4 Hz, 1H), 7.44 (d, J = 6.5 Hz, 1H), 7.04 (d, J = 7.3 Hz, 1H), 6.33 (t, J = 6.8 Hz, 1H), 4.50 - 4.44 (m, 1H), 4.37 - 4.30 (m, 1H), 2.16 - 2.07 (m, 2H), 2.06 (s, 3H), 2.00 - 1.94 (m, 1H), 1.90 - 1.85 (m, 1H), 1.75 - 1.69 (m, 1H), 1.67 - 1.61 (m, 1H), 1.57 - 1.50 (m, 1H), 0.85 - 0.81 (m, 2H), 0.62 - 0.57 (m, 2H).

[1519]

[1520] Example 129: Synthesis of N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1521]

[1522] N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 129] (12%) was prepared by a method similar to that of Preparation Examples 2-4.

[1523] ESI-MS m / z: 447.14[M+H] + .

[1524] 1H NMR (500 MHz, DMSO) δ 8.84 - 8.75 (m, 2H), 8.06 (d, J = 11.7 Hz, 3H), 7.75 (dd, J = 5.3, 2.2 Hz, 1H), 7.34 (dd, J = 7.0, 1.6 Hz, 1H), 7.04 (d, J = 7.3 Hz, 1H), 6.92 (dd, J = 7.5, 1.6 Hz, 1H), 6.34 (t, J = 7.2 Hz, 1H), 4.50 - 4.44 (m, 1H), 4.36 - 4.28 (m, 1H), 3.76 (s, 3H), 2.14 - 2.03 (m, 2H), 2.00 - 1.84 (m, 2H), 1.75 - 1.61 (m, 2H), 1.56 - 1.48 (m, 1H), 0.87 - 0.79 (m, 2H), 0.63 - 0.56 (m, 2H).

[1525]

[1526] Example 130: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-4-(6-oxopyridazine-1(6H)-yl)-1H-pyrrole-2-carboxamide

[1527]

[1528] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-4-(6-oxopyridazine-1(6H)-yl)-1H-pyrrole-2-carboxamide [Example 130] (8%) was prepared by a method similar to that of Preparation Examples 2-4.

[1529] ESI-MS m / z: 446.14[M+H] + .

[1530] 1H NMR (500 MHz, CDCl3) δ 8.20 (s, 2H), 7.90 (q, J = 1.5 Hz, 1H), 7.70 (d, J = 1.6 Hz, 1H), 7.21 (dd, J = 9.4, 3.8 Hz, 1H), 7.11 (d, J = 1.9) Hz, 1H), 7.06 (dt, J = 9.6, 1.3 Hz, 1H), 6.43 (t, J = 72.8 Hz, 1H), 6.01 (d, J = 7.3 Hz, 1H), 5.26 (d, J = 7.0 Hz, 1H), 4.54 (q, J = 7.0) Hz, 1H), 4.41 (q, J = 6.8 Hz, 1H), 3.99 (s, 3H), 2.40 - 2.27 (m, 2H), 2.05 (dt, J = 12.8, 5.1 Hz, 3H), 1.90 (d, J = 9.1 Hz, 1H).

[1531]

[1532] Example 131: Synthesis of 3-methyl-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1533]

[1534] 3-methyl-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 131] (37%) was prepared by a method similar to that of Preparation Examples 2-4.

[1535] ESI-MS m / z: 405.22[M+H] + .

[1536] 1H NMR (500 MHz, Chloroform-d) δ 8.64 (d, J = 5.3 Hz, 1H), 8.17 - 8.11 (m, 3H), 8.05 (d, J = 8.0 Hz, 1H), 7.72 (dd, J = 5.3, 2.1 Hz, 1H), 7.28 (dd, J = 6.7, 1.7 Hz, 1H), 6.24 (t, J = 6.8 Hz, 1H), 5.07 (d, J = 7.2 Hz, 1H), 4.61 (q, J = 7.2 Hz, 1H), 4.46 (q, J = 6.9 Hz, 1H), 2.35 (ddt, J = 13.2, 8.0, 3.6 Hz, 2H), 2.19 (s, 3H), 2.12 (s, 4H), 2.05 (dt, J = 13.7, 7.3 Hz, 1H), 1.69 - 1.56 (m, 2H).

[1537]

[1538] Example 132: Synthesis of 3-chloro-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1539]

[1540] 3-chloro-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 132] (31%) was prepared by a method similar to that of Preparation Examples 2-4.

[1541] ESI-MS m / z: 425.17[M+H] + .

[1542] 1H NMR (500 MHz, Chloroform-d) δ 8.68 (d, J = 5.3 Hz, 1H), 8.16 (d, J = 2.2 Hz, 1H), 8.13 (s, 2H), 8.05 (d, J = 8.0 Hz, 1H), 7.72 (dd, J = 5.4, 2.2 Hz, 1H), 7.63 (dd, J = 7.2, 1.8 Hz, 1H), 7.34 (dd, J = 7.0, 1.9 Hz, 1H), 6.31 (t, J = 7.1 Hz, 1H), 5.11 (d, J = 7.1 Hz, 1H), 4.62 (p, J = 7.0 Hz, 1H), 4.46 (q, J = 6.8 Hz, 1H), 2.35 (tt, J = 10.7, 5.6 Hz, 2H), 2.12 (s, 4H), 2.09 - 2.02 (m, 1H), 1.69 - 1.56 (m, 2H).

[1543]

[1544] Example 133: Synthesis of 3-Methoxy-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1545]

[1546] 3-methoxy-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 133] (32%) was prepared by a method similar to that of Preparation Examples 2-4.

[1547] ESI-MS m / z: 421.29[M+H] + .

[1548] 1H NMR (500 MHz, Chloroform-d) δ 8.65 (d, J = 5.3 Hz, 1H), 8.17 (d, J = 2.1 Hz, 1H), 8.13 (s, 2H), 8.06 (d, J = 8.1 Hz, 1H), 7.74 (dd, J = 5.3, 2.2 Hz, 1H), 7.01 (dd, J = 7.0, 1.7 Hz, 1H), 6.67 (dd, J = 7.4, 1.6 Hz, 1H), 6.26 (t, J = 7.2 Hz, 1H), 5.11 (d, J = 7.2 Hz, 1H), 4.61 (q, J = 7.0 Hz, 1H), 4.45 (q, J = 6.9 Hz, 1H), 3.87 (s, 3H), 2.38 - 2.31 (m, 2H), 2.12 (s, 4H), 2.05 (ddd, J = 13.5, 7.8, 6.1 Hz, 2H), 1.70 - 1.55 (m, 2H).

[1549]

[1550] Example 134: Synthesis of 3-chloro-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1551]

[1552] 3-chloro-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 134] (11%) was prepared by a method similar to that of Preparation Examples 2-4.

[1553] ESI-MS m / z: 451.23[M+H] + .

[1554] 1H NMR (500 MHz, DMSO) δ 8.88 - 8.81 (m, 2H), 8.12 (d, J = 2.1 Hz, 1H), 8.09 (s, 2H), 7.91 (dd, J = 7.3, 1.8 Hz, 1H), 7.82 (td, J = 6.4, 5.5, 2.0 Hz, 2H), 7.06 (d, J = 7.2 Hz, 1H), 6.45 (t, J = 7.1 Hz, 1H), 4.53 - 4.45 (m, 1H), 4.39 - 4.32 (m, 1H), 2.15 - 2.05 (m, 2H), 2.03 - 1.95 (m, 1H), 1.92 - 1.85 (m, 1H), 1.77 1.64 (m, 2H), 1.59 - 1.50 (m, 1H), 0.88 - 0.83 (m, 2H), 0.64 - 0.59 (m, 2H).

[1555]

[1556] Example 135: Synthesis of N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)pyridine-2-carboxamide

[1557]

[1558] N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)pyridine-2-carboxamide [Example 135] (11%) was prepared by a method similar to that of Preparation Examples 2-4.

[1559] ESI-MS m / z: 467.24[M+H] + .

[1560] 1H NMR (500 MHz, DMSO) δ 8.92 (d, J = 5.1 Hz, 1H), 8.86 (d, J = 8.2 Hz, 1H), 8.09 (d, J = 12.3 Hz, 2H), 7.98 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 7.9, 1.6 Hz, 1H), 7.72 (dd, J = 5.1, 2.0 Hz, 1H), 7.44 (t, J = 8.0 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 7.05 (d, J = 7.2 Hz, 1H), 6.71 (d, J = 9.6 Hz, 1H), 6.60 (d, J = 8.4 Hz, 1H), 4.52 - 4.44 (m, 1H), 4.39 - 4.30 (m, 1H), 2.17 - 2.02 (m, 2H), 2.04 - 1.96 (m, 1H), 1.93 - 1.81 (m, 1H), 1.77 - 1.62 (m, 2H), 1.58 - 1.48 (m, 1H), 0.93 - 0.75 (m, 2H), 0.69 - 0.47 (m, 2H).

[1561]

[1562] Example 136: Synthesis of N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)pyridine-2-carboxamide

[1563]

[1564] N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)pyridine-2-carboxamide [Example 136] (12%) was prepared by a method similar to that of Preparation Examples 2-4.

[1565] ESI-MS m / z: 470.25[M+H] + .

[1566] 1H NMR (500 MHz, DMSO) δ 8.88 - 8.81 (m, 2H), 8.12 (d, J = 2.1 Hz, 1H), 8.09 (s, 2H), 7.91 (dd, J = 7.3, 1.8 Hz, 1H), 7.82 (td, J = 6.4, 5.5, 2.0 Hz, 2H), 7.06 (d, J = 7.2 Hz, 1H), 6.45 (t, J = 7.1 Hz, 1H), 4.53 - 4.45 (m, 1H), 4.39 - 4.32 (m, 1H), 2.15 - 2.05 (m, 2H), 2.03 - 1.95 (m, 1H), 1.92 - 1.85 (m, 1H), 1.77 1.64 (m, 2H), 1.59 - 1.50 (m, 1H), 0.88 - 0.83 (m, 2H), 0.64 - 0.59 (m, 2H).

[1567]

[1568] Example 137: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)furan-2-carboxamide

[1569]

[1570] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)furan-2-carboxamide [Example 137] (3%) was prepared by a method similar to that of Preparation Examples 2-4.

[1571] ESI-MS m / z: 433.21[M+H] + .

[1572] 1H NMR (500 MHz, CDCl3) δ 8.58 (s, 1H), 8.18 (s, 2H), 7.95 (dd, J = 3.9, 1.7 Hz, 1H), 7.67 (s, 1H), 7.26 - 7.21 (m, 1H), 7.06 (dd, J = 9.4, 1.6 Hz, 1H), 6.46 - 6.40 (m, 1H), 5.29 (d, J = 7.2 Hz, 1H), 4.58 (p, J = 7.2 Hz, 1H), 4.44 - 4.36 (m, 1H), 2.36 - 2.30 (m, 2H), 2.10 - 2.03 (m, 2H), 1.63 - 1.57 (m, 2H).

[1573]

[1574] Example 138: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-3-(6-oxopyridazine-1(6H)-yl)-1H-pyrazol-5-carboxamide

[1575]

[1576] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-3-(6-oxopyridazine-1(6H)-yl)-1H-pyrazol-5-carboxamide [Example 138] (2%) was prepared by a method similar to that of Preparation Examples 2-4.

[1577] ESI-MS m / z: 447.14[M+H] + .

[1578] 1H NMR (500 MHz, CDCl3) δ 8.18 (s, 2H), 7.93 (dd, J = 3.9, 1.6 Hz, 1H), 7.32 (dd, J = 9.6, 3.8 Hz, 1H), 7.07 (dd, J = 9.7, 1.7 Hz, 1H), 6.92 (s, 1H), 6.88 (d, J = 7.9 Hz, 1H), 6.41 (s, 1H), 5.22 (d, J = 7.1 Hz, 1H), 4.58 (p, J = 7.0 Hz, 1H), 4.40 (p, J = 6.8 Hz, 1H), 3.76 (s, 3H), 3.69 - 3.63 (m, 3H), 2.36 - 2.29 (m, 2H), 2.11 - 2.01 (m, 2H), 1.63 - 1.53 (m, 3H).

[1579]

[1580] Example 139: Synthesis of N-((1S,3S)-3-((5-cyclohexyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[1581]

[1582] N-((1S,3S)-3-((5-cyclohexyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide [Example 139] (40%) was prepared by a method similar to that of Preparation Example 4-2.

[1583] ESI-MS m / z: 450.36[M+H] + .

[1584] 1H NMR (500 MHz, Chloroform-d) δ 8.62 (d, J = 5.4 Hz, 1H), 8.55 (d, J = 2.1 Hz, 1H), 8.07 - 8.00 (m, 2H), 7.96 (dd, J = 3.7, 1.7 Hz, 1H), 7.28 (d, J = 3.7 Hz, 1H), 7.06 (dd, J = 9.5, 1.7 Hz, 1H), 4.60 (h, J = 7.0 Hz, 1H), 4.42 (d, J = 6.7 Hz, 1H), 4.11 (h, J = 6.2 Hz, 1H), 2.78 (ddt, J = 11.3, 7.6, 3.7 Hz, 1H), 2.32 (qt, J = 9.0, 4.8 Hz, 2H), 2.14 - 2.06 (m, 2H), 2.06 - 2.00 (m, 2H), 1.80 (dp, J = 11.0, 3.6 Hz, 3H), 1.71 - 1.63 (m, 3H), 1.59 - 1.51 (m, 3H), 1.36 (dt, J = 12.7, 3.2 Hz, 2H), 1.31 - 1.24 (m, 3H).

[1585]

[1586] Example 140: Synthesis of N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3,4-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1587]

[1588] N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3,4-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 140] (30%) was prepared by a method similar to that of Preparation Examples 2-4.

[1589] ESI-MS m / z: 445.13[M+H] + .

[1590] 1H NMR (500 MHz, Chloroform-d) δ 8.62 (d, J = 5.3 Hz, 1H), 8.13 (d, J = 2.1 Hz, 1H), 8.08 (s, 2H), 8.05 (d, J = 8.0 Hz, 1H), 7.72 (dd, J = 5.2, 2.1 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.15 (d, J = 7.2 Hz, 1H), 5.07 (d, J = 7.2 Hz, 1H), 4.60 (h, J = 7.2 Hz, 1H), 4.45 (h, J = 6.9 Hz, 1H), 2.37 - 2.29 (m, 2H), 2.22 (s, 3H), 2.14 - 2.09 (m, 4H), 2.04 (ddd, J = 13.8, 7.9, 6.3 Hz, 1H), 1.84 (s, 1H), 1.75 - 1.62 (m, 2H), 1.57 (ddd, J = 12.0, 10.2, 6.2 Hz, 1H), 0.93 - 0.86 (m, 2H), 0.58 (dt, J = 6.5, 4.7 Hz, 2H).

[1591]

[1592] Example 141: Synthesis of 3-cyclopropyl-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1593]

[1594] 3-cyclopropyl-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 141] (34%) was prepared by a method similar to that of Preparation Examples 2-4.

[1595] ESI-MS m / z: 457.26[M+H] + .

[1596] 1H NMR (500 MHz, Chloroform-d) δ 8.64 (dd, J = 5.2, 0.7 Hz, 1H), 8.18 - 8.14 (m, 1H), 8.08 (s, 2H), 8.05 (d, J = 8.0 Hz, 1H), 7.73 (dd, J = 5.2, 2.1 Hz, 1H), 7.20 (dd, J = 7.0, 1.9 Hz, 1H), 6.95 (ddd, J = 6.9, 1.9, 0.8 Hz, 1H), 6.23 (t, J = 6.9 Hz, 1H), 5.06 (d, J = 7.2 Hz, 1H), 4.60 (h, J = 7.2 Hz, 1H), 4.45 (h, J = 6.9 Hz, 1H), 2.34 (dddd, J = 14.8, 9.6, 5.7, 3.1 Hz, 2H), 2.18 - 2.10 (m, 2H), 2.08 - 2.01 (m, 1H), 1.78 (s, 1H), 1.74 - 1.63 (m, 2H), 1.60 - 1.53 (m, 1H), 1.00 - 0.95 (m, 2H), 0.92 - 0.87 (m, 2H), 0.70 - 0.65 (m, 2H), 0.61 - 0.55 (m, 2H).

[1597]

[1598] Example 142: Synthesis of 3-acetyl-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1599]

[1600] 3-acetyl-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 142] (27%) was prepared by a method similar to that of Preparation Examples 2-4.

[1601] ESI-MS m / z: 459.20[M+H] + .

[1602] 1H NMR (500 MHz, Chloroform-d) δ 8.70 (d, J = 5.2 Hz, 1H), 8.24 (dd, J = 7.1, 2.3 Hz, 1H), 8.19 (d, J = 2.0 Hz, 1H), 8.08 (s, 2H), 8.04 (d, J = 8.0 Hz, 1H), 7.65 (dd, J = 5.2, 2.2 Hz, 1H), 7.59 (dd, J = 6.7, 2.3 Hz, 1H), 6.46 (t, J = 6.9 Hz, 1H), 5.06 (d, J = 7.2 Hz, 1H), 4.61 (h, J = 7.1 Hz, 1H), 4.45 (h, J = 6.8 Hz, 1H), 2.68 (s, 3H), 2.38 - 2.31 (m, 2H), 2.13 (ddd, J = 13.6, 7.3, 5.9 Hz, 1H), 2.08 - 2.02 (m, 1H), 1.73 - 1.63 (m, 3H), 1.57 (ddd, J = 8.8, 6.9, 4.9 Hz, 1H), 0.92 - 0.87 (m, 2H), 0.58 (dt, J = 6.3, 4.7 Hz, 2H).

[1603]

[1604] Example 143: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1H-indazole-1-yl)pyridine-2-carboxamide

[1605]

[1606] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1H-indazole-1-yl)pyridine-2-carboxamide [Example 143] (26%) was prepared by a method similar to that of Preparation Examples 2-4.

[1607] ESI-MS m / z: 466.10[M+H] + .

[1608] 1H NMR (500 MHz, CDCl3) δ 8.67 (d, J = 2.3 Hz, 1H), 8.64 (d, J = 5.4 Hz, 1H), 8.28 (s, 1H), 8.19 (s, 2H), 8.14 (d, J = 7.9 Hz, 1H), 8.03 (d, J = 8.6 Hz, 1H), 7.97 (dd, J = 5.5, 2.3 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.55 (ddd, J = 8.3, 7.0, 1.2 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 6.42 (s, 1H), 5.27 (d, J = 7.1 Hz, 1H), 4.65 (q, J = 7.1 Hz, 1H), 4.46 (q, J = 6.8 Hz, 1H), 2.43 - 2.33 (m, 2H), 2.22 - 2.14 (m, 1H), 2.14 - 2.05 (m, 1H), 1.75 - 1.68 (m, 1H), 1.34 - 1.21 (m, 1H).

[1609]

[1610] Example 144: Synthesis of N-((1S,3S)-3-((5-(methylsulfonyl)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[1611]

[1612] Example 32 N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide (90.00 mg, 0.21 mmol) was dissolved in dichloromethane (2 mL), then mCPBA (142.88 mg, 0.64 mmol) was added at 0 °C and stirred at room temperature for 2 hours. Distilled water (10 mL) was added to the reaction mixture and extracted with dichloromethane. The organic layer was dried with magnesium sulfate, filtered, and then concentrated. The residue was purified by MPLC to produce N-((1S,3S)-3-((5-(methylsulfonyl)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide [Example 144] (60.00 mg, 0.13 mmol, 62%).

[1613] ESI-MS m / z: 456.25[M+H] + .

[1614] 1H NMR (500 MHz, Chloroform-d) δ 8.74 (d, J = 3.1 Hz, 1H), 8.64 (dd, J = 7.4, 4.1 Hz, 2H), 8.59 (d, J = 2.1 Hz, 1H), 8.08 (d, J = 7.9 Hz, 1H), 8.02 (dd, J = 5.4, 2.2 Hz, 1H), 7.97 (dd, J = 3.8, 1.6 Hz, 1H), 7.29 - 7.27 (m, 1H), 7.07 (dd, J = 9.6, 1.7 Hz, 1H), 6.20 (d, J = 7.2 Hz, 1H), 4.67 - 4.56 (m, 2H), 3.08 (s, 3H), 2.38 (td, J = 10.6, 4.0 Hz, 2H), 2.16 - 2.12 (m, 2H), 1.74 - 1.62 (m, 3H).

[1615]

[1616] Example 145: Synthesis of 3-cyclopropyl-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1617]

[1618] 3-cyclopropyl-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 145] (43%) was prepared by a method similar to that of Preparation Examples 2-4.

[1619] ESI-MS m / z: 483.24[M+H] + .

[1620] 1H NMR (500 MHz, Chloroform-d) δ 8.65 (d, J = 5.2 Hz, 1H), 8.19 - 8.16 (m, 3H), 8.05 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 5.3, 2.1 Hz, 1H), 7.20 (dd, J = 6.9, 1.9 Hz, 1H), 6.95 (dd, J = 6.8, 2.0 Hz, 1H), 6.57 - 6.23 (m, 2H), 5.25 (d, J = 7.0 Hz, 1H), 4.61 (q, J = 7.2 Hz, 1H), 4.44 (q, J = 6.9 Hz, 1H), 2.35 (ddq, J = 11.5, 7.5, 3.7 Hz, 2H), 2.19 - 2.05 (m, 3H), 1.69 - 1.58 (m, 5H), 1.01 - 0.95 (m, 2H), 0.71 - 0.64 (m, 2H).

[1621]

[1622] Example 146: Synthesis of 3-acetyl-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1623]

[1624] 3-acetyl-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 146] (39%) was prepared by a method similar to that of Preparation Examples 2-4.

[1625] ESI-MS m / z: 485.25[M+H] + .

[1626] 1H NMR (500 MHz, Chloroform-d) δ 8.71 (dd, J = 5.2, 0.7 Hz, 1H), 8.24 (dd, J = 7.2, 2.2 Hz, 1H), 8.20 - 8.16 (m, 3H), 8.04 (d, J = 7.9 Hz, 1H), 7.66 (dd, J = 5.2, 2.2 Hz, 1H), 7.60 (dd, J = 6.7, 2.2 Hz, 1H), 6.56 - 6.26 (m, 2H), 5.28 (d, J = 7.0 Hz, 1H), 4.62 (p, J = 7.1 Hz, 1H), 4.45 (p, J = 6.9 Hz, 1H), 2.68 (s, 3H), 2.40 - 2.32 (m, 2H), 2.15 - 2.04 (m, 2H), 1.71 - 1.62 (m, 2H), 1.61 - 1.58 (m, 3H).

[1627]

[1628] Example 147: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3,4-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1629]

[1630] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3,4-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 147] (40%) was prepared by a method similar to that of Preparation Examples 2-4.

[1631] ESI-MS m / z: 471.19[M+H] + .

[1632] 1H NMR (500 MHz, Chloroform-d) δ 8.62 (d, J = 5.3 Hz, 1H), 8.21 - 8.14 (m, 3H), 8.05 (d, J = 7.9 Hz, 1H), 7.73 (dd, J = 5.3, 2.1 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.41 (t, J = 72.9 Hz, 1H), 6.16 (d, J = 7.2 Hz, 1H), 5.28 (d, J = 7.1 Hz, 1H), 4.61 (h, J = 7.3 Hz, 1H), 4.44 (h, J = 6.8 Hz, 1H), 2.34 (ddq, J = 15.0, 7.5, 3.7 Hz, 2H), 2.22 (s, 3H), 2.13 (s, 3H), 2.13 - 2.02 (m, 2H), 1.66 (d, J = 11.7 Hz, 2H), 1.59 (dddd, J = 14.2, 12.3, 9.4, 4.8 Hz, 1H).

[1633]

[1634] Example 148: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4,5-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1635]

[1636] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4,5-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 148] (38%) was prepared by a method similar to that of Preparation Examples 2-4.

[1637] ESI-MS m / z: 471.12[M+H] + .

[1638] 1H NMR (500 MHz, Chloroform-d) δ 8.62 (d, J = 5.3 Hz, 1H), 8.17 (s, 2H), 8.15 (d, J = 2.1 Hz, 1H), 8.05 (d, J = 7.9 Hz, 1H), 7.75 (dd, J = 5.3, 2.1 Hz, 1H), 7.12 (d, J = 1.4 Hz, 1H), 6.56 - 6.23 (m, 2H), 5.36 (d, J = 7.0 Hz, 1H), 4.61 (h, J = 7.2 Hz, 1H), 4.43 (h, J = 6.9 Hz, 1H), 2.39 - 2.31 (m, 2H), 2.19 (d, J = 1.1 Hz, 3H), 2.15 - 2.07 (m, 2H), 2.05 (d, J = 1.1 Hz, 3H), 1.72 - 1.58 (m, 3H).

[1639]

[1640] Example 149: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3,5-dimethyl-1H-pyrazole-1-yl)pyridine-2-carboxamide

[1641]

[1642] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3,5-dimethyl-1H-pyrazole-1-yl)pyridine-2-carboxamide [Example 149] (11%) was prepared by a method similar to that of Preparation Examples 2-4.

[1643] ESI-MS m / z: 444.26[M+H] + .

[1644] 1H NMR (500 MHz, CDCl3) δ 8.56 (d, J = 5.3 Hz, 1H), 8.27 (d, J = 2.2 Hz, 1H), 8.17 (s, 2H), 8.08 (d, J = 7.9 Hz, 1H), 7.76 (dd, J = 5.4, 2.2 Hz, 1H), 6.41 (s, 1H), 6.07 (s, 1H), 5.26 (d, J = 7.0 Hz, 1H), 4.61 (q, J = 7.2 Hz, 1H), 4.44 (q, J = 6.9 Hz, 1H), 2.51 (s, 3H), 2.40 - 2.33 (m, 2H), 2.29 (s, 3H), 2.15 - 2.05 (m, 2H), 1.70 - 1.56 (m, 4H), 1.25 (s, 1H).

[1645]

[1646] Example 150: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3,5-dimethyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide

[1647]

[1648] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3,5-dimethyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide [Example 150] (11%) was prepared by a method similar to that of Preparation Examples 2-4.

[1649] ESI-MS m / z: 445.13[M+H] + .

[1650] 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J = 5.3 Hz, 1H), 8.31 (d, J = 2.2 Hz, 1H), 8.18 (s, 2H), 8.08 (d, J = 7.9 Hz, 1H), 7.73 (dd, J = 5.3, 2.2 Hz, 1H), 6.42 (s, 1H), 5.38 (d, J = 7.1 Hz, 1H), 4.66 - 4.57 (m, 1H), 4.50 - 4.40 (m, 1H), 2.69 (s, 3H), 2.43 (s, 3H), 2.38 - 2.29 (m, 2H), 2.22 - 1.91 (m, 3H), 1.72 - 1.56 (m, 2H), 1.34 - 1.19 (m, 1H).

[1651]

[1652] Example 151: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-5-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1653]

[1654] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-5-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 151] (35%) was prepared by a method similar to that of Preparation Examples 2-4.

[1655] ESI-MS m / z: 457.19[M+H] + .

[1656] 1H NMR (500 MHz, DMSO) δ 8.76 (d, J = 8.1 Hz, 1H), 8.71 (d, J = 5.2 Hz, 1H), 8.17 (s, 2H), 8.00 (d, J = 2.1 Hz, 1H), 7.69 (dd, J = 5.3, 2.2 Hz, 1H), 7.52 (d, J = 2.5 Hz, 1H), 7.45 (d, J = 7.2 Hz, 1H), 7.38 (dd, J = 9.5, 2.5 Hz, 1H), 6.97 (s, 1H), 6.42 (d, J = 9.4 Hz, 1H), 4.46 - 4.37 (m, 1H), 4.32 - 4.22 (m, 1H), 2.10 - 1.89 (m, 6H), 1.87 - 1.79 (m, 1H), 1.65 - 1.54 (m, 1H), 1.54 - 1.43 (m, 1H).

[1657]

[1658] Example 152: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1659]

[1660] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 152] (39%) was prepared by a method similar to that of Preparation Examples 2-4.

[1661] ESI-MS m / z: 457.26[M+H] + .

[1662] 1H NMR (500 MHz, DMSO) δ 8.75 (d, J = 8.1 Hz, 1H), 8.71 (d, J = 5.2 Hz, 1H), 8.17 (s, 2H), 7.99 (d, J = 2.1 Hz, 1H), 7.67 (dd, J = 5.2, 2.2 Hz, 1H), 7.62 (d, J = 7.1 Hz, 1H), 7.45 (d, J = 7.2 Hz, 1H), 6.97 (s, 1H), 6.29 (s, 1H), 6.21 (dd, J = 7.1, 1.8 Hz, 1H), 4.45 - 4.35 (m, 1H), 4.31 - 4.22 (m, 1H), 2.13 (s, 3H), 2.10 - 1.98 (m, 2H), 1.96 - 1.89 (m, 1H), 1.87 - 1.80 (m, 1H), 1.62 - 1.54 (m, 1H), 1.54 - 1.45 (m, 1H).

[1663]

[1664] Example 153: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(5-methyl-1H-pyrazol-1-yl)pyridine-2-carboxamide

[1665]

[1666] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(5-methyl-1H-pyrazole-1-yl)pyridine-2-carboxamide [Example 153] (25%) was prepared by a method similar to that of Preparation Examples 2-4.

[1667] ESI-MS m / z: 430.13[M+H] + .

[1668] 1H NMR (500 MHz, CDCl3) δ 8.56 (d, J = 5.5 Hz, 1H), 8.31 (d, J = 2.3 Hz, 1H), 8.20 (s, 2H), 8.13 (d, J = 8.0 Hz, 1H), 8.07 (d, J = 2.6 Hz, 1H), 7.93 (dd, J = 5.5, 2.3 Hz, 1H), 6.44 (t, J = 72.8 Hz, 1H), 6.37 (d, J = 2.6 Hz, 1H), 5.27 (d, J = 7.0 Hz, 1H), 4.70 - 4.59 (m, 1H), 4.52 - 4.41 (m, 1H), 2.41 (s, 3H), 2.39 - 2.32 (m, 2H), 2.21 - 2.03 (m, 2H), 1.76 - 1.65 (m, 2H).

[1669]

[1670] Example 154: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(5-methyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide

[1671]

[1672] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(5-methyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide [Example 154] (21%) was prepared by a method similar to that of Preparation Examples 2-4.

[1673] ESI-MS m / z: 431.20[M+H] + .

[1674] 1H NMR (500 MHz, CDCl3) δ 8.83 (s, 1H), 8.67 (d, J = 5.3 Hz, 1H), 8.46 (d, J = 2.2 Hz, 1H), 8.21 (s, 2H), 8.11 (d, J = 8.0 Hz, 1H), 7.89 (dd, J = 5.4, 2.2 Hz, 1H), 6.44 (t, J = 72.8 Hz, 1H), 5.43 (d, J = 7.1 Hz, 1H), 4.73 - 4.61 (m, 1H), 4.55 - 4.41 (m, 1H), 2.55 (s, 3H), 2.44 - 2.33 (m, 2H), 2.21 - 2.04 (m, 2H), 1.76 - 1.66 (m, 2H).

[1675]

[1676] Example 155: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-isopropyl-5-methyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide

[1677]

[1678] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-isopropyl-5-methyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide [Example 155] (32%) was prepared by a method similar to that of Preparation Examples 2-4.

[1679] ESI-MS m / z: 473.26[M+H] + .

[1680] 1H NMR (500 MHz, CDCl3) δ 8.68 (d, J = 5.3 Hz, 1H), 8.35 (d, J = 2.2 Hz, 1H), 8.20 (d, J = 5.1 Hz, 2H), 8.10 (d, J = 7.9 Hz, 1H), 7.75 (dd, J = 5.4, ​​2.2 Hz, 1H), 6.44 (t, J = 72.9 Hz, 1H), 5.34 (d, J = 7.1 Hz, 1H), 4.64 (q, J = 7.1 Hz, 1H), 4.46 (dt, J = 15.0, 7.5 Hz, 1H), 3.15 - 3.05 (m, 1H), 2.72 (s, 3H), 2.38 (tdt, J = 9.5, 6.9, 3.4 Hz, 2H), 2.23 - 2.00 (m, 2H), 1.75 - 1.58 (m, 2H), 1.39 (d, J = 6.9 Hz, 6H).

[1681]

[1682] Example 156: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3,5-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1683]

[1684] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3,5-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 156] (40%) was prepared by a method similar to that of Preparation Examples 2-4.

[1685] ESI-MS m / z: 471.12[M+H] + .

[1686] 1H NMR (500 MHz, Chloroform-d) δ 8.62 (d, J = 5.3 Hz, 1H), 8.16 (d, J = 12.5 Hz, 3H), 8.05 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 5.3, 2.2 Hz, 1H), 7.17 (dd, J = 2.6, 1.3 Hz, 1H), 7.04 (s, 1H), 6.41 (t, J = 72.9 Hz, 1H), 5.25 (d, J = 7.1 Hz, 1H), 4.61 (h, J = 7.2 Hz, 1H), 4.44 (h, J = 6.8 Hz, 1H), 2.36 (tq, J = 11.1, 3.7 Hz, 2H), 2.17 (s, 3H), 2.14 - 2.05 (m, 5H), 1.71 - 1.55 (m, 5H).

[1687]

[1688] Example 157: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-6-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1689]

[1690] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-6-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 157] (10%) was prepared by a method similar to that of Preparation Examples 2-4.

[1691] ESI-MS m / z: 457.06[M+H] + .

[1692] 1H NMR (500 MHz, CDCl3) δ 8.45 (d, J = 5.5 Hz, 1H), 8.18 (s, 2H), 8.07 (d, J = 7.9 Hz, 1H), 7.83 (d, J = 2.5 Hz, 1H), 7.68 (t, J = 7.7 Hz, 1H), 7.18 (dd, J = 5.6, 2.5 Hz, 1H), 7.03 (d, J = 7.4 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 6.41 (s, 1H), 5.28 (d, J = 7.0 Hz, 1H), 4.63 - 4.53 (m, 1H), 4.48 - 4.38 (m, 1H), 2.48 (s, 3H), 2.38 - 2.29 (m, 2H), 2.14 - 2.02 (m, 2H), 1.68 - 1.61 (m, 1H), 1.32 - 1.24 (m, 1H).

[1693]

[1694] Example 158: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(pyrazolo[1,5-a]pyridine-7-yl)pyridine-2-carboxamide

[1695]

[1696] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(pyrazolo[1,5-a]pyridine-7-yl)pyridine-2-carboxamide [Example 158] (28%) was prepared by a method similar to that of Preparation Examples 2-4.

[1697] ESI-MS m / z: 466.23[M+H] + .

[1698] 1H NMR (500 MHz, DMSO) δ 8.75 (dd, J = 8.7, 6.6 Hz, 2H), 8.57 (d, J = 1.7 Hz, 1H), 8.15 (d, J = 23.8 Hz, 2H), 8.14 - 8.08 (m, 1H), 8.02 (d, J) = 2.3 Hz, 1H), 7.80 (dd, J = 8.7, 1.3 Hz, 1H), 7.44 (d, J = 7.3 Hz, 1H), 7.30 (dd, J = 8.8, 7.0 Hz, 1H), 7.25 - 7.20 (m, 1H), 6.97 (s, 1H), 6.74 (d, J = 2.3 Hz, 1H), 4.48 - 4.40 (m, 1H), 4.33 - 4.24 (m, 1H), 1.99 - 1.83 (m, 2H), 1.67 - 1.56 (m, 1H), 1.55 - 1.44 (m, 1H), 1.43 - 1.38 (m, 1H), 1.10 - 1.05 (m, 1H).

[1699]

[1700] Example 159: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-2-oxo-1,2-dihydro-[3,4'-bipyridine]-2'-carboxamide

[1701]

[1702] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-2-oxo-1,2-dihydro-[3,4'-bipyridine]-2'-carboxamide [Example 159] (68%) was prepared by a method similar to that of Preparation Examples 2-4.

[1703] ESI-MS m / z: 457.12[M+H] + .

[1704] 1H NMR (500 MHz, CDCl3) δ 8.55 (d, J = 5.2 Hz, 1H), 8.32 (d, J = 1.8 Hz, 1H), 8.18 (s, 2H), 8.17 - 8.04 (m, 2H), 7.75 (dd, J = 7.1, 2.1 Hz, 1H), 7.46 - 7.37 (m, 1H), 6.58 - 6.22 (m, 2H), 5.25 (d, J = 7.1 Hz, 1H), 4.68 - 4.57 (m, 1H), 4.49 - 4.39 (m, 1H), 3.65 (s, 3H), 2.45 - 2.27 (m, 2H), 2.18 - 2.00 (m, 2H), 1.65 - 1.61 (m, 2H).

[1705]

[1706] Example 160: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyrimidine-2-carboxamide

[1707]

[1708] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyrimidine-2-carboxamide [Example 160] (16%) was prepared by a method similar to that of Preparation Examples 2-4.

[1709] ESI-MS m / z: 445.13[M+H] + .

[1710] 1H NMR (500 MHz, CDCl3) δ 9.03 (d, J = 5.4 Hz, 1H), 8.20 (s, 2H), 8.07 (dd, J = 3.7, 1.6 Hz, 1H), 8.01 (t, J = 5.5 Hz, 2H), 7.35 (dd, J = 9.6, 3.7 Hz, 1H), 7.10 (dd, J = 9.5, 1.6 Hz, 1H), 6.44 (t, J = 72.8 Hz, 1H), 5.29 (d, J = 7.1 Hz, 1H), 4.70 (q, J = 7.2 Hz, 1H), 4.45 (q, J = 6.9 Hz, 1H), 2.47 - 2.31 (m, 3H), 2.22 - 2.04 (m, 3H).

[1711]

[1712] Example 161: Synthesis of Methyl 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylate

[1713]

[1714] Methyl 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylate [Example 161] (38%) was prepared by a method similar to that of Preparation Examples 2-4.

[1715] ESI-MS m / z: 501.13[M+H] + .

[1716] 1H NMR (500 MHz, Chloroform-d) δ 8.67 (d, J = 5.3 Hz, 1H), 8.26 (dd, J = 7.1, 2.2 Hz, 1H), 8.16 (d, J = 12.5 Hz, 3H), 8.03 (d, J = 7.9 Hz, 1H), 7.71 (dd, J = 5.3, 2.1 Hz, 1H), 7.59 (dd, J = 6.8, 2.2 Hz, 1H), 6.57 - 6.27 (m, 2H), 5.23 (d, J = 7.1 Hz, 1H), 4.61 (p, J = 7.3 Hz, 1H), 4.44 (h, J = 6.8 Hz, 1H), 3.92 (s, 3H), 2.36 (ddd, J = 13.5, 7.8, 3.7 Hz, 2H), 2.11 (ddt, J = 26.8, 13.7, 6.8 Hz, 2H), 1.65 (ddd, J = 26.8, 13.8, 7.2 Hz, 2H).

[1717]

[1718] Example 162: Synthesis of 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylic acid

[1719]

[1720] [Example 161] 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylate (55.00 mg, 0.11 mmol) was dissolved in methanol (2 mL), then lithium hydroxide (7.90 mg, 0.33 mmol) was added and stirred at 50 °C for 18 hours. After concentrating the reaction mixture, it was purified by MPLC to prepare 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylic acid [Example 162] (50.00 mg, 0.10 mmol, 93%).

[1721] ESI-MS m / z: 487.06[M+H] + .

[1722] 1H NMR (500 MHz, DMSO-d6) δ 8.85 (dd, J = 11.2, 6.6 Hz, 2H), 8.43 (dd, J = 7.2, 2.1 Hz, 1H), 8.25 - 8.18 (m, 4H), 7.85 (dd, J = 5.2, 2.1 Hz, 1H), 7.49 (d, J = 7.2 Hz, 1H), 7.18 - 6.88 (m, 1H), 6.78 (t, J = 6.9 Hz, 1H), 4.49 (h, J = 7.6 Hz, 1H), 4.39 - 4.30 (m, 1H), 2.10 (dddd, J = 19.3, 15.4, 7.7, 3.8 Hz, 2H), 2.00 (dt, J = 14.2, 7.4 Hz, 1H), 1.90 (ddd, J = 13.3, 8.2, 5.4 Hz, 1H), 1.70 - 1.63 (m, 1H), 1.60 - 1.52 (m, 1H).

[1723]

[1724] Example 163: Synthesis of N-((1S,3S)-3-((5-(methylsulfinyl)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[1725]

[1726] Example 32 N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide (90.00 mg, 0.21 mmol) was dissolved in dichloromethane (2 mL), then mCPBA (52.39 mg, 0.23 mmol) was added at 0 °C and stirred at room temperature for 1 hour. After concentrating the reaction mixture, the residue was purified by MPLC to produce N-((1S,3S)-3-((5-(methylsulfinyl)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide [Example 163] (90.00 mg, 0.20 mmol, 96%).

[1727] ESI-MS m / z: 440.11[M+H] + .

[1728] 1H NMR (500 MHz, Chloroform-d) δ 8.63 (d, J = 5.4 Hz, 1H), 8.59 - 8.50 (m, 3H), 8.06 (d, J = 7.8 Hz, 1H), 8.03 (dd, J = 5.4, 2.2 Hz, 1H), 7.96 (dd, J = 3.8, 1.7 Hz, 1H), 7.25 (s, 1H), 7.06 (dd, J = 9.5, 1.7 Hz, 1H), 5.67 (d, J = 7.1 Hz, 1H), 4.63 (q, J = 7.2 Hz, 1H), 4.54 (q, J = 6.9 Hz, 1H), 2.82 (s, 3H), 2.36 (tt, J = 7.7, 4.3 Hz, 2H), 2.19 - 2.06 (m, 2H), 1.74 - 1.64 (m, 2H).

[1729]

[1730] Example 164: Synthesis of 4-(dibenzo[b,d]furan-4-yl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide

[1731]

[1732] 4-(dibenzo[b,d]furan-4-yl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide [Example 164] (55%) was prepared in the same manner as in Preparation Example 5-1.

[1733] ESI-MS m / z: 516.13[M+H] + .

[1734] 1H NMR (500 MHz, Chloroform-d) δ 8.73 (dd, J = 1.8, 0.8 Hz, 1H), 8.69 (dd, J = 5.1, 0.8 Hz, 1H), 8.18 (d, J = 11.0 Hz, 3H), 8.11 (dd, J = 5.1, 1.9) Hz, 1H), 8.05 (dd, J = 7.6, 1.2 Hz, 1H), 8.02 - 7.99 (m, 1H), 7.77 (dd, J = 7.7, 1.2 Hz, 1H), 7.65 (d, J = 8.2 Hz, 1H), 7.53 - 7.47 (m, 2H), 7.40 (td, J = 7.4, 0.9 Hz, 1H), 6.48 (d, J = 72.9 Hz, 1H), 5.25 (d, J = 7.0 Hz, 1H), 4.67 (h, J = 7.0 Hz, 1H), 4.47 (h, J = 6.8 Hz, 1H), 2.42 - 2.36 (m, 2H), 2.18 (dt, J = 13.8, 7.0 Hz, 1H), 2.14 - 2.07 (m, 1H), 1.72 (ddd, J = 14.0, 10.4, 6.3 Hz, 1H), 1.66 - 1.60 (m, 1H).

[1735]

[1736] Example 165: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(4-methyl-6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide

[1737]

[1738] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(4-methyl-6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide [Example 165] (44%) was prepared by a method similar to that of Preparation Examples 2-4.

[1739] ESI-MS m / z: 458.06[M+H] + .

[1740] 1H NMR (500 MHz, DMSO) δ 8.82 (dd, 1H), 8.78 (s, 1H), 8.40 (d, 1H), 8.26 (d, 2H), 8.11 (s, 1H), 8.02 (s, 1H), 7.53 (s, 2H), 6.97 (s, 1H), 4.53 - 4.49 (m, 1H), 4.38 - 4.34 (m, 1H), 2.28 (s, 3H), 2.14 - 2.10 (m, 2H), 2.04 - 2.01 (m, 1H), 1.95 - 1.91 (m, 1H), 1.71 - 1.67 (m, 1H), 1.59 - 1.55 (m, 1H).

[1741]

[1742] Example 166: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1-oxophthalazine-2(1H)-yl)pyridine-2-carboxamide

[1743]

[1744] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1-oxophthalazine-2(1H)-yl)pyridine-2-carboxamide [Example 166] (44%) was prepared by a method similar to that of Preparation Examples 2-4.

[1745] ESI-MS m / z: 494.16[M+H] + .

[1746] 1H NMR (500 MHz, DMSO) δ 8.72 (dd, J = 15.1, 6.7 Hz, 2H), 8.64 (s, 1H), 8.41 (d, J = 2.2 Hz, 1H), 8.31 (d, J = 7.8 Hz, 1H), 8.17 (s, 2H), 8.04 - 7.94 (m, 3H), 7.93 - 7.84 (m, 1H), 7.45 (d, J = 7.2 Hz, 1H), 6.97 (s, 1H), 4.47 - 4.39 (m, 1H), 4.31 - 4.24 (m, 1H), 2.13 - 1.99 (m, 2H), 1.95 - 1.80 (m, 2H), 1.64 - 1.45 (m, 2H).

[1747]

[1748] Example 167: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-phenyl-2H-[1,4'-bipyridine]-2'-carboxamide

[1749]

[1750] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-phenyl-2H-[1,4'-bipyridine]-2'-carboxamide [Example 167] (38%) was prepared by a method similar to that of Preparation Examples 2-4.

[1751] ESI-MS m / z: 519.21[M+H] + .

[1752] 1H NMR (500 MHz, DMSO) δ 8.81 - 8.68 (m, 2H), 8.17 (s, 2H), 8.06 (d, J = 2.1 Hz, 1H), 7.80 - 7.70 (m, 2H), 7.67 (dd, J = 6.8, 1.9 Hz, 1H), 7.63 (d, J = 7.4 Hz, 2H), 7.42 (d, J = 7.2 Hz, 1H), 7.39 - 7.31 (m, 2H), 7.31 - 7.25 (m, 1H), 6.96 (s, 1H), 6.46 (t, J = 6.9 Hz, 1H), 4.48 - 4.37 (m, 1H), 4.31 - 4.25 (m, 1H), 2.11 - 1.98 (m, 2H), 1.98 - 1.90 (m, 1H), 1.89 - 1.80 (m, 1H), 1.66 - 1.55 (m, 1H), 1.55 - 1.44 (m, 1H).

[1753]

[1754] Example 168: Synthesis of 4-(2-cyclopropoxyphenyl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide

[1755]

[1756] 4-(2-cyclopropoxyphenyl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide [Example 168] (73%) was prepared by a method similar to that of Preparation Example 5-1.

[1757] ESI-MS m / z: 482.24[M+H] + .

[1758] 1H NMR (500 MHz, Chloroform-d) δ 8.51 (d, J = 5.0 Hz, 1H), 8.31 (s, 1H), 8.17 (s, 2H), 8.10 (d, J = 7.9 Hz, 1H), 7.58 (dd, J = 5.0, 1.7 Hz, 1H), 7.44 - 7.36 (m, 3H), 7.12 - 7.05 (m, 1H), 6.40 (t, J = 72.9 Hz, 1H), 5.25 (d, J = 7.1 Hz, 1H), 4.63 (q, J = 7.2 Hz, 1H), 4.45 (q, J = 6.9 Hz, 1H), 3.76 (dq, J = 6.0, 2.9 Hz, 1H), 2.35 (qt, J = 6.6, 3.2 Hz, 2H), 2.10 (dh, J = 27.7, 7.0 Hz, 2H), 1.67 (dt, J = 13.9, 7.6 Hz, 1H), 1.61 - 1.54 (m, 1H), 0.78 (tt, J = 8.8, 4.1 Hz, 4H).

[1759]

[1760] Example 169: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-(dimethylamino)phenyl)pyridine-2-carboxamide

[1761]

[1762] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-(dimethylamino)phenyl)pyridine-2-carboxamide [Example 169] (59%) was prepared by a method similar to that of Preparation Example 5-1.

[1763] ESI-MS m / z: 469.18[M+H] + .

[1764] 1H NMR (500 MHz, Chloroform-d) δ 8.52 (d, J = 5.0 Hz, 1H), 8.39 (d, J = 1.7 Hz, 1H), 8.18 (s, 2H), 8.13 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 5.1, 1.8 Hz, 1H), 7.33 (td, J = 7.7, 1.7 Hz, 1H), 7.24 (d, J = 1.7 Hz, 1H), 7.09 - 7.02 (m, 2H), 6.41 (t, J = 72.9 Hz, 1H), 5.25 (d, J = 7.1 Hz, 1H), 4.63 (h, J = 7.3 Hz, 1H), 4.45 (h, J = 6.9 Hz, 1H), 2.55 (s, 6H), 2.36 (qt, J = 7.1, 3.6 Hz, 2H), 2.15 (dt, J = 13.8, 6.9 Hz, 1H), 2.12 - 2.05 (m, 1H), 1.73 - 1.65 (m, 1H), 1.59 (ddd, J = 14.0, 7.1, 3.7 Hz, 1H).

[1765]

[1766] Example 170: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-(4-methylpiperazine-1-carbonyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1767]

[1768] Example 162 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylic acid (30.00 mg, 0.06 mmol) was dissolved in dichloromethane (2 mL), then HATU (35.18 mg, 0.09 mmol) and N,N-diisopropylethylamine (23.91 mg, 0.19 mmol) were added and stirred at room temperature for 30 minutes. 1-methylpiperazine (12.35 mg, 0.12 mmol) was added to the reaction mixture and stirred at room temperature for 2 hours. Distilled water (10 mL) was added to the reaction mixture and extracted with dichloromethane. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by MPLC to produce N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-(4-methylpiperazine-1-carbonyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 170] (28.00 mg, 0.05 mmol, 80%).

[1769] ESI-MS m / z: 569.24[M+H] + .

[1770] 1H NMR (500 MHz, Chloroform-d) δ 8.67 (d, J = 5.2 Hz, 1H), 8.17 (d, J = 6.5 Hz, 3H), 8.03 (d, J = 7.9 Hz, 1H), 7.69 (dd, J = 5.4, 2.1 Hz, 1H), 7.61 (dd, J = 6.9, 2.0 Hz, 1H), 7.45 (dd, J = 7.0, 2.0 Hz, 1H), 6.56 - 6.26 (m, 2H), 5.22 (d, J = 7.0 Hz, 1H), 4.61 (h, J = 7.2 Hz, 1H), 4.44 (h, J = 6.8 Hz, 1H), 3.79 (s, 2H), 3.38 (t, J = 5.2 Hz, 2H), 2.48 (t, J = 5.1 Hz, 2H), 2.42 (t, J = 5.1 Hz, 2H), 2.40 - 2.33 (m, 2H), 2.30 (s, 3H), 2.10 (dq, J = 25.5, 6.8 Hz, 2H), 1.60 (dt, J = 14.8, 7.6 Hz, 2H).

[1771]

[1772] Example 171: Synthesis of 3-Bromo-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1773]

[1774] 3-bromo-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 171] (22%) was prepared by a method similar to that of Preparation Examples 2-4.

[1775] ESI-MS m / z: 521.02[M+H] + .

[1776] 1H NMR (500 MHz, DMSO) δ 8.83 - 8.69 (m, 2H), 8.17 (s, 2H), 8.08 - 7.92 (m, 2H), 7.77 (dd, J = 6.9, 1.9 Hz, 1H), 7.71 (dd, J = 5.2, 2.1 Hz, 1H), 7.42 (d, J = 7.2 Hz, 1H), 7.11 - 6.81 (m, 1H), 6.29 (t, J = 7.1 Hz, 1H), 4.46 - 4.36 (m, 1H), 4.31 - 4.24 (m, 1H), 2.10 - 1.97 (m, 2H), 1.97 - 1.89 (m, 1H), 1.88 - 1.79 (m, 1H), 1.65 - 1.54 (m, 1H), 1.54 - 1.43 (m, 1H).

[1777]

[1778] Example 172: Synthesis of 5-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1779]

[1780] 5-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 172] (20%) was prepared by a method similar to that of Preparation Examples 2-4.

[1781] ESI-MS m / z: 507.02[M+H] + .

[1782] 1H NMR (500 MHz, DMSO) δ 8.80 - 8.65 (m, 2H), 8.17 (s, 2H), 8.01 (d, J = 2.1 Hz, 1H), 7.69 (dd, J = 5.2, 2.1 Hz, 1H), 7.57 (d, J = 2.5 Hz, 1H), 7.42 (d, J = 7.2 Hz, 1H), 7.09 - 6.85 (m, 2H), 4.44 - 4.39 (m, 1H), 4.29 - 4.23 (m, 1H), 3.73 (s, 3H), 2.13 - 1.96 (m, 2H), 1.97 - 1.88 (m, 1H), 1.88 - 1.79 (m, 1H), 1.65 - 1.54 (m, 1H), 1.54 - 1.44 (m, 1H).

[1783]

[1784] Example 173: Synthesis of N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-(trifluoromethyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[1785]

[1786] N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-(trifluoromethyl)-2H-[1,4'-bipyridine]-2'-carboxamide [Example 173] (3%) was prepared by a method similar to that of Preparation Examples 2-4.

[1787] ESI-MS m / z: 511.11[M+H] + .

[1788] 1H NMR (500 MHz, CDCl3) δ 8.68 (d, J = 5.2 Hz, 1H), 8.21 - 8.11 (m, 3H), 8.02 (d, J = 7.9 Hz, 1H), 7.88 - 7.83 (m, 1H), 7.73 (dd, J = 5.3, 2.2 Hz, 1H), 7.58 (dd, J = 7.0, 2.1 Hz, 1H), 6.56 - 6.26 (m, 2H), 5.24 (d, J = 7.0 Hz, 1H), 4.66 - 4.56 (m, 1H), 4.49 - 4.39 (m, 1H), 2.41 - 2.31 (m, 2H), 2.18 - 2.04 (m, 2H), 1.70 - 1.60 (m, 2H).

[1789]

[1790] Example 174: Synthesis of N2'-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-N3,N3-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2',3-dicarboxamide

[1791]

[1792] Example 162 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylic acid (25.00 mg, 0.05 mmol) was dissolved in dichloromethane (2 mL), then HATU (29.13 mg, 0.08 mmol) and N,N-diisopropylethylamine (19.93 mg, 0.15 mmol) were added and stirred at room temperature for 30 minutes. N-methylmethanolamine (6.95 mg, 0.15 mmol) was added to the reaction mixture and stirred at room temperature for 2 hours. Distilled water (10 mL) was added to the reaction mixture and extracted with dichloromethane. The organic layer was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by MPLC to produce N2'-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-N3,N3-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2',3-dicarboxamide [Example 174] (21.20 mg, 0.05 mmol, 80%).

[1793] ESI-MS m / z: 514.12[M+H] + .

[1794] 1H NMR (500 MHz, Chloroform-d) δ 8.67 (d, J = 5.3 Hz, 1H), 8.17 (d, J = 4.5 Hz, 3H), 8.04 (d, J = 7.9 Hz, 1H), 7.71 (dd, J = 5.3, 2.2 Hz, 1H), 7.61 (dd, J = 6.8, 2.1 Hz, 1H), 7.46 (dd, J = 7.0, 2.1 Hz, 1H), 6.56 - 6.27 (m, 2H), 5.25 (d, J = 7.0 Hz, 1H), 4.61 (h, J = 7.2 Hz, 1H), 4.44 (h, J = 6.9 Hz, 1H), 3.09 (s, 3H), 2.98 (s, 3H), 2.35 (dp, J = 10.9, 4.1 Hz, 2H), 2.16 - 2.05 (m, 2H), 1.68 - 1.62 (m, 2H).

[1795]

[1796] Example 175: Synthesis of 3-Methoxy-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-Carboxamide

[1797]

[1798] 3-methoxy-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide [Example 175] (32%) was prepared by a method similar to that of Preparation Examples 2-4.

[1799] ESI-MS m / z: 475.07[M+H] + .

[1800] 1H NMR (500 MHz, Chloroform-d) δ 8.66 (d, J = 5.3 Hz, 1H), 8.47 (s, 2H), 8.20 (d, J = 2.1 Hz, 1H), 8.05 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 5.3, 2.1 Hz, 1H), 7.01 (dd, J = 7.1, 1.6 Hz, 1H), 6.67 (dd, J = 7.5, 1.6 Hz, 1H), 6.27 (t, J = 7.2 Hz, 1H), 5.61 (d, J = 7.2 Hz, 1H), 4.63 (q, J = 7.3 Hz, 1H), 4.54 (q, J = 6.9 Hz, 1H), 3.87 (s, 3H), 2.38 (dtd, J = 14.1, 7.5, 3.5 Hz, 2H), 2.19 - 2.06 (m, 2H), 1.73 - 1.61 (m, 2H).

[1801]

[1802] Example 176: Synthesis of 3-Methoxy-2-oxo-N-((1S,3S)-3-((5-Ethenylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-Bipyridine]-2'-Carboxamide

[1803]

[1804] 3-methoxy-2-oxo-N-((1S,3S)-3-((5-ethenylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide [Example 176] (38%) was prepared by a method similar to that of Preparation Examples 2-4.

[1805] ESI-MS m / z: 433.01[M+H] + .

[1806] 1H NMR (500 MHz, Chloroform-d) δ 8.65 (d, J = 5.3 Hz, 1H), 8.34 (s, 2H), 8.17 (d, J = 2.1 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.74 (dd, J = 5.3, 2.2 Hz, 1H), 7.01 (dd, J = 7.1, 1.6 Hz, 1H), 6.67 (dd, J = 7.4, 1.6 Hz, 1H), 6.49 (dd, J = 17.7, 11.1 Hz, 1H), 6.26 (t, J = 7.2 Hz, 1H), 5.60 (d, J = 17.7 Hz, 1H), 5.27 (d, J = 7.2 Hz, 1H), 5.15 (d, J = 11.2 Hz, 1H), 4.62 (q, J = 7.1 Hz, 1H), 4.50 (q, J = 6.9 Hz, 1H), 3.86 (s, 3H), 2.39 - 2.31 (m, 2H), 2.16 - 2.04 (m, 2H), 1.67 - 1.56 (m, 2H).

[1807]

[1808] Example 177: Synthesis of N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1809]

[1810] N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 177] (44%) was prepared by a method similar to that of Preparation Examples 2-4.

[1811] ESI-MS m / z: 449.22[M+H] + .

[1812] 1H NMR (500 MHz, Chloroform-d) δ 8.65 (d, J = 5.3 Hz, 1H), 8.17 (d, J = 1.9 Hz, 3H), 8.05 (d, J = 8.0 Hz, 1H), 7.74 (dd, J = 5.3, 2.2 Hz, 1H), 7.01 (dd, J = 7.1, 1.6 Hz, 1H), 6.67 (dd, J = 7.5, 1.7 Hz, 1H), 6.26 (t, J = 7.2 Hz, 1H), 5.04 (d, J = 7.1 Hz, 1H), 4.61 (h, J = 7.2 Hz, 1H), 4.47 (h, J = 6.9 Hz, 1H), 3.87 (s, 3H), 2.77 (p, J = 7.0 Hz, 1H), 2.39 - 2.31 (m, 2H), 2.17 - 2.05 (m, 2H), 1.68 - 1.61 (m, 3H), 1.23 (d, J = 7.0 Hz, 6H).

[1813]

[1814] Example 178: Synthesis of 3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[1815]

[1816] 3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide [Example 178] (36%) was prepared by a method similar to that of Preparation Examples 2-4.

[1817] ESI-MS m / z: 485.19[M+H] + .

[1818] 1H NMR (500 MHz, Chloroform-d) δ 8.65 (d, J = 5.3 Hz, 1H), 8.47 (s, 2H), 8.20 (d, J = 2.1 Hz, 1H), 8.05 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 5.2, 2.2 Hz, 1H), 7.20 (dd, J = 7.0, 1.9 Hz, 1H), 6.95 (dd, J = 6.9, 1.9 Hz, 1H), 6.24 (t, J = 6.9 Hz, 1H), 5.68 (d, J = 7.2 Hz, 1H), 4.62 (p, J = 7.2 Hz, 1H), 4.54 (h, J = 7.0 Hz, 1H), 2.37 (dtt, J = 11.3, 6.7, 3.3 Hz, 2H), 2.13 (dddd, J = 20.0, 13.9, 7.8, 4.4 Hz, 3H), 1.71 - 1.64 (m, 2H), 1.01 - 0.95 (m, 2H), 0.71 - 0.64 (m, 2H).

[1819]

[1820] Example 179: Synthesis of 3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-ethenylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide

[1821]

[1822] 3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-ethenylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide [Example 179] (39%) was prepared by a method similar to that of Preparation Examples 2-4.

[1823] ESI-MS m / z: 443.26[M+H] + .

[1824] 1H NMR (500 MHz, Chloroform-d) δ 8.64 (d, J = 5.3 Hz, 1H), 8.17 (d, J = 2.1 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H), 7.74 (dd, J = 5.3, 2.1 Hz, 1H), 7.20 (dd, J = 6.9, 2.0 Hz, 1H), 6.95 (dd, J = 6.9, 2.0 Hz, 1H), 6.50 (dd, J = 17.7, 11.1 Hz, 1H), 6.24 (t, J = 6.9 Hz, 1H), 5.61 (d, J = 17.7 Hz, 1H), 5.23 (d, J = 7.3 Hz, 1H), 5.15 (d, J = 11.1 Hz, 1H), 4.62 (q, J = 7.1 Hz, 1H), 4.50 (q, J = 6.9 Hz, 1H), 2.36 (dq, J = 11.9, 4.8 Hz, 2H), 2.15 (ddd, J = 13.9, 8.1, 5.6 Hz, 2H), 2.10 - 2.04 (m, 1H), 1.71 - 1.65 (m, 1H), 1.62 - 1.55 (m, 1H), 1.01 - 0.95 (m, 2H), 0.70 - 0.65 (m, 2H).

[1825]

[1826] Example 180: Synthesis of 3-cyclopropyl-N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide

[1827]

[1828] 3-cyclopropyl-N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide [Example 180] (42%) was prepared by a method similar to that of Preparation Examples 2-4.

[1829] ESI-MS m / z: 459.32[M+H] + .

[1830] 1H NMR (500 MHz, Chloroform-d) δ 8.64 (d, J = 5.3 Hz, 1H), 8.17 (d, J = 3.4 Hz, 3H), 8.05 (d, J = 7.9 Hz, 1H), 7.74 (dd, J = 5.2, 2.1 Hz, 1H), 7.20 (dd, J = 7.0, 1.9 Hz, 1H), 6.95 (dd, J = 6.9, 1.9 Hz, 1H), 6.24 (t, J = 6.9 Hz, 1H), 5.03 (d, J = 7.2 Hz, 1H), 4.88 (s, 1H), 4.61 (h, J = 7.1 Hz, 1H), 4.47 (q, J = 6.9 Hz, 1H), 2.77 (p, J = 6.9 Hz, 1H), 2.35 (td, J = 9.6, 7.8, 4.2 Hz, 2H), 2.15 (ddd, J = 14.5, 9.1, 6.0 Hz, 2H), 2.09 - 2.04 (m, 1H), 1.69 - 1.64 (m, 1H), 1.57 (t, J = 7.4 Hz, 1H), 1.23 (d, J = 7.0 Hz, 6H), 1.00 - 0.96 (m, 2H), 0.68 (dt, J = 6.3, 3.1 Hz, 2H).

[1831]

[1832] Example 181: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide

[1833]

[1834] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide [Example 181] (13%) was prepared as in Preparation Examples 2-4.

[1835] ESI-MS m / z: 458.17[M+H] + .

[1836] 1H NMR (DMSO-d6, 400 MHz) Shift 8.7-8.8 (m, 2H), 8.38 (d, 1H, J=1.6 Hz), 8.24 (s, 2H), 8.06 (d, 1H, J=4.0 Hz), 7.99 (dd, 1H, J=2.3, 5.4 Hz), 7.50 (d, 1H, J=7.1 Hz), 7.43 (dd, 1H, J=1.3, 3.9 Hz), 7.22 (s, 1H), 7.04 (s, 1H), 6.85 (s, 1H), 2.18 (d, 3H, J=1.1 Hz), 1.9-2.1 (m, 4H), 1.5-1.7 (m, 2H).

[1837]

[1838] Example 182: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carvothioamide

[1839]

[1840] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carbothioamide [Example 182] (32%) was prepared by a method similar to that of Preparation Examples 1-4.

[1841] ESI-MS m / z: 459.13 [M+H] + .

[1842] 1H NMR (DMSO-d6, 400 MHz) δ 10.79 (br d, 1H, J=7.8 Hz), 8.77 (d, 1H, J=5.3 Hz), 8.44 (d, 1H, J=2.3 Hz), 8.25 (s, 2H), 7.7-7.8 (m, 2H), 7.5-7.6 (m, 2H), 7.22 (s, 1H), 7.04 (s, 1H), 6.85 (s, 1H), 6.55 (d, 1H, J=9.3 Hz), 6.42 (dt, 1H, J=1.3, 6.8 Hz), 5.0-5.1 (m, 1H), 4.3-4.4 (m, 1H), 2.2-2.3 (m, 1H), 2.1-2.2 (m,2H), 2.0-2.1 (m, 1H), 1.79 (br dd, 1H, J=8.0, 12.8 Hz), 1.6-1.7 (m, 1H).

[1843]

[1844] Example 183: Synthesis of 4-[3-chloro-5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1845]

[1846] 4-[3-chloro-5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 183] (22%) was prepared by a method similar to that of Preparation Examples 1-4.

[1847] ESI-MS m / z: 558.12[M+H] + .

[1848] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.8 (m, 2H), 8.3-8.3 (m, 1H), 8.24 (s, 2H), 7.95 (dd, 1H, J=2.1, 5.4 Hz), 7.50 (d, 1H, J=7.3 Hz), 7.26 (s, 1H), 7.22 (s, 1H), 6.8-7.2 (m, 1H), 6.3-6.7 (m, 1H), 4.4-4.6 (m, 3H), 4.3-4.4 (m, 1H), 2.0-2.2 (m, 2H), 2.0-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[1849]

[1850] Example 184: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-[6-oxo-5-(2,2,2-trifluoroethoxy)pyridazine-1-yl]pyridine-2-carboxamide

[1851]

[1852] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-[6-oxo-5-(2,2,2-trifluoroethoxy)pyridazine-1-yl]pyridine-2-carboxamide [Example 184] (36%) was prepared by a method similar to that of Preparation Examples 1-4.

[1853] ESI-MS m / z: 542.15[M+H] + .

[1854] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.8 (m, 2H), 8.36 (d, 1H, J=2.1 Hz), 8.25 (s, 2H), 8.14 (d, 1H, J=4.9 Hz), 7.99 (dd, 1H, J=2.1, 5.4 Hz), 7.50 (d, 1H, J=7.3 Hz), 7.22 (s, 1H), 7.0-7.1 (m, 2H), 6.85 (s, 1H), 4.95 (q, 2H, J=8.6 Hz), 4.4-4.5 (m, 1H), 4.3-4.4 (m, 1H), 2.0-2.2 (m, 2H), 2.0-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[1855]

[1856] Example 185: Synthesis of 4-[3-chloro-6-oxo-5-(2,2,2-trifluoroethoxy)pyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1857]

[1858] 4-[3-chloro-6-oxo-5-(2,2,2-trifluoroethoxy)pyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 185] (25%) was prepared by a method similar to that of Preparation Examples 1-4.

[1859] ESI-MS m / z: 576.11[M+H] + .

[1860] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.8 (m, 2H), 8.33 (dd, 1H, J=0.6, 2.1 Hz), 8.24 (s, 2H), 7.9-8.0 (m, 1H), 7.50 (d, 1H, J=7.1 Hz), 7.3-7.3 (m, 1H), 6.8-7.2 (m, 1H), 5.00 (q, 2H, J=8.7 Hz), 4.4-4.6 (m, 1H), 4.3-4.4 (m, 1H), 2.1-2.1 (m, 2H), 2.0-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.66 (td, 1H, J=7.7, 12.6 Hz), 1.56 (br dd, 1H, J=7.1, 12.4 Hz).

[1861]

[1862] Example 186: Synthesis of 4-[5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1863]

[1864] 4-[5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 186] (20%) was prepared by a method similar to that of Preparation Examples 1-4.

[1865] ESI-MS m / z: 524.16[M+H] + .

[1866] 1H NMR (DMSO-d6, 400 MHz) δ 8.7-8.8 (m, 2H), 8.3-8.4 (m, 1H), 8.24 (s, 2H), 8.10 (d, 1H, J=4.9 Hz), 7.99 (dd, 1H, J=2.2, 5.4 Hz), 7.50 (d, 1H, J=7.3 Hz), 7.22 (s, 1H), 7.04 (s, 1H), 7.01 (d, 1H, J=5.0 Hz), 6.85 (s, 1H), 6.3-6.7 (m, 1H), 4.4-4.5 (m, 3H), 4.3-4.4 (m, 1H), 2.0-2.2 (m, 2H), 2.0-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[1867]

[1868] Example 187: Synthesis of 4-[3-chloro-5-(3-methoxyazetidine-1-yl)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1869]

[1870] 4-[3-chloro-5-(3-methoxyazetidin-1-yl)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 187] (35%) was prepared by a method similar to that of Preparation Examples 1-4.

[1871] ESI-MS m / z: 563.17[M+H] + .

[1872] 1H NMR (400 MHz, DMSO-d6) δ ppm 8.71 - 8.79 (m, 2H), 8.33 (d, J=1.75 Hz, 1 H), 8.23 ​​(s, 2H), 7.92 (dd, J=5.38, 2.13 Hz, 1H), 7.49 (d, J=7.25 Hz, 1H), 6.06 (s, 1H), 4.44 - 4.53 (m, 1H), 4.28 - 4.36 (m, 2H), 3.85 - 4.20 (m, 2H), 3.24 (s, 3H), 1.86 - 2.16 (m, 6H), 1.48 - 1.72 (m, 3H).

[1873]

[1874] Example 188: Synthesis of 4-(3-chloro-6-oxo-5-pyrrolidin-1-ylpyridazine-1-yl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1875]

[1876] 4-(3-chloro-6-oxo-5-pyrrolidin-1-ylpyridazine-1-yl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 188] (57%) was prepared by a method similar to that of Preparation Examples 1-4.

[1877] ESI-MS m / z: 547.17[M+H] + .

[1878] 1H NMR (400 MHz, DMSO-d6) δ ppm 8.71 - 8.79 (m, 2H), 8.30 (d, J=2.13 Hz, 1H), 8.24 (s, 1H), 7.90 (dd, J=5.38, 2.13 Hz, 1H), 7.50 (d, J=7.25 Hz, 1H), 6.08 (s, 1H), 4.44 - 4.55 (m, 1H), 4.30 - 4.39 (m, 1H), 1.96 - 2.17 (m, 4H), 1.86 - 1.93 (m, 5H), 1.50 - 1.73 (m, 3H), 1.24 (s, 6H).

[1879]

[1880] Example 189: Synthesis of 4-(3-chloro-5-morpholine-4-yl-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1881]

[1882] 4-(3-chloro-5-morpholine-4-yl-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 189] (20%) was prepared by a method similar to that of Preparation Examples 1-4.

[1883] ESI-MS m / z: 563.17[M+H] + .

[1884] 1H NMR (400 MHz, DMSO-d6) δ ppm 8.74 - 8.82 (m, 2H), 8.29 (d, J=2.13 Hz, 1H), 8.25 (s, 2H), 7.90 (dd, J=5.38, 2.13 Hz, 1H), 7.50 (d, J=7.25 Hz, 1H), 6.84 - 7.24 (m, 1H), 6.68 (s, 1H), 4.44 - 4.54 (m, 1H), 4.31 - 4.39 (m, 1H), 3.69 - 3.75 (m, 4H), 3.57 - 3.62 (m, 4H), 2.08 - 2.16 (m, 2H), 1.90 - 2.00 (m, 2H), 1.55 - 1.69 (m, 2H).

[1885]

[1886] Example 190: Synthesis of 4-[3-chloro-5-(oxetane-3-ylmethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1887]

[1888] 4-[3-chloro-5-(oxetane-3-ylmethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide [Example 190] (48%) was prepared by a method similar to that of Preparation Examples 2-4.

[1889] ESI-MS m / z: 564.15[M+H] + .

[1890] 1H NMR (DMSO-d6, 400 MHz) δ 8.8-8.8 (m, 2H), 8.33 (d, 1H, J=2.1 Hz), 8.24 (s, 2H), 7.95 (dd, 1H, J=2.2, 5.4 Hz), 7.50 (d, 1H, J=7.1 Hz), 7.22 (s, 1H), 7.16 (s, 1H), 7.04 (s, 1H), 6.85 (s, 1H), 4.74 (dd, 2H, J=6.2, 7.8 Hz), 4.4-4.5 (m, 1H), 4.4-4.4 (m, 4H), 4.3-4.4 (m, 1H), 3.4-3.5 (m, 1H), 2.0-2.2 (m, 2H), 2.0-2.0 (m, 1H), 1.9-1.9 (m, 1H), 1.5-1.7 (m, 2H).

[1891]

[1892] Example 191: Synthesis of N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-[5-(3-methoxyazetidine-1-yl)-6-oxopyridazine-1-yl]pyridine-2-carboxamide

[1893]

[1894] N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-[5-(3-methoxyazetidine-1-yl)-6-oxopyridazine-1-yl]pyridine-2-carboxamide [Example 191] (32%) was prepared by a method similar to that of Preparation Examples 1-4.

[1895] ESI-MS m / z: 529.20[M+H] + .

[1896] 1H NMR (DMSO-d6, 400 MHz) δ 8.0-8.5 (m, 3H), 7.66 (br d, 1H, J=8.9 Hz), 7.01 (br d, 1H, J=2.3 Hz), 6.5-6.8 (m, 2H), 4.2-4.3 (m, 2H), 3.98 (s, 3H), 3.06 (s, 3H), 2.10 (td, 2H, J=6.8, 13.4 Hz), 1.8-1.9 (m, 2H), 1.7-1.8 (m, 1H), 1.4-1.5 (m, 2H), 0.8-0.9 (m, 2H), 0.59 (q, 2H, J=5.0 Hz).

[1897]

[1898] Example 192: Synthesis of 4-[5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide

[1899]

[1900] 4-[5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide [Example 192] (19%) was prepared by a method similar to that of Preparation Examples 1-4.

[1901] ESI-MS m / z: 484.18[M+H] + .

[1902] 1H NMR (DMSO-d6, 400 MHz) δ 8.7-8.8 (m, 2H), 8.3-8.5 (m, 3H), 8.08 (d, 1H, J=4.9 Hz), 7.98 (dd, 1H, J=2.3, 5.4 Hz), 7.44 (d, 1H, J=7.3) Hz), 7.00 (d, 1H, J=4.9 Hz), 6.3-6.6 (m, 2H), 5.68 (dd, 1H, J=0.9, 17.8 Hz), 5.0-5.1 (m, 1H), 4.4-4.5 (m, 4H), 1.9-2.2 (m, 4H), 1.4-1.7 (m, 2H).

[1903]

[1904] Example 193: Synthesis of 4-[5-(2,2-difluoroethoxy)-6-oxo-3-(1H-pyrazole-4-yl)pyrizine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide

[1905]

[1906] tert-butyl 4-[5-(2,2-difluoroethoxy)-1-[2-[[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]carbamoyl]-4-pyridinyl]-6-oxopyridazine-3-yl]pyrazole-1-carboxylate (17.00 mg, 0.024 mmol) was dissolved in methanol (0.04 ml), and then 4 M HCl in 1,4-dioxane (13 mg, 0.123 mmol) was added at room temperature. The mixture was stirred a...

Claims

Compounds represented by the following chemical formula 1, and their pharmaceutically acceptable salts, hydrates, solvates, tautomers, isotopic variants, enantiomers, or diastereomers: [Chemical Formula 1] In the above chemical formula 1, A is a mono- or bicyclic ternary to 15-membered heterocycle containing at least two Ns, and m is an integer from 0 to 5, wherein if m is 2 or more, a plurality of R1s are independent of each other, and B is C 1-7 Hydrocarbon group, C 3-10 It is a divalent linker that is a hydrocarbon ring or a 4- to 15-membered bicyclic ring, where n is an integer from 0 to 5, and when n is 2 or greater, a plurality of R2 are independent of each other, and X is O, S, or NH, and C is C 5-12 Arrylene, 3 to 15-membered heteroarylene, C 3-12 Cycloalkylene, ternary to fifteenth-membered heterocycloalkylene, C 3-12 Cycloalkenylene, 3- to 15-membered heterocycloalkenylene, C 3-12 It is a divalent linker that is a cycloalkynylene, a ternary to fifteen-membered heterocycloalkynylene, or a quaternary to fifteen-membered polycyclic heterocycle, where o is an integer from 0 to 5, and when o is 2 or more, a plurality of R3s are independent of each other, and D is C 5-12 Aril, C 3-12 Cycloalkyl, C 3-12 Cycloalkenyl, C 3-12 It is a cycloalkynyl, a ternaryl to 15-membered heteroaryl, a ternaryl to 15-membered heterocycloalkyl, a ternaryl to 15-membered heterocycloalkenyl, a ternaryl to 15-membered heterocycloalkynyl, or a quaternaryl to 15-membered polycyclic heterocycle, where p is an integer from 0 to 5, and when p is 2 or more, a plurality of R4s are independent of each other, and The above R1 to R4 are independently hydrogen, iodine, and C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkinyl, C 1-6 Alkoxy, C 1-6 Haloalkyl, C 1-6 Hydroxyalkyl, C 1-6 Cyanoalkyl, C 1-6 Alkylthio, C 3-6 Cycloalkyl, ternary to hexavalent heterocycloalkyl, C 5-12 Aryl, 3- to 6-membered heteroaryl, C 1-6 Halogenated alkoxy, C 1-6 Alkyl thio, acetyl, acetylamino, hydroxy, cyano, nitro, amino, C 1-3 Aminoalkyl, C 1-3 Alkylamino, thio, deuterium, C 1-6 As a deuterium alkyl, sulfonyl, sulfinyl, halogen, or -CO-R', wherein R' is C 1-3 Alkyl, C 3-6 Cycloalkyl, ternary to hexavalent heterocycloalkyl, methyl-substituted piperazine, C 1-3 Alkoxy, hydroxy, C 1-3 alkylamino, or C 1-3 It is an aminoalkyl, and The above R1 to R4 are each independently halogen, C 1-3 Alkyl, C 1-3 Haloalkyl, C 1-3 Alkoxy, iodine, acetyl, C 3-6 It is substituted or unsubstituted with one or more selected from the group consisting of cycloalkyl and ternary to hexavalent heterocycloalkyl. In paragraph 1, The above compound is a compound represented by the following chemical formula 1-1, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof: [Chemical Formula 1-1] . In paragraph 1, The above compound is a compound represented by any one of the following chemical formulas 1-2 to 1-6, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof: [Chemical Formula 1-2] [Chemical Formula 1-3] [Chemical Formula 1-4] [Chemical Formula 1-5] [Chemical Formula 1-6] In the above chemical formulas 1-2 to 1-6, Q1 to Q3 are each independently C, O, S, or N, and Z1 to Z3 are each independently C or N, and Y1 to Y3 are each independently C, O, S, or N, and W1 to W3 are each independently C or N, and represents a single or double bond. In paragraph 1, The above compound is a compound represented by any one of the following chemical formulas 1-7 to 1-11, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof: [Chemical Formula 1-7] [Chemical Formula 1-8] [Chemical Formula 1-9] [Chemical Formula 1-10] [Chemical Formula 1-11] In the above chemical formulas 1-7 to 1-11, Q1 to Q3 are each independently C, O, S, or N, and Z1 to Z3 are each independently C or N, and Y1 to Y3 are each independently C, O, S, or N, and W1 to W3 are each independently C or N, and V1 to V4 are each independently C or N, and represents a single or double bond. In paragraph 1, A has one of the following structures: Here, Q1 to Q3 are each independently C, O, S, or N, and Z1 to Z3 are each independently C or N, and Y1 to Y3 are each independently C, O, S, or N, and W1 to W3 are each independently C or N, and When m is an integer greater than or equal to 1, a compound, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof, wherein a singular or mutually independent plurality of R1s are selected from the functional groups below: In paragraph 1, B has one of the following structures: When n is an integer greater than or equal to 1, a compound, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof, wherein a singular or mutually independent plurality of R2 are selected from the functional groups below: In paragraph 1, C has one of the following structures: When o is an integer greater than or equal to 1, a compound, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof, wherein a singular or mutually independent plurality of R3s are selected from the functional groups below: In paragraph 1, D has one of the following structures: When p is an integer greater than or equal to 1, the singular or mutually compound plural R4 is selected from the functional groups below, a compound, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof: In paragraph 1, The above compound is a compound selected from the group consisting of the following compounds 1 to 231, a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof: Compound 1: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 2: N-[(1S,3S)-3-[(5-methoxypyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 3: N-[(1S,3S)-3-[(5-ethoxypyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 4: N-[(1S,3S)-3-[(5-fluoropyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 5: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 6: 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-propane-2-ylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide Compound 7: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 8: 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 9: N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 10: N-[(1S,3S)-3-[[5-(difluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 11: N-[(1S,3S)-3-(6,7-dihydro-5H-cyclopenta[d]pyrimidine-2-ylamino)cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 12: 4-(2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(trifluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 13: N-[(1S,3S)-3-[(5-ethylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 14: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(3-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 15: N-[(1S,3S)-3-[[5-(difluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 16: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide Compound 17: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide Compound 18: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide Compound 19: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide Compound 20: N-[(1S,3S)-3-[(5-ethoxypyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 21: N-[(1S,3S)-3-[(5-methoxypyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 22: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 23: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 24: N-[(1S,3S)-3-[(5-fluoropyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 25: N-[(1S,3S)-3-[(5-cyclopropyl-4-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 26: 4-(6-oxopyridazine-1-yl)-N-[3-(pyrimidine-2-ylamino)cyclopentyl]pyridine-2-carboxamide Compound 27: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide Compound 28: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide Compound 29: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]pyridine-2-carboxamide Compound 30: N-[(1S,3S)-3-(5,7-dihydrofuro[3,4-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 31: N-[(1S,3S)-3-(6,7-dihydro-5H-cyclopenta[d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 32: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 33: N-[(1S,3S)-3-[(5-ethynylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 34: 3-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]benzamide Compound 35: N-[(1S,3S)-3-(6,7-dihydrothieno[3,2-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 36: N-[(1S,3S)-3-(5,7-dihydrothieno[3,4-d]pyrimidine-2-ylamino)cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 37: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[4-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 38: N-[(1S,3S)-3-[[4-methylsulfanyl-5-(trifluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 39: N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 40: N-[(1S,3S)-3-[(5-cyanopyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 41: N-[(1S,3S)-3-[(4-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 42: N-[(1S,3S)-3-[[5-(difluoromethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 43: N-[(1S,3S)-3-[(5-acetylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 44: N-[(1S,3S)-3-[[5-(1-hydroxyethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 45: N-[(1S,3S)-3-[[5-(2-hydroxypropane-2-yl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 46: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-propane-2-ylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide Compound 47: N-[(1S,3S)-3-[[5-(hydroxymethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 48: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(trifluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 49: N-[(1S,3S)-3-[[5-(cyclopropylmethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 50: N-[(1S,3S)-3-[[5-(difluoromethylsulfanyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 51: N-[(1R,4R)-4-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-hydroxycyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 52: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-1-(3-methyl-2-pyridinyl)azetidine-3-carboxamide Compound 53: 1-(3-cyano-2-pyridinyl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]azetidine-3-carboxamide Compound 54: 4-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(2,2,2-trifluoroethyl)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 55: N-[(1S,3S)-3-[[5-(cyanomethyl)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 56: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-3-(6-oxopyridazine-1-yl)benzamide Compound 57: N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-1-bicyclo[1.1.1]fentanyl]-4-(6-oxopyridazine-1-yl)benzamide Compound 58: N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclobutyl]-4-(6-oxopyridazine-1-yl)benzamide Compound 59: N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]ethyl]-4-(6-oxopyridazine-1-yl)benzamide Compound 60: N-[(1S,2S)-2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopropyl]-4-(6-oxopyridazine-1-yl)benzamide Compound 61: N-[(1S,2S)-2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopropyl]-3-(6-oxopyridazine-1-yl)benzamide Compound 62: N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]ethyl]-3-(6-oxopyridazine-1-yl)benzamide Compound 63: N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclobutyl]-3-(6-oxopyridazine-1-yl)benzamide Compound 64: N-[3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-1-bicyclo[1.1.1]fentanyl]-3-(6-oxopyridazine-1-yl)benzamide Compound 65: N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-methylpropyl]-3-(6-oxopyridazine-1-yl)benzamide Compound 66: N-[2-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]-2-methylpropyl]-4-(6-oxopyridazine-1-yl)benzamide Compound 67: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 68: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide Compound 69: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(2-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-1-yl)pyridine-2-carboxamide Compound 70: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(1-methyl-3-oxoindazole-2-yl)pyridine-2-carboxamide Compound 71: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-2-yl)pyridine-2-carboxamide Compound 72: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(5-methyl-2-oxo-1,3,4-thiadiazole-3-yl)pyridine-2-carboxamide Compound 73: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-methyl-5-oxo-4H-pyrazole-1-yl)pyridine-2-carboxamide Compound 74: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxomorpholine-4-yl)pyridine-2-carboxamide Compound 75: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(3,4-diethyl-5-oxo-1,2,4-triazole-1-yl)pyridine-2-carboxamide Compound 76: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide Compound 77: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxoindazole-2-yl)pyridine-2-carboxamide Compound 78: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-oxo-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine-2-yl)pyridine-2-carboxamide Compound 79: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-fluoro-2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 80: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methyl-2-oxo-1,3,4-thiadiazole-3-yl)pyridine-2-carboxamide Compound 81: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-ethoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 82: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(4-methoxy-2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 83: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-fluoro-2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 84: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-oxo-3H-pyrrolo[3,4-c]pyridine-2-yl)pyridine-2-carboxamide Compound 85: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-c]pyridine-2-yl)pyridine-2-carboxamide Compound 86: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-b]pyridine-2-yl)pyridine-2-carboxamide Compound 87: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxopyrazolo[3,4-b]pyrazine-2-yl)pyridine-2-carboxamide Compound 88: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-4,5,6,7-tetrahydroindazole-2-yl)pyridine-2-carboxamide Compound 89: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-5,7-dihydro-4H-pyrano[3,4-c]pyrazole-2-yl)pyridine-2-carboxamide Compound 90: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(1-methyl-3-oxo-6,7-dihydro-4H-pyrano[4,3-c]pyrazole-2-yl)pyridine-2-carboxamide Compound 91: 4-(3-cyano-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 92: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(3-methyl-5-oxo-2-propane-2-ylpyrazole-1-yl)pyridine-2-carboxamide Compound 93: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-2-(6-oxopyridazine-1-yl)pyridine-4-carboxamide Compound 94: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 95: N-[(1S,3S)-3-[(5-cyclopropylpyrimidine-2-yl)amino]cyclopentyl]-6-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 96: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 97: 5-(6-oxopyridazine-1-yl)-N-[(1S,3S)-3-(pyrrolo[2,1-f][1,2,4]triazine-2-ylamino)cyclopentyl]pyridine-3-carboxamide Compound 98: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(6-oxopyridazine-1-yl)benzamide Compound 99: 4-(3-methyl-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide Compound 100: 4-(3-methoxy-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide Compound 101: 4-(3-chloro-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide Compound 102: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide Compound 103: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-2-yl)pyridine-2-carboxamide Compound 104: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole-2-yl)pyridine-2-carboxamide Compound 105: N-[(1S,3S)-3-[(5-methylsulfanylpyrimidine-2-yl)amino]cyclopentyl]-4-(3-oxo-6,8-dihydro-5H-[1,2,4]triazolo[3,4-c][1,4]oxazine-2-yl)pyridine-2-carboxamide Compound 106: 4-(3-chloro-2-oxo-1-pyridinyl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide Compound 107: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(5-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 108: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(4-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 109: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(3-methyl-2-oxo-1-pyridinyl)pyridine-2-carboxamide Compound 110: 4-(5-chloro-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide Compound 111: 4-(5-methoxy-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide Compound 112: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(1-oxo-2,7-naphthiridine-2-yl)pyridine-2-carboxamide Compound 113: N-[(1S,3S)-3-[(5-chloropyrimidine-2-yl)amino]cyclopentyl]-4-(4-oxofuro[3,2-c]pyridine-5-yl)pyridine-2-carboxamide Compound 114: N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 115: N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide Compound 116: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 117: 3-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 118: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 119: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 120: 5-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 121: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)pyridine-2-carboxamide Compound 122: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1,1-deoxydoisothiazolidine-2-yl)pyridine-2-carboxamide Compound 123: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)pyridine-2-carboxamide Compound 124: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2,5-dioxomidazolidine-1-yl)pyridine-2-carboxamide Compound 125: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)thiophene-2-carboxamide Compound 126: N-((1S,3S)-3-((5-cyclopropyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide Compound 127: N-((1S,3S)-3-((5-methyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide Compound 128: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 129: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 130: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-4-(6-oxopyridazine-1(6H)-yl)-1H-pyrrole-2-carboxamide Compound 131: 3-methyl-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 132: 3-chloro-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 133: 3-methoxy-N-((1S,3S)-3-((5-methylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 134: 3-chloro-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 135: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)pyridine-2-carboxamide Compound 136: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)pyridine-2-carboxamide Compound 137: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)furan-2-carboxamide Compound 138: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-3-(6-oxopyridazine-1(6H)-yl)-1H-pyrazol-5-carboxamide Compound 139: N-((1S,3S)-3-((5-cyclohexyl-1,2,4-oxadiazole-3-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide Compound 140: N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-3,4-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 141: 3-cyclopropyl-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 142: 3-acetyl-N-((1S,3S)-3-((5-cyclopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 143: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1H-indazole-1-yl)pyridine-2-carboxamide Compound 144: N-((1S,3S)-3-((5-(methylsulfonyl)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide Compound 145: 3-cyclopropyl-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 146: 3-acetyl-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 147: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3,4-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 148: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4,5-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 149: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3,5-dimethyl-1H-pyrazol-1-yl)pyridine-2-carboxamide Compound 150: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3,5-dimethyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide Compound 151: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-5-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 152: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 153: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(5-methyl-1H-pyrazol-1-yl)pyridine-2-carboxamide Compound 154: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(5-methyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide Compound 155: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-isopropyl-5-methyl-1H-1,2,4-triazole-1-yl)pyridine-2-carboxamide Compound 156: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3,5-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 157: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-6-methyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 158: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(pyrazolo[1,5-a]pyridine-7-yl)pyridine-2-carboxamide Compound 159: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-1-methyl-2-oxo-1,2-dihydro-[3,4'-bipyridine]-2'-carboxamide Compound 160: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyrimidine-2-carboxamide Compound 161: Methyl 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylate Compound 162: 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-3-carboxylic acid Compound 163: N-((1S,3S)-3-((5-(methylsulfinyl)pyrimidine-2-yl)amino)cyclopentyl)-4-(6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide Compound 164: 4-(dibenzo[b,d]furan-4-yl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide Compound 165: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(4-methyl-6-oxopyridazine-1(6H)-yl)pyridine-2-carboxamide Compound 166: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(1-oxophthalazine-2(1H)-yl)pyridine-2-carboxamide Compound 167: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-phenyl-2H-[1,4'-bipyridine]-2'-carboxamide Compound 168: 4-(2-cyclopropoxyphenyl)-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)pyridine-2-carboxamide Compound 169: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-(dimethylamino)phenyl)pyridine-2-carboxamide Compound 170: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-(4-methylpiperazine-1-carbonyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 171: 3-Bromo-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 172: 5-chloro-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 173: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-(trifluoromethyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 174: N2'-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-N3,N3-dimethyl-2-oxo-2H-[1,4'-bipyridine]-2',3-dicarboxamide Compound 175: 3-methoxy-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 176: 3-methoxy-2-oxo-N-((1S,3S)-3-((5-ethenylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 177: N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 178: 3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 179: 3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-ethenylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 180: 3-cyclopropyl-N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 181: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(5-methyl-6-oxopyridazine-1-yl)pyridine-2-carboxamide Compound 182: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-(2-oxo-1-pyridinyl)pyridine-2-carvothioamide Compound 183: 4-[3-chloro-5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 184: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-[6-oxo-5-(2,2,2-trifluoroethoxy)pyridazine-1-yl]pyridine-2-carboxamide Compound 185: 4-[3-chloro-6-oxo-5-(2,2,2-trifluoroethoxy)pyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 186: 4-[5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 187: 4-[3-chloro-5-(3-methoxyazetidine-1-yl)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 188: 4-(3-chloro-6-oxo-5-pyrrolidin-1-ylpyridazine-1-yl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 189: 4-(3-chloro-5-morpholine-4-yl-6-oxopyridazine-1-yl)-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 190: 4-[3-chloro-5-(oxetane-3-ylmethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 191: N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]-4-[5-(3-methoxyazetidine-1-yl)-6-oxopyridazine-1-yl]pyridine-2-carboxamide Compound 192: 4-[5-(2,2-difluoroethoxy)-6-oxopyridazine-1-yl]-N-[(1S,3S)-3-[(5-ethenylpyrimidine-2-yl)amino]cyclopentyl]pyridine-2-carboxamide Compound 193: 4-[5-(2,2-difluoroethoxy)-6-oxo-3-(1H-pyrazole-4-yl)pyrizine-1-yl]-N-[(1S,3S)-3-[[5-(difluoromethoxy)pyrimidine-2-yl]amino]cyclopentyl]pyridine-2-carboxamide Compound 194: N-((1S,3S)-3-((6-cyclopropyl-1,2,4-triazine-3-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 195: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-3-cyclopropyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 196: 5-chloro-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 197: 5-chloro-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 198: 5-chloro-2-oxo-N-((1S,3S)-3-((5-vinylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 199: 5-chloro-N-((1S,3S)-3-((5-isopropylpyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 200: 3-cyano-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 201: 2-oxo-3-(trifluoromethyl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 202: 5-chloro-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-3-methoxy-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 203: 5-chloro-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-3-cyclopropyl-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 204: 5-chloro-3-cyclopropyl-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 205: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-2-oxo-3-(trifluoromethyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 206: 5-chloro-3-methoxy-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 207: 4-(5-methyl-6-oxopyridazine-1(6H)-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide Compound 208: 4-(5-methoxy-6-oxopyridazine-1(6H)-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide Compound 209: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-3-cyano-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 210: 3-acetyl-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 211: 3-acetyl-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 212: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-oxoisoquinoline-2(3H)-yl)picolinamide Compound 213: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(3-oxo-3,4,4a,8a-tetrahydroisoquinoline-2(1H)-yl)picolinamide Compound 214: Methyl 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-5-carboxylate Compound 215: 5-Bromo-N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 216: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[b]pyridine-1-yl)picolinamide Compound 217: 2'-(((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)carbamoyl)-2-oxo-2H-[1,4'-bipyridine]-5-carboxylic acid Compound 218: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-5-(morpholine-4-carbonyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 219: 5-Bromo-N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-2-oxo-2H-[1,4'-bipyridine]-2'-carboxamide Compound 220: 5-bromo-2-oxo-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 221: 5-bromo-2-oxo-N-((1S,3S)-3-((5-vinylpyrimidine-2-yl)amino)cyclopentyl)-2H-[1,4'-bipyridine]-2'-carboxamide Compound 222: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-yl)picolinamide Compound 223: 4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide Compound 224: 4-(3-methyl-5-oxo-4,5-dihydro-1H-pyrazole-1-yl)-N-((1S,3S)-3-((5-vinylpyrimidine-2-yl)amino)cyclopentyl)picolinamide Compound 225: N-((1S,3S)-3-((5-(difluoromethoxy)pyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxo-3,4-dihydroquinoline-1(2H)-yl)picolinamide Compound 226: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-4-(2-oxoquinoline-1(2H)-yl)picolinamide Compound 227: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-4-(5-oxo-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-1-yl)picolinamide Compound 228: 4-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-1-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide Compound 229: 4-(5-oxo-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole-1-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide Compound 230: N-((1S,3S)-3-((5-chloropyrimidine-2-yl)amino)cyclopentyl)-4-(4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazole-1-yl)picolinamide, and Compound 231: 4-(2-oxoquinoline-1(2H)-yl)-N-((1S,3S)-3-((5-(trifluoromethyl)pyrimidine-2-yl)amino)cyclopentyl)picolinamide. A pharmaceutical composition for the prevention or treatment of PCSK9-related diseases, comprising as an active ingredient a compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof. A pharmaceutical composition according to claim 10, wherein the PCSK9-related disease is a lipid or lipoprotein metabolic disorder. In Paragraph 11, The above lipid or lipoprotein metabolic disorders include atherosclerosis, dyslipidemia, hypertriglyceridemia, hypertension, heart failure, cardiac arrhythmias, low HDL levels, high LDL levels, sudden death, stable angina, coronary heart disease, acute myocardial infarction, cardiomyopathy, endocarditis, type 2 diabetes, insulin resistance, impaired glucose tolerance, hypercholesterolemia, stroke, hyperlipidemia, hyperlipoproteinemia, chronic kidney disease, intermittent claudication, Hyperphosphatemia, carotid atherosclerosis, peripheral arterial disease, diabetic nephropathy, hypercholesterolemia in HIV infection, acute coronary syndrome (ACS), non-alcoholic fatty liver disease, arterial occlusive disease, cerebral arteriosclerosis, cerebrovascular disorder,A pharmaceutical composition comprising one or more selected from the group consisting of myocardial ischemia, nonalcoholic steatohepatitis (NASH), and diabetic autonomic neuropathy. In Paragraph 10, The above pharmaceutical composition is a pharmaceutical composition that inhibits the activity of PCSK9. A food composition for the prevention or improvement of PCSK9-related diseases, comprising as an active ingredient a compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, isotopic variant, enantiomer, or diastereomer thereof. A composition for inhibiting the activity of PCSK9, comprising as an active ingredient a compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, enantiomer, or diastereomer thereof. A composition for promoting lipid or lipoprotein metabolism, comprising as an active ingredient a compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt, hydrate, solvate, tautomer, enantiomer, or diastereomer thereof. A method for preparing a compound represented by the chemical formula 1-1', comprising the following steps: (S1) A step of obtaining a compound of formula 5 by reacting a compound of formula 3 with a compound of formula 4 to produce an amide reaction; (S2) The compound of Chemical Formula 5 above A step of obtaining a compound of Formula 6 by performing a Suzuki-Miyaura coupling reaction or a Ullmann coupling reaction with a compound represented by; (S3) A step of obtaining a compound of Formula 7 by deprotecting the compound of Formula 6 with trifluoroacetic acid (CF3COOH); and (S4) A step of obtaining a compound of formula 1-1' by performing a nucleophilic aromatic substitution reaction (SnAr) on the compound of formula 7 with the compound of formula 8, [Chemical Formula 1-1'] [Chemical Formula 3] [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8] (In the above structural formulas, A, C, D, X, R1 to R4, and m to p are as defined in Paragraph 1.) A method for preparing a compound represented by the chemical formula 1-1', comprising the following steps: (i) a step of obtaining a compound of formula 9 by performing a nucleophilic aromatic substitution reaction (SnAr) on a compound of formula 3 with a compound of formula 8; (ii) a step of obtaining a compound of formula 10 by deprotecting the compound of formula 9 with trifluoroacetic acid (CF3COOH); (iii) a step of obtaining a compound of Formula 11 by reacting the compound of Formula 10 with the compound of Formula 4 in an amide reaction; and (iv) the compound of Chemical Formula 11 above A step of obtaining a compound of formula 1-1' by performing a Suzuki-Miyaura coupling reaction or a Ullmann coupling reaction with a compound represented by [Chemical Formula 1-1'] [Chemical Formula 3] [Chemical Formula 8] [Chemical Formula 9] [Chemical Formula 10] [Chemical Formula 11] (In the above structural formulas, A, C, D, X, R1 to R4, and m to p are as defined in Paragraph 1.) A method for preparing a compound represented by the chemical formula 1-1', comprising the following steps: (a) A compound of chemical formula 12 A step of obtaining a compound of Formula 13 by performing a Suzuki-Miyaura coupling reaction or a Ullmann coupling reaction with a compound represented by; (b) a step of hydrolyzing the compound of Formula 13 to obtain the compound of Formula 14; and (c) a step of obtaining a compound of formula 1-1' by reacting the compound of formula 14 with the compound of formula 10 in an amide reaction, [Chemical Formula 1-1'] [Chemical Formula 12] [Chemical Formula 13] [Chemical Formula 14] [Chemical Formula 10] (In the above structural formulas, A, C, D, X, R1 to R4, and m to p are as defined in Paragraph 1.)

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