Title - PYRAZOLE DERIVATIVE COMPOUND

Abstract

Compounds are provided that have lysine-specific demethylase-1 (LSD1) inhibitory activity, an optical isomer, a solvate, a tautomer, or a pharmaceutically acceptable salt thereof that is effective in preventing or treating a disease caused by abnormal activation of LSD1.

Description

COMPOUND DERIVED FROM PYRAZOLE AND ITS USE [Technical field] The present disclosure relates to a pyrazole-derived compound and its use, and more especially to a pyrazole-derived compound having lysine-specific histone demethylase-1 (LSD1) inhibitory activity and a pharmaceutical composition which includes the compound derived from pyrazole. [Previous Technique] Cancer stem cells or cancer-initiating cells have some characteristics of pluripotent stem cells that contribute to the heterogeneity of cancer cells. This characteristic can make cancer cells more resistant to traditional therapies, such as chemotherapy or radiotherapy, and therefore can cause recurrence after treatment. Therefore, attempts are still being made to develop anti-cancer drugs that are more advanced than conventional chemotherapy or radiotherapy. Epigenetics is a study of a phenomenon in which the genetic expression pattern and activity are altered and where the genetic expression pattern and activity are transmitted to the next generation without altering the DNA sequence. These epigenetic studies focus on mechanisms such as DNA methylation, histone modification, and chromatin remodeling. Epigenetic modification has been observed to be an important cause of outbreaks of various diseases. It was observed that the initiation and maintenance of epigenetic modification IF-2019-01451929-APN-ANP#INPI Page 1 of 160 involve DNA methylation, histone modification and genetic modifications to non-coding RNA (ncRNA), and many epigenetic regulatory genes are often mutated or the expression of epigenetic regulatory genes is abnormal in many cancer types. Histone lysine-specific demethylase-1 (LSD1, also known as KDM1A) can remove a methyl group, thereby regulating gene expressions that are important in cancer development and cell proliferation (Shi, Y. , et al., Histone demethylation mediated by the nuclear amine oxidase homolog Cell, 2004. 119(7): p. The LSD1 inhibitors studied to date do not show sufficiently selective LSD1 inhibitory activity or have side effects such as the presence of drug resistance or the presence of toxicity to normal cells and therefore cannot be used in any way. effective way for the treatment of cancer and neoplastic diseases. [Prior Art Document] [Patent-type document] (Patent-type document 1) WO 2016 / 007722 (Patent-type document 2) WO 2012 / 135113 [Non-patent document] (Non-patent document 1) Cell, 2004. 119(7): p. 941-53 [Disclosure of the invention] [Technical objective of the invention] IF-2019-01451929-APN-ANP#INPI Page 2 of 160 One aspect of the present disclosure provides a novel compound having sufficient histone lysine-specific demethylase-1 (LSD1) inhibitory activity. Another aspect of the present disclosure provides a pharmaceutical use of the novel compound to prevent or treat a disease caused by abnormal activation of LSD1. [Means to achieve the technical objective] One aspect of the present disclosure provides a compound represented by Formula 1, an optical isomer, a solvate or a tautomer or a pharmaceutically acceptable salt thereof: Formula 1 Another aspect of the present disclosure provides a pharmaceutical composition for preventing or treating a disease caused by abnormal activation of lysine-specific demethylase-1 (LSD1), wherein the pharmaceutical composition includes: the compound represented by Formula 1, an optical isomer , a solvate, a tautomer or a pharmaceutically acceptable salt thereof as an active ingredient; and a pharmaceutically acceptable carrier. IF-2019-01451929-APN-ANP#INPI Page 3 of 160 Yet another aspect of the present disclosure provides a method of treating a disease caused by abnormal activation of LSD1, wherein the method includes administering to a subject a therapeutically effective amount of the compound represented by Formula 1, an optical isomer, a solvate or a tautomer or a pharmaceutically acceptable salt thereof. [Effect of invention] As is evident from the above description, the compound represented by Formula 1 according to one aspect of the present disclosure, an optical isomer, a solvate or a tautomer or a pharmaceutically acceptable salt thereof can suppress the activity of LSD1. [Description of the realization] The present disclosure will be described in more detail. Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as they are commonly understood by one skilled in the art to which this invention pertains. Although illustrative methods or materials are mentioned herein, similar or equivalent methods or materials are also included within the scope of the present invention. Furthermore, numerical values ​​set forth herein are deemed to include the meaning of “approximately” unless explicitly stated. All publications disclosed by reference herein are incorporated in their entirety by reference. The term "alkyl", as used herein, refers, for example, to a straight or branched chain hydrocarbon having between 1 and 20 IF-2019-01451929-APN-ANP#INPI Page 4 of 160 carbon atoms (C1-C20). Examples of alkyl groups include methyl, ethyl, n-propyl, / -propyl, n-butyl, / -butyl and Ebutyl, but embodiments are not limited to these. The term “alkoxy, as used herein, refers to -O-alkyl. The term "alkylthio", as used herein, refers to -S-alkyl. The term "alkenyl" as used herein refers to a straight-chain or branched C2-C20 hydrocarbon having at least one C=C double bond and between 2 and 20 carbon atoms. Examples of alkenyl groups include vinyl, 2-propenyl and 2-butenyl, but embodiments are not limited to these. The term "alkynyl", as used herein, refers to a straight or branched chain C2-C20 hydrocarbon having at least one C^C triple bond and between 2 and 20 carbon atoms. Examples of alkynyl groups include ethynyl, 2-propynyl and 2-butynyl, but embodiments are not limited to these. The term "halogen", as used herein, refers to fluorine, chlorine, bromine or iodine. The terms "amine" or "amino", as used herein, refer to an unsubstituted or substituted -NH2, respectively. The term “alkylamino,” as used herein, refers to an amino linked to a parent molecule via an alkyl. Alkylamino includes groups of compounds in which the -NH2 nitrogen is linked to at least one alkyl, for example, a C1-C15 alkyl having between 1 and 15 carbon atoms. The IF-2019-01451929-APN-ANP#INPI Page 5 of 160 examples of alkylamino groups include benzylamino, methylamino, ethylamino and phenethylamino. The term "dialkylamino", as used herein, refers to groups in which the -NH2 nitrogen is attached to at least two additional alkyls. Examples of dialkylamino groups include dimethylamino and diethylamino. The term “C1-C4 alkylhydroxy, as used herein, refers to a Ci to C4 hydroxyalkyl. The terms and expressions “carbocyclic group”, “carbocycle”, “carbocyclyl” and “carbocyclic ring” can be used interchangeably. The term “Cs-Cso carbocyclic group, as used herein, refers to a monocyclic group, a bicyclic group or a polycyclic group that has only carbon atoms as ring-forming atoms and has between 3 and 30 atoms. carbon. The C3-C30 carbocyclic group may be an aromatic carbocyclic group or a non-aromatic carbocyclic group. The C3-C30 carbocyclic group may be a ring such as benzene, a monovalent group such as phenyl or a divalent group such as phenylene. Also, depending on the number of substituents connected to the C3-C30 carbocyclic group, the C3-C30 carbocyclic group may be a trivalent group or a tetravalent group. In some embodiments, the C3-C20 carbocyclic group may be a C2 to C20 aromatic or non-aromatic, saturated or unsaturated hydrocarbon. Examples of carbocyclic groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentene, cyclohexyl, cyclohexene, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptene, IF-2019-01451929-APN-ANP#INPI Page 6 of 160 bicyclo[3.1.1 Jheptyl, bicyclo[3.1,1]heptyl, bicyclo[2.2.2]octyl, adamantyl, benzyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, indolyl, pyrazolopyridinyl, pyrrolopyridinyl, benzimidazolyl , benzopyrazolyl, benzothiophenyl, quinolinyl, benzothiazolyl, indazolyl, benzofuryl, benzodioxinyl, benzopyryl, indanyl, naphthalenyl and anthracenyl. Each of these carbocyclic groups may be independently substituted with at least one substituent described herein. The terms and expressions “heterocyclic group”, “heterocycle”, “heterocyclyl” and “heterocyclic ring” can be used interchangeably. The term “C1-C30 heterocyclic group,” as used herein, refers to a group having substantially the same structure as the C3-C30 carbocyclic group, except that at least one heteroatom selected from N, O is used. , P and S as a ring-forming atom in addition to carbon atoms (e.g., 1 to 30 carbon atoms). Examples of these include pindinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, indolyl, pyrazolopyridinyl, benzimidazolyl, benzopyrazolyl, benzothiophenyl, benzofuranyl, benzodioxynyl, benzopyranyl, pyrrolopyridinyl, quinolinyl, benzothiazolyl and indazolyl. Examples of the monocyclic heterocyclic group include piperidinyl, pyrrolidinyl, piperazinyl, azepinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, triazolyl, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolidinyl, furyl , tetrahydrofuryl, thienyl, oxadiazolyl, 2-oxopiperazinyl, 2oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, 4-piperidonyl, pyridyl, / V IF-2019-01451929-APN-ANP#INPI Page 7 of 160 pyridyl oxide, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide and thiamorpholinylsulfonyl. Examples of the bicyclic heterocyclic group include diazaspirononanyl (e.g., diazaspiro[3.5]nonanyl), diazaspirodecanyl (e.g., diazaspiro[4.5]decanyl), azabicycloheptanyl, azabicyclooctanyl, diazabicyclononanyl (e.g., diazabicyclo[3.3.1]nonanyl), diazabicyclodecanyl. , octahydro-1H-pyrrolo[2,3c]pyridinyl, indolyl, dihydroindolyl, benzothiazolyl, benzoxazinyl, benzoxazolyl, benzothienyl, benzothiazinyl, quinuclidinyl, quinolinyl, tetrahydroquinolinyl, decahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, decahydroisoquinolinyl, cimidazolyl, benzopyranyl, indolicinyl, benzofuryl,cromonyl , coumarinyl, benzopyranyl, cinolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridinyl, dihydroisoindolyl, dihydroquinazolinyl and phthalazinyl. Examples of the tricyclic heterocyclic group include carbazolyl, dibenzoazepinyl, dithienoazepinyl, benzindolyl, phenanthrolinyl, acridinyl, phenanthridinyl, phenoxazinyl, phenothiazinyl, xanthenyl and carbolinyl. The term “cycloalkyl,” as used herein, refers to a monovalent saturated hydrocarbon ring system having between 3 and 20 carbon atoms (e.g., C3-C12). Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. The term "cycloalkoxy", as used herein, refers to -Ocycloalkyl. The term "cycloalkenyl", as used herein, refers to a monovalent non-aromatic hydrocarbon ring system having between 3 IF-2019-01451929-APN-ANP#INPI Page 8 of 160 and 20 carbon atoms (for example, C3-C12) and at least one double bond. For example, cycloalkenyl includes cyclopentenyl, cyclohexenyl and cycloheptenyl. The term “heterocycloalkyl,” as used herein, refers to a 3- to 20-membered monovalent unsaturated hydrocarbon ring system having at least one heteroatom (e.g., O, N, or S). For example, the heterocycloalkyl may be a 5- to 8-membered monocyclic system, an 8- to 12-membered dicyclic system, or an 11- to 14-membered tricyclic system. Examples of heterocycloalkyl groups include piperazinyl, a pyrrolidinyl, dioxanyl, morpholinyl and tetrahydrofuranyl, but embodiments are not limited to these. The term “heterocycloalkenyl,” as used herein, refers to a 3- to 20-membered monovalent unsaturated hydrocarbon ring system having at least one heteroatom (e.g., O, N, or S) and at least one double. link. For example, heterocycloalkenyl may be a non-aromatic 5- to 8-membered monocyclic system, a non-aromatic 8- to 12-membered dicyclic system, or a non-aromatic 11- to 14-membered tricyclic system. The term "aryl", as used herein, refers, for example, to a C6-C20 monovalent aromatic hydrocarbon having between 6 and 20 carbon atoms obtained by removing a hydrogen atom bonded to a carbon atom in an aromatic ring mother system. The aryl may include a dicyclic radical that includes an aromatic ring fused to a saturated ring or a partially unsaturated ring. Examples of aryl groups include a radical obtained from benzene (phenyl), substituted benzyl, IF-2019-01451929-APN-ANP#INPI Page 9 of 160 naphthalenyl, anthracenyl, biphenyl, indenyl, indanyl, 1,2-dihydronaphthalenyl and 1,2,3,4-tetrahydronaphthyl. The term "aryloxy", as used herein, refers to -O-aryl. The term "arylthio, as used herein, refers to -S-aryl. The term "heteroaryl" refers, for example, to a monovalent aromatic hydrocarbon having between 5 and 30 atoms that includes at least one heteroatom selected from N, O and S and at least one carbon atom (e.g., Ci-C2o ). The term "heteroaryloxy", as used herein, refers to -O-heteroaryl. The term "heteroarylthio", as used herein, refers to -S-heteroaryl. The heteroaryl may include a fused ring system of, for example, 5-, 6-, or 7-membered rings (where at least one of which is aromatic). Examples of heteroaryl groups include monocyclic or bicyclic aryl, for example, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, tetrazole, isothiazolyl, furyl, thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, A / -pyridyl oxide, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, benzothiazolyl, benzoxazolyl, benzothienyl, quinolinyl, isoquinolinyl, benzimidazolyl and benzofuryl. Each of the groups “carbocyclic, heterocyclic, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkoxy, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio and amine” may be independently substituted with at least one substituent described herein. Likewise, with respect to the term Ca, A" indicates the number of carbon atoms in a substituted or unsubstituted hydrocarbon or the number of carbon atoms of a substituent in a substituted hydrocarbon. For example, him IF-2019-01451929-APN-ANP#INPI Page 10 of 160 number of carbon atoms, including substituents of substituted C3-C20 carbocyclic group, substituted C1-C20 heterocyclic group, substituted C1-C20 alkyl, substituted C1-C20 alkoxy, substituted C2-C20 alkenyl , substituted C2-C20 alkynyl, substituted C3-C20 cycloalkyl, substituted C3-C20 cycloalkoxy, substituted C3-C20 cycloalkenyl, substituted C1-C20 heterocycloalkyl, substituted C1-C20 heterocycloalkenyl, substituted C6-C20 aryl, substituted C6-C20 aryloxy, C6-C20 arylthio, C1-C20 heteroaryl, C1-C20 heteroaryloxy or C1-C20 heteroarylthio is 20 or less. For example, the substituent can be selected from halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, an amino group, an oxo group, a substituted or unsubstituted C1-C10 alkyl group, a C2 alkenyl group -substituted or unsubstituted C10, a substituted or unsubstituted C2-C10 alkynyl group, a substituted or unsubstituted C3-C10 carbocyclic group, a substituted or unsubstituted C1-C10 heterocyclic group, a substituted or unsubstituted C1-C10 alkoxy group , a substituted or unsubstituted C3-C10 cycloalkoxy group, a substituted or unsubstituted C1-C10 alkylthio group, a substituted or unsubstituted Ce-Cio aryloxy group, a substituted or unsubstituted Ce-Cw arylthio group, a C1-heteroaryloxy group substituted or unsubstituted C10, a substituted or unsubstituted C1-C10 heteroarylthio group, a substituted or unsubstituted Ce-Cw aryl group, a substituted or unsubstituted C1-C10 heteroaryl group, -N(Q3)(Q4), -C (=O)(Q3), -NC(=O)(Q3), -N-C(=O)-N(Q3)(Q4), -O-C(=O)(Q3), -S(=O)( Q3), -S(=O)2(Q3), P(=O)(Q3)(Q4) and -N-C(=NH)-N(Q3)(Q4). A substituent of substituted C1-C10 alkyl group, substituted C2C10 alkenyl group, substituted C2-Cio alkynyl group, C3-Cw carbocyclic group IF-2019-01451929-APN-ANP#INPI Page 11 of 160 -Substituted cyo, substituted C1-C10 heteroaryloxy group, substituted C1-C10 heteroarylthio group, substituted Ce-Cw aryl group or substituted C1-C10 heteroaryl group may be at least one selected from: halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, an oxo group, a C1-C10 alkyl group, a C2-C10 alkenyl group, a C2-C10 alkynyl group, a C3-C10 cycloalkyl group, a C1C10 heterocycloalkyl group, a C1-C10 alkoxy group, a C3-C10 cycloalkoxy group, a C1C10 alkylthio group, a Ce-Cío aryloxy group, a Ce-Cío arylthio group, a C1C10 heteroaryloxy group, a C1-C10 heteroarylthio group, -N(Q5)(Qe), -C(=O)(Qe), -N-C(=O)(Qe), -NC(=O)-N(Q5)(Q6), -O-C(=O) (Q5), -S(=O)(Q5), -S(=O)2(Q5), -P(=O)(Q5)(Q6) and -NC(=NH)-N(Q5)( Q6), where each of Q3 to Qe can be independently selected from hydrogen, halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a substituted or unsubstituted C1-C10 alkyl group, a C2 alkenyl group -substituted or unsubstituted C10, a substituted or unsubstituted C2-C10 alkynyl group, a substituted or unsubstituted C3-C10 carbocyclic group, a substituted or unsubstituted C1-C10 heterocyclic group, a substituted or unsubstituted C1-C10 alkoxy group , a substituted or unsubstituted C3-C10 cycloalkoxy group, a substituted or unsubstituted C1-C10 alkylthio group, a substituted or unsubstituted Ce-Cw aryloxy group, a substituted or unsubstituted Ce-Cw arylthio group, a IF-2019-01451929-APN-ANP#INPI Page 12 of 160 substituted or unsubstituted C1-C10 heteroaryloxy, a substituted or unsubstituted C1-C10 heteroarylthio group, a substituted or unsubstituted C1-C10 alkylamino group, a substituted or unsubstituted C1-C10 dialkylamino group, a Ce aryl group -Substituted or unsubstituted cyo and a C1-C10 heteroaryl group. A substituent of the substituted C1-C10 alkyl group, the substituted C2C10 alkenyl group, the substituted C2-C10 alkynyl group, the substituted C3-C10 carbocyclic group, the substituted C1-C10 heterocyclic group, the substituted C1-C10 alkoxy group, the substituted Ca-Cw cycloalkoxy, substituted C1-C10 alkylthio group, substituted Ce-Cw aryloxy group, substituted Ce-Cw arylthio group, substituted C1-C10 heteroaryloxy group, substituted C1-C10 heteroarylthio group, C1 alkylamino group -C10 substituted, the substituted C1-C10 dialkylamino group, the substituted Ce-Cw aryl group and the substituted C1-C10 heteroaryl group may be at least one selected from: halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a C1-C10 alkyl group, a C2-C10 alkenyl group, a Cz-Cw alkynyl group, a C3-C10 carbocyclic group, a C1 heterocyclic group -C10, a C1C10 alkoxy group, a C3-C10 cycloalkoxy group, a C1-C10 alkylthio group, a CeCw aryloxy group, a Ce-Cw arylthio group, a C1-C10 heteroaryloxy group, a C1-C10 heteroarylthio group, a C1-C10 alkylamino group, a C1-C10 dialkylamino group, a Ce-Cw aryl group and a C1-C10 heteroaryl group. The inventors herein have made extensive efforts to develop a new anticancer drug using lysine-specific demethylase-1 (LSD1) as a key target for anticancer therapy. As a result, a pyrazole-derived compound was developed IF-2019-01451929-APN-ANP#INPI Page 13 of 160 novel capable of sufficiently suppressing the activity of LSD1 that participates in the transcription of several genes important for the evolution of cancer and cell proliferation from the point of view of epigenetics. One aspect of the present disclosure provides a compound represented by Formula 1, an optical isomer, a solvate or a tautomer or a pharmaceutically acceptable salt thereof: Formula 1 where, in Formula 1, Cl) can be a C3-C30 carbocyclic group or a C1C30 heterocyclic group, X can be C (R5) or N, each from R1 (s) to R5 can be independently a monovalent radical selected between hydrogen, halogen, a cyano group, a hydroxy group, a Tiol group, a nitro group, an alquilo group C1 -C20 substituted or unsubstituted, a substituted or unsubstituted C2-C20 alkenyl group, a substituted or unsubstituted C2-C20 alkynyl group, a substituted or unsubstituted C3-C20 carbocyclic group, a substituted or unsubstituted C1-C20 heterocyclic group , a substituted or unsubstituted C1-C20 alkoxy group, a cycloalkoxy group IF-2019-01451929-APN-ANP#INPI Page 14 of 160 substituted or unsubstituted C3-C20, a substituted or unsubstituted C1-C20 alkylthio group, a substituted or unsubstituted C6-C20 aryloxy group, a substituted or unsubstituted CeC20 arylthio group, a substituted or unsubstituted C1-C20 heteroaryloxy group, a substituted or unsubstituted Ci-C2o heteroarylthio group, a C1-C20 alkylamino group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C1-C20 heteroaryl group, -N(Qi)(Q2), - C(=O)(Qi), -NC(=O)(Qi), -N-C(==O)-N(Qi)(Q2), -O-C(=O)(Qi), -S(=O )(Qi), -S(=O)2(Qi), P(=O)(Qi)(Q2) and -N-C(=NH)-N(Qi)(Q2), when the R1(s) ) or R2(s) is / are optionally two or more, two of the R1(s) or R2(s) are substituents on two adjacent ring atoms that are consecutively connected to a corresponding ring, two adjacent substituents R1 (s) or R2(s) may be connected together to form a substituted or unsubstituted C3-C30 carbocyclic group or a substituted or unsubstituted Cí-Cso heterocyclic group, to thereby form a ring fused with the corresponding ring, R3 and R4 may optionally be joined to form a substituted or unsubstituted C1-C30 heterocyclic group with an amide nitrogen of Formula 1, k may be an integer from 0 to 4; when k is 2 or more, at least two R1(s) may be identical or different from each other, and m may be an integer from 0 to 7; when m is 2 or more, at least two R2(s) can be identical or different from each other, where each of Q1 and Q2 can be independently selected from IF-2019-01451929-APN-ANP#INPI Page 15 of 160 hydrogen, halogen, a hydroxy group, a substituted or unsubstituted C1-C10 alkyl group, a substituted or unsubstituted C2-C10 alkenyl group, a substituted or unsubstituted C2-C10 alkynyl group, a C3-cycloalkyl group substituted or unsubstituted C10, a substituted or unsubstituted C1-C10 heterocycloalkyl group, a substituted or unsubstituted C1-C10 alkoxy group, a substituted or unsubstituted C3-C10 cycloalkoxy group, a substituted or unsubstituted C1-C10 alkylthio group, a substituted or unsubstituted Ce-Cio aryloxy group, a substituted or unsubstituted Ce-Cio arylthio group, a substituted or unsubstituted C1-C10 heteroaryloxy group, a substituted or unsubstituted C1-C10 heteroarylthio group, a substituted or unsubstituted C1C10 alkylamino group unsubstituted, a substituted or unsubstituted Ce-Cw aryl group and a substituted or unsubstituted C1-C10 heteroaryl group. (ΊβΊ In an exemplary embodiment, in Formula 1, it may be a C3-C30 carbocyclic group or a C1-C30 heterocyclic group. In some embodiments, one can select from a phenyl group, a pyridinyl group, a pyridazinyl group, a pyrimidinyl group, a pyrazinyl group, a pyrrolyl group, a pyrazolyl group, an indolyl group, a pyrazolopyridinyl group, a pyrrolopyridinyl group, a benzimidazolyl group, a benzopyrazolyl group, a benzothiophenyl group, a quinolinyl group, a benzothiazolyl group, an indazolyl group, a benzofuranyl group, a benzodioxanyl group, a benzopyranyl group, an indanyl group and a naphthyl group. In an exemplary embodiment, in Formula 1, the R2(s) may be selected from hydrogen, halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a C1 alkyl group. -C15 substituted or unsubstituted, a substituted or unsubstituted C2-C15 alkenyl group, a group IF-2019-01451929-APN-ANP#INPI Page 16 of 160 substituted or unsubstituted C2-C15 alkynyl, a substituted or unsubstituted C3-C15 carbocyclic group, a substituted or unsubstituted C1-C15 heterocyclic group, a substituted or unsubstituted C1-C15 alkoxy group, a C3 cycloalkoxy group -substituted or unsubstituted C15, a substituted or unsubstituted C1-C15 alkylthio group, a substituted or unsubstituted C6-C15 aryloxy group, a substituted or unsubstituted CeC15 arylthio group, a substituted or unsubstituted C1-C15 heteroaryloxy group, a substituted or unsubstituted CuCis heteroarylthio group, a C1-C15 alkylamino group, -N(Q3)(Q4), -C(=O)(Q3), -N-C(=O)(Q3), -N-C(=O) -N(Q3)(Q4), -O-C(=O)(Q3), -S(=O)(Q3), -S(=O)2(Q3), -P(=O)(Q3)( Q4) and -N-C(=NH)-N(Q3)(Q4), where each of Q3 and Q4 can be independently selected from hydrogen, halogen, a hydroxy group, a substituted or unsubstituted Ci-Ce alkyl group, an alkenyl group substituted or unsubstituted C2-C6, a substituted or unsubstituted C2-C6 alkynyl group, a substituted or unsubstituted C3-Ce cycloalkyl group, a substituted or unsubstituted C1-C6 heterocycloalkyl group, a substituted or unsubstituted Ci-Ce alkoxy group substituted, a substituted or unsubstituted C3-Ce cycloalkoxy group, a substituted or unsubstituted Ci-Ce alkylthio group, a substituted or unsubstituted C6-C9 aryloxy group, a substituted or unsubstituted C6-C9 arylthio group, a Ci heteroaryloxy group -substituted or unsubstituted Ce, a substituted or unsubstituted Ci-Ce heteroarylthio group, a substituted or unsubstituted Ci-Ce alkylamino group, a substituted or unsubstituted C6-C9 aryl group and a substituted or unsubstituted Ci-Ce heteroaryl group . In some embodiments, R2 can be selected from a C3-C15 cycloalkyl group. IF-2019-01451929-APN-ANP#INPI Page 17 of 160 substituted or unsubstituted and a substituted or unsubstituted C1-C15 heterocycloalkyl group. In an exemplary embodiment, in Formula 1, each of R3 and R4 can be independently selected from hydrogen, halogen, a substituted or unsubstituted C1-C15 alkyl group, a substituted or unsubstituted C3-C15 carbocyclic group, a heterocyclic group substituted or unsubstituted C1-C15, a substituted or unsubstituted C1-C15 alkoxy group, a substituted or unsubstituted C3-C15 cycloalkoxy group, a substituted or unsubstituted C1-C15 alkylthio group, a substituted or unsubstituted C6-C15 aryloxy group substituted, a substituted or unsubstituted Ce-Cis arylthio group, a substituted or unsubstituted C1-C15 heteroaryloxy group, a substituted or unsubstituted C1-C15 heteroarylthio group, a substituted or unsubstituted C6-C15 aryl group and a C1 heteroaryl group -C15 substituted or not substituted. In an exemplary embodiment, R3 and R4 may be linked together to form a substituted or unsubstituted C1-C30 heterocyclic group with an amide nitrogen of Formula 1 and, for example, the substituted or unsubstituted C1-C30 heterocyclic group can be selected from a piperidinyl group, a pyrrolidinyl group, a piperazinyl group, an azepinyl group, a diazaspirononanyl group, a diazaspirodecanyl group, an azabicycloheptanyl group, an azabicyclooctanyl group, a diazabicyclononanyl group and a diazabicyclodecanyl group. In an exemplary embodiment, at least one substituent of the substituted or unsubstituted C1-C30 heterocyclic group formed by the union of R3 and R4 with the nitrogen of the amide of Formula 1 can be selected from: IF-2019-01451929-APN-ANP#INPI Page 18 of 160 halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a substituted or unsubstituted C1-C15 alkyl group, a substituted or unsubstituted C2-C15 alkenyl group, a C2-C15 alkynyl group substituted or unsubstituted, a substituted or unsubstituted C3-C20 carbocyclic group, a substituted or unsubstituted 61-615 heterocyclic group, a substituted or unsubstituted C1-C20 alkoxy group, a substituted or unsubstituted 63-620 cycloalkoxy group, a alkylthio group 61-620 substituted or unsubstituted, -N(Qs)(Q6), -6(=O)(Qs), -N-6(=O)(Qs), -N-6(=O)- N(Q5)(Q6), -O-6(=O)(Q5), -S(=O)(Q5), -S(=O)2(Q5), -P(=O)(Q5) (Q6) and N-G(=NH)-N(Q5)(Q6), where each of Qs and Qe can be independently selected from hydrogen, halogen, a hydroxy group, a substituted or unsubstituted 61-65 alkyl group, a substituted or unsubstituted 62-66 alkenyl group, a substituted or unsubstituted 62-66 alkynyl group, a substituted or unsubstituted 63-66 cycloalkyl group, a substituted or unsubstituted 61-65 heterocycloalkyl group, a substituted 61-65 alkoxy group or unsubstituted, a substituted or unsubstituted 63-66 cycloalkoxy group, a substituted or unsubstituted 61-65 alkylthio group, a substituted or unsubstituted 65-69 aryloxy group, a substituted or unsubstituted 66-69 arylthio group, a substituted or unsubstituted 61-66 heteroaryloxy, a substituted or unsubstituted 6ι-6β heteroarylthio group, a substituted or unsubstituted 6i-6e alkylamino group, a substituted or unsubstituted 65-69 aryl group and a substituted or unsubstituted 6i-6e heteroaryl group not replaced. In an exemplary embodiment, Cj?) can be selected from a phenyl group, a pyridinyl group, a quinolinyl group, a group IF-2019-01451929-APN-ANP#INPI Page 19 of 160 Or benzothiazolyl, an indazolyl group, a benzodioxinyl group, an indanyl group and a naphthyl group, X can be C (R5), where R5 can select between hydrogen, halogen, a hydroxy group, a group C1-C4 rents replaced or not replaced and an Alcoxi C1-C4 group replaced or not replaced, R2(s) may be selected from hydrogen, halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a substituted or unsubstituted C1-C15 alkyl group, a substituted C2-C15 alkenyl group or unsubstituted, a substituted or unsubstituted C2-C15 alkynyl group, a substituted or unsubstituted C3-C15 cycloalkyl group, a substituted or unsubstituted C3-C15 cycloalkenyl group, a substituted or unsubstituted C1-C15 heterocycloalkyl group, a heterocycloalkenyl group substituted or unsubstituted C1-C15, a substituted or unsubstituted CiC15 alkoxy group, a substituted or unsubstituted C3-C15 cycloalkoxy group, a substituted or unsubstituted C1-C15 alkylthio group, a substituted or unsubstituted Ce-Oís aryloxy group, a substituted or unsubstituted C6-C15 arylthio group, a substituted or unsubstituted C1-C15 heteroaryloxy group, a substituted or unsubstituted C1-C15 heteroarylthio group, a C1-C20 alkylamino group, N(Q7)(Qe), -C (=O)(Q7), -N-C(=O)(Q7), -N-C(=O)-N(Q7)(Q8), -O-C(=O)(Q7), S(=O)(Q7) ), -S(=O)2(Q7), -P(=O)(Q7)(Q8) and -N-C(=NH)-N(Q7)(Q8), R3 and R4 can be joined to form a group selected from a substituted or unsubstituted piperidinyl group, a substituted or unsubstituted pyrrolidinyl group, a substituted or unsubstituted piperazinyl group, a substituted or unsubstituted azepinyl group, a substituted or unsubstituted diazaspirononanyl group, a substituted or unsubstituted diazaspirodecanyl group, a group IF-2019-01451929-APN-ANP#INPI Page 20 of 160 substituted or unsubstituted azabicycloheptanyl, a substituted or unsubstituted azabicyclooctanyl group, a substituted or unsubstituted diazabicyclononanyl group, a substituted or unsubstituted diazabicyclodecanyl group and an octahydro-1 / - / -pyrrolo[2,3-c] group ]pyridyl substituted or unsubstituted, with an amide nitrogen of Formula 1, at least one substituent of the substituted piperidinyl group, the substituted pyrrolidinyl group, the substituted piperazinyl group, the substituted azepinyl group, the substituted diazaspirononanyl group, the diazaspirodecanyl group substituted, the substituted azabicycloheptanyl group, the substituted azabicyclooctanyl group, the substituted diazabicyclononanyl group, the substituted diazabicyclodecanyl group and the substituted octahydro-1H-pyrrolo[2,3-c]pyridyl group can be selected from: a substituted or unsubstituted C1-C15 alkyl group, a substituted or unsubstituted C2C15 alkenyl group, a substituted or unsubstituted C2-C15 alkynyl group, a substituted or unsubstituted C3-C15 cycloalkyl group, a substituted or unsubstituted C1-C15 heterocycloalkyl group -N( Qg)(Qio), -C(=O)(Qg), -N-C(=O)(Q9), -N-C(=O)N(Qg)(Qio), -O-C(=O)(Q9), -S(=O)(Q9), -S(=O)2(Q9), -P(=0)(Qg)(Qio) and -NC(=NH)-N(Qg)(Qio), where each of Q7 to Q10 can be selected independently from IF-2019-01451929-APN-ANP#INPI Page 21 of 160 hydrogen, halogen, a hydroxy group, a substituted or unsubstituted Ci-Ce alkyl group, a substituted or unsubstituted C2-C6 alkenyl group, a substituted or unsubstituted C2-C6 alkynyl group, a C3-cycloalkyl group substituted or unsubstituted C6, a substituted or unsubstituted Ci-Ce heterocycloalkyl group, a substituted or unsubstituted C1-C6 alkoxy group, a substituted or unsubstituted Cs-Ce cycloalkoxy group, a substituted or unsubstituted Ci-Ce alkylthio group, a substituted or unsubstituted Ce-Cg aryl group, a substituted or unsubstituted Ce-Cg aryloxy group, a substituted or unsubstituted Ce-Cg arylthio group, a substituted or unsubstituted Ci-Ce heteroaryl group, a Ci-Ce heteroaryloxy group substituted or unsubstituted and a substituted or unsubstituted Ci-Ce heteroarylthio group, k may be 0, and m may be an integer from 0 to 2. ib) In some embodiments, in Formula 1, when it is a phenyl group or a pyridinium group, and m is an integer from 1 to 5, at least one selected from the R2(s) may be selected from a hydroxy group. , a thiol group, a substituted or unsubstituted C2-C10 alkenyl group, a substituted or unsubstituted C2-C10 alkynyl group, a substituted or unsubstituted C3-C10 carbocyclic group, a substituted or unsubstituted C1-C10 heterocyclic group, a substituted or unsubstituted C3-C10 cycloalkoxy group, a substituted or unsubstituted Ce-Cw aryloxy group, a substituted or unsubstituted Ce-Cio arylthio group, a substituted or unsubstituted C1-C10 heteroaryloxy group, a substituted Ci-Cw heteroarylthio group or unsubstituted, a substituted or unsubstituted Ce-Cw aryl group, a substituted or unsubstituted C1-C10 heteroaryl group, -N(Q3)(Q4), IF-2019-01451929-APN-ANP#INPI Page 22 of 160 -C(=O)(Q3), -N-C(=O)(Q3), -N-C(=O)-N(Q3)(Q4), -O-C(=O)(Q3), -S(=O )(Q3), S(=O)2(Q3), -P(=O)(Q3)(Q4) and -N-C(=NH)-N(Q3)(Q4), R3 and R4 can be joined to form a substituted or unsubstituted C1-C15 heterocyclic group, and at least one substituent of the substituted C1C15 heterocyclic group can be selected from a cyano group, a thiol group, a nitro group, a substituted C2-C10 alkenyl group or unsubstituted, a substituted or unsubstituted C2-C10 alkynyl group, a substituted or unsubstituted C3-C10 carbocyclic group, a substituted or unsubstituted C1-C10 heterocyclic group, a substituted or unsubstituted C3-Cw cycloalkoxy group, a substituted or unsubstituted C1-C10 alkylthio, a substituted or unsubstituted Ce-Cio aryloxy group, a substituted or unsubstituted Ce-Cio arylthio group, a substituted or unsubstituted C1-C10 heteroaryloxy group, a substituted or unsubstituted C1-C20 heteroarylthio group unsubstituted, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C1-C20 heteroaryl group, -N(Q5)(Qe), -C(=0)(Q5), -NC(=O) (Q5), -N-C(=O)-N(Q5)(Q6), -O-C(=O)(Q5), -S(=O)(Qs), -S(=O)2(Q5), P(=O)(Q5)(Q6) and -N-C(=NH)-N(Q5)(Qe). Likewise, at least one substituent of the substituted C2-C10 alkenyl group, the substituted C2-C10 alkynyl group, the substituted C3-C10 carbocyclic group, the substituted C1-C10 heterocyclic group, the substituted C3-C10 cycloalkoxy group, the C1 alkylthio group -C10 substituted, substituted Ce-Cio aryloxy group, substituted Ce-Cw arylthio group, substituted C1-C10 heteroaryloxy group, substituted C1-C10 heteroarylthio group, substituted Ce-Cío aryl group and C1-C10 heteroaryl group substituted can be selected from: a C2Cw alkenyl group, a C2-C10 alkynyl group, a C3-C10 cycloalkyl group, a IF-2019-01451929-APN-ANP#INPI Page 23 of 160 Ci-Cw heterocycloalkyl, a C3-C10 cycloalkoxy group, a Ce-Cw aryloxy group, a Ce-Cw arylthio group, a Ci-Cw heteroaryloxy group, a C1Cw heteroarylthio group, a Ce-Cw aryl group, a C1-C10 heteroaryl group and a C1-C10 alkylamino group. In an exemplary embodiment, in Formula 1, it may be a phenyl group or a pyridinyl group. X can be C (RA), where it raps to be hydrogen or a C1C4 alkyl group, the R1 (s) can be hydrogen or fluoride, each of the R2 (s) can be selected independently between halogen , a Ci-Ce alkyl group, a Ci-Ce alkoxy group, a Ci-Ce alkylamino group, a Ci-Ce alkylthio group, a substituted or unsubstituted Cs-Ce cycloalkyl group, a substituted or unsubstituted pyrrolidinyl group linked through of N, a substituted or unsubstituted piperidinyl group linked through N and a substituted or unsubstituted azetidinyl group linked through N, at least one substituent of the substituted Cs-Ce cycloalkyl group, the substituted pyrrolidinyl group linked through N , the substituted or unsubstituted piperidinyl group linked through N and the substituted or unsubstituted azetidinyl group linked through N can be selected from: halogen, a hydroxy group, a C1-C4 alkyl group, a C1C4 alkoxy group, a C1-C4 alkylhydroxy group and a Ci-Ce heterocyclic group, when R2(s) is(are) two or more, two R2(s) They can bond together and condense with each other to form a Cs-Cw carbocyclic group. IF-2019-01451929-APN-ANP#INPI Page 24 of 160 substituted or unsubstituted or a substituted or unsubstituted C6-C12 heterocyclic group, R3 and R4 can be joined to form a substituted or unsubstituted piperidinyl group, a substituted or unsubstituted azepanyl group, or a substituted or unsubstituted azabicyclooctanyl group, with the nitrogen of the amide of Formula 1, and at least one substituent of the piperidinyl group substituted, the substituted azepanyl group or the substituted azabicyclooctanyl group can be selected from an amino group, a Ci~C4 alkylamino group and N(Qa)(Qb), where each of Qa and Qb can be independently selected from hydrogen and an alkyl group Ci-Ce. In an exemplary embodiment, in Formula 1, each of the R2(s) can be independently selected from halogen, a Ci-Ce alkyl group, a Ci-Ce alkoxy group, a Ci-Ce alkylamino group, a Ci-Ce alkylthio, a substituted or unsubstituted Cb-Cb cycloalkyl group, a substituted or unsubstituted pyrrolidinyl group linked through N, a substituted or unsubstituted piperidinyl group linked through N and a substituted or unsubstituted azetidinyl group linked through N, at least one substituent of the substituted Cb-Cb cycloalkyl group or the substituted azetidinyl group linked through N can be selected from halogen and a hydroxy group, at least one substituent of the substituted pyrrolidinyl group linked through N or the substituted piperidinyl group linked through N can be selected IF-2019-01451929-APN-ANP#INPI Page 25 of 160 between halogen, a hydroxy group, a C1-C4 alkyl group, a C1-C4 alkoxy group, a C1-C4 alkylhydroxy group and a piperidinium group, and when R2(s) is(are) two or more, two R2(s) can be joined and condensed with to form a heterocyclic group or a carbocyclic group selected from an indazolyl group, a benzothiazolyl group, an indanyl group, a dihydrobenzodioxynyl group, a quinolinyl group and a pyrrolopyridinyl group, where the heterocyclic group or a carbocyclic group are unsubstituted or substituted with a C1-C3 alkyl group. In an exemplary embodiment, R3 and R4 in the compound represented by Formula 1 can be joined to form a compound represented by Formula 2. Formula 2 where, in Formula 2, it may be a C1-C30 heterocyclic group including a nitrogen atom, for example, the C1-C30 heterocyclic group including a nitrogen atom may be selected from a piperidinyl group, a pyrrolidinyl group, a piperazinyl group, an azepinyl group, a diazaspirononanyl group, a diazaspirodecanyl group, an azabicycloheptanyl group, an azabicyclooctanyl group, a diazabicyclononanyl group IF-2019-01451929-APN-ANP#INPI Page 26 of 160 and a diazabicyclodecanyl group, each unsubstituted or substituted with at least one substituent described herein. In Formula 2, R\ R2, k and m can be defined as identical to those in Formula 1. In Formula 2, n can be an integer from 0 to 6; when n is 2 or more, at least two R6(s) may be identical or different from each other and each of R6(s) may be independently selected from hydrogen, halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a substituted or unsubstituted C1-C15 alkyl group, a substituted or unsubstituted C2C15 alkenyl group, a substituted or unsubstituted C2-C15 alkynyl group, a substituted or unsubstituted C3-C15 carbocyclic group, a C1 heterocyclic group -C15 substituted or unsubstituted, a substituted or unsubstituted C1-C20 alkoxy group, a substituted or unsubstituted C3-C20 cycloalkoxy group, a substituted or unsubstituted C1-C20 alkylthio group, -N(Q25)(Q26), - C(=O)(Q25), -NC(=O)(Q25), -N-C(=O)-N(Q25)(Q26), -O-C(=O)(Q25), -S(=O) (Q25), -S(=O)2(Q25), P(=O)(Q25)(Q26) and -N-C(=NH)-N(Q25)(Q26), where at least one substituent of the alkyl group substituted C1-C15, substituted C2-C15 alkenyl group, substituted C2-C15 alkynyl group, substituted C3-C15 carbocyclic group, substituted C1-C15 heterocyclic group, substituted C1-C15 alkoxy group, C3-cycloalkoxy group substituted C15, substituted C1-C15 alkylthio group and substituted C1-C15 alkylamino group can be selected from halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a C1-C15 alkyl group, an alkenyl group C2-C15, a C2-C15 alkynyl group, a C3-C15 carbocyclic group, a C1-C15 heterocyclic group, a C1C15 alkoxy group, a C3-C15 cycloalkoxy group, a C1-C15 alkylthio group, -N(Q27)( Q2e), IF-2019-01451929-APN-ANP#INPI Page 27 of 160 C(=O)(Q27), -N-C(=O)(Q27), -N-C(=O)-N(Q27)(Q28), -O-C(=O)(Q27), -S(=O) (Q27), -S(=O)2(Q27), -P(=O)(Q27)(Q28) and -N-C(=NH)-N(Q27)(Q28), and each of Q25 to Q2s can be independently selected from hydrogen, halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a substituted or unsubstituted C1-C15 alkyl group, a substituted or unsubstituted C2C15 alkenyl group, a C2-alkynyl group substituted or unsubstituted C15, a substituted or unsubstituted C3-C15 cycloalkyl group, a substituted or unsubstituted C1-C15 heterocycloalkyl group, a substituted or unsubstituted C1-C15 alkoxy group, a substituted or unsubstituted C3-C15 cycloalkoxy group and a substituted or unsubstituted C1-C15 alkylthio group. At least one substituent of the substituted C1-C15 alkyl group, the substituted C2-Ci5 alkenyl group, the substituted C2-Ci5 alkynyl group, the substituted C3-C15 cycloalkyl group, the substituted C1-C15 heterocycloalkyl group, the C1-C15 alkoxy group substituted, the substituted C3-C15 cycloalkoxy group, the substituted C1-C15 alkylthio group, the substituted Cs-Ci5 aryloxy group and the substituted CeC16 arylthio group can be selected from halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a C1-C15 alkyl group, a C2-C15 alkenyl group, a C2-C15 alkynyl group, a C3-C15 cycloalkyl group, a C1-C15 heterocycloalkyl group, a C1-C15 alkoxy group, a C3-cycloalkoxy group C15 and a C1-C15 alkylthio group. In an exemplary embodiment, in Formula 1, at least one substituent of the substituted or unsubstituted C1-C30 heterocyclic group formed by the union of R3 and R4 with the nitrogen of the amide of Formula 1 or at least one O substituent of the compound represented by Formula 2 is IF-2019-01451929-APN-ANP#INPI Page 28 of 160 you can select between -N(Q29)(Q3o), -N-C(=O)(Q29), -N-C(=0)-N(Q29)(Q3o) and N-C(=NH)-N(Q29 )(Q3o), where each of Q29 and Q30 can be independently selected from hydrogen, halogen, a hydroxy group, a C1-C15 alkyl group unsubstituted or substituted with F, Cl, Br or I, a cycloalkyl group C3-C15 unsubstituted or substituted with F, Cl, Br or I, a C2-C15 cycloalkenyl group unsubstituted or substituted with F, Cl, Br or I, a C1-C20 alkoxy group unsubstituted or substituted with F, Cl, Br or I, a C3-Ci5 cycloalkoxy group unsubstituted or substituted with F, Cl, Br or I and a C1-C15 alkylamino group unsubstituted or substituted with F, Cl, Brol. In an exemplary embodiment, the group of the compound represented by Formula 2 may be substituted with at least one substituent to form a compound represented by Formula 3. where, in Formula 3, each of R1, R2, k and m can be defined (aS as identical to those in Formula 1 and each of O and n can be defined as identical to those in Formula 2. In Formula 3, r can be an integer from 0 to 6; when r is 2 or more, at least two R6'(s) may be identical or different from each other, and R6'(s) may be defined as identical to the R6(s) in Formula 2. IF-2019-01451929-APN-ANP#INPI Page 29 of 160 In Formula 3, each R7 can be independently selected from hydrogen, halogen, a hydroxy group, a substituted or unsubstituted C1-C15 alkyl group, a substituted or unsubstituted C1-C15 alkoxy group, a substituted or unsubstituted C3-C15 carbocyclic group substituted and a substituted or unsubstituted C1-C15 heterocyclic group, each of R8 and R9 may be independently selected from hydrogen, halogen, a substituted or unsubstituted C1-C15 alkyl group, a substituted or unsubstituted C1-C15 alkoxy group, a substituted or unsubstituted C3-C15 carbocyclic group and a substituted or unsubstituted C1-C15 heterocyclic group. In an exemplary embodiment, in Formula 1, be C(R5), R5 may be selected from hydrogen, halogen, a hydroxy group, a substituted or unsubstituted C1-C4 alkyl group and a substituted or unsubstituted C1-C4 alkoxy group, R2(s) may be select from hydrogen, halogen, a cyano group, a hydroxy group, a thiol group, a nitro group, a substituted or unsubstituted C1-C15 alkyl group, a substituted or unsubstituted C2-C15 alkenyl group, a C2-C15 alkynyl group substituted or unsubstituted, a substituted or unsubstituted C3C15 carbocyclic group, a substituted or unsubstituted C1-C15 heterocyclic group, a substituted or unsubstituted C1-C15 alkoxy group, a substituted or unsubstituted C3-C15 cycloalkoxy group, an alkylthio group Substituted or unsubstituted C1-C15, a substituted or unsubstituted Ce-C-is aryloxy group, an arylthio group CeIF-2019-01451929-APN-ANP#INPI Page 30 of 160 Substituted or unsubstituted cis, a substituted or unsubstituted C1-C15 heteroaryloxy group, a substituted or unsubstituted C1-C15 heteroarylthio group, -N(Q3)(Q4), C(=O)(Q3), -N-C(= O)(Q3), -N-C(=O)-N(Q3)(Q4), -O-C(=O)(Q3), -S(=O)(Q3), S(=O)2(Q3) , -P(=O)(Q3)(Q4) and -N-C(=NH)-N(Q3)(Q4), ('a') may be a substituted or unsubstituted Ci-C3o heterocyclic group one selected from a piperidinyl group, a pyrrolidinyl group, a piperazinyl group, an azepinyl group, a diazaspirononanyl group, a diazaspirodecanyl group, an azabicycloheptanyl group, an azabicyclooctanyl group, a diazabicyclononanyl group and a diazabicyclodecanyl group, at least one substituent of the substituted Ci-C3o heterocyclic group can be selected between -N(Q5)(Qe), -N-C(=O)(Q5), -N-C(=O)-N(Q5)(Q6) and -N-C(=NH)-N(Q5)( Q6); and a C1-C15 alkyl group, a C2-C15 alkenyl group, a C2-C15 alkynyl group, a C3-C15 carbocyclic group, a C1-C15 heterocyclic group, a C1C15 alkoxy group, a C3-C15 cycloalkoxy group, a C1-C15 alkylthio and a C1-C15 alkylamino group, each substituted with at least one selected from N(Q5)(Q6), -N-C(=O)(Qs), -N-C(=O)-N(Q5 )(Q6), and -N-C(=NH)-N(Q5)(Q6), k can be 0, and m can be an integer from 0 to 2. In an exemplary embodiment, the compound represented by Formula 1 may be a compound represented by Formula 4, an optical isomer, a solvate or a tautomer or a pharmaceutically acceptable salt thereof: Formula 4 IF-2019-01451929-APN-ANP#INPI Page 31 of 160 where, in Formula 4, A may be hydrogen or a C1-C4 alkyl group, each of W(s) may independently be halogen, n may be a natural number between 1 and 4, And it may be a substituted or unsubstituted C3-C6 cycloalkyl group, a substituted or unsubstituted pyrrolidinyl group linked through N, or a substituted or unsubstituted piperidinyl group linked through N, where the substituted Cs-Ce cycloalkyl group can be be a Cs-Ce cycloalkyl group in which at least one hydrogen is substituted with a functional group, each of which is independently selected from halogen and a hydroxy group, and each of the substituted pyrrolidinyl group linked through N and the N-linked substituted piperidinyl group may be an N-linked pyrrolidinyl group and an N-linked piperidinyl group, respectively, in which at least one ring hydrogen atom has been substituted by a functional group, each one of which is independently selected from a C1-C4 alkyl group, halogen, a C1-C4 alkoxy group, a hydroxy group and a C1-C10 heterocyclic group, and Z may be a substituted or unsubstituted pyrrolidinyl group linked through N, a substituted or unsubstituted piperidinyl group linked through N or a IF-2019-01451929-APN-ANP#INPI Page 32 of 160 substituted or unsubstituted azepanyl group linked through N, where at least one substituent of the substituted pyrrolidinyl group linked through N, the substituted piperidinyl group linked through N or the substituted azepanyl group linked through N can be selected from an amino group, a C1-C4 alkylamino group, a Ci-C4 alkyl group:halogen, a C1-C4 alkoxy group and a C1-C10 heterocyclic group. In an exemplary embodiment, in the compound represented by Formula 4, A can be hydrogen, W(s) can be fluorine, n can be the natural number 1, And it may be a substituted or unsubstituted pyrrolidinyl group linked through N or a substituted or unsubstituted piperidinyl group linked through N, where each of the substituted pyrrolidinyl group linked through N and the substituted piperidinyl group linked through N may be a pyrrolidinyl group linked through N and a piperidinyl group linked through N, respectively, in which at least one hydrogen atom of the ring has been replaced by a functional group, each of which is independently selected between a C1-C4 alkyl group, halogen, a C1-C4 alkoxy group and a hydroxy group, and Z may be a substituted piperidinyl group linked through N or an unsubstituted piperidinyl group in which at least one substituent is substituted with a functional group selected from an amino group, a C1-C4 alkylamino group, a C1-C4 alkyl group , halogen and a C1-C4 alkoxy group. IF-2019-01451929-APN-ANP#INPI Page 33 of 160 In an exemplary embodiment of the present disclosure, examples of the compound represented by Formula 1 are described below. Likewise, the scope of the present disclosure may include an isomer, for example, an optical isomer or a tautomer, a solvate or a pharmaceutically acceptable salt of the following compounds: 1) (F?)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(4-cyclop rop i Ife n i I)-1H- pyrazol-5-yl)benzonitrile 2) (R)-4-(1-(4-cyclopropylphenyl)-3-(3-methylaminopiperidine-1-carbonyl)-1Hpyrazol-5-yl)benzonitrile 3) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-cyclopropyl-2-fluorophenyl)1 / 7-pyrazol-5-yl)benzonitrile 4) (R)-4-(1 -(4-cyclopropyl-2-fluorophenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1 H-pyrazol-5-yl)benzonitrile 5) (R)-4-(3-(3-aminopyridine-1-carbonyl)-1-(4-cyclopropyl-2-fluorophenyl)1H-pyrazol-5-yl)-2-fluorobenzonitrile 6) (R)-4-(1 -(4-cyclopropyl-2-fluorophenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1 H-pyrazole-5-ii)benzonitrile 7) (R)-4-(3-(3-aminoazepane-1 -carbonyl)-1 -(4-(cyclopropylphenyl)-1 Hpyrazol-5-yl)benzonitrile 8) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(4-cyclopropyl-2-fluorophenyl)1H-pyrazol-5-yl)-2-fluorobenzonitrile 9) 4-(3-((3R,5R)-3-amino-5-methylpiperidine-1-carbonyl)-1-(4-cyclopropyl-2fluorophenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitride it IF-2019-01451929-APN-ANP#INPI Page 34 of 160 10) (R)-4-(3-(3-aminopiperidine-1-carbonii)-1-(4-cyclopropyl-2,6-difluorophenyl)-1 / - / -pyrazol-5-yl)-2-fluorobenzonitrile 11) (R)-4“(3-(3-aminoazepane-1-carbonyl)-1-(4-cyclopropyl-2,6-difluorophenyl)-1 / - / -pyrazol-5-yl)-2-fluorobenzonitrile 12) (R)-4-(3“(3-aminopiperidine-1-carbonyl)-1-(2-chloro-4-cyclopropylphenyl)1H-pyrazol-5-yl)-2-fluorobenzonitrile 13) (R)4-(3-(3-aminoazepane-1-carbonyl)-1 “(2-chloro-4-cyclopropylphenyl)1 / - / -pyrazol-5-yl)-2-fluorobenzonitrile 14) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-phenyl-1H-pyrazol-5-yl)benzonitrile 15) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(pyridin-2-yl)-1 / 7-pyrazol-5-yl)benzonitrile 16) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-fluorophenyl)-1H-pyrazole-5yl)benzonitrile 17) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(4-chlorophenyl)-1 H-pyrazole-5yl)benzonitrile 18) (R)-4-(1 -(4-chlorophenyl)-3-(3-methylaminopiperidine-1-carbonyl)-1 H-pyrazol-5-yl)benzonitrile 19) (F?)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(3-chlorophenyl)-1H-pyrazol-5yl)benzonitrile 20) (R)-4-(3-(3“aminopiperidine-1-carbonyl)-1-(4-bromophenyl)-1 / - / -pyrazol5-yl)benzonitrile 21) (R)-4-(1 -(4-bromophenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1Hpyrazol-5-yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 35 of 160 22) (S)-4~(3-(3-aminopyrrolidino-1 -carbonyl)-1 -(p-tolyl)-l H-pyrazol-5yl)benzonitrile 23) (S)-4-(3-(3-(methylamino)pyrrolidino-1-carbonyl)-1-(p-tolyl)-lH-pyrazol-5yl)benzonitrile 24) (S)-4-(3-(3-(dimethylamino)pyrrolidino-1-carbonyl)-1 -(p-tolyl)-l / - / -pyrazol5-yl)benzonitriium 25) (R)-4-(3-(3-(dimethylamino)pyrroÍidino-1-carbonyl)-1-(p-tolyl)-1 / 7-pyrazol5-yl)benzonitrile 26) (R)-4-(3-(3-(methylamino)pyrrolidino-1-carbonyl)-1 -(p-tolyl)-l H-pi razo 1-5yl)benzonitrile 27) ( / ?)-4-(3-(3-aminopyrrolidino-1-carbonyl)-1-(p-tolyl)~1 / - / -pyrazol-5-yl)benzonitrile 28) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile 29) (R)-4-(3-(3-(methylamino)piperidine-1-carbonyl)-1-(p-tolyl)-1 / 7-pyrazol-5yl)benzonitrile 30) (R)-4-(3-(3-(dimethylamino)piperidine-1-carbonyl)-1-(p-tolyl)-1H-pyrazol·5-yl)benzonitrile 31) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(m-tolyl)-1 / - / -pyrazol-5yl)benzonitrile 32) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(o-tolyl)-l H-pyrazol-5-yl)benzonitrile 33) ( / ?)“4-(3-(3-aminopiperidine“1-carbonyl)-1-(4-ethylphenyl)-1 / 7-pyrazol-5yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 36 of 160 34) (R)-4-(1 -(4“ethylphenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1 / 7-pyrazol-5-yl)benzonitrile 35) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-isopropylphenyl)-1Hpyrazol-5-yl)benzonitrile 36) (R)-4-(1 -(4-isopropylphenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1Hpyrazol-5-yl)benzonitrile 37) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-isopropylphenyl)1H-pyrazol-5-yl)benzonitrile 38) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(2-f luoro-4-isopropylphenyl)- 1 / - / -pyrazoi-5-yl)-2-fluorobenzonitrile 39) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(2-cyclopropy!-2,6difluorophenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile 40) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(4-(fer-butyl)phenyl)-1 Hpyrazol-5-yl)benzonitrile 41) (R)-4-(1 -(4-(fer-butyl)phenyl-3-(3-methylaminopiperidine-1-carbonyl)-1Hpyrazol-5-yl)benzonitrile 42) (R)-4-(3-(3-aminopiperidine-1-carbonyl)“1-(4-(tert-butyl)-2-fluorophenyl)1 H-p i razol-5-i I) be nzon ¡tri Io 43) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(4-(tert-butyl-2-fluorophenyl)1 / - / -pyrazol-5yl)-2-fluorobenzonitrile 44) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(4-(fer-butyl-2-fluorophenyl)-1 / - / pyrazol-5-yl)-2-fluorobenzonitrile 45) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(trifluoromethoxy)phenyl)-1 / - / pyrazol-5-yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 37 of 160 46) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(methylsulfonyl)phenyl)-1Hpyrazol-5-yl)benzonitrile 47) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(trifluoromethyl)phenyl)-1 / - / pyrazol-5-yl)benzonitrile 48) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-methylphenyl)-1 / 7pyrazol-5-yl)benzonitrile 49) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(3-fluoro-4-methoxyphenyl)-1 / 7pyrazol-5-yl)benzonitrile 50) (R)-4,4'-(3-(3-aminopiperidine-1-carbonyl)-1 / ~ / -pyrazole-1,5-diyl)dibenzonitrile 51) (R)-4-(1 -(4“(dimethylamino)phenyl)-3-(3-(methylamino) pipend ina-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile 52) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-((2- (dimethylamino)ethyl)(methyl)amino)phenyl)-1H-pyrazol-5-yl ) benzonitrile 53) ((R)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(4-(dimethylamino)phenyl)-1 Hpyrazol-5-yl)benzonitrile 54) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(dimethylamino)-2fluorophenyl)-1H-pyrazol-5-yl)benzonitrile 55) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(4-(diethylamino)-2-fluorophenyl)-1H-pyrazol-5-yl)benzonitrile 56) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(azetidin-1-ii)-2-fluorophenyl)-1H-pyrazol-5-yl)benzonitrile 57) (R)-4-(3“(3“aminopiperidine-1 -carbonyl)-1 -(2-f luoro-4-(pyrrolid in-1 ~yl)phenyl)-1 H-pyrazole-5-yl ) benzonitrile IF-2019-01451929-APN-ANP#INPI Page 38 of 160 58) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(2-fluoro-4-(pyrrolidin-1-yl)phenyl)-1 H-pyrazol-5-yl)-2 -fluorobenzonitrile 59) (R)-2-fluoro-4-(1-(2-fluoro-4-(pyrrolidin-1-yl)phenyl)-3-(3(methylamino)pipendin“1-carbonyl)-1 / 7- pyrazoi“5-yl)benzonitol 60) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(2-fluoro-4-(pyrrolidin-1yl)phenyl)-1 H-pyrazol-5-yl)-2- fluorobenzonitrile 61) 4-(3-((R)-3-aminopiperidine-1 -carbonyl)-1 -(2-fluoro-4-((R)-3fluoropyrrolidin-1 -yl)phenyl)-1 H-pyrazole-5 -yl)-2-fluorobenzonitrile 62) 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-((S)-3fluoropyrrolidin-1-yl)phenyl)-1H-pyrazole-5- il)-2-fluorobenzonitrile 63) ( / ?)-4-(3-(3-aminopiperidine-1 -carbonyl)-1-(4-(3,3-difluoropyrrolidin-1 i!)-2-fluorophenyl)-1 / - / -pyrazole -5-yl)-2-fluorobenzonitrile 64) (R)-4-(1 -(4-(3,3-difluoropyrrolidin-1-yl)-2-fluorophenyl)-3-(3- (methylamino)piperidine-1-carbonyl)-1H-pyrazole- 5-yl)-2-fluorobenzonityl 65) 4-(3-((R)-3-aminopipendine-1-carbonyl)-1-(2-fluoro-4-(3methoxypyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2 -fluorobenzonitrile 66) 2-fluoro-4-(1 ~(2-fluoro~4-(3-methoxypyrrolidin-1 -yl)phenyl)-3-(( / ?)-3(methylamino)piperidine-1-carbonyl)-1H -pyrazol-5-yl)benzonitrile 67) 4-(3-(( / ?)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-((S)-3methoxypyrrolidin-1-yl)phenyl)-1 H-pyrazole- 5-yl)-2-fluorobenzonitrile 68) 2-fluoro-4-(1-(2-fluoro-4-((S)-3-methoxy pyrrolidin-1 -yl)phenyl)-3-(( / ?)-3(methylamino)piperidine-1 -carbonyl)-1 / 7-pyrazol-5-yl)benzonitrile 69) 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-((R)-3“ methoxypyrrolidin-1-yl)phenyl)-1 H-pyrazole -5-yl)-2-fluorobenzonitrile IF-2019-01451929-APN-ANP#INPI Page 39 of 160 70) 2-f I uo ro-4-( 1 -(2-fluoro-4-((R)-3-methoxy¡ pyrrolidin-1 -yl)fe n i 1)-3-(( R)-3- (methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonityl 71) 2-fluoro-4-(1 -(2-fluoro-4-((S)-3-ethoxypyrrolidin-1 -yl)phenyl)-3-((R)-3- (methylamino)piperidine-1- carbonyl)-1H-pyrazol-5-yl)benzonityl 72) 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(3-hydroxypyrrolidin-1-yl)phenyl)-1 H-pyrazol-5-yl )-2-fluorobenzonitrile 73) 2-fluoro-4-(1-(2-fluoro-4-((S)-3-chloropyrrolidin-1 -yl)phenyl)-3-((R)-3(methylamino)piperidine-1-carbonyl )-1H-pyrazol-5-yl)benzonitrile 74) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2,6-difluoro-4-(pyrrolidin-1yl)phenyl)-1H-pyrazol-5-yl)-2 -fluorobenzonitrile 75) (R)-4-(3-(3-aminopipendine-1-carbonyl)-1-(2-chloro-4-(pyrrolidin-1yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile 76) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-methoxy-4-(pyrrolidin-1-yl)phenyl)-1 / - / -pyrazol-5-yl )-2-fluorobenzonitrile 77) (R)-4-(3-(3-aminopiperidine-1-carbonii)-1-(2-fluoro-4-(piperidin-1-yl)phenyl)-1 / 7-pyrazol-5-yl) benzonitrile 78) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(piperidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2 -fluorobenzonitrile 79) (R)-2-fluoro-4-(1-(2-fluoro-4-(piperidin-1-yl)phenyl)-3-(3- (methylamino)pipendin-1-carbonyl)“1 / - / -pyrazole“5-yl)benzonitrile 80) 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(3-methylpipendin-1-yl)phenyl)-1H-pyrazol-5-yl) -2-fluorobenzonitrile 81) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(4-methylpiperidin-1-yl)phenyl)-1H-pyrazol-5-yl) -2-fluorobenzonitrile IF-2019-01451929-APN-ANP#INPI Page 40 of 160 82) 4-(3-((R)3-aminopiperidine-1-carbonyl)-1 -(4-(3,5-dimethylpipendin-l-yl)2-fluorophenyl)-1H-pyrazol-5-yl)- 2-fluorobenzonitrile 83) (R)-4-(1 -(4-([1,4'-bipiperidino]-1'-yl)-2-fluorophenyl)-3-(3-aminopiperidine-1-carbonyl)-1 / 7 -pyrazol-5-yl)-2-fluorobenzonitol 84) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(2-fluoro-4-(piperidin-1yl)phenyl)-1 H-pyrazol-5-yl)-2- fluorobenzonitrile 85) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(1-methyl-1H-indazol-6-yl)- / 7-pyrazol-5-yl)benzonitrile 86) ( / ?)-4-(3-(3-aminopiperidine-1-carbonyl)-1~(2-methylbenzo[c(|thiazol-5-yl)1H-pyrazol-5-yl)benzonitrile 87) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2,3-dihydro-1H-indan-5-yl)1 H-pyrazol-5-yl)benzonitrile 88) (F?)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2,3-dihydro-1 / - / -inden-5-yl)1H-pyrazol-5“yl) -2-fluorobenzonitrile 89) (R)-4-(1-(2,3-dihydro-1H-inden-5-yl)-3-(3-(methylamino)piperidine-1carbonyl)-1 H-pyrazol-5-yl)benzonitrile 90) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2,3dihydrobenzo[b][1,4]dioxin-6-yl)-1 H-pyrazole-5-iS ) benzonitrile 91) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(quinolin-6-yl)-1 / - / -pyrazol-5yl)benzonitrile 92) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(quinolin-3-yl)-1 / - / -pyrazol-5yl)benzonitrile 93) ( / ?)-4-(3-(3-aminopiperidine-1-carbonyl)-1 -(1 -methyl-1 H-pyrrolo[2,3b]pyridin-5-yl)-1 H-pyrazole- 5-yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 41 of 160 94) ( / ?)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(2-hydroxy¡-2methylpropyl)phenyl)-1H-pyrazol-5-yl) -2-fluorobenzonitrile 95) 4-(3-(piperazine-1 -carbonyl)-1 -(p-tol i I)-1 H-p i razol-5-i l)be nzo n ytri Io 96) 4-(3-(3-(aminomethyl)piperazine-1-carbontl)-1-(p-tolyl)-1 / - / -pyrazole-5yljbenzonitol 97) (S)-5-(4-cyanophenyl)- / V-(1 -(methylsulfonyl)piperid in-3-yl)-1 -(p-tolyl)-l Hpyrazole-3-carboxamide 98) 4-(3-(2,7-diazaspiro[3.5]nonane-7-carbonyl)-1-(p-tolyl)-1H-pyrazol-5yl)benzonitrile 99) 4-(3-(2,8-diazaspiro[4.5]decane-8-carbonyl)-1-(p-tolyl)-1H-pyrazol-5yl)benzonitrile 100) 4-(3-(octahydro-1H-pyrrolo[2,3-c]pyridino-6-carbonyl)-1-(p-tolyl)-1Hpyrazol-5-yl)benzonitrile 101) 4-(3-(3,7-diazabicyclo[3.3.1]nonane-3-carbonyl)-1-(2-fluoro-4-isopropylphenyl)-1 H-pyrazol-5-yl)-2-fluorobenzonitrile 102) 4-(3-(3-amino-8-azabicyclo[3,2.1]octane-8-carbonyl)-1-(2-fluoro-4-isopropylphenyl)-1H-pyrazol-5-yl)-2- fluorobenzonitrile 103) 4-(3-(3-amino-8-azabicyclo[3.2.1]octane-8-carbonyl)-1 -(2-fluoro-4-pyrrolidin-1-yl)phenyl-1 H-pyrazole-5 -yl)-2-fluorobenzonitrile 104) 4-(3-(3,7-diazabicyclo[3.3.1]nonane-3-carbonyl)-1-(p-tolyl)-1 H-pyrazol5-yl)benzonitrile 105) 5-(4-cyanophenyl)-A / -(piperidin-4-yl)-1-(p-tolyl)-1 H-pyrazole-3-carboximide 106) 5-(4-cyanophenyl)- / V-(1 -methylpiperidin-4-yl)-1 -(p-tolyl)-l H-pyrazole-3carboximide IF-2019-01451929-APN-ANP#INPI Page 42 of 160 107) ( / ?)-5-(4-cyanophenyl)- / \ / -(1 -methylpiperidin-3-yl)-1-(p-tolyl)-1 H-pyrazole-3carboximide 108) (S)-5-(4-cyanophenyl)- / \ / -(1 -methylpiperidin-3-yl)-1 -(p-tolyl)-l H-pyrazole-3carboximide 109) (R)-5“(4-cyanophenyl)- / V-(1 -methylpyrrolidin-3-yl)-1-(p-tolyl)-1 H-pyrazole-3-carboximide 110) 5-(4-cyano-3-fluorophen¡I)-1 ~(2“fluoro-4-(pyrrolidin-1 -yl)phenyl)-A / -methyl- / \ / (piperidin-3-yl) -1H-pyrazole-3-carboximide 111) (S)-5-(4-cyano-3-fluorophenyl)-1 -(2-f luoro-4-(pyrrolid in-1 -yl)phenyl)- / \ / - methyl4V“(piperidin-3 -yl)-1H-pyrazole-3-carboximide 112) (R)5(4-cyano-3-fluorophenyl)-1 -(2-fluoro-4-(pyrrolidin-1 -yl)phenyl)-A / methyl-A / -(piperidin-3-yl)- 1 / - / -pyrazole-3-carboximide 113) ( / ?)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-cyclopropyl-2-fluorophenii)-4-methyl-1 H-pyrazol-5-yl)benzonitrile. In an exemplary embodiment, examples of the compound represented by Formula 4 include Compounds 5), 6), 8) to 13), 58) to 75), and 78) to 84) of the compound represented by Formula 1 and an optical isomer, a solvate, a tautomer or a pharmaceutically acceptable salt thereof. Another aspect of the present disclosure provides a pharmaceutical composition for preventing or treating a disease caused by abnormal activation of lysine-specific demethylase-1 (LSD1), wherein the pharmaceutical composition includes the compounds represented by Formulas 1 to 4, a optical isomer, a solvate, a tautomer or a salt pharmaceutically IF-2019-01451929-APN-ANP#INPI Page 43 of 160 acceptable of these as an active ingredient; and a pharmaceutically acceptable carrier. The term "isomer", as used herein, refers to different compounds that have the same molecular formula but differ in the arrangement and coordination of atoms and includes structural isomers and stereoisomers. The term "structural isomer", as used herein, refers to a compound that has the same molecular formula but has a different order in the arrangement of atoms. “Tautomer” is one of the structural isomers, which refers to a compound that interconverts into both isomers and whose structure changes. The term "stereoisomer", as used herein, refers to any of the various stereoisomeric coordinations that may exist for a compound of the present disclosure and includes geometric isomers and optical isomers. The term "diastereomer," as used, refers to stereoisomers that have at least two asymmetric atoms and are not mirror images of each other. The term "geometric isomers", as used herein, refers to isomers in which a spatial position of an atom or a functional group attached to a carbon atom of a double bond in a planar structure that has a double bond between carbon atoms is different. The term "optical isomer", as used herein, refers to any of the various stereoisomeric coordinations that may exist. IF-2019-01451929-APN-ANP#INPI Page 44 of 160 for a compound of the present disclosure and includes geometric isomers. Since the compounds of Formulas 1 to 4 of the present disclosure may have a center of an asymmetric carbon (asymmetric carbon), the compounds of Formulas 1 to 4 according to one aspect of the present disclosure may have the shape of a enantiomer (R or S isomer), racemate, diastereomer or any mixture of these. All of these isomers and mixtures are included in the scope of the present disclosure. The term "enantiomer", as used herein, refers to a pair of stereoisomers that are mirror images of each other and not superimposable. A pair of enantiomers with a 1:1 mixing ratio is called a “racemic” mixture. The term "solvate", as used herein, can include a molecular complex that includes the compound and at least one molecule of pharmaceutically acceptable solvent, for example, ethanol or water. The term “pharmaceutically acceptable salts,” as used herein, refers to a salt that maintains the biological properties and efficacy according to the present disclosure and is not undesirable from a biological or other point of view. For example, the salt may include a base addition salt or a nontoxic organic or inorganic acid addition salt, but the embodiments are not limited to these. In an exemplary embodiment, to prevent or treat a disease caused by abnormal activation of LSD1, the pharmaceutical composition can be used in combination with an additional pharmaceutically acceptable drug. In an exemplary embodiment, the IF-2019-01451929-APN-ANP#INPI Page 45 of 160 pharmaceutical composition formulated in a pharmaceutically acceptable form includes a tablet, a lozenge, powder, a capsule, syrup, emulsion and microemulsion. Herein, LSD1, which may be related to an important histone modification, is an enzyme that plays a key role from the point of view of epigenetics in terms of the mechanism of transcription regulation. . LSD1 includes an N-terminal SWIRM domain (Swi3p, Rsc8p and Moira), as a result of selective splicing there may be two types of LSD1 transcript variants present, and LSD1 may have structural similarity and amino acid uniformity / homogeneity with polyamine oxidases and monoamine oxidase (MAO). Likewise, LSD1 demethylates H3K4, and simultaneously suppresses transcription and demethylates H3K9 to activate gene expression of a nuclear hormone receptor complex (e.g., androgen receptor). This suggests that LSD1 may regulate alternative gene expression in a situation-dependent manner, just as the substrate specificity of LSD1 is determined by related factors. Additionally, as cancer cells divide and grow rapidly, blood vessels become compressed within a solid tumor, creating a low-oxygen environment. Expression of the hypoxia-induced factor-1 (HIF-1) protein, which is known to promote the development of cancer metastasis in such a low-oxygen environment, may be regulated by LSD1 in a methylation-dependent manner. . LSD1 may also participate in the activation of some proteins such as E2F, STAT3, Tat and the IF-2019-01451929-APN-ANP#INPI Page 46 of 160 subset 1 that targets myosin phosphatase (MYPT1), which are not histones, and such as p53 and DNMT1, which play an important role in cancer. This suggests a mechanism of tumorigenesis due to a problem in the regulation of chromatin remodeling due to LSD1. Furthermore, LSD1 can increase the activity of another epigenetic regulator, for example, DNA-methyltransferase 1 (DNMT1) and histone deacetylase (HDAC) complexes. LSD1 may also contribute to various biological processes, including cell proliferation, epithelial-mesenchymal transition (EMT), and stem cell biology (cancer stem cells and embryonic stem cells) or cell self-renewal and transformation. somatic. Furthermore, since LSD1 contributes to tumorigenesis by altering epigenetic markers on histone- and nonhistone-like proteins, aberrant activation of LSD1 can lead to several types of cancer. According to the result of Experimental Example 1 described herein, it was observed that the compounds represented by Formulas 1 to 4 have significant enzymatic activity of suppressing the effects of LSD1. Likewise, as described above, since LSD1 contributes to tumorigenesis by altering epigenetic markers in histone and non-histone proteins, the suppression activity of LSD1 can normalize gene expression, and thus induce a differentiation program for obtain mature cell type, reduce cell proliferation and promote apoptosis of cancer cells. Therefore, the IF-2019-01451929-APN-ANP#INPI Page 47 of 160 compounds represented by Formulas 1 to 4 can be used to prevent or treat various diseases caused by abnormal activation of LSD1. In an exemplary embodiment, the pharmaceutical composition may include a pharmaceutically acceptable excipient, vehicle or additive. The pharmaceutical composition of the present disclosure can be formulated according to a conventional method and can be formulated into various oral pharmaceutical forms such as a tablet, a lozenge, powder, a capsule, syrup, emulsion and microemulsion; or in parenteral dosage forms, for example, for intramuscular, intravenous or subcutaneous administration. When the pharmaceutical composition of the present disclosure is prepared in the form of an oral formulation, examples of additives or vehicles that can be used include cellulose, calcium silicate, corn starch, lactose, sucrose, dextrose, calcium phosphate, stearic acid , magnesium stearate, gelatin, talc, a surfactant, a suspension, an emulsifier and a diluent. When the pharmaceutical composition of the present disclosure is prepared in the form of an injection, examples of additives or vehicles may include water, saline, aqueous glucose solution, pseudosaccharide solution, alcohol, glycol, ether (for example, polyethylene glycol 400) , oil, fatty acid, fatty acid ester, glyceride, a surfactant, a suspension and an emulsifier. The dose of the pharmaceutical composition as an active ingredient is an effective amount to carry out treatment or prevention in a subject or a IF-2019-01451929-APN-ANP#INPI Page 48 of 160 patient. The compound can be administered orally or parenterally, as desired. When the compound is administered orally, the active ingredient can be administered in an amount within the range between 0.01 milligrams (mg) and 1000 mg, more especially, between 0.1 mg and 300 mg per kilogram (kg) of body weight per day. When the compound is administered parenterally, the active ingredient can be administered one to several times in an amount within the range between 0.01 mg and 100 mg, more especially, between 0.1 mg and 50 mg per kg of weight. body a day. The dose for a specific subject or patient should be determined taking into account the weight, age, sex, and health status of the patient, diet, time of administration, method of administration, severity of the disease, etc. It should be understood that the doctor can appropriately adjust the dosage. The dosage is not intended to limit the scope of the present disclosure in any way. Yet another aspect of the present disclosure provides a method of treating a disease caused by abnormal activation of LSD1, wherein the method includes administering to a subject a therapeutically effective amount of the compounds represented by Formulas 1 to 4, an optical isomer, a solvate or tautomer or a pharmaceutically acceptable salt thereof. The details of the prevention or treatment method may be the same as those described above in reference to the pharmaceutical composition according to one aspect of the present disclosure. Likewise, the dose used in the prevention or treatment method is an amount effective in the treatment or prevention of a IF-2019-01451929-APN-ANP#INPI Page 49 of 160 subject or a patient. The dosage of the pharmaceutical composition can be applied without any change. The terms "treat" or "treatment", as used herein, refer to the inhibition of a disease, for example, to the inhibition of a disease, condition or disorder in a subject who has experienced or exhibited a pathology or a symptom of the disease, condition or disorder. In other words, the terms "treat" or "treatment" refer to the prevention of further occurrence of a pathology and / or symptom or the improvement of a disease, for example, the improvement of a disease, condition or disorder in a subject who has experienced or shown a pathology or a symptom of the disease, condition or disorder. In other words, the terms “treat” or “treatment” refer to the alleviation of a pathology and / or a symptom, for example, reducing the severity of the disease. The terms "prevent" or "prevention", as used herein, refer to the prevention of a disease, for example, to the prevention of a disease, condition or disorder in a subject who may be predisposed to suffering from the disease. disease, condition or disorder but who has not yet experienced or shown a pathology or symptom of the disease. The terms "subject" or "patient" as used herein refer to any animal, including mammals, for example, mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep. , horses or primates and humans. IF-2019-01451929-APN-ANP#INPI Page 50 of 160 A method for preparing the compounds of the present disclosure will be described in detail hereinafter. Each of the abbreviations used in the following Preparation Examples, Preparation Methods and Examples indicate: P(C6Hh)3: tricyclohexylphosphine Pd(OAc)2: palladium acetate K2CO3: potassium carbonate PtO2: platinum oxide NaNO2: sodium nitrite LiOH H2O: lithium hydroxide SnCb: tin(II) chloride HATU: (2-(1 / 7-9-azabenzotriazol-1-yl)-1,1,3,3tetramethyluronium hexafluorophosphate) TFA: tñfluoroacetic acid HOBt: / V-hydroxybenzotriazole EDCI: 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide Mel: iodomethane DIPEA: / V, / V-diisopropylethylamine THF: tetrahydrofuran DMSO: dimethyl sulfoxide AE: ethyl acetate 1,4-dioxane: 1,4-dioxane CH2CI2: dichloromethane Na2SO4:anhydrous sodium sulfate IF-2019-01451929-APN-ANP#INPI Page 51 of 160 The synthesis of a pyrazole derivative according to the present disclosure can be carried out using an intermediate prepared in Reaction Scheme 1 or Reaction Scheme 2 or using an intermediate of commercial origin. Mass analysis of the pyrazole derivative obtained was performed using the MicroMass ZQ™ which can be obtained from Waters. A pharmaceutical composition that includes as active ingredient the compounds represented by Formulas 1 to 4 synthesized according to the method of preparation, an optical isomer, a solvate, a tautomer or a pharmaceutically acceptable salt thereof, can be used in the prevention and the treatment of a disease that can be treated by regulating LSD1. A method for preparing the compounds represented by Formulas 1 to 4 can be shown as Reaction Schemes 1 and 2. Reaction scheme 1 (O compound 1 (H) »(^65 stepl2)step 2m(R2)compound 2 where, in Formula 1, B, R1, R2, k and m may be identical to those defined in Formula 1. IF-2019-01451929-APN-ANP#INPI Page 52 of 160 The steps of the method will be described in detail according to an exemplary embodiment. (Yo) Between 1 and 2 equivalents of sodium ethoxide were dissolved in ethanol and the mixture was cooled to a temperature within the range between 0 °C and 5 °C. To this, 2 to 3 equivalents of diethyl oxalate were added dropwise over 30 minutes. To this was added dropwise 1 equivalent (standard equivalent) of a 4-acetylbenzonitrile type derivative in ethanol at a temperature within the range between 0 °C and 5 °C. Its internal temperature was raised to room temperature and the mixture was stirred overnight. Once the reaction was complete, the solvent was removed from the mixture under reduced pressure and water was added to it. The resulting mixture was titrated with an aqueous HCl solution to a pH within the range between 2 and 3 and an organic phase was extracted using ethyl acetate. The organic phase was washed with soft water, dried using anhydrous sodium sulfate and concentrated under reduced pressure. Methyl ether butyl ether was added to the residue and the solid formed was filtered under reduced pressure to obtain the desired compound. (Il-Step 1) 1 equivalent (standard equivalent) of the nitrosubstituted compound, i.e. a compound substituted with a nitro group, was dissolved in a mixture of tetrahydrofuran and ethanol with a mixing ratio of 1:1. To this was added a platinum catalyst or a palladium catalyst, and then it was stirred overnight at room temperature in a IF-2019-01451929-APN-ANP#INPI Page 53 of 160 hydrogen atmosphere. Once the reaction had finished, filtration was carried out through celite under reduced pressure for concentration and in this way the desired compound was obtained. (I I-Step 2) 1 equivalent (standard equivalent) of the amino group-substituted compound synthesized in ll-Step 1 was dissolved in an aqueous HCl solution and the solution was cooled to a temperature between 0 °C and 5 °C. To this, between 1 and 2 equivalents of an aqueous solution of sodium nitrite were slowly added dropwise, and then stirred at a temperature of between 0 °C and 5 °C for between 1 and 3 hours, to form this way a diazonium salt. To this, between 2 and 3 equivalents of tin (II) chloride dissolved in an aqueous solution of HCl were slowly added dropwise at a temperature between 0 °C and 5 °C. Its reaction temperature was raised to room temperature and the mixture was stirred. Once the reaction was complete, the solid formed was subjected to filtration and the resulting product was washed with water and ether, and then dried under vacuum to obtain the desired compound. Reaction scheme 2 compound 2 O OH jQr^ compound 1 step 3 step 2 step 4 Formula 2 IF-2019-01451929-APN-ANP#INPI Page 54 of 160 where, in Reaction Scheme 2, A, B, X, R1, R2, R6, k, m and n are defined as identical to those in Formula 1 or 2. In Reaction Scheme 2, the amine protecting group (PG) can be butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), 9-fluorenylmethoxycarbonyl (Fmoc), acetyl, benzoyl or tosyl. The steps of the method will be described in detail according to an exemplary embodiment. Step 1) 1 equivalent of Compound 1 and 1 equivalent (standard equivalent) of Compound 2 were dissolved in ethanol. To this, 1 equivalent of hydrochloric acid dissolved in dioxane was added and the temperature was raised to between 50 °C and 70 °C. Once the reaction was complete, the temperature was reduced to room temperature. The solid formed was subjected to filtration under reduced pressure and washed with cooled ethanol, in order to obtain the desired compound. Step 2) 1 equivalent (standard equivalent) of the compound synthesized in Step 1 was dissolved in a mixture of tetrahydrofuran and water mixed in a ratio of 1:1. To this, between 3 and 5 equivalents of lithium hydroxide were added and then stirred at room temperature. Once the reaction was complete, the mixture was titrated with an aqueous HCl solution to a pH within the range between 2 and 3 and the ethanol was removed from the mixture by distillation under reduced pressure. The solid formed was subjected to IF-2019-01451929-APN-ANP#INPI Page 55 of 160 filtration under reduced pressure, in order to obtain the desired compound. Step 3) 1 equivalent (standard equivalent) of a carbonic acid derivative synthesized in Step 2 was dissolved in dichloromethane, then 2 to 3 equivalents of HATU and 3 to 5 equivalents of DIPEA were added. The reaction mixture was stirred at room temperature and 1 equivalent of an A-ring substituted amine was added. The mixture was stirred at room temperature. Once the reaction was complete, dichloromethane and water were added to the reaction mixture. An organic phase was then separated from it. The organic phase was washed with soft water, dried using anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the desired compound. Step 4) 1 equivalent (standard equivalent) of the PG-protected carbamate derivative synthesized in Step 3 was dissolved in dichloromethane. Trifluoroacetic acid was added to this and then stirred at room temperature. Once the reaction was complete, water was added to the reaction mixture. An organic phase was then extracted using dichloromethane and separated. The organic phase was washed with soft water, dried using anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to obtain the desired compound. IF-2019-01451929-APN-ANP#INPI Page 56 of 160 The compounds represented by Formulas 1, 3 and 4 were also obtained in a manner similar to the preparation of the compound represented by Formula 2. The method of synthesis of the compounds represented by Formulas 1 to 4 is not limited to the method described in the present. One skilled in the field of organic chemistry can prepare these compounds using various methods known in the art. Although the method has been described by specific examples herein, the specific reaction conditions, such as an amount of a reaction solvent, a base and a reagent to be used, are not limited to those described herein. descriptive and should not be considered limiting the scope of this disclosure. The present disclosure will now be described in more detail with reference to the following Preparation Examples and Examples. However, these Preparation Examples and Examples are intended to assist in understanding the present disclosure and the scope of the present disclosure is not limited to these in any way. Preparation example 1: Preparation of ethyl (Z)-4-(4-cyanophenyl)-2hydroxy-4-oxo-2-butenoate compound 1 9.4 grams (g, 137.7 millimole (mmol)) of sodium ethoxide were dissolved in 150 milliliters (mL) of ethanol and then cooled to a IF-2019-01451929-APN-ANP#INPI Page 57 of 160 temperature within the range between 0 °C and 5 °C. 18.7 mL (137.7 mmol) of diethyl oxalate was added dropwise over 30 minutes. To this, 10 g (68.9 mmol) of 4-acetylbenzonitrile in 50 mL of ethanol were added dropwise for 30 minutes at a temperature within the range between 0 °C and 5 °C. Its internal temperature was raised to room temperature and the mixture was stirred overnight. Once the reaction was complete, the solvent was removed from the mixture under reduced pressure. Next, 100 mL of water was added to this. The resulting mixture was titrated with a 1 N aqueous HCl solution to a pH in the range between 2 and 3 and an organic phase was extracted twice using ethyl acetate. The organic phase was washed with soft water, dried using anhydrous sodium sulfate and concentrated under reduced pressure. 100 mL of methyl fer-butyl ether was added to the residue to form a solid. The solid formed was subjected to filtration under reduced pressure to obtain 9.0 g of the desired compound (yield: 53%). 1H-NMR (300 MHz, CDCIs): δ 8.07 (d, 2H), 7.81 (d, 2H), 7.07 (s, 1H), 4.38 (c, 2H), 1.42 (t, 3H) Preparation example 2: Preparation of (4cyopropylphenylhydrazine hydrochloride zU10;pH PdíOAcií, K2C03PtOz.Hi 1, HCl, H20 ^ILu [I Ί+p-B __:___2__:__► ► (I J2 Br'-' OH 2. HCF, SnCI2, H20HCI compound 2 Step 1) Preparation of 1-cyclopropyl-4-nitrobenzene ^NO2N. „0HPd(OAc)2, K2C03<V° JI J + P>-B JFz) OH\7 IF-2019-01451929-APN-ANP#INPI Page 58 of 160 3.0 g (14.9 mmol) of 4-bromonitrobenzene and 1.7 g (19.4 mmol) of cyclopropylboronic acid were dissolved in 40 mL of toluene and 4 mL of water. To this were added 133 mg (0.6 mmol) of palladium acetate (Pd(OAc)2), 418 mg (1.49 mmol) of tricyclohexylphosphine (P(CeHii)3) and 6.8 g (49, 2 mmol) potassium carbonate (K2CO3). A purge was performed with argon gas for 30 minutes, heated to a temperature within the range between 100 °C and 110 °C and then allowed to react for three hours. Once the reaction was complete, filtration was carried out through celite under reduced pressure for concentration. The residue obtained by concentration was purified by column chromatography (ethyl acetate:hexane = 1:9 (v / v)), to obtain 2.1 g of the desired compound (yield: 86%). 1H-NMR (300 MHz, CDCI3): δ 8.09 (d, 2H), 7.17 (d, 2H), 1.96 (m, 1H), 1.12 (m,2H), 0.82 (m, 2H) Step 2) Preparation of 4-cyclopropylaniline 2.1 g (12.8 mmol) of 1-cyclopropyl-4-nitrobenzene was dissolved in 20 mL of tetrahydrofuran and ethanol with a mixing ratio of 1:1. To this was added 200 mg of a platinum catalyst (PtO2), then stirred overnight at room temperature in a hydrogen atmosphere. Once the reaction had finished, filtration was carried out through celite under reduced pressure for concentration and in this way 1.3 g of the desired compound was obtained (yield: 76%). IF-2019-01451929-APN-ANP#INPI Page 59 of 160 1H-NMR (300 MHz, CDCI3): δ 6.97 (d, 2H), 6.57 (d, 2H), 3.52 (s a, 2H), 1.82 (m, 1H), 0.84 (m, 2H), 0.58 (m, 2H) Step 3) Preparation of (4-cyclopropylphenyl)hydrazine hydrochloride NH21. HCl, NaNO?, H20 ' 0 ΊNH2 2, HCI, SnCI2, H20 HCI 1.3 g (9.76 mmol) of 4-cyclopropylaniline was dissolved in a 6 N HCl aqueous solution, and then cooled to a temperature within the range between 0 °C and 5 °C. To this, 6mL of an aqueous solution of 673 mg (9.76 mmol) of sodium nitrite (NaNO2) was slowly added dropwise and then stirred at a temperature within the range between 0 °C and 5 °C for 1 hour, to thus form a diazonium salt. To this, 4.63 g (24.4 mmol) of tin (II) chloride (SnCl2) dissolved in 20 mL of conc. HCl were added dropwise. for 30 minutes at a temperature within the range between 0 °C and 5 °C. The reaction temperature was raised to room temperature and then stirred for 5 hours. Once the reaction was complete, the solid formed was subjected to filtration and the resulting product was washed with water and ether, and then dried under vacuum to obtain 1.1 g of the desired compound (yield: 76 %). Ή-NMR (300 MHz, DMSO-c / 6): δ 10.21 (s a, 2H), 8.11 (s a, 1H), 6.99 (d, 2H), 6.89 (d, 2H) , 1.82 (m, 1H), 0.86 (m, 2H), 0.58 (m, 2H) Example 1: Preparation of ( / ?)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4cyclopropylphenyl)-1 H-pyrazol-5-yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 60 of 160 Step 1) Preparation of ethyl 5-(4-cyanophenyl)-1-(4-cyclopropylphenyl)-1H-pyrazole3-carboxylate 300 mg (1.22 mmol) of ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-4oxobut-2-enolate and 181 mg (1.22 mmol) of (4-cyclopropylphenyl)hydrazine were dissolved in a solution in 10 mL of ethanol. To this was added 0.3 ml_ (1.22 mmol) of 4 N HCl in dioxane and then the temperature was raised to 50 °C. The mixture was stirred overnight at a temperature of 50 °C. Once the reaction was complete, the temperature was reduced to room temperature. The solid formed was subjected to filtration under reduced pressure and the result was washed with 10 mL of cooled ethanol, thus obtaining 115 mg of the desired compound (yield: 26%). 1H-NMR (300 MHz, CDCI3): δ 7.58 (d, 2H), 7.34 (d, 2H) 7.12 (d, 2H), 7.04 (m, 3H), 4.43 ( c, 2H), 1.93 (m, 1H), 1.45 (t, 3H), 0.97 (m, 2H), 0.70 (m, 2H) Step 2) Preparation of 5-(4-cyanophenyl)-1-(4-cyclopropylphenyl)-1Hpyrazole-3-carboxylic acid IF-2019-01451929-APN-ANP#INPI Page 61 of 160rN O thf,h2o** ι-Ν 9s)“A 115 mg (0.32 mmol) of ethyl 5-(4-cyanophenyl)-1-(4cyclopropylphenyl)-1H-pyrazole-3-carboxylate were dissolved in 10 mL of a mixture of tetrahydrofuran and water with a mixing ratio of 1:1. To this was added 41 mg (0.97 mmol) of lithium hydroxide (LIOHH2O) and then stirred at room temperature for 6 hours. Once the reaction was complete, the mixture was titrated with a 1 N aqueous HCl solution to a pH in the range between 2 and 3 and ethanol was removed from the mixture by distillation under reduced pressure. The solid formed was subjected to filtration under reduced pressure to obtain 110 mg of the desired compound (yield: 97%). 1H-NMR (300 MHz, CDCh): δ 7.63 (d, 2H), 7.33 (d, 2H) 7.16 (d, 2H), 7.04 (m, 3H), 1.90 ( m, 1H), 1.02 (m, 2H), 0.71 (m, 2H) Step 3) Preparation of tert-butyl (R)-(1-(5-(4-cyanophenyl)-1-(4-cyclopropylphenyl)-1 / - / pyrazole-S-carboniOpiperidin-S-iDcarbamate -NO HN-x Boc 110 mg (0.35 mmol) of 5-(4-cyanophenyl)-1-(4cyclopropylphenyl)-1H-pyrazole-3-carboxylic acid were dissolved in 2 mL of dichloromethane and then 200 mg (0.53 mmol) of HATU and 0.18 mL (1.05 mmol) of DIPEA. The reaction mixture was stirred at room temperature for 30 minutes and then 69 mg (0.35 mmol) of (R)-piperidin-3-tertylcarbamate was added. IF-2019-01451929-APN-ANP#INPI Page 62 of 160 butyl. The mixture was stirred at room temperature for 12 hours. Once the reaction was complete, dichloromethane and water were added to the reaction mixture and an organic phase was then separated from it. The organic phase was washed with soft water, dried using anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was purified using column chromatography (dichloromethane:methanol = 20:1 (v / v)), to obtain 70 mg of the desired compound (yield: 89%). 1H-NMR (300 MHz, DMSO-d6): δ 7.61 (d, 2H), 7.33 (d, 2H), 7.16 (m, 2H), 7.00 (m, 3H), 5 .45 (m, 1H), 4.99 (m, 2H), 3.69 (m, 2H), 1.84 (m, 4H), 1.59 (s, 9H), 1.50 (m, 2H), 0.94 (m, 2H), 0.72 (m, 2H) Step 4) Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4cyclopropylphenyl)-1H-pyrazol-5-yl)benzonitrile 70 mg (0.25 mmol) of (R)-(1-(5-(4-cyanophenyl)-1-(4-cyclopropylphenyl)-1H-pyrazole-3-carbonyl)piperidine-3-yl)carbamate were dissolved -butyl in 6 mL of dichloromethane. To this, 1 mL of trifluoroacetic acid (TFA) was added and then stirred at room temperature for 3 hours. Once the reaction was complete, water was added to the reaction mixture. An organic phase was then extracted using dichloromethane and separated therefrom. The organic phase was washed with soft water, dried using anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was purified using column chromatography (dichloromethane:methanol = 10:1 (v / v)), to IF-2019-01451929-APN-ANP#INPI Page 63 of 160 obtain in this way 50 mg of the desired compound (yield: 37%). 1H-NMR (300 MHz, DMSO-d6): 7.82 (d, 2H), 7.41 (d, 2H) 7.13 (m, 4H), 7.04 (m, 1H), 4.27 (m, 2H), 3.13 (m, 3H), 2.74 (m, 2H), 1.94 (m, 1H), 1.89 (m, 2H), 1.70 (m, 2H) , 0.99 (m, 2H), 0.68 (m, 2H) MS (ESI+): [M+H]+m / z 412.2, Example 2: Preparation of (R)-4-(1-(4-cyclopropylphenyl)-3-(3methylaminopiperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that fer-butyl (R)~methyl(piperidin-3-yl)carbamate was used in Step 3) of Example 1 instead of tert-butyl (R)-piperidin-3ylcarbamate. 1H-NMR (300 MHz, CDCI3): 7.62 (d, 2H), 7.33 (d, 2H), 7.10 (m, 4H), 6.97 (d, 1H), 4.48 ( m, 2H), 3.21 (m, 2H), 2.67 (m, 1H), 2.47 (d, 3H), 2.01 (m, 1H), 1.92 (m, 2H), 1.61 (m, 2H), 1.02 (m 2H), 0.73 (m, 2H). MS (ESI+): [M+H]+m / z 372.2 Example 3: Preparation of (R)-4-(3-(3~aminopiperidine-1-carbonyl)-1-(4cyclopropyl-2-fluorophenyl)-1 / - / -pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 IF-2019-01451929-APN-ANP#INPI Page 64 of 160 used (4-cyclopropyl-2-fluorophenyl)hydrazine hydrochloride instead of (4-cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 7.59 (d, 2H), 7.32 (m, 3H), 6.96 (m, 2H), 6.77 (d, 1H), 4.43 (m, 2H), 3.21 (m, 3H), 1.90 (m, 3H), 1.42 (m, 2H), 1.07 (m, 2H), 0.75 (m, 2H) MS (ESI4*): [M+H]+m / z 430.2 Example 4: Preparation of (R)-4-(1-(4-cyclopropyl-2-fluorophenyl)-3-(3(methylamino)piperidine-1-carbonyl)-1 / 7-pyrazol-5-yl)benzon trilo The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (4-cyclopropyl-2-fluorophenyl)hydrazine hydrochloride was used instead of (4-cyclopropyl-2-fluorophenyl)hydrazine hydrochloride. cyclopropylphenyl)hydrazine and in Step 3) of Example 1 ( / ?)methyl(piperidin-3“yl)fer-butylcarbamate was used instead of (R)-piperidin-3ylcarbamate of fer-butyl. 1H-NMR (300 MHz, CDCI3): δ 7.64 (d, 2H), 7.37 (m, 3H), 6.98 (m, 2H), 6.77 (d, 1H), 4.52 (m, 2H), 3.24 (m, 2H), 2.72 (m, 1H), 2.48 (d, 3H), 1.94 (m , 2H), 0.75 (m, 2H) MS (ESI1 * * 4-): [M+H]+m / z 444.2 IF-2019-01451929-APN-ANP#INPI Page 65 of 160 Example 5: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4cyclopropyl-2-fluorophenyl)-1 / - / -pyrazol-5-yl)-2-fluorobenzonitride it The desired compound was obtained in substantially the same manner as in Example 1, except that (Z)4“(4-cyano-3-fluorophenyl)-2-hydroxy-4 was used in Step 1) of Example 1 -ethyl oxo-2-butenoate instead of ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxo-2-butenoate and (4-cyclopropyF2-fluorophenyl)hydrazine hydrochloride was used in instead of (4cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 7.54 (t, 1H), 7.31 (m, 1H), 7.10 (m, 2H), 7.08 (m, 2H), 6.78 (d, 1H), 4.17 (m, 2H), 3.72 (m, 1H), 3.56 (m, 1H), 3.31 (m, 1H), 1.84 (m,4H) , 1.11 (m, 1H), 0.75 (m, 2H) MS (ESI+): [M+HJ* m / z 448.2 Example 6: Preparation of (R)-4-(1-(4-cyclopropyl-2-fluorophenyl)-3-(3“ (methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)-2- fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy- was used in Step 1) of Example 1. ethyl 4-oxobut-2-enolate instead of ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut-2-enolate and (4-cyclopropyl-2-fluorophenyl hydrochloride) was used )hydrazine instead of (4-cyclopropylphenyl)hydrazine hydrochloride, and in Step 3) of Example 1 (R)-methyl(piperidin-3yl)fer-butylcarbamate instead of (R)-piperidin-3 -tert-butylylcarbamate. IF-2019-01451929-APN-ANP#INPI Page 66 of 160 1H-NMR (300 MHz, CDCh): δ 7.56 (m, 1H), 7.32 (m, 1H), 7.07 (m, 4H), 7.79 (d, 1H), 4.52 (m, 2H), 3.22 (m, 2H), 2.68 (m, 1H), 2.47 (d, 3H), 1.93 (m, 2H), 1.49 (m, 2H) , 1.09 (m, 2H), 0.75 (m, 2H) MS (ESP): [M+H]+m / z 462.2 Example 7: Preparation of (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(4cyclopropylphenyl)-1 / -Lpyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 3) of Example 1 tert-butyl (R)-azepane-3-ylcarbamate was used instead of ( / ?) -tert-butyl piperidin-3ylcarbamate. 1H-NMR (300 MHz, CDCI3): δ 7.60 (d, 2H), 7.33 (d, 2H), 7.09 (m, 5H), 3.46 (dd, 1H), 3.31 (dd, 1H), 2.13 (m, 5H), 1.92 (m, 4H), 1.08 (c, 2H). MS (ESl·): [M+H]* m / z 426.2 Example 8: Preparation of ( / ?)-4-(3-(3-aminoazepane-1-carbonyl)-1-(4cyclopropyl-2-fluorophenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 IF-2019-01451929-APN-ANP#INPI Page 67 of 160 used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2-enolate instead of (Z)-4-(4-cyanophenyl)-2 -ethyl hydroxy-4-oxobut-2-enolate and (4-cyclopropyl-2-fluorophenyl)hydrazine hydrochloride was used instead of 4-cyclopropylphenylhydrazine hydrochloride and in Step 3) of Example 1 (R)- fer-butyl azepane-3-ylcarbamate instead of fer-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, CDCI3): δ 7.52 (t, 1H), 7.33 (t, 1H), 7.09 (m, 3H), 6.94 (d, 1H), 6.79 (dd, 1H), 3.46 (dd, 1H), 3.31 (dd, 1H), 2.13 (m, 5H), 1.92 (m, 4H), 1.08 (c, 2H) . MS (ESl·): [M+H]+m / z 462.2 Example 9: Preparation of 4-(3-((3R,5R)-3-amino-5-methylpiperidine-1carbonyl)-1-(4-cyclopropyl-2-fluorophenyl)-1 / - / -pyrazol-5-yl )-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (4-cyclopropyl-2-fluorophenyl)hydrazine hydrochloride was used instead of (4-cyclopropyl-2-fluorophenyl)hydrazine hydrochloride. cyclopropylphenyl)hydrazine and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy4-oxobut-2-enolate was used instead of (Z)-4-(4-cyanophenyl)- ethyl 2-hydroxy-4-oxobut-2enolate and in Step 3) of Example 1, fer-butyl ((3R,5R)-5methylpiperidin-3-yl)carbamate was used instead of (R)-piperidin-3ylcarbamate of fer-butyl. IF-2019-01451929-APN-ANP#INPI Page 68 of 160 1H-NMR (300 MHz, CDCb): δ 7.56 (t, 1H), 7.28 (m, 1H), 7.08 (m, 3H), 6.97 (d, 1H), 6.80 (d, 1H), 4.32 (m, 2H), 3.49 (m, 1H), 3.26 (m, 2H), 1.94 (m, 1H), 1.74 (m, 1H) , 1.32 (m, 2H), 1.09 (m, 2H), 0.94 (dd, 3H), 0.76 (m, 2H) MS (ESI+): [M+H]+m / z 462.2 Example 10: Preparation of ( / ?)-4-(3-(3-aminopiperidine1“Carbonyl)-1-(4cyclopropyl-2,6-difluorophenyl)-1 / - / -pyrazol-5-yl)-2-fluorobenzon yttrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (4-cyclopropyl--2,6-difluorophenyl)hydrazine hydrochloride was used instead of (4-cyclopropyl--2,6-difluorophenyl)hydrazine hydrochloride. -cyclopropylphenyl)hydrazine and ethyl (Z)-4-(4-cyano-3fluorophenyl)-2-hydroxy-4-oxobuF2-enolate was used instead of (Z)-4-(4-cyanophenyl)2-hydroxy- Ethyl 4-oxobut“2-enolate. 1H-NMR (300 MHz, CDCh): δ 7.58 (t, 1H), 7.17 (t, 2H), 7.10 (s, 1H), 6.71 (d, 2H), 4.35 (m, 2H), 3.10 (m, 3H), 1.70 (m, 5H), 1.13 (m, 2H), 0.77 (m, 2H) MS (ESP): [M+H]+m / z 466.2 Example 11: Preparation of (R)-4-(3-(3~aminoazepane-1-carbonyl)-1-(4cyclopropyl-2,6-difluorophenyl)-1 / - / -pyrazol-5-yl)- 2-fluorobenzonitrile IF-2019-01451929-APN-ANP#INPI Page 69 of 160 The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (4-cyclopropyl-2,6-difluorophenyl)hydrazine hydrochloride was used instead of (4-cyclopropyl-2,6-difluorophenyl)hydrazine hydrochloride. 4-cyclopropylphenyl)hydrazine and ethyl (Z)-4-(4-cyano-3fluorophenyl)"2-hydroxy-4"oxobut-2"enolate was used instead of (Z)-4-(4-cyanophenyl) ethyl 2-hydroxy-4-oxobut-2-enolate and in Step 3) of Example 1 tert-butyl (R)-azepane-3-ylcarbamate was used instead of (R)-piperidin-3-ylcarbamate tert-butyl. 1H-NMR (300 MHz, CDCIs): δ 7.56 (t, 1H), 7.12 (m, 3H), 6.70 (d, 2H), 4.08 (m, 2H), 3.31 (m, 3H), 1.88 (m, 5H), 1.43 (m, 2H), 1.13 (m, 2H), 0.76 (m, 2H) MS (ESI+): [M+H]+m / z 480. Example 12: Preparation of (R)4-(3-(3-aminopiperidine-1-carbonyl)-1-(2chloro-4-cyclopropiphenyl)-1 / - / -pyrazol-5-yl)-2-fluorobenzonítr it The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (2-chloro-4-cyclopropylphenyl)hydrazine hydrochloride was used instead of (4- cyclopropylphenyl)hydrazine and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy4-oxobut-2-enolate was used instead of (Z)-4-(4-cyanophenyl)-2- ethyl hydroxy-4-oxobut-2enolate. IF-2019-01451929-APN-ANP#INPI Page 70 of 160 1H-NMR (300 MHz, CDCh): δ 7.54 (t, 1H), 7.24 (m, 1H), 7.17 (s, 1H), 7.05 (m, 4H), 4.36 (m, 2H), 3.36 (m, 4H), 1.37 (m, 4H), 1.10 (m, 2H), 0.78 (m, 2H) MS (ESI+): [M+H]+m / z 464.2 Example 13: Preparation of (R)4-(3-(3-aminoazepane-1-carbonyl)-1-(2chloro-4-cyclopropy!phenyl)-1 / - / -pyrazol-5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (2-chloro-4-cyclopropylphenyl)hydrazine hydrochloride was used instead of (4- cyclopropylphenyl)hydrazine and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy4-oxobut-2-enolate was used instead of (Z)-4-(4-cyanophenyl)-2- ethyl hydroxy-4-oxobuL2enolate and in Step 3) of Example 1 tert-butyl ( / ?)-azepane-3-ylcarbamate was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, CDCh): δ 7.56 (t, 1H), 7.17 (m, 2H), 7.06 (m, 4H), 4.04 (m, 2H), 3.89 (m, 1H), 3.31 (m, 3H), 1.85 (m, 3H), 1.37 (m, 4H), 1.10 (m, 2H), 0.77 (m, 2H) MS (ESI+): [M+H]+m / z 478.2 IF-2019-01451929-APN-ANP#INPI Page 71 of 160 Example 14: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1pheniM / 7-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 phenylhydrazine hydrochloride was used instead of (4-cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCh): 7.60 (d, 2H), 7.39 (t, 3H), 7.33 (d, 2H), 6.97 (s, 1H), 4.51 ( m, 2H), 3.21 (m, 2H), 2.98 (m, 1H), 1.84 (m, 2H), 1.67 (m, 2H). MS (ESI+): [M+H]+m / z 372.2 Example 15: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1(pyridin-2-yl)-1 H-pyrazol-5-íl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 2-hydrazinopyridine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCh): 8.30 (m, 1H), 7.98 (t, 1H), 7.63 (m, 3H), 7.28 (m, 3H), 6.92 ( m, 1H), 4.56 (m, 2H), 3.34 (m, 2H), 2.98 (m, 2H), 1.89 (m, 3H) MS (ESP): [M+H]+m / z 373.2 IF-2019-01451929-APN-ANP#INPI Page 72 of 160 Example 16: Preparation of (f?)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4fluorophenyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-fluorophenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCb): δ 7.63 (m, 2H), 7.34 (m, 4H), 7.09 (m, 2H), 6.97 (m, 1H), 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H), 1.84 (m, 2H), 1.67 (m, 2H). MS (ESI+): [M+H]+m / z 390.2 Example 17: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-chlorophenyl)-1 / - / -pyrazol5“yl)benzonityl The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-chlorophenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl)hydrazine hydrochloride. Ck 1H-NMR (300 MHz, CDCI3): δ 7.63 (d, 2H), 7.38 (t, 4H), 7.21 (d, 2H), 6.97 (d, 1H), 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H), 1.84 (m, 2H), 1.67 (m, 2H). IF-2019-01451929-APN-ANP#INPI Page 73 of 160 MS (ESP): [M+H]+m / z 406.1 Example 18: Preparation of (R)-4-(1-(4-chlorophenyl)-3-(3(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-chlorophenyl)hydrazine hydrochloride was used instead of 4-cyclopropylphenylhydrazine hydrochloride and in Step 3) in Example 1, tert-butyl (R)methyl(piperidin-3-yl)carbamate was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, CDCh): 7.64 (d, 2H), 7.32 (m, 4H), 7.19 (d, 2H), 6.97 (d, 1H), 4.48 ( m, 2H), 3.21 (m, 2H), 2.67 (m, 1H), 2.47 (d, 3H), 1.92 (m, 2H), 1.61 (m, 2H). MS (ESI+): [M+H]+m / z 372.2 Example 19: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(3chlorophenyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (3-chlorophenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl)hydrazine hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 74 of 160 1H-NMR (300 MHz, CDCI3): δ 7.64 (d, 2H), 7.34 (m, 4H), 7.29 (s, 1H), 7.03 (m, 1H), 6.97 (m, 1H), 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H), 1.84 (m, 2H), 1.67 (m, 2H) . MS (ESE): [M+H]+m / z 406.0 Example 20: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4bromophenyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that (4-bromophenyl)hydrazine hydrochloride was used in Step 1) of Example 1 instead of (4-cyclopropylphenyl)hydrazine hydrochloride. na. 1H-NMR (300 MHz, DMSO-cfe): δ 8.27 (t, 1H), 7.83 (d, 2H), 7.44 (d, 2H), 7.28 (m, 4H), 7 .13 (s, 1H), 3.50 (m, 12H). MS (ESI+): [M+H]+m / z 450.1 Example 21: Preparation of ( / ?)-4-(1-(4-bromophenyl)-3-(3-(methylamino)pipehdine1-carbonyl)1 H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (4-bromophenyl)hydrazine hydrochloride was used instead of (4~) hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 75 of 160 cyclopropylphenyl)hydrazine and in Step 3) of Example 1 tert-butyl (R)methyl(piperidin-3-yl)carbamate was used instead of (R)-piperidin-3-ylcarbamate. -butyl. 1H-NMR (300 MHz, DMSO-d6): δ 7.85 (d, 2H), 7.38 (d, 2H), 7.21 (d, 2H), 7.14 (d, 2H), 6 .72 (m, 1H), 2.32 (s, 3H), 1.84 (m, 2H), 1.42 (m, 10H). MS (ESI+): [M+H]+m / z 464.1 Example 22: Preparation of (S)-4-(3-(3-aminopyrrolidino-1-carbonyl)-1-(ptolyl)-1 / 7-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) In Example 1, tert-butyl (S)-pyrrolidin-3-ylcarbamate was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.83 (d, 2H), 7.44 (d, 2H), 7.23 (c, 4H), 7.12(s, 1H), 3 .94 (m, 2H), 3.48 (m, 4H), 2.34 (s, 3H), 1.94 (m, 2H), 1.57 (m, 1H) MS (ESP): [M+H]+m / z 372.2 Example 23: Preparation of (S)-4-(3-(3-(methylamino)pyrrolidino-1carbon¡l)-1-(p-tolyl)-1 / - / -pyrazol-5-yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 76 of 160 Step 1) Preparation of tert-butyl (S)-(1-(5-(4-cyanophenyl)-1-(p-tolyl)-1 / - / -pyrazol-3carbonyl)pyrrolidin-3-yl)carbamate The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylpheníl)hydrazine hydrochloride and in In Step 3) of Example 1, tert-butyl (S)-pyrrolidin-3ylcarbamate was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, DMSO-cfe): δ 7.85 (d, 2H), 7.46 (d, 2H), 7.19 (m, 5H), 7.13 (d, 1H), 3 .85 (m, 2H), 3.40 (m, 2H), 3.37 (m, 1H), 2.34 (s, 3H), 1.90 (m, 1H), 1.70 (m, 1H), 1.39 (d, 9H) Step 2) Preparation of (S)-(1-(5-(4-cyanophenyl)-1-(p-tolyl)-1H-pyrazol-3carbonyl)pyrrolidin-3-yl)(methyl) tert-carbamate butyl 244 mg (0.52 mmol) of (S)-(1 -(5-(4-cyanophenyl)-1 -(p-tolyl)1H-pyrazole-3-carbonyl)pyrrolidin-3-yl)carbamate were dissolved tert-butyl in 2 mL of dimethylformamide (DMF). Next, 207 mg (5.17 mmol) of NaH was added to this and then stirred at room temperature for 30 minutes. After an interval of 30 minutes, 0.07 mL (1.04 IF-2019-01451929-APN-ANP#INPI Page 77 of 160 mmol) of Mel and then stirred at room temperature for 4 hours. Once the reaction was complete, water was slowly added to this, an organic layer was extracted using ethyl acetate and separated. The organic phase was washed with soft water, dried using anhydrous sodium sulfate and concentrated under reduced pressure, thus obtaining 220 mg of the desired compound (yield: 87%). 1H-NMR (300 MHz, DMSO-c / 6): δ 7.85 (d, 2H), 7.46 (d, 2H), 7.25 (c, 4H), 7.15 (d, 1H) , 4.61 (, 1H), 4.08 (m, 1H), 3.69 (m, 2H), 3.46 (m, 1H), 2.75 (d, 3H), 2.34 (s , 3H), 1.98 (m, 2H), 1.38 (d, 9H) Step 3) Preparation of (S)4-(3-(3-(methylamino)pyrrolidino-1-carbon¡l)-1(p-tol¡l)-1 / - / -pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as Example 1, except that in Step 4) of Example 1 (S)-(1-(5-(4-cyanophenyl)-1-(p- tolyl)-1 / 7-pyrazole-3-carbonyl)pyrrolidin-3-i() fer-butyl carbamate instead of ( / ?)-(1-(5-(4-cyanophenyl)-1-(4- fer-butyl cyclopropylphenyl)-1 / 7-pyrazole3-carbonyl)piperidin-3“yl)carbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.84 (d, 2H), 7.44 (d, 2H), 7.20 (c, 4H), 7.12 (s, 1H), 3 .91 (m, 2H), 3.50 (m, 3H), 3.14 (m, 1H), 2.34 (s, 3H), 2.24 (d, 3H), 1.93 (m, 1H), 1.71 (m, 1H) MS: [M+H]+m / z 386.2 Example 24: Preparation of (S)-4-(3-(3-(dimethylamino)pyrrolidino-1carbonyl)-1 -(p-tolyl)-l / 7-pyrazol-5-yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 78 of 160 CHOO, AcOH NaBH3CN,MeOH 74 mg (0.19 mmol) of (S)-4-(3-(3-(methylamino)pyrrolidino1-carbonyl)-1-(p-tolyl)-lH-pyrazol-5-yl)benzonitrile prepared in Step 3 of Example 23 in 1 mL of methanol and to this were added dropwise 0.07 mL (0.96 mmol) of a formaldehyde solution and 0.02 mL (0.39 mmol) of a acetic acid at room temperature. The temperature was then reduced to a temperature within the range between 0 °C and 5 °C. To this was added 24 mg (0.39 mmol) of sodium cyanoborohydride at a temperature within the range between 0 °C and 5 °C. The temperature was then raised to room temperature and then stirred for 3 hours. Once the reaction was complete, saturated aqueous sodium bicarbonate solution was slowly added to this, an organic layer was extracted using ethyl acetate and separated. The organic phase was washed with soft water, dried using anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was purified using column chromatography (dichloromethaneimethanol = 8:1 (v / v)), to obtain 48 mg of the desired compound (yield: 63%). 1H-NMR (300 MHz, DMSO-d6): δ 7.84 (d, 2H), 7.44 (d, 2H), 7.24 (c, 4H), 7.14 (s, 1H), 4 .12 (m, 1H), 3.74 (m, 2H), 2.70 (m, 1H), 2.34 (s, 3H), 2.17 (d, 6H), 2.07 (m, 1H), 1.73 (m, 1H), 3.23 (m, 1H). MS: [M+H]+m / z 400.2 Example 25: Preparation of (R)-4-(3-(3~(dimethylamino)pyrrolidino-1carbonyl)-1-(p-tolyl)-1 / 7-pyrazoL5-yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 79 of 160 The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) In Example 1, (R)- / V, / Vdimethylpyrrolidino-3-amine was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.84 (d, 2H), 7.44 (d, 2H), 7.24 (m, 4H), 7.14 (s, 1H), 4 .15 (m, 1H), 3.80 (m, 1H), 3.44 (m 1H), 3.30 (m, 1H), 2.70 (m, 1H), 2.35 (s, 3H) ), 2.17 (d, 6H), 1.75 (m, 1H). [M+H]+m / z 400.2 Example 26: Preparation of (R)-4-(3-(3-(methylamino)pyrrolidino-1carbonyl)-1-(p-tolyl)-1 / 7-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) In Example 1, tert-butyl (R)methyl(pyrrolidin-3-yl)carbamate was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. IF-2019-01451929-APN-ANP#INPI Page 80 of 1601H“NMR (300 MHz, DMSO-d6): δ 7.97 (d, 1H), 7.84 (d, 2H), 7.44 (d, 2H), 7.26 (s, 3H) ), 7.17 (s, 1H), 3.97 (m, 1H), 2.60 (m, 1H), 2.02 (m, 2H), 1.65 (m, 2H), 1.49 (m,2H). [M+H]+m / z 386.2 Example 27: Preparation of (R)-4-(3-(3-aminopyrrolidino-1-carbonyl)-1-(pto I i I)-1 H-pyrazol-5-yl) benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) in Example 1, tert-butyl (R)-pyrrolidin-3-ylcarbamate was used instead of tert-butyl ( / ?)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.84 (d, 2H), 7.45 (d, 2H), 7.25 (m, 4H), 7.12 (s, 1H), 4 .02 (m, 2H), 3.66 (m, 3H), 2.35 (s, 3H), 1.99 (m, 3H), 1.67 (m, 1H) [M+H]+m / z 372.2 Example 28: Preparation of ( / ?)-4-(3-(3-aminopipehdine-1-carbonyl)-1-(ptolyl)-1 / 7-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 IF-2019-01451929-APN-ANP#INPI Page 81 of 160 used p-tolylhydrazine hydrochloride instead of (4cyclopropylphenyl)hydrazine hydrochloride. 1H NMR spectrum (300 MHz, CDCIs) δ 7.60 (d, 2H), 7.44 (d, 2H), 7.20 (m, 4H), 6.96 (s, 1H), 4.58 ( m, 2H), 3.34 (m, 1H), 2.96 (m, 1H), 2.78 (m, 1H), 2.39 (s, 3H), 2.00 (m, 1H), 1.82 (m, 1H), 1.60 (m, 1H), 1.28 (m, 3H). MS (ESP): [M+H]+m / z 386.2 Example 29: Preparation of (R)-4-(3-(3-(methylamino)piperidine-1carbonyl)-1 “(p-tolyl)-l / - / -pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) In Example 1, tert-butyl (R)methyl(piperidin-3-yl)carbamate was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.85 (d, 2H), 7.44 (d, 2H), 7.24 (c, 4H), 7.05 (d, 1H), 4 .50 (m, 2H), 3.08 (m, 1H), 2.81 (m, 1H), 2.34 (s, 5H), 2.20 (s, 1H), 1.94 (m, 1H), 1.70 (m, 1H), 1.41 (m, 3H). [M+H]+m / z 400.2 Example 30: Preparation of (R)-4-(3-(3-(dimethylamino)piperidine-1carbonyl)-1-(p“tol¡l)-1 / - / -pyrazol-5-¡l)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 82 of 160 -NO The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) In Example 1, A / ,A / -dimethyl (R)-piperidin-3-ylcarbamate was used instead of (R)-tert-butyl piperidin-3-ylcarbamate. 1H-NMR (300 MHz, DMSO-cfe): δ 7.84 (d, 2H), 7.44 (d, 2H), 7.24 (c, 4H), 7.05 (d, 1H), 4 .76 (m, 3H), 3.16 (m, 1H), 2.80 (m, 1H), 2.34 (s, 3H), 2.25 (s, 3H), 2.14 (s, 3H), 1.90 (m, 1H), 1.80 (m, 1H), 1.49 (m, 2H). [M+H]+m / z 414.2 Example 31: Preparation of (R)-4-(3-(3“aminopiperidine-1~carbonyl)-1( / 77“tolyl)-1 H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 m-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride. *1 p IF-2019-01451929-APN-ANP#INPI Page 83 of 1601H-NMR (300 MHz, CDCh): δ 7.61 (m, 2H), 7.58 (m, 6H), 6.96 (s, 1H), 4.52 (m, 2H), 4.26 (m, 1H), 3.47 (m, 2H), 2.97 (m, 2H), 2.77 (m, 1H), 2.35 (s, 3H), 2.03 (m , 1H), 1.83 (m, 1H) MS (ESI+): [M+H]+m / z 386.2 Example 32: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(otolyl)-1 / 7-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 o-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 7.55 (m, 2H), 7.41 (m, 5H), 7.20 (m, 1H), 7.06 (s, 1H0, 4.55 ( m, 2H), 4.28 (m, 1H), 3.47 (m, 2H), 2.99 (m, 1H), 2.82 (m, 1H), 2.01 (s, 3H), 1.96 (m, 1H), 1.81 (m, 1H). MS (ESI+): [M+H]+m / z 386.2 Example 33: Preparation of ( / ?)-4“(3“(3-aminopiperidine-1“Carbonyl)-1-(4ethylphenií)-1 / 7-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (4-ethylphenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl-hydrazine hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 84 of 160 1H-NMR (300 MHz, CDCI3): δ 7.62 (d, 2H), 7.36 (m, 2H), 7.24 (m, 4H), 6.98 (s, 1H), 4.59 (m, 2H), 4.26 (m, 1H), 3.33 (m, 2H), 3.0 (m, 1H), 2.81 (m, 1H), 2.76 (m, 2H) , 2.03 (m, 1H), 1.83 (m, 1H), 1.29 (m, 3H) MS (ESE): [M+H]+m / z 400.2 Example 34: Preparation of (R)-4-(1-(4-ethylphenyl)-3-(3(methylamino)piperidine“1~carbonyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-ethylphenyl)hydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in the Step 3) of Example 1, tert-butyl (R)methyl(pipehdin-3-¡l)carbamate was used instead of tert-butyl (R)-piperidin-3ylcarbamate. Q O1H-NMR (300 MHz, CDCI3): δ 7.63 (d, 2H), 7.37 (m, 2H), 7.24 (m, 4H), 7.02 (m, 1H), 4, 79 (m, 3H), 3.49 (m, 1H), 3.28 (m, 2H), 2.72 (m, 3H), 2.56 (d, 3H), 2.04 (m, 1H ), 1.86 (m, 1H), 1.27 (m, 3H) MS (ESE): [M+H]+m / z 414.2 Example 35: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbon¡l)-1-(4isopropylphenyl)“1 / 7-pyrazol-5-yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 85 of 160 The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-isopropylphenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 7.63 (d, 2H), 7.37 (m, 2H), 7.29 (m, 4H), 6.92 (s, 1H), 4.58 (m, 2H), 4.26 (m, 1H), 3.38 (m, 2H), 3.00 (m, 2H), 2.81 (m, 1H), 2.00 (m, 1H) , 1.84 (m, 1H), 1.28 (dd, 6H) MS (ESI+): [M+H]+m / z 414.2 Example 36: Preparation of (R)-4-(1-(4-isopropylphenyl)-3-(3(methylamino)piperidine-1-carbonyl)-1 / - / -pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-isopropylphenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl)hydrazine hydrochloride and In Step 3) of Example 1, fer-butyl (R)methyl(piperidin-3-yl)carbamate was used instead of fer-butyl (R)-piperidin-3-ylcarbamate. IF-2019-01451929-APN-ANP#INPI Page 86 of 1601H-NMR (300 MHz, CDCI3): δ 7.62 (m, 2H), 7.35 (m, 6H), 7.03 (s, 1H), 4.92 (m, 1H), 4.38 (m, 2H), 3.32 (m, 1H), 3.01 (m, 4H), 2.92 (d, 3H), 2.06 (m, 1H), 1.88 (m , 1H), 1.25 (m, 6H). MS (ESP): [M+H]+m / z 428.2 Example 37: Preparation of (R)-4“(3-(3-aminopiperidine-1“Carbonyl)-1-(2fluoro-4-isopropylphenyl)-1 / 7-pyrazol-5-yl) benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (2-fiuoro-4-isopropylphenyl)hydrazine hydrochloride was used instead of (4- cyclopropylphenyl)hydrazine. 1H-NMR (300 MHz, CDCb): δ 7.60 (m, 2H), 7.34 (m, 3H), 7.11 (m,1H), 7.05 (s, 1H), 6.98 (m, 1H), 4.50 (m, 2H), 3.35 (m, 2H), 2.99 (m, 2H), 2.83 (m, 1H), 2.02 (m, 1H) , 1.82 (m, 1H), 1.40 (m, 2H), 1.27 (dd, 6H) MS (ESP): [M+H]+m / z 432.2 Example 38: Preparation of (R)4-(3-(3-aminopipendine-1-carbonyl)-1-(2fluoro-4-isopropylphenyl)-1H-pyrazol-5-yl)-2~fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (2-fluoro-4-isopropylphenyl)hydrazine hydrochloride was used instead of (4- cyclopropylphenyl)hydrazine and (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy¡IF-2019-01451929-APN-ANP#INPI was used Page 87 of 160 Ethyl 4-oxobut-2-enolate instead of ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut-2enolate. 1H-NMR (300 MHz, CDCI3): δ 7.57 (m, 1H), 7.36 (m, 1H), 7.13 (m, 5H), 4.47 (m, 2H), 3.35 (m, 2H), 2.98 (m, 2H), 2.80 (m, 1H), 2.01 (m, 1H), 1.78 (m, 1H), 1.28 (m, 1H) , 1.27 (dd, 6H) MS (ESI+): [M+H]+m / z 450.2 Example 39: Preparation of (R)4-(3-(3-aminoazepane-1-carbonyl)-1-(2fluoro-4-isopropylphenyl)-1 / - / -pyrazol-5-yl)-2-fluorobenzon trilo The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (2-fluoro-4-isopropylphenyl)hydrazine hydrochloride was used instead of (4- cyclopropylphenyl)hydrazine and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy4-oxobut-2-enolate was used instead of (Z)-4-(4-cyanophenyl)- ethyl 2-hydroxy-4-oxobut-2enolate and in Step 3) of Example 1 tert-butyl (R)-azepane-3ylcarbamate was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, CDCh): δ 7.60 (m, 1H), 7.38 (m, 2H), 7.15 (m, 2H), 7.06 (m, 2H), 4.31 (m, 1H), 4.05 (m, 2H), 3.50 (m, 3H), 3.01 (m, 1H), 2.04 (m, 1H), 1.93 (m, 2H) , 1.50 (m, 2H), 1.28 (dd, 6H) IF-2019-01451929-APN-ANP#INPI Page 88 of 160 MS (ESI+): [M+H]+m / z 464.2 Example 40: Preparation of ( / ?)“4-(3“(3-aminopiperidine-1-carbonyl)-1-(4(fer-butyl)phenyl)-1 / - / -pyrazol-5-yl) benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-(fer-butyl)phenyl)hydrazine hydrochloride was used in instead of (4cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCI3): δ 7.60 (d, 2H), 7.38 (m, 4H), 7.17 (dd, 2H), 6.97 (dd, 1H), 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H), 1.84 (m, 2H), 1.67 (m, 2H), 1.31 (s, 9H) MS (ESI+): [M+H]+m / z 428.2 Example 41: Preparation of (F?)-4-(1-(4-(fer-butyl)phenyl-3-(3methylaminopiperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-(fer-butyl)phenyl)hydrazine hydrochloride was used instead of 4-cyclopropylphenylhydrazine hydrochloride and in Step 3) of Example 1, fer-butyl ( / ?)methyl(piperidin-3-yl)carbamate was used instead of fer-butyl (R)-piperidin-3-ylcarbamate. IF-2019-01451929-APN-ANP#INPI Page 89 of 160 1H-NMR (300 MHz, CDCh): 7.61 (d, 2H), 7.37 (m, 4H), 7.17 (dd, 2H), 6.97 (d, 1H), 4.48 ( m, 2H), 3.21 (m, 2H), 2.67 (m, 1H), 2.47 (d, 3H), 1.92 (m, 2H), 1.61 (m, 2H), 1.31 (s, 9H) MS (ESP): [M+H]+m / z 442.3 Example 42: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4(ferbutyl)-2-fluorophenyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that (4-(tert-butyl)-2-fluorophenyl)h hydrochloride was used in Step 1) of Example 1. Drazine instead of (4-cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 7.58 (d, 2H), 7.33 (m, 3H), 7.22 (m, 1H), 7.09 (dd, 1H), 6.96 (s, 1H), 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H), 1.84 (m, 2H), 1.67 (m,2H) , 1.31(s, 9H) MS (ESP): [M+H]+m / z 446.2 Example 43: Preparation of (R)“4-(3-(3-aminopiperidine-1-carbonyl)-1“(4“ (fer-butyl-2-fluorophenyl)-1H-pyrazol-5-yl)-2- fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 IF-2019-01451929-APN-ANP#INPI Page 90 of 160 used (4-(tert-butyl-2-fluorophenyl)hydrazine hydrochloride instead of 4~cyclopropylphenylhydrazine hydrochloride and (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy was used Ethyl -4oxobut-2-enolate instead of ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxo-2butenoate. 1H-NMR (300 MHz, CDCI3): δ 7.56 (t, 1H), 7.38 (c, 1H), 7.30 (t, 1H), 7.15 (m, 2H), 7.03 (m, 1H), 7.01 (s, 1H) 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H), 1.84 (m, 2H), 1.67 (m, 2H), 1.31 (s, 9H) MS (ESI+): [M+H]+m / z 464.2 Example 44: Preparation of (R)~4-(3-(3-aminoazepane-1-carbonyl)-1-(4(tert-butyl-2-fluorophenyl)-1H-pyrazol-5-yl)-2-fluorobenzon Trilo The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-(tert-butyl-2-fluorophenyl)hydrazine hydrochloride was used instead of hydrochloride. 4-cyclopropylphenylhydrazine and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy¡-4oxobut-2-enolate was used instead of (Z)-4-(4-cyanophenyl)-2 -ethyl hydroxy-4-oxo-2butenoate and in Step 3) of Example 1 tert-butyl (R)-azepane-3ylcarbamate was used instead of tert-butyl ( / ?)-piperidin-3-ylcarbamate. IF-2019-01451929-APN-ANP#INPI Page 91 of 1601H-NMR (300 MHz, CDCh): δ 7.55 (t, 1H), 7.34 (c, 1H), 7.28 (t, 2H), 7.15 (m, 3H) 3 .34 (m, 2H), 1.91 (m, 6H)), 1.46 (m, 2H), 1.34 (s, 9H) MS (ESP): [M+H]+m / z 478.2 Example 45: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)“1-(4(trifluoromethoxy)phenyl)-1H-pyrazol-5“yl) benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-(trifluoromethoxy)phenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl hydrochloride). )hydrazine. 1H-NMR (300 MHz, CDCh): δ 7.64 (d, 2H), 7.29 (m, 6H), 6.97 (s, 1H), 4.34 (m, 2H), 3.19 (m, 3H), 2.49 (a, 2H), 2.05 (m, 1H), 1.95 (m, 1H), 1.57 (m, 2H). MS (ESP): [M+H]+m / z 456.2 Example 46: Preparation of (R)“4“(3-(3-aminopiperidine-1-carbonyl)-1-(4(methylsulfonyl)phenyl)-1 H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-(methylsulfonyl)phenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl hydrochloride). )hydrazine. IF-2019-01451929-APN-ANP#INPI Page 92 of 160 1H-NMR (300 MHz, CDCh): δ 7.97 (d, 2H), 7.68 (d, 2H), 7.49 (d, 2H), 7.37 (d, 2H), 6.99 (s, 1H), 4.40 (m, 2H), 3.24 (m, 2H), 3.10 (s, 3H), 3.00 (m, 1H), 1.95 (m, 2H) , 1.56 (m, 2H). MS (ESP): [M+H]+m / z 450.2 Example 47: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4(trifluoromethyl)phenyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-(trifluoromethyl)phenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl hydrochloride). )hydrazine. 1H-NMR (300 MHz, CDCI3): δ 7.67 (m, 4H), 7.37 (m, 4H), 6.99 (s, 1H), 4.50 (m, 2H), 3.21 (m, 2H), 2.89 (m, 2H), 2.04 (m, 1H), 1.65 (m, 1H), 1.50 (m, 3H). MS (ESP): [M+H]+m / z 440.2 Example 48: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbon¡l)-1-(2fluoro-4-methylphenyl)-1 H-pyrazole-5-iI) benzonitrile IF-2019-01451929-APN-ANP#INPI Page 93 of 160 The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 2-fluoro-4-methylphenyl)hydrazine hydrochloride was used instead of (4cyclopropylphenyl)h hydrochloride. Drazine. 1H-NMR (300 MHz, CDCh): δ 7.58 (d, 2H), 7.32 (m, 3H), 7.04 (d, 1H), 6.98 (s, 1H), 6.92 (d, 1H), 4.32 (m, 2H), 3.31 (m, 3H), 2.70 (a, 2H), 2.40 (s, 3H), 2.00 (m, 1H) , 1.82 (m, 1H), 1.56 (m, 2H). MS (ESP): [M+H]+m / z 404.2 Example 49: Preparation of (R)-4-(3-(3-aminopipendine-1“Carbonyl)-1-(3fluoroA-methoxyphenylJ-IH-pyrazol-S-yl) benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (3-fluoro-4-methoxyphenyl)hydrazine hydrochloride was used instead of (4- cyclopropylphenyl)hydrazine. 1H-NMR (300 MHz, CDCI3): δ 7.61 (m, 2H), 7.33 (m, 2H), 7.10 (m, 1H), 6.93 (m, 3H), 4.52 (m, 2H), 3.93 (s, 3H), 3.29 (m, 2H), 2.97 (m, 1H), 1.84 (m, 2H), 1.58 (m, 2H) . IF-2019-01451929-APN-ANP#INPI Page 94 of 160 MS (ESI+): [M+H]+m / z 420.2 Example 50: Preparation of (R)-4,4'-(3-(3-aminopiperidine-1-carbonyl)1 H-pyrazole-1,5-diyl) dibenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (4-hydrazinylbenzonitril)hydrazine hydrochloride was used instead of (4-cyclopropylphení hydrochloride). l)hydrazine. 1H-NMR (300 MHz, CDCh): δ 7.70 (c, 4H), 7.40 (m, 4H), 7.99 (d, 1H), 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H), 1.84 (m, 2H), 1.67 (m, 2H). MS (ESI+): [M+H]+m / z 397.2 Example 51: Preparation of (R)-4-(1-(4-(dimethylamino)phenyl)-3-(3(methylamino)piperidine-1-carbon!l)-1 / -Lpyrazole-5-l)benzon try it Step 1) Preparation of ethyl 5-(4-cyanophenyl)-1-(4-iodophenyl)-1H-pyrazole-3carboxylate The desired compound was obtained in substantially the same manner as in Step 1) of Example 1, except that in Step 1) of Example 1 4-iodophenylhydrazine hydrochloride was used instead of (4-cyclopropylphenyl)hydrazine hydrochloride. . IF-2019-01451929-APN-ANP#INPI Page 95 of 1601H-NMR (300 MHz, CDCb): δ 7.60 (m, 2H), 7.41 (m, 2H), 7.10 (m, 3H), 6.45 (m, 2H), 4.45 (c, 2H), 1.42 (t, 3H). Step 2) Preparation of ethyl 5-(4-cyanophenyl)-1-(4-(dimethylamino)phenyl)-1H pyrazole-3-carboxylate Perceive) 3 Xantphos CÍI2CO3 toluene, 1101C 200 mg (0.45 mmol) of ethyl 5-(4-cyanophenyl)-1-(4-iodophenyl)1 / 7-pyrazole-3-carboxylate, 41 mg (0.045 mmol) of Pd2(dba)3 were dissolved , 294 mg (0.90 mmol) CS2CO3, 52 mg (0.09 mmol) Xantphos and 44 mg (0.54 mmol) dimethylamine hydrochloride in 1,4-dioxane. This reaction mixture was stirred at a temperature of 100 °C for 12 hours. The mixture was cooled to room temperature, then filtered through celite and concentrated under reduced pressure. The residue obtained was purified using column chromatography (dichloromethane:methanol = 10:1 (v / v)), to obtain 110 mg of the desired compound (yield: 67%). 1H-NMR (300 MHz, CDCI3): δ 7.80 (m, 2H), 7.42 (m, 2H), 6.98 (m, 3H), 6.68 (m, 2H), 4.34 (c, 2H), 2.92 (s, 6H), 1.42 (t, 3H). Step 3) Preparation of (R)-4-(1-(4-(dimethylamino)phenyl)-3-(3(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 96 of 160 The desired compound was obtained in substantially the same manner as in Example 1, except that 5-(4-cyanophenyl)-1-(4-(dimethylamino)phenyl)-1H was used in Step 3) of Example 1. -ethyl pyrazole-3-carboxylate prepared in Step 2), and tertulium (R)-methyl(pipendin-3-yl)carbamate was used instead of fer-butyl (R)-pipendin-3-ylcarbamate. 1H-NMR (300 MHz, CDCh): δ 7.60 (m, 2H), 7.36 (m, 2H), 7.10 (m, 2H), 6.98 (s, 1H), 6.65 (m, 2H), 4.48 (m, 2H), 3.21 (m, 2H), 2.99 (s, 6H), 2.75 (m, 1H), 2.56 (d, 3H) , 2.07 (m, 1H), 1.82 (m, 1H), 1.40 (m, 2H) MS (ESP): [M+H]+m / z 429.2 Example 52: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4((2-(dimethylamino)ethyl)(methyl)amino)phenyl)-1 / 7-pyrazole -5“yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 2) of Example 51 N1,N1,A / 2-trimethylethane-1,2-diamine was used instead of hydrochloride. diethylamine and in Step 3) of Example 51, ferbutyl (R)-piperidin-3-ylcarbamate was used instead of fer-butyl (R)-methyl(piperidin-3-yl)carbamate. IF-2019-01451929-APN-ANP#INPI Page 97 of 1601H“NMR (300 MHz, CDCh): δ 7.61 (m, 2H), 7.38 (m, 2H), 7.10 (m, 2H), 7.07 (s, 1H), 6.65 (m, 2H), 4.49 (m, 2H), 3.51 (m, 2H), 3.22 (m, 2H), 3.00 (s, 3H), 2.75 (m , 1H), 2.52 (m, 2H), 2.31 (s, 6H), 2.05 (m, 1H), 1.82 (m, 1H), 1.42 (m, 2H) MS (ESI+): [M+H]+m / z 472.3 Example 53: Preparation of ((R)-4-(3-(3-aminopiperidine-1-carbonyl)-1(4-(dimethylamino)phenyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 46, except that in Step 3) of Example 51 tert-butyl (R)-piperidin-3-ylcarbamate was used instead of (R)- tert-butyl methyl(piperidin-3yl)carbamate. 1H-NMR (300 MHz, DMSO-cfe): δ 7.83 (d, 2H), 7.42 (d, 2H), 7.10 (m, 3H), 6.68 (m, 2H), 4 .44 (m, 2H), 3.39 (m, 3H), 2.48 (s, 6H), 1.94 (m, 2H), 1.69 (m, 2H), 1.23 (m, 2H). MS (ESI+): [M+H]+m / z 415.2 Example 54: Preparation of (R)-4-(3-(3-aminopyridine-1-carbonyl)-1-(4(dimethylamino)-2-fluorophenyl)-1 / - / -pyrazol-5-yl) benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51, (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 98 of 160 iodophenylhydrazine and in Step 3) of Example 51, fer-butyl (R)-piperidin-3ylcarbamate was used instead of (R)-methyl(piperidin-3-yl)tert-butylcarbamate. 1H-NMR (300 MHz, CDCh): δ 7.60 (m, 2H), 7.38 (m, 2H), 7.22 (m, 1H), 7.00 (s, 1H), 6.97 (m, 1H), 6.35 (m, 1H), 4.48 (m, 2H), 3.33 (m, 2H), 3.07 (m, 1H), 3.00 (s, 6H) , 2.85 (m, 1H), 2.00 (m, 1H), 1.62 (m, 1H), 1.46 (m, 1H) MS (ESP): [M+H]+m / z 433.2 Example 55: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4(diethylamino)-2-fluorophenyl)-1 / - / -pyrazol~5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride, in in Step 2) of Example 51 diethylamine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 fer-butyl (R)piperidin-3-ylcarbamate was used instead of (R)-methyl(piperidin- fer-butyl 3yl)carbamate. IF-2019-01451929-APN-ANP#INPI Page 99 of 160 1001H-NMR (300 MHz, CDCh): δ 7.61 (m, 2H), 7.37 (m, 2H), 7.27 (m, 1H), 7.01 (m, 1H), 6.43 (m, 1H), 6.31 (m, 1H), 4.50 (m, 2H), 3.47 (m, 4H), 3.27 (m, 2H), 2.98 (m, 1H) , 2.00 (m, 1H), 1.82 (m, 1H), 1.44 (m, 2H), 1.21 (m, 6H) MS (ESP): [M+H]+m / z 461.2 Example 56: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4(azetidin-1-yl)-2-fluorophenyl)-1 H-pyrazol-5-yl) benzon ytril The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride, in in Step 2) of Example 51 azetidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 tert-butyl (R)pipehdin-3-ylcarbamate was used instead of (R)-methyl(piperidin- tert-butyl 3yl)carbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.84 (d, 2H), 7.46 (d, 2H), 7.32 (m, 1H), 7.09 (m, 1H), 6 .28 (m, 2H), 4.37 (m, 2H), 3.84 (m, 3H), 3.05 (m, 2H), 2.36 (m, 5H), 1.88 (m, 5H) MS (ESP): [M+H]* m / z 445.2 Example 57: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2fluoro-4-(pyrrolidin-1-yl)phenyl)-1 / 7-pyrazole-5-¡ l)benzonitetrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 IF-2019-01451929-APN-ANP#INPI Page 100 of 160 101 used (2-fluoro-4-iodophenyl)hydrazine hydrochloride instead of 4-iodophenylhydrazine hydrochloride, in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 ( R)fer-butyl piperidin-3-ylcarbamate instead of (R)-methyl(piperidin-3yl)fer-butyl carbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.84 (d, 2H), 7.47 (d, 2H), 7.37 (m, 1H), 7.03 (m, 1H), 6 .39 (m, 2H), 4.37 (m, 1H), 4.21 (m, 1H), 3.23 (m, 5H), 3.00 (m, 3H), 1.94 (m, 4H), 1.87 (m, 1H), 1.68 (m, 1H), 1.41 (m, 1H), 1.21 (m, 2H). MS (ESI+): [M+H]+m / z 459.2 Example 58: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2fluoro-4-(pyrrolidin-1-yl)phenyl)-1 H-pyrazol-5-yl) -2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate, in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 fer-butyl (R)-piperidin-3ylcarbamate was used instead of ( Ferbutyl R)-methyl(piperidin-3-yl)carbamate. IF-2019-01451929-APN-ANP#INPI Page 101 of 160 102 1H-NMR (300 MHz, CDCh): δ 7.56 (m, 1H), 7.25 (m, 3H), 6.99 (s, 1H), 6.34 (m, 1H), 6.21 (m, 1H), 4.44 (m, 2H), 3.31 (m, 6H), 2.91 (m, 2H), 2.07 (m , 5H), 1.60 (m, 1H), 1.48 (m, 1H) MS (ESP): [M+H]+m / z 477.2 Example 59: Preparation of (R)-2-fluoro-4-(1-(2-fluoro-4-(pyrrolidin-1yl)phenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H- pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate and in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 7.55 (m, 1H), 7.17 (m, 2H), 7.10 (m, 1H), 7.02 (m, 1H), 6.32 (m, 1H), 6.19 (m, 1H), 4.75 (m, 2H), 3.52 (m, 6H), 2.81 (m, 1H), 2.58 (m, 4H) , 2.08 (m, 4H), 1.61 (m, 3H), 0.86 (m, 1H) MS (ESP): [M+H]+m / z 491.2 IF-2019-01451929-APN-ANP#INPI Page 102 of 160 103 Example 60: Preparation of (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(2fluoro-4-(pyrrolidin-1-yl)phenyl)-1 / - / -pyrazole-5- il)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate, in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 fer-butyl (R)-azepane-3ylcarbamate was used instead of ( Tert-butyl R)-methyl(piperidin-3-yl)carbamate. 1H-NMR (300 MHz, CDCI3): δ 7.57 (m, 1H), 7.25 (m, 4H), 6.33 (m, 1H), 6.21 (m, 1H), 4.47 (m, 1H), 4.27 (m, 1H), 3.94 (m, 4H), 3.29 (m, 3H), 2.16 (m, 1H), 2.04 (m, 4H) , 1.86 (m, 2H), 1.44 (m, 2H) MS (ESP): [M+H]+m / z 491.2 Example 61: Preparation of 4-(3-((R)-3-aminopyrrolidin-1-carbonyl)“1“(2“ fluoro-4-((R)-3-fluoropyrrolidin-1 -yl) phenyl)-1 / 7-pyrazol-5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2 IF-2019-01451929-APN-ANP#INPI Page 103 of 160 104 ethyl enolate instead of ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut-2-enolate, in Step 2) of Example 51 (R)-3-fluoropyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51, fer-butyl (R)piperidin-3-ylcarbamate was used instead of (R)-methyl(peridin-3yl)fer-butylcarbamate. 1H-NMR (300 MHz, CDCI3): δ 7.56 (m, 1H), 7.12 (m, 3H), 6.67 (s, 1H), 6.35 (m, 1H), 6.19 (m, 1H), 4.41 (m, 2H), 3.49 (m, 5H), 3.35 (m, 2H), 2.96 (m, 2H), 2.42 (m, 1H) , 2.35 (m, 1H), 2.09 (m, 2H), 1.77 (m, 2H), 1.24 (m, 1H). MS (ESP): [M+H]+m / z 495.2 Example 62: Preparation of 4-(3-((R)-3-aminopiperidine-1-carbon¡l)-1-(2fluoro-4-((S)-3-fluoropyrrolidin-1 -yl)phenyl)-1H -pyrazole“5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy -ethyl 4-oxobut-2-enolate, in Step 2) of Example 51 (S)-3-fluoropyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 (R)piperidin- was used Fer-butyl 3-ylcarbamate instead of (R)-methyl(piperidin-3yl)fer-butyl carbamate. IF-2019-01451929-APN-ANP#INPI Page 104 of 160 1051H-NMR (300 MHz, CDCh): δ 7.57 (m, 1H), 7.14 (m, 4H), 6.36 (m, 1H), 6.19 (m, 1H), 4.46 (m, 2H), 3.51 (m, 4H), 3.24 (m, 2H), 2.94 (m, 1H), 2.41 (m, 2H), 2.03 (m, 1H) , 1.96 (m, 2H), 1.76 (m, 1H), 1.24 (m, 1H). MS (ESP): [M+H]+m / z 495.2 Example 63: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4(3,3-difluoropyrrolidin-1-yl)-2-fluorophenyl)-1 / - / -pyrazol-5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxyl-4-oxobut-2~ enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy- ethyl 4-oxobut-2-enolate, in Step 2) of Example 51 3,3-difluoropyrrolidine hydrochloride was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 (R)-piperidin- tert-butyl 3-ylcarbamate instead of (R)-methyl(piperidin-3yl)fer-butylcarbamate. IF-2019-01451929-APN-ANP#INPI Page 105 of 160 1061H-NMR (300 MHz, CDCh): δ 7.60 (m, 1H), 7.12 (m, 2H), 7.00 (s, 1H), 6.37 (m, 1H), 6.26 (m, 1H), 3.75 (m, 4H), 3.24 (m, 1H), 2.97 (m, 1H), 2.60 (m, 2H), 2.49 (m, 1H) , 2.00 (m, 1H), 1.82 (m, 5H) MS (ESP): [M+H]+m / z 513.2 Example 64: Preparation of (R)-4-(1-(4-(3,3-difluoropyrrolidin-1-yl)-2fluorophenyl)-3-(3-(methylamino)piperidinea-1-carbonyl)-1 / 7-pyrazol-5-yl)-2fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy¡-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4- ethyl oxobut-2-enolate and in Step 2) of Example 51 3,3-difluoropyrrolidine was used instead of dimethylamine hydrochloride. 1H-NMR (300 MHz, CDCI3): δ 7.56 (t, 1H), 7.15 (d, 1H), 7.09 (d, 1H), 7.00 (m, 1H), 6.35 (m, 1H), 6.22 (d, 1H), 4.47 (m, 2H), 3.69 (t, 2H), 3.56 (t, 3H), 3.15 (m, 2H) , 2.67 (m, 2H), 2.54 (s, 3H), 1.99 (m, 1H), 1.82 (m, 2H), 1.54 (m, 2H) MS (ESP): [M+H]+m / z 527.2 Example 65: Preparation of 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2fluoro-4-(3-methoxypyrrolidin-1-yl)phenyl)-1 / 7-pyrazole-5 -yl)-2-fluorobenzonitrile IF-2019-01451929-APN-ANP#INPI Page 106 of 160 107 The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate, in Step 2) of Example 51 methoxypyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 fer-butyl (R)piperidin-3-ylcarbamate was used instead of Fer-butyl (R)-methyl(piperidin-3yl)carbamate, 1H-NMR (300 MHz, CDCh): δ 7.59 (m, 1H), 7.25 (m, 3H), 7.01 (s, 1H), 6.37 (m, 1H), 6.24 (m, 1H), 4.47 (s, 2H), 4.24 (m, 1H), 4.14 (s, 1H) 3.52 (m, 7H), 3.32 (m, 1H), 3.01 (s, 1H), 2.91 (m, 1H), 2.21 (m, 2H), 2.02 (s, 1H), 1.60 (m, 2H), 1.49 (s , 1 HOUR) MS (ESI+): [M+H]+m / z 507.2 Example 66: Preparation of 2-fluoro-4-(1-(2-fluoro-4-(3-methoxypyrrolidin1-yl)phenyl)-3-((R)-3-(methylamino)piperidin-1 -carbonyl)-1H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, in Step 1) of Example 51 except that (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut -2-enolate IF-2019-01451929-APN-ANP#INPI Page 107 of 160 108 ethyl and in Step 2) of Example 51 methoxypyrrolidine was used instead of dimethylamine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 7.59 (m, 1H), 7.21 (m, 3H), 7.03 (m, 1H), 6.35 (m, 1H), 6.23 (m, 1H), 4.43 (m, 2H), 4.14 (s, 1H), 3.51 (m, 8H), 3.28 (m, 1H), 2.77 (s, 1H) , 2.58 (s, 3H), 2.22 (m, 3H), 1.83 (s, 1H), 1.59 (m, 2H) MS (ESP): [M+H]+m / z 521.2 Example 67: Preparation of 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2fluoro-4-((S)-3-methoxypyrrolidin-1 -yl)phenyl)-1H-pyrazole -5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate, in Step 2) of Example 51, (S)-3-methoxypyrrolidine hydrochloride was used instead of dimethylamine hydrochloride and in Step 3) of Example 51, (R)-piperidin-3-ylcarbamate was used of tert-butyl instead of tert-butyl (R)methyl(piperidin-3-yl)carbamate. either / IF-2019-01451929-APN-ANP#INPI Page 108 of 160 1091H-NMR (300 MHz, CDCh): δ 7.59 (m, 1H), 7.25 (m, 3H), 7.01 (s, 1H), 6.37 (m, 1H), 6.24 (m, 1H), 4.47 (s, 2H), 4.24 (m, 1H), 4.14 (s, 1H) 3.52 (m, 7H), 3.32 (m, 1H), 3.01 (s, 1H), 2.91 (m, 1H), 2.21 (m, 2H), 2.02 (s, 1H), 1.63 (m, 2H), 1.49 (s , 1H) (ESI*): [M+Hj* m / z 507.2 Example 68: Preparation of 2-fluoro-4-(1-(2-fluoro-4-((S)-3methoxypyrrolidin-1-yl)phenyl)-3-((R)-3-(methylamino)piperidine-1 -carbonyl)-1Hpyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate and in Step 2) of Example 51 (S)-3methoxypyrrolidine hydrochloride was used instead of dimethylamine hydrochloride. F [ j i ft J ( / 'NH1H-NMR (300 MHz, CDCh): δ 7.59 (m, 1H), 7.21 (m, 3H), 7.03 (m, 1H), 6.35 (m, 1H ), 6.23 (m, 1H), 4.43 (m, 2H), 4.14 (s, 1H), 3.51 (m, 8H), 3.28 (m, 1H), 2.77 (s, 1H), 2.58 (s, 3H), 2.22 (m, 3H), 1.83 (s, 1H), 1.59 (m, 2H) MS (ESI*): [M+H]* m / z 521.2 Example 69: Preparation 4-(3-((R)-3-aminopiperididine-1-carbonyl)-1-(2fluoro-4-((R)-3-methoxypyrrolidin-1 -yl)phenyl)-1 H -pyrazol-5-yl)-2-fluorobenzonitrile IF-2019-01451929-APN-ANP#INPI Page 109 of 160 110 The desired compound was obtained in substantially the same manner as in Example 51, in Step 1) of Example 51 except that (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate, in Step 2) of Example 51, (R)-3-methoxypyrrolidine hydrochloride was used instead of dimethylamine hydrochloride and in Step 3) of Example 51, (R)-piperidin-3-ylcarbamate was used of fer-butyl instead of (R)methyl(piperidin-3-yl)carbamate of fer-butyl. 1H-NMR (300 MHz, DMSO-cfe): δ 7.95 (t, 1H), 7.53 (d, 1H), 7.42 (m, 1H), 7.25 (d, 1H), 7 .15 (m, 1H), 6.47 (m, 2H), 4.35 (m, 3H), 3.43 (m, 5H), 2.08 (m, 2H), 2.06 (m, 4H), 1.23 (m, 1H), 1.11 (m, 1H) MS (ESP): [M+H]+m / z 507.2 Example 70: Preparation of 2-fluoro-4-(1-(2-fluoro-4-((R)-3~methoxypyrrolídin-1-yl)pheníl)3-((R)-3-(methylamino ) piperidine-1-carbonyl)-1H-pyrazole-5-l)benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut -2-enolate IF-2019-01451929-APN-ANP#INPI Page 110 of 160 Ill ethyl and in Step 2) of Example 51 (R)-3methoxypkrolidine hydrochloride was used instead of dimethylamine hydrochloride. 1H-NMR (300 MHz, DMSO-d6): δ 7.95 (t, 1H), 7.56 (d, 1H), 7.41 (m, 1H), 7.35 (d, 1H), 7 .25 (s, 1H), 6.46 (m, 2H), 4.35 (m, 3H), 3.43 (m, 2H), 2.88 (m, 1H), 2.33 (m, 3H), 2.10 (m, 2H), 1.90-1.85 (m, 2H), 1.35 (m, 2H) MS (ESP): [M+H]+m / z 521.2 Example 71: Preparation of 2-fluoro-4-(1-(2-fluoro-4-((S)-3ethoxypyrrolidin-1 -yl)phenyl)-3-((R)-3-(methylamino)pipendine-1 -carbonyl)-1 / - / -pyrazol5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate and in Step 2) of Example 51 (S)-3ethoxypyrrolidine hydrochloride was used instead of dimethylamine hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 111 of 160 1121H-NMR (300 MHz, CDCh): δ 7.58 (m, 1H), 7.16 (m, 4H), 6.33 (d, 1H), 6.21 (dd, 1H), 4.32 (m, 2H), 3.62 (m, 4H), 3.40 (m, 2H), 3.18 (s, 1H), 2.74 (m, 3H), 2.22 (m, 3H) , 1.89 (m, 2H), 1.66 (m, 4H), 1.25 (t, 3H) MS (ESP): [M+H]+m / z 535.2 Example 72: Preparation of 4-(3-((R)3-aminopiperidine-1-carbonyl)-1-(2fluoro-4“(3-hydroxypyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl) -2“fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride, used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut -ethyl 2-enolate, in Step 2) of Example 3-hydroxypyrroiidine was used instead of dimethylamine hydrochloride 51 and in Step 3) of Example 51 tert-butyl (R)piperidin-3-ylcarbamate was used in instead of tert-butyl (R)-methyl(piperidin-3yl)carbamate. 1H-NMR (300 MHz, CDCI3): δ 7.47 (t, 1H), 7.07 (m, 3H), 6.87 (s, 1H), 6.25 (d, 1H), 6.11 (d, 1H), 4.46 (m, 1H), 4.30 (m, 2H), 3.50 (m, 2H), 3.26 (m, 2H), 3.00 (m, 3H) , 2.02 (m, 3H), 1.53 (m, 3H) MS (ESP): [M+H]+m / z 493.2 IF-2019-01451929-APN-ANP#INPI Page 112 of 160 113 Example 73: Preparation of 2-fluoro-4-(1-(2-fluoro-4-((S)-3chloropyrrolidin-1-yl)phenyl)-3-(( / ?)-3-(methylamino)piperidine- 1-carbonyl)-1 / 7-pyrazol5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride, used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut~2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate and in Step 2) of Example 51 (S)-3-chloropyrrolidine hydrochloride was used instead of dimethylamine hydrochloride. cl 1H-NMR (300 MHz, CDCh): δ 7.58 (t, 1H), 7.22 (m, 3H), 7.03 (s, 1H), 6.35 (d, 1H), 6.24 (dd, 1H), 4.68 (m, 1H), 4.32 (s, 1H), 3.81 (m, 6H), 2.94 (s, 1H), 2.64 (s, 1H) , 2.64 (m, 3H), 2.47 (m, 2H), 2.04 (s, 1H), 1.88 (s, 1H), 1.65 (s, 2H) MS (ESP): [M+H]+m / z 526.2 Example 74: Preparation of (ft)-4-(3-(3-aminopiperidine-1-carbonyl)-1(2,6-difluoro-4-(pyrrolidin-1-yl)phenyl)-1H-pyrazole-5- il)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51, (2,6-difluoro-4-iodophenyl)hydrazine hydrochloride was used instead of hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 113 of 160 114 of 4-iodophenylhydrazine, ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4 oxobut-2-enolate was used instead of (Z)-4-(4-cyanophenyl) -2-hydroxy-4-oxobut-2 enolate ethyl, in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 (R)piperidin-3-ylcarbamate was used of tert-butyl instead of tert-butyl (R)-methyl(piperidin-3yl)carbamate. 1H-NMR (300 MHz, CDCI3): δ 7.58 (t, 1H), 7.21 (d, 1H), 7.15 (d, 1H), 7.00 (m, 1H), 6.07 (d, 2H), 4.34 (m, 2H), 3.28 (m, 4H), 2.97 (m, 2H), 2.06 (m, 4H), 2.06 (m, 4H) MS (ESP): [M+H]+m / z 495.2 Example 75: Preparation of (R)-4-(3-(3-am¡nopiperidine-1-carbonyl)-1-(2chloro-4-(pyrrolidin-1-¡l)phenyl)-1 / 7-pyrazole- 5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-chloro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut -2-enolate IF-2019-01451929-APN-ANP#INPI Page 114 of 160 115 ethyl, in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 tert-butyl (R)-piperidin-3ylcarbamate was used instead of (R)-methyl terbutyl (piperidn-3-yl)carbamate. 1H-NMR (300 MHz, CDCI3): or 7.85 (d, 2H), 7.38 (d, 2H), 7.21 (d, 2H), 7.14 (d, 2H), 6.72 (m, 1H), 2.32 (s, 3H), 1.84 (m, 2H), 1.42-1.29 (m, 10H). MS (ESI+): [M+H]+m / z 493.2 Example 76: Preparation of (R)-4-(3-(3-aminopyridine-1-carbonyl)-1-(2methoxy-4-(pyrrolidin-1-yl)phenyl)-1 / - / - pyrazol-5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (4-bromo-2-methoxyphenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride. , ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate was used instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4 -ethyl oxobut-2-enolate, in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 tert-butyl (R)-piperidin-3ylcarbamate was used instead of (R)-methyl(piperidin-3-¡l)carbamate of ter- 1H-NMR (300 MHz, CDCI3): δ 7.50 (t, 1H), 7.13 (m, 3H), 6.98 (s, 1H), 6.16 (d, 1H), 5.97 (d, 1H), 4.43 (m, 2H), 3.49 (s, 3H), 3.32 (m, 4H), 3.00 (m, 2H), 2.04 (m,4H) , 1.48 (m, 5H) IF-2019-01451929-APN-ANP#INPI Page 115 of 160 116 MS (ESl·): [M+H]+m / z 489.2 Example 77: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2fluoro-4-(piperidin-1-yl)phenyl)-1 / 7-pyrazol-5-yl )benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that Step 1) of Example 51 used (2-fluoro-4-iodophenyl)hydrazine hydrochloride instead of 4-iodophenylhydrazine hydrochloride, in which Step 2) of Example 51 piperidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 fer-butyl (R)piperidin-3-ylcarbamate was used instead of (R)-methyl(piperidin-3yl )fer-butyl carbamate. 1H-NMR (300 MHz, DMSO-cfe): δ 7.84 (d, 2H), 7.47 (d, 2H), 7.44 (m, 1H), 7.05 (m, 1H), 6 .82 (m, 2H), 4.37 (m, 1H), 4.20 (m, 1H), 3.37 (m, 5H), 3.14 (m, 5H), 1.94 (m, 2H), 1.55 (m, 5H), 1.21 (m, 2H). MS (ESI+): [M+H]+m / z 473.2 Example 78: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2fluoro-4-(piperidin-1-yl)phenyl)-1 / 7-pyrazol-5-yl )-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride, used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy¡-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4- oxobut-2-enolate IF-2019-01451929-APN-ANP#INPI Page 116 of 160 117 ethyl, in Step 2) of Example 51 piperidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 tert-butyl (R)-piperidin-3ylcarbamate was used instead of (R)-methyl terbutyl (piperidin-3-yl)carbamate. 1H-NMR (300 MHz, CDCh): δ 7.59 (m, 1H), 7.24 (m, 3H), 7.02 (m, 1H), 6.73 (m, 1H), 6.59 (m, 1H), 4.46 (m, 2H), 3.42 (m, 5H), 3.00 (m, 2H), 2.16 (m, 1H), 2.04 (m, 4H) , 1.86 (m, 2H), 1.44 (m, 2H) MS (ESP): [M+H]+m / z 491.2 Example 79: Preparation of (R)-2-fluoro-4-(1-(2-fluoro-4-(pipendin-1“yl)phenyl)-3-(3-(methylamino)piperidine-1-carbonyl)- 1 / 7-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate and in Step 2) of Example 51 piperidine was used instead of dimethylamine hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 117 of 160 1181H-NMR (300 MHz, CDCh): δ 7.59 (m, 1H), 7.21 (m, 3H), 6.69 (m, 1H), 7.05 (m, 1H), 6.63 (m, 1H), 4.77 (m, 1H), 4.40 (m, 1H), 3.27 (m, 4H), 3.09 (m, 1H), 2.76 (m, 2H) , 2.45 (m, 2H), 2.18 (m, 1H), 1.83 (m, 6H), 1.67 (m, 4H). MS (ESP): [M+H]+m / z 422.2 Example 80: Preparation of 4-(3-((R)3-aminopiperidine-1“Carbonyl)-1-(2fluoro-4-(3-methylpiperidin-1-yl)phenyl)-1H-pyrazol-5-yl) -2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate and in Step 2) of Example 51 3-methylpiperidine was used instead of dimethylamine hydrochloride. 1H-NMR (300 MHz, CDCI3): δ 7.54 (t, 1H), 7.16 (m, 4H), 6.69 (d, 1H), 6.51 (d, 1H), 4.43 (m, 2H), 3.63 (m, 2H), 3.17 (m, 7H), 2.45 (m, 1H), 1.71 (m, 7H), 1.21 (m, 1H) , 0.96 (d, 3H). MS (ESP): [M+H]+m / z 505.2 Example 81: Preparation of ( / ?)-4-(3(3-aminopiperidine-1-carbonyl)-1-(2fluoro-4-(4-methylpiperidin-1-yl)phenyl)-1 / - / - pyrazol-5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 IF-2019-01451929-APN-ANP#INPI Page 118 of 160 119 used (2-fluoro-4-iodophenyl)hydrazine hydrochloride instead of 4-iodophenylhydrazine hydrochloride and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate was used instead of ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut-2-enolate and in Step 2) of Example 51 4-methylpiperidine was used instead of dimethylamine hydrochloride. 1H-NMR (300 MHz, CDCh): 7.68 (m, 1H), 7.27 (m, 4H), 6.79 (d, 1H), 6.64 (d, 1H), 4.52 ( m, 1H), 3.84 (m, 2H), 3.42 (m, 2H) 3.05 (m, 2H), 2.89 (m, 2H), 1.82 (m, 9H), 1 .47 (m, 2H), 1.16 (d, 3H) MS (ESP): [M+H]+m / z 505.2 Example 82: Preparation of 4-(3-((R)3-aminopiperidine-1-carbonyl)-1-(4(3,5-dimethylpiperidin-l -yl)-2-fluorophenyl)-1 / 7-pyrazole- 5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy¡-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4- ethyl oxobut-2-enolate and in Step 2) of Example 51 3,5-dimethylpiperidine was used instead of dimethylamine hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 119 of 160 1201H-NMR (300 MHz, CDCh): δ 7.94 (d, 2H), 7.48 (m, 3H), 7.22 (m, 2H), 6.82 (a, 2H), 4.16 (m, 3H), 3.77 (m, 2H), 2.87 (m, 2H), 2.32 (m, 2H), 1.67 (m, 4H), 1.40 (m, 4H) , 1.50 (d, 6H) MS (ESP): [M+H]+m / z 519.3 Example 83: Preparation of (R)-4-(1-(4-([1,4'-bipiperidino]-T-yl)-2fluorophenyl)-3-(3-aminopiperidine-1-carbonyl)-1 / - / -pyrazol-5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut ethyl -2-enolate and in Step 2) of Example 51 1,4-bipiperidine was used instead of dimethylamine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 7.94 (m, 1H), 7.51 (m, 2H), 7.25 (m, 2H), 6.82 (m, 2H), 4.34 (m, 4H), 3.83 (m, 4H), 3.31 (m, 6H), 2.75 (m, 4H), 1.86 (m, 4H), 1.36 (m, 6H) MS (ESP): [M+H]+m / z 574.2 Example 84: Preparation of (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(2fluoro-4-(piperidin-1-yl)phenyl)-1 H-pyrazol-5-yl) -2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 51, except that in Step 1) of Example 51 IF-2019-01451929-APN-ANP#INPI Page 120 of 160 121 used (2-fluoro-4-iodophenyl)hydrazine hydrochloride instead of 4-iodophenylhydrazine hydrochloride, (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate was used of ethyl instead of ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut-2-enolate, in Step 2) of Example 51 piperidine was used instead of dimethylamine hydrochloride and in In Step 3) of Example 51 tert-butyl (R)-azepane-3ylcarbamate was used instead of (R)-methyl(piperidin-3-yl)tert-butylcarbamate. 1H-NMR (300 MHz, CDCh): δ 7.59 (m, 1H), 7.27 (m, 4H), 6.72 (m, 1H), 6.69 (m, 1H), 4.32 (m, 1H), 4.29 (m, 1H), 3.86 (m, 4H), 3.49 (m, 1H), 3.29 (m, 5H), 3.01 (m, 1H) , 1.95 (m, 3H), 1.71 (m, 3H) MS (ESP): [M+H]+m / z 505.3 Example 85: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(1“methyl-1 H-indazol-6-yl)-1 H-pyrazol-5-yl) benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, 6-hydrazinyl-1-methyl-1 H-indazole hydrochloride was used instead of ( 4-cyclopropylphenyl)hydrazine. IF-2019-01451929-APN-ANP#INPI Page 121 of 160 1221H-NMR (300 MHz, CDCI3): δ 8.29 (s, 2H), 7.79 (m, 3H), 7.39 (m, 3H), 7.08 (m, 1H), 4.29 (m, 2H), 4.06 (s, 3H), 3.05 (m, 2H), 1.84 (m, 3H), 1.61 (m, 2H) MS (ESP): [M+H]+m / z 426.2 Example 86: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2methylbenzo[c(|thiazol~5-yl)-1 H-pyrazol-5-yl) benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, 5-hydrazinyl-2-methylbenzo[c / ]thiazole hydrochloride was used instead of ( 4-cyclopropylphenyl)h idrazine. 1H-NMR (300 MHz, CDCI3): δ 7.84 (m, 2H), 7.56 (m, 2H), 7.36 (m, 3H), 7.01 (s, 1H), 4.29 (m, 2H), 4.12 (s, 2H), 3.23 (m, 2H), 2.23 (s, 3H), 1.61 (m, 2H), 1.56 (m, 1H) . MS (ESP): [M+H]+m / z 373.2 Example 87: Preparation of (R)-4-(3-(3-aminopiper¡dine-1-carbonyl)-1(2,3-dihydro-1H-indan-5-yl)-1 / 7-pyrazole -5-yl)benzoniumtrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (2,3,-dihydro-1H-indan-5-yl)hydrazine hydrochloride was used in instead of (4-cyclopropylphenyl)hydrazine hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 122 of 160 123 1H-NMR (300 MHz, DMSO-ó6): δ 7.85 (d, 2Η), 7.45 (d, 2H), 7.26 (d, 2H), 6.99 (m, 2H), 4 .16 (m, 2H), 3.09 (m, 2H), 2.88 (c, 4H), 2.63 (m, 2H), 2.04 (m, 2H), 1.87 (m, 2H), 1.70 (m, 1H), 1.35 (m, 1H), 1.28 (m, 1H). MS (ESP): [M+H]+m / z 412.2 Example 88: Preparation of (R)-4-(3-(3-aminopiperidine~1~carbon¡l)-1“ (2,3-dihydrO“1H“inden-5-yl)-1 / - / -pyrazole -5“yl)“2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that (2,3-dihydro-1 / 7-inden-5-yl)hydrazine hydrochloride was used in Step 1) of Example 1. instead of (4-cyclopropylphenyl)hydrazine hydrochloride and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy4-oxobut-2-enolate was used instead of (Z)- Ethyl 4-(4-cyanophenyl)-2-hydroxy-4-oxobuL2enolate. 1H-NMR (300 MHz, CDCI3): δ 7.54 (t, 1H), 7.13 (m, 4H), 6.93 (m, 2H), 4.43 (m, 2H), 4.16 (m, 3H), 3.99 (m, 1H), 3.32 (m, 1H), 2.95 (m, 4H), 2.18 (m, 4H), 1.87 (m, 2H) . MS (ESP): [M+H]+m / z 430.2 IF-2019-01451929-APN-ANP#INPI Page 123 of 160 124 Example 89: Preparation of (R)-4-(1 -(2,3-dihydro-1 / 7-índen-5-yl)-3-(3(methylamino)piperidine-1-carbonyl)-1 / - / -pyrazole-5-l)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that (2,3-dihydro-1 / 7-inden-5-yl)hydrazine hydrochloride was used in Step 1) of Example 1. instead of (4-cyclopropylphenyl)hydrazine hydrochloride and in Step 3) of Example 1 tert-butyl (R)methyl(piperidin-3-yl)carbamate was used instead of (R)-piperidin-3-ylcarbamate tert-butyl. 1H-NMR (300 MHz, DMSO-c / 6): δ 7.84 (d, 2H), 7.46 (d, 2H), 7.25 (d, 2H), 7.04 (s, 1H) , 6.97 (d, 1H), 4.07 (m, 2H), 2.98 (m, 2H), 2.88 (c, 4H), 2.77 (m, 1H), 2.43 ( m, 1H), 2.20 (d, 3H), 2.04 (m, 2H), 1.90 (m, 1H), 1.73 (m, 1H), 1.31 (m, 2H). MS (ESP): [M+H]+m / z 426.2 Example 90: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1(2,3“dihydrobenzo[b][1,4]dioxin-6-yl)-1 / 7- pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that (2,3-dihydrobenzo-[b][1,4]dioxin-6 hydrochloride was used in Step 1) of Example 1 -yl)hydrazine instead of (4-cyclopropylphenyl)hydrazine hydrochloride. IF-2019-01451929-APN-ANP#INPI Page 124 of 160 125 1H-NMR (300 MHz, CDCh): δ 7.61 (d, 2H), 7.36 (d, 2H), 6.95 (d, 1H), 6.83 (m, 2H), 6.87 (d, 1H), 4.44 (m, 2H), 4.28 (s, 4H), 3.28 (m, 2H), 2.98 (m, 1H), 1.91 (m, 2H) , 1.34 (m, 2H). MS (ESP): [M+H]+m / z 430.2 Example 91: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1(quinolin-6-yl)-1 H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 6-hydrazinylquinoline hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 8.99 (d, 1H), 8.11 (t, 2H), 7.75 (s, 1H), 7.60 (d, 3H), 7.48 (m, 1H), 7.37 (d, 2H), 7.03 (d, 1H), 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H) , 1.84 (m, 2H), 1.67 (m, 2H). MS (ESP): [M+H]+m / z 423.2 Example 92: Preparation of (R)-4-(3-(3-aminopiper¡dine-1-carbonyl)-1(quinolin-3-yl)-1 / - / -pyrazol“5”yl)benzonitrile IF-2019-01451929-APN-ANP#INPI Page 125 of 160 126 The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 3-hydrazinylquinoline hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCI3): δ 8.82 (s, 1H), 8.15 (d, 1H), 8.09 (s, 1H), 7.81 (t, 2H), 7.64 (t, 3H), 7.38 (d, 2H), 7.06 (s, 1H), 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H) , 1.84 (m, 2H), 1.67 (m, 2H). MS (ESP): [M+H]+m / z 423.2 Example 93: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(1methyl-1 H-pyrrolo[2,3“¿)]pyridin-5-yl)-1 H -pyrazol-5-yl)benzonitriium The desired compound was obtained in substantially the same manner as in Example 1, except that 5-hydraziniM-methyl-1 H-p i rrolo[2,3-ó]p hydrochloride was used in Step 1) of Example 1 indine instead of (4-cyclopropylphenyl)hydrazine hydrochloride. 1H-NMR (300 MHz, CDCh): δ 8.19 (d, 1H), 7.83 (s, 2H), 7.54 (d, 2H), 7.30 (m, 3H), 7.01 (s, 1H), 6.47 (s, 1H), 4.51 (m, 2H), 3.21 (m, 2H), 2.98 (m, 1H), 1.84 (m,2H) , 1.67 (m, 2H). IF-2019-01451929-APN-ANP#INPI Page 126 of 160 127 MS (ESE): [M+H]+m / z 426.2 Example 94) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(2hydroxy-2-methylpropii)phenyl)-1H-pyrazol-5-yl)- 2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that 1-(3-fluoro-4-hydrazinylphenyl)-2-methylpropan-2-hydrochloride was used in Step 1) of Example 1. ol instead of (4-cyclopropylphenyl)hydrazine hydrochloride and ethyl (Z)-4-(4-cyano-3fluorophenyl)-2-hydroxy-4-oxobut-2-enolate was used instead of ( Z)ethyl-4-(4-cyanophenyl)2-hydroxy-4-oxobut-2-enolate. 1H-NMR (300 MHz, CDCh): or 7.62 (t, 1H), 7.41 (t, 1H), 7.19 (m, 2H), 7.10 (m, 1H), 7.05 (m, 2H), 4.42 (m, 2H), 3.49 (m, 2H), 3.21 (m, 2H), 2.11 (m, 1H), 1.87 (m, 4H) , 1.37 (s, 6H). MS (ESE): [M+H]+m / z 480.2 Example 95: Preparation of 4-(3-(piperazine-1-carbonyl)-1-(p-tolyl)~1 / 7pyrazole-5-¡l)benzonitril The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-methylphenyl)hydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in the Step 3) of Example 1, tert-butyl piperazine-1carboxylate was used instead of tert-butyl ( / ?)-piperidin-3-ylcarbamate. IF-2019-01451929-APN-ANP#INPI Page 127 of 160 128 Ή-NMR (300 MHz, DMSO-d6): δ 7.84 (d, 2H), 7.44 (d, 2H), 7.27 (m, 4H), 7.04 (s, 1H), 3 .83 (m, 2H), 3.56 (m, 2H), 2.72 (m, 4H), 2.33 (s, 1H). MS (ESP): [M+H]+m / z 372.2 Example 96: Preparation of 4-(3-(3-(aminomethyl)piperidine-1-carbonyl)-1(p-tolyl)-l H-pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-methylphenyl)hydrazine hydrochloride was used instead of (4-cyclopropylphenyl) hydrochloride. hydrazine and in Step 3) of Example 1 tert-butyl (piperidin-3ylmethyl)carbamate was used instead of (R)-piperidin-3-ílcarbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.84 (d, 2H), 7.44 (d, 2H), 7.27 (m, 4H), 7.02 (s, 1H), 4 .49 (m, 2H), 3.21 (m, 1H), 3.00 (m, 1H), 2.69 (m, 1H), 2.41 (m, 1H), 2.35 (s, 3H), 1.83 (m, 4H), 1.45 (m, 2H), 1.34 (m, 1H). MS (ESI+): [M+H]+m / z 400.2 Example 97: Preparation of (S)-5-(4-cyanophenyl)- / V-(1(methylsulfonyl)piperidin-3-yl)-1-(p-tolyl)-1 / - / -pyrazole-3-carboxamide IF-2019-01451929-APN-ANP#INPI Page 128 of 160 129 The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 3) of Example 1 (S)-1-(methylsulfonyl)piperidin-3-amine was used instead of (R). -fer-butyl piperidin-3ylcarbamate. 1H-MRI (300 MHz, CDCIs): or 7.60 (d, 2H), 7.32 (d, 2H), 7.19 (m, 4H), 7.10 (s, 1H), 4.35 (m, 1H), 3.49 (m, 1H), 3.22 (m, 3H), 2.82 (s, 3H), 2.41 (s, 3H), 1.84 (m, 4H) . MS (ESP): [M+H]+m / z 464.2 Example 98: Preparation of 4-(3-(2,7-diazaspiro[3.5]nonane-7carbonyl)-1-(p-tolyl)-1 / - / -pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 3) of Example 1, fer-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate was used instead of Fer-butyl (R)piperidin-3-ylcarbamate. 1H-NMR (300 MHz, CDCI3): or 7.61 (d, 2H), 7.34 (d, 2H), 7.18 (m, 4H), 6.97 (s, 1H), 4.01 (m, 2H), 3.88 (s, 4H), 3.72 (m, 2H), 2.39 (s, 3H), 1.98 (m, 4H). MS (ESP): [M+H]+m / z 412.2 IF-2019-01451929-APN-ANP#INPI Page 129 of 160 130 Example 99: Preparation of 4-(3-(2,8-diazaspiro[4.5]decane-8carbonyl)-1-(p-tolyl)-1 / - / -pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 3) of Example 1 tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate was used instead of (R) tert-butyl piperidin-3-ylcarbamate. 1H-NMR (300 MHz, CDCh): or 7.60 (d, 2H), 7.34 (d, 2H), 7.16 (m, 4H), 6.98 (s, 1H), 3.91 (m, 6H), 3.35 (m, 4H), 2.38 (s, 3H), 1.98 (m, 4H). MS (ESP): [M+H]+m / z 426.2 Example 100: Preparation of 4-(3-(octahydro-1H-pyrrolo[2,3-c]pyridino-6carbonyl)-1-(p-tolyl)-1 / - / -pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that tertiary octahydro-1H-pyrrolo[2,3-c]pindino-1-carboxylate was used in Step 3) of Example 1. butyl instead of tert-butyl (R)-piperidin-3-ylcarbamate. IF-2019-01451929-APN-ANP#INPI Page 130 of 160 1311H-NMR (300 MHz, CDCh): δ 7.61 (t, 2H), 7.32 (t, 2H), 7.18 (m, 4H), 7.00 (s, 1H), 4.24 (m, 1H), 3.82 (m, 2H), 3.77 (m 2H), 3.49 (m, 3H), 2.4 (s, 3H) 1.84 (m, 5H) MS (ESP): [M+H]+m / z 412.2 Example 101: Preparation of 4-(3-(3,7-diazabicyclo[3.3.1]nonane-3carbonyl)-1-(2-fluoro-4-isopropylphenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (2-fluoro-4-isopropylphenyl)hydrazine hydrochloride was used instead of (4- cyclopropylphenyl)hydrazine and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy4-oxobut-2-enolate was used instead of (Z)-4-(4-cyanophenyl)-2- ethyl hydroxy-4-oxobut-2enolate and in Step 3) of Example 1 fer-butyl 3,7diazabicyclo[3.3.1]nonane-3-carboxylate was used instead of (R)-piperidin-3ylcarbamate tert-butyl. 1H-NMR (300 MHz, CDCh): δ 7.59 (t, 1H), 7.37 (t, 1H), 7.15 (m, 1H), 7.06 (m, 2H), 6.99 (m, 2H), 4.80 (m, 2H), 3.35 (m, 4H), 3.02 (m, 2H), 2.93 (m, 1H), 2.05 (m, 2H) , 1.85 (d, 2H), 1.29 (d, 6H). MS (ESP): [M+H]+m / z 476.2 Example 102: Preparation of 4-(3-(3-amino-8-azabicyclo[3.2.1]octane-8carbonyl)-1-(2-fluoro-4-isopropylphenyl)-1 / 7-pyrazol-5-yl) -2-fluorobenzonitrile IF-2019-01451929-APN-ANP#INPI Page 131 of 160 132 The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1, (2-fluoro-4-isopropylphenyl)hydrazine hydrochloride was used instead of (4- cyclopropylphenyl)hydrazine and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy¡4-oxobut-2-enolate was used instead of (Z)-4-(4-cyanophenyl)- ethyl 2-hydroxy-4-oxobut-2enolate and in Step 3) of Example 1 tert-butyl (8azabicyclo[3.2.1]octane-3-yl)carbamate was used instead of (R)-piperidin-3ylcarbamate tert-butyl. 1H-NMR (300 MHz, CDCIs): δ 7.57 (t, 1H), 7.38 (t, 1H), 7.15 (m, 3H), 7.04 (m, 2H), 5.20 (m, 1H), 4.87 (m, 1H), 3.47 (m, 1H), 2.98 (m, 1H), 2.36 (m, 6H), 2.05 (m, 4H) , 1.27 (d, 6H). MS (ESP): [M+H]+m / z 476.2 Example 103: Preparation of 4-(3-(3-amino-8-azabicyclo[3.2.1]octane-8carbonyl)-1-(2-fluoro-4-pyrrolidin-1-yl)phenyl-1 / 7 -pyrazol-5-yl)-2-fluorobenzonitotrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2 IF-2019-01451929-APN-ANP#INPI Page 132 of 160 133 ethyl enolate instead of ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut-2-enolate, in Step 2) of Example 1 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 1 tert-butyl (8-azabicyclo[3.2.1]octane3“yl)carbamate was used instead of tert-butyl ( / ?)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, CDCh): δ 7.57 (t, 1H), 7.12 (m, 3H), 7.01 (m, 1H), 6.21 (m, 1H), 6.17 (d, 1H), 4.85 (m, 1H), 4.46 (m, 2H), 3.31 (m, 4H), 2.87 (m, 1H), 2.43 (m, 3H) , 2.05 (m, 6H), 1.57 (m, 2H). MS (ESI+): [M+H]+m / z 503.2 Example 104: Preparation of 4-(3-(3,7-diazabicyclo[3.3.1]nonane-3carbonyl)-1-(p-tolyl)-1 / - / -pyrazol-5-yl)benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that tert-butyl cyclo[3,3,1]nonane-3-diazabicarboxylate was used in Step 3) of Example 1. instead of tert-butyl ( / ?)piperidin-3-ylcarbamate. 1H-NMR (300 MHz, CDCh): δ 7.63 (d, 2H), 7.35 (t, 3H), 7.21 (m, 2H), 7.16 (m, 3H), 7.03 (s, 1H), 4.85 (d, 2H), 3.46 (m, 2H), 3.30 (m, 4H), 2.40 (s, 3H), 2.03 (m,2H) , 1.61 (m, 2H). MS (ESI+): [M+H]+m / z 412.2 Example 105: Preparation of 5-(4-cyanophenyl)- / V-(piperidín-4-yl)-1 -(p-tolyl)1H-pyrazole-3-carboxymide IF-2019-01451929-APN-ANP#INPI Page 133 of 160 134 The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) in Example 1, tert-butyl 4-aminopiperidine-1-carboxylate was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, DMSO-d6): δ 8.44 (d, 1H), 7.84 (d, 2H), 7.43 (d, 2H), 7.26 (c, 4H), 7 .18 (s, 1H), 4.05 (m, 1H), 3.26 (m, 2H), 2.94 (m, 2H), 2.35 (s, 3H), 1.90 (m, 2H), 1.73 (m, 2H), 1.23 (m, 1H). MS (ESP): [M+H]+m / z 386.2 Example 106: Preparation of 5-(4-cyanophenyl)- / V-(1-methylpiperidin-4-yl)-1(p-tolyl)-1 / 7-pyrazole-3-carboximide The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) In Example 1, 1-methylpiperidin-4-amine was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. IF-2019-01451929-APN-ANP#INPI Page 134 of 160 135 1H-NMR (300 MHz, DMSO-d6): δ 7.97 (d, 1H), 7.84 (d, 2H), 7.44 (d, 2H), 7.25 (c, 4H), 7 .16 (s, 1H), 3.97 (m, 1H), 2.60 (m, 2H), 2.35 (s, 3H), 2.15 (s, 3H), 2.00 (m, 2H), 1.63 (m, 2H), 1.42 (m, 2H). MS (ESP): [M+H]+ m / z 400.2 Example 107: Preparation of (R)-5-(4-cyanophenyl)- / V-(1-methylpiperidin-3-yl)1-(p-tolyl)-l H-pyrazole-3-carboximide The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) In Example 1, (R)-1methylpiperidin-3-amine was used instead of tert-butyl (R)-piperidin-3-ylcarbamate. 1H-NMR (300 MHz, DMSO-d6): δ 7.84 (d, 2H), 7.45 (d, 2H), 7.24 (c, 4H), 7.13 (s, 1H), 3 .93 (m, 2H), 3.72 (m, 2H), 3.36 (m, 2H), 3.17 (m, 2H), 2.39 (s, 3H), 2.32 (d, 3H), 1.96 (m, 2H), 1.72 (m, 1H). [M+H]+m / z 400.2 Example 108: Preparation of (S)-5-(4-cyanophenyl)- / V-(1-methylpiperidin-3-yl)1-(p-tolyl)-1 / 7-pyrazole-3-carboximide The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4 IF-2019-01451929-APN-ANP#INPI Page 135 of 160 136 cyclopropylphenyl)hydrazine and in Step 3) of Example 1 (S)-1methylpiperidin-3-amine was used instead of (R)-piperidin-3-ylcarbamate of fer-butyl. 1H-NMR (300 MHz, DMSO-de): δ 8.14 (d, 1H), 7.84 (d, 2H), 7.43 (d, 2H), 7.26 (c, 4H), 7 .15 (s, 1H), 3.68 (m, 1H), 2.73 (d, 2H), 2.34 (s, 3H), 2.15 (s, 3H), 1.94 (t, 2H), 1.60 (m,4H). MS (ESP): [M+H]+ m / z 400.2 Example 109: Preparation of (R)-5-(4-cyanophenyl)- / V-(1-methylpyrrolidin-3-yl)1 -(p-tolyl)-l H-pyrazole-3-carboximide The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 p-tolylhydrazine hydrochloride was used instead of (4cyclopropylphenyl)hydrazine hydrochloride and in Step 3) In Example 1, (R)-1methylpyrrolidino-3-amine was used instead of (R)-fer-butyl piperidin-3-ylcarbamate. 1H-NMR (300 MHz, DMSO-cfe): δ 8.19 (d, 1H), 7.84 (d, 2H), 7.44 (d, 2H), 7.26 (c, 4H), 7 .16 (s, 1H), 4.39 (m, 1H), 2.59 (m, 2H), 2.37 (m, 2H), 2.34 (s, 3H), 2.24 (s, 3H), 2.13 (m, 1H), 1.75 (m, 1H). MS (ESP): [M+H]+ m / z 386.2 IF-2019-01451929-APN-ANP#INPI Page 136 of 160 137 Example 110: Preparation of 5-(4-cyano-3-fluorophenyl)-1-(2-fluoro-4-(pyrrolidin-1 -yl)phenyl) / V-methyl-A / -(pipehdin-3-yl)-1H- pyrazole-3-carboximide The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride. and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate was used instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4 -ethyl oxobut-2-enolate, in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 3(methyl!amino)piperid¡n-1-carboxy was used tert-butyllate instead of tert-butyl (R)-piperidin-3ylcarbamate. 1H-NMR (300 MHz, CDCh): δ 7.57 (m, 1H), 7.12 (m, 3H), 6.95 (m, 1H), 6.33 (m, 1H), 6.16 (m, 1H), 4.59 (m, 1H), 3.29 (m, 6H), 3.17 (m, 2H), 2.86 (m, 3H), 2.04 (m, 4H) , 1.60 (m, 4H). MS (ESP): [M+H]+m / z 491.2 Example 111: Preparation of (S)-5-(4-cyano-3-fluorophenyl)-1-(2-fluoro-4(pyrrolidin-1-yl)phenyl)-A / -methyl-A / -(piperidin- 3-yl)-1 H-pyrazole-3-carboximide The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 51, (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4IF-2019 hydrochloride. -01451929-APN-ANP#INPI Page 137 of 160 138 iodophenylhydrazine and ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate was used instead of (Z)-4-(4-cyanophenyl)-2-hydroxy ethyl -4-oxobut-2-enolate, in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 (S)-3(methylamino)piperidin-l was used -fer-butyl carboxylate instead of (R)-fer-butyl piperidin-3ylcarbamate. 1H-NMR (300 MHz, CDCIs): δ 7.57 (m, 1H), 7.18 (m, 4H), 6.30 (m, 1H), 6.16 (m, 1H), 4.56 (m, 1H), 3.29 (m, 6H), 2.85 (m, 4H), 2.54 (m, 1H), 2.04 (m, 4H), 1.77 (m, 3H) , 1.57 (m, 1H). MS (ESP): [M+H]+m / z 491.2 Example 112: Preparation of (R)-5-(4-cyano-3-fluorophenyl)~1“(2-fluoro-4“ (pyrrolidin-1 -yl)phenyl)- / \ / -methyl-A / ~( piperidin-3-yl)-1H-pyrazole-3-carboximide The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 51 (2-fluoro-4-iodophenyl)hydrazine hydrochloride was used instead of 4-iodophenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyano-3-fluorophenyl)-2-hydroxy-4-oxobut-2enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut -2-enolate IF-2019-01451929-APN-ANP#INPI Page 138 of 160 139 ethyl, in Step 2) of Example 51 pyrrolidine was used instead of dimethylamine hydrochloride and in Step 3) of Example 51 fer-butyl (R)-3(methylamino)pipehdin-l-carboxylate was used instead of (R)-piperidin-3ylcarbamate of fer-butyl. 1H-NMR (300 MHz, CDCh): δ 7.45 (m, 1H), 7.08 (m, 4H), 6.11 (m, 1H), 6.07 (m, 1H), 4.78 (m, 1H), 3.50 (m, 8H), 2.19 (s, 3H), 1.60 (m, 8H). MS (ESP): [M+H]+m / z 491.2 Example 113: Preparation of (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1(4-cyclopropyl-2-fluorophenyl)-4-methyl-1 / 7-pyrazol-5-yl )benzonitrile The desired compound was obtained in substantially the same manner as in Example 1, except that in Step 1) of Example 1 (4-cyclo-2-fluorophenyl)hydrazine hydrochloride was used instead of 4-cyclopropylphenylhydrazine hydrochloride and used ethyl (Z)-4-(4-cyanophenyl)-2-hydroxy-3-methyl-4oxobut-2-enolate instead of (Z)-4-(4-cyanophenyl)-2-hydroxy-4-oxobut -2ethyl enolate. 1H-NMR (300 MHz, CDCh): δ 7.63 (t, 2H), 7.29 (t, 2H), 7.22 (m, 3H), 6.91 (d, 1H), 6.71 (d, 1H), 4.53 (m, 1H), 4.12 (d, 1H), 3.01 (m, 1H), 2.22 (s, 3H), 2.01 (m, 1H) , 1.86 (m, 2H), 1.06 (m, 2H), 0.72 (m, 2H). MS (ESP): [M+H]+m / z 444.2 Table 1 shows the structure of each compound obtained in Examples 1 to 113. IF-2019-01451929-APN-ANP#INPI Page 139 of 160 140 Table 1 Example Name Structure 1 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1-(4-cyclopropylphenyl)-1 H-pyrazol-5yl)benzonitrile O Ή^Ν\ / Ο Í_3^' NH2 2 (R)-4-(1-(4-cyclopropylphenyl)-3-(3methylaminopiperidine-1-carbonyl)-1Hpyrazol-5-yl)benzonitrile Cl or N | 3(R)-4-(3-(3-aminopiperidine-1-carbonyl)1-(4-cyclopropyl-2-fluorophenyl)-1H-pyrazol5-yl)benzon ytrile (IP 4(R)-4-(1 -(4-cyclopropyl-2-fluorophenyl)-3(3-(methylamino)piperidine-1-carbonyl)1 / 7-pyrazol-5-yl)benzonitrile 0 t \\___A ( )·”ΝΗ 5 (R)- 4-(3-(3-aminopiperidine-1-carbonyl)1-(4-cyclopropyl-2-fluorophenyl)-1H-pyrazol·5-yl)-2-fluorobenzonitrile z X 6 (R)-4-(1- (4-cyclopropyl-2-fluorophenyl)-3(3-(methylamino)piperidine-1-carbonyl)1H-pyrazol-5-yl)-2-fluorobenzonitrile L £ P and \\___( / X / Ο'ΛΗ ¡ . IF-2019-01451929-APN-ANP#INPI Page 140 of 160 141 7 (R)-4-(3-(3-aminoazepane-1-carbonyl)1 -(4-(cyclopropylphenyl)-1 / - / -pyrazol-5yl)benzonitrile Ό 8 (R)-4-(3-( 3-aminoazepane-1-carbonyl)1-(4-cyclopropyl-2-fluorophenyl)-1H-pyrazol5-yl)-2-fluorobenzonitrile ..: qX ZE w 9 4-(3-((3R,5R)-3 -amino-5methylpiperidine-1 -carbonii)-1 -(4cyclopropyl-2-fluorophenyl)-1H-pyrazol-5-yl)- 2-fluorobenzo nitri Io ζ / Γ n—\ Í 10 (R)4-(3- (3-aminopiperidine-1-carbonyl)1-(4-cyclopropyl-2,6-difluorophenyl)~1 Hpyrazol-5-yl)-2 “fluorobenzonitrile LT / ,p 11 (R)“4-(3-(3 -aminoazepane-1“Carbonyl)“ 1 -(4-cycloprop i I-2; 6-d ifluorophen i I)-1Hpyrazole-5yl)-2-fluorobenzonitrile V^^V-F cΓ O'*' F 12 (R)“ 4~(3-(3-aminopiperidine-1“Carbonyl)“ 1-(2-chloro-4-cyclopropylphenyl)-1H-pyrazol5-yl)-2-fluorobenzonitrile z I 13 (R)4“(3-(3 -aminoazepane-1 -carbonyl)-1 (2-chloro-4“Cyclopropylphenyl)-1H-pyrazole-5yl)-2-fluorobenzonitrile ijr ίι 'ίι N—< .Of O ' IF-2019-01451929-APN-ANP#INPI Page 141 of 160 142 14 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -phenyl-1 H-pyrazoF5-yl)benzonitrile OJQ Z X 15 (R)-4-(3-(3-aminopiperidine-1 -carbonyl)- 1 -(p i rid i n-2-i I)-1 H-ρί razol-5yl)benzonitrile 1 -(4-f I uorofen i I)-1 / 7-pyrazo!-5yljbenzonitrile F Q 0 17 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -(4-ciorofen i I)-1 H-pyrazol-5yl)benzonitrile Ck ' N H 2 18 (R)-4-(1-(4-chlorophenyl)-3-(3- (methylamino)piperidine-l -carbonyl)-1 HpyrazoF5-yl )benzonitrile Ck Λ \ )1 'NH n>- '-2 | 19 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -(3-chlorophenyl)-1 H-pyrazol-5yl)benzonitrile N 2 20 (R)-4-(3-(3 -aminopiperidine-1-carbonyl)- 1 -(4-bromophenyl)-1 / - / -pyrazol-5yl)benzonitrile V y' z z IF-2019-01451929-APN-ANP#INPI Page 142 of 160 143 21 (R)-4-(1-(4-bromophenyl)-3-(3- (methylamino)piperidine-1-carbonyl)-1Hpyrazol-5-yl)benzonitrile 22 (S)-4-(3-(3) -aminopyrrolidino-1-carbonyl)- 1 -(p-tolyl)-l H-pyrazol-5-yl)benzonitrile _0 23 (S)-4-(3-(3-(methylamino)pyrrolidino-1carbonyl)-1 - (p-to I i I)-1 H-pyrazol-5yl)benzonitrile —2 1 H-pyrazol-5yl)benzonitrile 25 (R)-4-(3-(3-(dimethylamino)pyrrolidino-1carbonyl)-1-(p-tolyl)-1H-pyrazol-5yl)benzonitrile cl __0 NT 1 26 (R)-4-(3-(3-(methylamino)pyrrolidino-1carbonyl)-1 -(p-tolyl)-l H-pyrazol-5yl)benzonitrile Q p 27 (R)-4-(3-(3 -aminopyrrolidino-1-carbonyl)- 1 -(p-to I i I)-1 / 7-pyrazol-5-yl)benzonitonlo X* z A IF-2019-01451929-APN-ANP#INPI Page 143 of 160 144 28 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -(p-tol il)-1 / 7-pi razo I-5-i I) benzon ytri Io CJ X Z γ O 29 (R)-4-(3-(3-(methylamino)piperidine-1carbonyl)-1 -(p-to I i I) -1 H-pyrazol-5yl)benzonitrile jC* OT 30 (R)-4-( 3-(3-(dimethylamino)piperidine-1carbonyl)-1 -(p-tolyl)-l H- py razo 1-5yl)benzonitrile A 31 (R)-4-(3-(3-aminopiperidine-1-carbonyl) )- 1 -(m-tolyl)-l H-pyrazol-5-yl)benzonitrile A. rV / 32 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -(o-tolyl )-l H-pyrazole-5-yl)benzonitrile x1 z o o 33 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1-(4-ethylphenyl)-1 / 7-pyrazole-5- yl)benzonitrile )benzonitrile V} O r I\ 35 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -(4-isopropylphenyl)-1 H-pyrazole-5yl)benzonitrile Q 'CX NH3 | IF-2019-01451929-APN-ANP#INPI Page 144 of 160 145 36 (R)-4-(1-(4-isopropylphenyl)-3-(3- (methylamino)piperidine-1-carbonyl)1 / 7- pyrazol-5-yl)benzonitrile Q PjO- / 37 (R)- 4-(3-(3-aminopiperidine-1-carbonyl)1 -(2-fluoro-4-isopropylphenyl)-1 H-pyrazol5-yl)benzonitrile L Γ 38 (R)-4-(3-(3-aminopiperidine -1-carbonyl)1-(2-fluoro-4-isopropylphenyl)-1H-pyrazol5-yl)-2-fluorobenzonitrile k Γ I 39 (R)-4-(3-(3-aminoazepane-1-carbonyl)1 -(2-fluoro-4-isopropylphenyl)-1 H-pyrazol5-yl)“2“fluorobenzonitrile IJJ \ J 40 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -(4- (ter-b uti l)phenyl)-1 H-pyrazole-5ii)benzonitnyl / X'lNHo 41 (R)-4-(1-(4-(tert-butyl)phenyl-3-(3methylaminopipendine-1 - carbonyl)-1 Hpyrazol-5-yl)benzonitrile Q W | 42 (R)-4-(3-(3-aminopiperidine-1-carbonyl)~ 1 -(4-(tert-butyl)-2-f I uo rofe n i I)-1 H-pyrazol5-yl)benzonitrile LA N o N x\_J' IF-2019-01451929-APN-ANP#INPI Page 145 of 160 146 43 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -(4-(tert-buty l-2-fl uorophen i I)-1 H-pyrazole· 5-yl)-2 -fluorobenzonitrile QÁO fluorobenzonitrile —\NH2 tA ​​T <^7 45 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1-(4-(trifluoromethoxy)phenyl)-1 / 7-pyrazole-5yl)benzonitrile w n \ O O z 3-(3-aminopiperidine-1-carbonyl)- 1 -(4-(trifluoromethyl)phenyl)-1 H-pyrazol-5yl)benzonitrile % \ ω X O o X 48 (R)-4-(3-(3- aminopiperidine-1-carbonyl)1-(2-fluoro-4-methylphenyl)-1 / - / -pyrazol-5yl)benzonitrile CT 0 X Λ \ / 'NHs na V- / 49 (R)-4-(3- (3-aminopiperidine-1-carbonyl)1 -(3-fluoro-4-methoxyphenyl)-1 H-pyrazol-5yl)benzonitrile X A V / w *3 Ξ. IF-2019-01451929-APN-ANP#INPI Page 146 of 160 147 50 (R)-4,4'-(3-(3-aminopiperidine-1carbonyl)-1H-pyrazole-1,5diyl)dibenzonitrile KN 0 O·™* 51 (R)-4-(1-(4-( dimethylamino)phenyl)-3-(3(methylamino)piperidine-l -carbonyl)-1 / 7pyrazole-5-ii)benzonitrile J X.2 A 52 (R)-4-(3-(3-aminopiperidine-1 -carbonyl)1-(4-((2- (dimethylamino)ethyl)(methyl)amino)phenyl)1H-pyrazol-5-yl)benzonitrile 1 <θ-ΝΗ2 53 ((R)-4-(3-( 3-aminopiperidine-1- carbonyl)-1-(4-(dimethylamino)phenyl)-1 / 7pyrazol-5-yl)benzonitrile 'op' z I w 54 (R)-4-(3-(3-aminopipendine- 1-carbonyl)- 1 -(4-(dimethylamino)-2-fluorophenyl)-1 Hpyrazol-5-yl)benzonitrile )1 -(4-(diethylamino)-2-fluorophenyl)-1 Hpyrazol-5-yl)benzonitrile ^2>·μΝΗ2 56 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1 -( 4-(azetidin-1 -i l)-2-fl uorofen i I) -1Hpyrazol-5-yl)benzonitrile mJH 1 Κ Ov^'0 z X ►J IF-2019-01451929-APN-ANP#INPI Page 147 of 160 148 57 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -(2-fluoro-4-(p i rro I id i n -1 -yl)phenyl)-1 Hpyrazol-5-yl) benzonitrile -yl)-2-fluorobenzonitrile iN (methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile Χφ,Ζ I' 60 (R)-4-(3-(3-aminoazepane-1-carbonyl)1 -(2-fluoro- 4-(pyrrolidin-1-yl)phenyl)-1 Hpyrazol“5-yl)-2-fluorobenzonitrile \ 0 -Q 0 )—z ' / / \ Ί z X 61 4-(3-((R)-3 -aminopiperidine-1-carbonyl)1-(2-fluoro-4-((R)-3-fluoropyrrolidin-1yl)phenyl)-1H-pyrazol-5-yl)-2fluorobenzonitrile If *N“\ 0J>NH2 N p 62 4-(3-((R)-3-aminopiperidine-1-carbonyl)1-(2-fluoro-4-((S)-3“fluoropyrrolidin-1 yl)phenyl)-1 H-pyrazole-5- il)-2- fluorobenzonitrile CM X 2 IF-2019-01451929-APN-ANP#INPI Page 148 of 160 149 63 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1 -(4-(3,3-difluoropyrrolidin-1 -yl)-2fluorophenyl)-1 / 7-pyrazol-5-yl)- 2fluorobenzonitrile Z z O^Z^ u. O & Q- *== 64 (R)-4-(1-(4-(3,3-difluoropyrrolidin-1-yl)-2fluorophenyl)-3-(3-(methylamino)piperidine1 -carbonyl)-1 H -pyrazol-5-yl)-2fluorobenzonitrile 1- ΰ 65 4-(3-((R)-3-aminopiperidine-1-carbonyl)- 1-(2-fluoro-4-(3-methoxypyrrolidin-1-yl) phenyl)-1 / 7-pyrazol-5-yl)-2- fluorobenzonitrile “fl—\ \ / 1^' 66 2-fluoro-4-(1 -(2-fluoro-4-(3- methoxypyrrolidin-1 - yl)phenyl)-3-((R)-3(methylamino)piperidine-1-carbonyl)-1H- pyrazol-5-yl)benzonitol oz LI Αχ O*H NXF 67 4-(3-((R)- 3-aminopiperidine-1-carbonyl)1 -(2-fluoro-4-((S)-3-methoxypyrrolidin-1 i l)phen i I)-1 H-pi razol-5-i l)-2fluorobenzonitrile z 68 2- fluoro-4-(1-(2-fluoro-4-((S)-3methoxypyrrolidin-1-yl)phenyl)-3-((R)-3(methylamino)piperidine-l -carbonyl)-1 H-pyrazole -5-yl)benzonitrile oZ θ-V^F LI .....nh 'F IF-2019-01451929-APN-ANP#INPI Page 149 of 160 150 69 4(3-((R)“3-aminopiperidine-1-carbonyl)1-(2-fluoro-4-((R)-3-methoxypyrrolidin-1yl)phenyl)-1 H-p i razol-5-i l) -2fluorobenzonitrile oz Ó F fij ·\_ / ΝΗ2 n^f 70 2-fluoro-4-(1-(2-fluoro-4-((R)-3- methoxypyrrolidin-1-yl)phenyl)-3-( (R)-3(methylamino)piperidine-l -carbonyl)-1 Hpyrazol-5-yl)benzonitrile oz O'NH F 71 2-fluoro-4-(1-(2-fluoro-4-((S)- 3ethoxypyrrolidin-1 -yl)phenyl)-3-(( / ?)-3(methylamino)piperidine-1-carbonyl)-1H- pyrazol-5-yl)benzonitrile F N--y f ft \ I \.... .NH J: 72 4-(3-((R)-3-aminopiperidine-1-carbonyl)1-(2-fluoro-4-(3-hydroxypyrrolidin-1- i l)phenyl)“1 / -Lpyrazole-5 -yl)-2- fluorobenzonitrile HO IT N~\ F 73 2-fluoro-4-(1-(2-fluoro-4-((S)-3chloropyrrolidin-1 -yl)phenyl)-3-(( / ? )-3(methylamino)piperidine-1-carbonyl)-1 / - / pyrazol-5-yl)benzonitrile fi \ ( 3.....NH F IF-2019-01451929-APN-ANP#INPI Page 150 of 160 151 74 (R)-4-(3-(3-aminopiperidine-1-carbonyl)~ 1 -(2,6-difluoro-4-(pyrrolidin-1-yl)phenyl)-1 Hpyrazole-5-ii)-2 -fluorobenzonitrile L Γ F , / w n-^ F 75 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1 -(2-chloro-4-(pyrrolidin-1-yl)phenyl)- 1 Hpyrazol-5-yl)-2-fluorobenzonitrile L Γ N--\ A F 76 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1 -(2-methoxy-4-(pyrrolidin-1 -yl)phenyl)-1 Hpyrazol-5-yl)-2-fluorobenzonitrile Li N \ 77 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1 -(2-fluoro-4-(piperidin -1-yl)phenyl)-1 / -7pyrazoi-5-yl)benzonitnyl 0 L IL n o Λα 78 (R)-4-(3-(3-aminopiperidine-1-carbonyl)~ 1 -(2-fluoro- 4-(piperidin-1-yl)phenyl)-1 Hpyrazol-5-yl)-2-fluorobenzonitrile L Γ / ° ΓΎ ς2)'ΝΗ2 NT J: 79 (R)-2-fluoro-4-(1-( 2-fluoro-4-(piperidin- 1 -yl)phenyl)-3-(3-(methylamino)piperidine-1- carbonyl)-1H-pyrazol-5-yl)benzonitnyl Oy>yF ONH NxF IF-2019-01451929-APN-ANP#INPI Page 151 of 160 152 80 4-(3-((R)-3-aminopiperidine-1-carbonyl)1 -(2-fluoro-4-(3-methylpiperidin-1 -yl)phenyl)1H-pyrazol-5-yl)-2- fluorobenzonitrile \ / -Q —- / X ****-.' —1 il)-2-fluorobenzonitrile A 0 -n J 1H-pyrazol-5-yl)-2fluorobenzonitrile 3-aminopiperidine-1carbonyl)-1 H-pyrazol-5-yl)-2- fluorobenzonitrile kJL ,N >9 / ^\ ( Y“NH2 A? F 84 (R)-4-(3-(3-aminoazepane- 1-carbonyl)1 “(2-fluoro-4-(piperidin-1 -yl)phenyl)-1 Hpyrazol-5-yl)-2-fluorobenzonitrile n X z u. (3-aminopiperidine-1-carbonyl)1 -(1 -methyl-1 H-i nd azole-6-i I)-1 H-pyrazol-5yl)benzonitrile T A IF-2019-01451929-APN-ANP#INPI Page 152 of 160 153 86 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1 -(2-methylbenzo [c / ]thiazol-5-i I)-1 H-pyrazoi5-yl)benzonitrile . 87 (R)-4-(3-(3-aminopiperidine-1-carbonyl)~ 1 -(2,3-dihyd ro-1 H-indan-5-yl)-1 / 7-pyrazol5-yl)benzonitrile J ? 88 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1 -(2,3-dihydro-1 H-inden-5-yl)-1 H-pyrazol5-yl)-2-fluorobenzonitrile I 2 1ΓΛ 2 benzonitrile cP ^2 90 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1 -(2,3-dihydrobenzo[b][1,4]d ioxin-6-yl)1 H“pyrazole -5-yl)benzonitrile ...... 91 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 -(quinolin-6-yl)-1 H-pyrazol-5yl)benzonitrile N X 2 I i i Yo Yo IF-2019-01451929-APN-ANP#INPI Page 153 of 160 154 92 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1 “(quinoin-3-yl)-1 H-pyrazol-5yl)benzonitrile X z 93 (R)-4-(3- (3-aminopiperidine-1-carbonyl)~ 1 -(1 -methyl-1 H-pyrrolo[2,3-b]pyridin-5-yl)- 1 H-pyrazol-5-yl)benzonitrile N z ¢7 Q 1 1 94 (R)-4-(3-(3-aminopiperidine-1-carbonyl)- 1-(2-fluoro-4-(2-hydroxy-2- methylpropyl)phenyl)-1 / - / -pyrazole- 5-yl)-2- fluorobenzonitrile Ο V-1 96 4-(3-(3-(aminomethyl)piperidine-1carbonyl)-1-(p-tolyl)-1 / - / -pyrazol-5yl)benzonitrile J T ¿ MH2 WK \— / 97 (S) -5-(4-cyanophenyl)- / V-(1- (methylsulfonyl)piperidin-3-yl)-1-(p-tolyl)- 1H-pyrazole-3-carboxamide Q 0 xly Ψ o ί J. o LX IF-2019-01451929-APN-ANP#INPI Page 154 of 160 155 99 4-(3-(2,8-diazaspiro[4.5]decane-8carbonyl)-1-(p-tolyl)-1H-pyrazol-5yl)benzonitrile 100 4-(3-(octahydro-1H-pyrrolo[2, 3-c]pyridino- 6-carbonyl)-1 -(p-tolyl)-1 H-pyrazol-5yl)benzonitrile O i CXnh 101 4-(3-(3,7-diazabicyclo[3.3.1]nonane-3carbonyl )-1-(2-fluoro-4-isopropylphenyl)1H-pyrazol-5-yl)-2-fluorobenzonitrile carbonyl)-1-(2fluoro-4-isopropylphenyl)-1 H-pyrazol-5-yl)-2fluorobenzoniiryl LI - .nh2 F 103 4-(3-(3-amino-8-azabicyclo[3.2.1]octane- 8-carbonyl)-1-(2fluoro-4-pyrrolidin-1 -yl)phenyl-1 H-pyrazol-5yl)-2-fluorobenzonitrile p Cp 0 104 4-(3-(3,7-diazabicyclo[3.3.1 ]nonane-3carbonyl)-1-(p-tolyl)-1 H-pyrazol-5yl)benzonitrile or IF-2019-01451929-APN-ANP#INPI Page 155 of 160 156 105 5-(4-cyanophenyl)- / V-(piperidin-4-yl)-1-(ptolyl)-1 / 7-pyrazole-3-carboximide / Cl C / or 106 5-(4-cyanophenyl)- / V-(1 -methylpiperidin-4-yl)- 1 -(p-to I i I)-1 H-pyrazole-3-carboximide / NA HN—( N— 107 (R)-5-(4-cyanophenyl) -A / -(1-methylpiperidin- 3-yl)-1 -(p-tolyl)-l H-pyrazole-3-carboximide P Q 108 (S)-5-(4-cyanophenyl)-A / -(1- methylpipendin- 3-yl)-1 -(p-tolyl)-l H-pyrazole-3-carboximide 0 0 109 (R)-5-(4-cyanopheniI)- / V-(1 -methylpyrrolidin- 3-yl) -1-(p-tolyl)-1H-pyrazole-3-carboximide M 0 110 5-(4-cyano-3-fluorophenyl)-1-(2-fluoro-4(pyrrolidin-1 -yl)phenyl)- / V-methyl- / V-(piperidin3-yl)-1 H-pyrazole-3-carboximide z O cl 111 (S)-5-(4-cyano-3-fluorophenyl)-1-(2-fluoro- 4- (pyrrolidin-1 -yl)phenyl)-A / -methyl-A / (piperidin-3-yl)-1H-pyrazole-3-carboximide 2 Y p\ 000 ? IF-2019-01451929-APN-ANP#INPI Page 156 of 160 157 112 (R)-5-(4-cyano-3-fluorophenyl)-1-(2-fluoro- 4-(pyrrolidin-1-yl)phenyl)- / V-methyl- / V(piperidin-3“yl) -1 / 7-pyrazole-3-carboximide w nA T F 113 (R)-4-(3-(3-aminopiperidine-1-carbonyl)1-(4-cyclopropyl-2-fluorophenyl)-4-methiF1 / 7pyrazole- 5-yl)benzonitrile. The compounds prepared in the Examples were subjected to bioassays as follows. Experimental example 1: Biochemical analysis of the histone demethylase inhibitor LSD1 The biochemical inhibition activity of the synthesized compounds on LSD1 was measured. Activity measurement was performed using a fluorescence LSD1 assay kit (available from BPS Bioscience Co., Ltd., Catalog No.: 50106). This test kit is designed to measure the activity of the LSD1 enzyme. The H2O2 generated after the demethylation of the Lys4 residue of histone H3 by LSD1 is reacted with the HRP / Amplex Red reagent to form fluorescent Resorufin, which is measured with this kit, thus confirming the demethylation. Table 2 shows the inhibition activity of the compounds on LSD1. The results are expressed as an IC50 value. As a control, GSK2879552 (available from GlaxoSmithKline USA) was used. Table 2 IF-2019-01451929-APN-ANP#INPI Page 157 of 160 158 Example IC50 on LSD1(nM) Example IC50 on LSD1(nM) Example Clso on LSD1(nM) Control 311 39 33 65 53 1 57 40 36 66 34 2 29 41 34 67 41 3 46 42 36 68 22 4 38 43 21 69 26 5 21 44 23 70 28 6 21 45 162 74 48 7 49 47 229 77 20 8 28 48 149 78 26 9 234 49 364 79 38 10 34 50 379 84 30 12 70 51 5 85 125 17 248 52 231 86 222 18 231 53 44 87 46 20 195 54 42 89 28 21 100 55 56 90 164 22 952 56 40 91 568 30 374 57 21 93 376 32 710 58 28 96 531 33 46 5 9 56 98 163 34 47 60 46 99 427 IF-2019-01451929-APN-ANP#INPI Page 158 of 160 159 36 67 61 35 101 185 37 36 62 41 102 87 38 61 63 55 103 33 Experimental Example 2: Cell Growth Suppression Test Cell growth suppression effects of the synthesized compounds on NCI-H1417 cells were identified. The cells were treated with the synthesized compounds for 10 days. Next, in order to study the suppression of cell growth, the CelITiter-Glo luminescence cell viability assay (available from Promega, USA) was used. This test measures emission signals proportional to the number of ATP based on a fixed amount of ATP, which represents the presence of metabolically active cells, to determine the number of viable cells. Table 3 shows the 50% suppression of the compounds on NCI-H1417 cells. The results are expressed as an IC50 value (50% growth inhibition). As a control, GSK2879552 (available from GlaxoSmithKline USA) was used. Tab a3 Example NCI-H1417 ICso (nM) Example NCI-H1417 IC50 (nM) Example NCI-H1417 IC50 (nM) Control 591 42 226 69 38 1 94 43 69 70 18 2 120 44 133 71 10 3 49 53 102 38 IF-2019-01451929-APN-ANP#INPI Page 159 of 160 160 4 24 54 84 73 39 5 48 57 45 74 8.8 6 48 58 24 75 52 8 101 59 9.7 76 43 10 108 60 53 77 67 35 145 61 82 78 34 36 91 63 33 2 119 37 215 64 19 83 and 7| 38 79 65 58 84 84 39 139 66 16 87 142 40 226 67 30 88 173 41 126 68 6.8 89 71 IF-2019-01451929-APN-ANP#INPI Page 160 of 160 Argentine Republic - National Executive Branch 2019 - Year of Export Additional Signature Sheet Graphic report Number: IF-2019-01451929-APN-ANP#INPI BUENOS AIRES CITY Tuesday, January 8, 2019 Reference: 20180102593 The document was imported by the GEDO system with a total of 160 page / s. Digitally signed by GESTION DOCUMENTAL ELECTRONICA - GDE DN: cn=ELECTRONIC DOCUMENTARY MANAGEMENT - GDE, c=AR, o=MINISTRY OF MODERNIZATION, ou=SECRETARY OF ADMINISTRATIVE MODERNIZATION, serialNumber=CUIT 30715117564 Date: 2019.01.08 22:17:39 -03'00' Jose Emmanuel Luzuriaga Administrative assistant National Patent Administration National Institute of Industrial Property Digitally signed by GESTION DOCUMENTAL ELECTRONICA GDE DN: cn=GEST10N ELECTRONIC DOCUMENTARY - GDE, c=AR, o=MINISTRY OF MODERNIZATION, ou=SECRETARY OF ADMINISTRATIVE MODERNIZATION, serialNumber=CUIT 30715117564 Date: 2019.01.08 22:17:39 -03'00'

Claims

1. A compound characterized by selecting among the Compuestos 1) to 113), an optical isomer, a solvate, a tautómer or a pharmaceutically acceptable salt of these: 1) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-cyclopropylphenyl)-1H-pyrazol-5-yl)benzonitrile, 2) (R)-4-(1-(4-cyclopropylphenyl)-3-(3-methylaminopiperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 3) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-cyclopropyl-2-fluorophenyl)-1H-pyrazol-5-yl)benzonitrile, 4) (R)-4-(1-(4-cyclopropyl-2-fluorophenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 5) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-cyclopropyl-2-fluorophenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 6) (R)-4-(1-(4-cyclopropyl-2-fluorophenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)-2-fluoro benzonitrile, 7) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(4-(cyclopropylphenyl)-1H-pyrazol-5-yl)benzonitrile,8) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(4-cyclopropyl-2-fluorophenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 9) 4-(3-((3R,5R)-3-amino-5-methylpiperidine-1-carbonyl)-1-(4-cyclopropyl-2-fluorophenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 10) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-cyclopropyl-2,6-difluorophenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 11) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(4- cyclopropyl-2,6-difluorophenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 12) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-chloro-4-cyclopropylphenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 13) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(2-chloro-4-cyclopropylphenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 14) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-phenyl-1H-pyrazol-5-yl)benzonitrile, 15) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(pyridin-2-yl)-1H-pyrazol-5-yl)benzonitrile, 16) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-fluorophenyl)-1H-pyrazol-5-yl)benzonitrile,17) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-chlorophenyl)-1H-pyrazol-5-yl)benzonitrile, 18) (R)-4-(1-(4-chlorophenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 19) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(3-chlorophenyl)-1H-pyrazol-5-yl)benzonitrile, 20) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-bromophenyl)-1H-pyrazol-5-yl)benzonitrile, 21) (R)-4-(1-(4-bromophenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 22) (S)-4-(3-(3-aminopyrrolidino-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 23) (S)-4-(3-(3-(methylamino)pyrrolidino-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 24) (S)-4-(3-(3-(dimethylamino)pyrrolidino-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 25) (R)-4-(3-(3-(dimethylamino)pyrrolidino-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 26) (R)-4-(3-(3-(methylamino)pyrrolidino-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile,27) (R)-4-(3-(3-aminopyrrolidino-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrilo, 28) (R)-4-(3-(3-aminopiperidina-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrilo, 29) (R)-4-(3-(3-(methylamino)piperidina-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrilo, 30) (R)-4-(3-(3-(dimethylamino)piperidina-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrilo, 31) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(m-tolyl)-1H-pyrazol-5-yl)benzonitrile, 32) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(o-tolyl)-1H-pyrazol-5-yl)benzonitrile, 33) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-ethylphenyl)-1H-pyrazol-5-yl)benzonitrile, 34) (R)-4-(1-(4-ethylphenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 35) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-isopropylphenyl)-1H-pyrazol-5-yl)benzonitrile, 36) (R)-4-(1-(4-isopropylfenil)-3-(3-(metilamino)piperidina-1-carbonyl)-1H-pyrazol-5-yl)benzonitrilo,37) (R)-4-(3-(3-aminopiperidina-1-carbonil)-1-(2-fluoro-4-isopropilfenil)-1H-pirazol-5-il)benzonitrilo, 38) (R)-4-(3-(3-aminopiperidina-1-carbonil)-1-(2-fluoro-4-isopropilfenil)-1H-pirazol-5-il)-2-fluorobenzonitrilo, 39) (R)-4-(3-(3-aminoazepano-1-carbonil)-1-(2-fluoro-4-isopropilfenil)-1H-pirazol-5-il)-2-fluorobenzonitrilo, 40) (R)-4-(3-(3-aminopiperidina-1-carbonil)-1-(4-(ter-butil)fenil)-1H-pirazol-5-il)benzonitrilo, 41) (R)-4-(1-(4-(ter-butil)fenil-3-(3-metilaminopiperidina-1-carbonil)-1H-pirazol-5-il)benzonitrilo, 42) (R)-4-(3-(3-aminopiperidina-1-carbonil)-1-(4-(ter-butil)-2-fluorofenil)-1H-pirazol-5-il)benzonitrilo, 43) (R)-4-(3-(3-aminopiperidina-1-carbonil)-1-(4-(ter-butil-2-fluorofenil)-1H-pirazol-5-il)-2-fluorobenzonitrilo, 44) (R)-4-(3-(3-aminoazepano-1-carbonil)-1-(4-(ter-butil-2-fluorofenil)-1H-pirazol-5-il)-2-fluorobenzonitrilo, 45) (R)-4-(3-(3-aminopiperidina-1-carbonil)-1-(4-(trifluorometoxi)fenil)-1H-pirazol-5-il)benzonitrilo,46) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(methylsulfonyl)phenyl)-1H-pyrazol-5-yl)benzonitrile, 47) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-5-yl)benzonitrile, 48) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-methylphenyl)-1H-pyrazol-5-yl)benzonitrile, 49) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(3-fluoro-4-methoxyphenyl)-1H-pyrazol-5-yl)benzonitrile, 50) (R)-4,4'-(3-(3-aminopiperidine-1-carbonyl)-1H-pyrazol-1,5-diyl)dibenzonitrile, 51) (R)-4-(1-(4-(dimethylamino)phenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 52) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)-1H-pyrazol-5-yl)benzonitrile, 53) ((R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(dimethylamino)phenyl)-1H-pyrazol-5-yl)benzonitrile, 54) (R)-4-(3-(3-aminopiperidina-1-carbonyl)-1-(4-(dimethylamino)-2-fluorofenil)-1H-pyrazol-5-yl)benzonitrilo,55) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(diethylamino)-2-fluorophenyl)-1H-pyrazol-5-yl)benzonitrile, 56) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-(azetidin-1-yl)-2-fluorophenyl)-1H-pyrazol-5-yl)benzonitrile, 57) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(pyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)benzonitrile, 58) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(pyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 59) (R)-2-fluoro-4-(1-(2-fluoro-4-(pyrrolidin-1-yl)phenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 60) (R)-4-(3-(3-aminoazepane-1-carbonyl)-1-(2-fluoro-4-(pyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 61) 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-((R)-3-fluoropyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 62) 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-((S)-3-fluoropyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile,63) (R)-4-(3-(3-aminopiperidina-1-carbonyl)-1-(4-(3,3-difluoropyrrolidin-1-yl)-2-fluorofenil)-1H-pyrazol-5-yl)-2-fluorobenzonitrilo, 64) (R)-4-(1-(4-(3,3-difluoropyrrolidin-1-yl)-2-fluorofenil)-3-(3-(metilamino)piperidina-1-carbonyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrilo, 65) 4-(3-((R)-3-aminopiperidina-1-carbonyl)-1-(2-fluoro-4-(3-methoxypyrrolidin-1-yl)fenil)-1H-pyrazol-5-yl)-2-fluorobenzonitrilo, 66) 2-fluoro-4-(1-(2-fluoro-4-(3-methoxypyrrolidin-1-yl)phenyl)-3-((R)-3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 67) 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-((S)-3-methoxypyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 68) 2-fluoro-4-(1-(2-fluoro-4-((S)-3-methoxypyrrolidin-1-yl)phenyl)-3-((R)-3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 69) 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-((R)-3-methoxypyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile,70) 2-fluoro-4-(1-(2-fluoro-4-((R)-3-methoxipyrrolidin-1-yl)phenyl)-3-((R)-3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 71) 2-fluoro-4-(1-(2-fluoro-4-((S)-3-ethoxipyrrolidin-1-yl)phenyl)-3-((R)-3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 72) 4-(3-((R)-3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(3-hydroxypyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 73) 2-fluoro-4-(1-(2-fluoro-4-((S)-3-chloropyrrolidin-1-yl)phenyl)-3-((R)-3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 74) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2,6-difluoro-4-(pyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 75) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-chloro-4-(pyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 76) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-methoxy-4-(pyrrolidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile,77) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(piperidin-1-yl)phenyl)-1H-pyrazol-5-yl)benzonitrile, 78) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(piperidin-1-yl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 79) (R)-2-fluoro-4-(1-(2-fluoro-4-(piperidin-1-yl)phenyl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 80) 4-(3-((R)-3-aminopiperidina-1-carbonyl)-1-(2-fluoro-4-(3-metilpiperidin-1-yl)fenil)-1H-pyrazol-5-yl)-2-fluorobenzonitrilo, 81) (R)-4-(3-(3-aminopiperidina-1-carbonyl)-1-(2-fluoro-4-(4-metilpiperidin-1-yl)fenil)-1H-pyrazol-5-yl)-2-fluorobenzonitrilo, 82) 4-(3-((R)-3-aminopiperidina-1-carbonyl)-1-(4-(3,5-dimethylpiperidin-1-yl)-2-fluorofenil)-1H-pyrazol-5-yl)-2-fluorobenzonitrilo, 83) (R)-4-(1-(4-([1,4'-bipiperidino]-1'-yl)-2-fluorofenil)-3-(3-aminopiperidina-1-carbonyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrilo, 84) (R)-4-(3-(3-aminoazepano-1-carbonyl)-1-(2-fluoro-4-(piperidin-1-yl)fenil)-1H-pyrazol-5-yl)-2-fluoro benzonitrilo,85) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(1-methyl-1H-indazol-6-yl)-1H-pyrazol-5-yl)benzonitrile, 86) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-methylbenzo[d]thiazol-5-yl)-1H-pyrazol-5-yl)benzonitrile, 87) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2,3-dihydro-1H-indan-5-yl)-1H-pyrazol-5-yl)benzonitrile, 88) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2,3-dihydro-1H-inden-5-yl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 89) (R)-4-(1-(2,3-dihydro-1H-inden-5-yl)-3-(3-(methylamino)piperidine-1-carbonyl)-1H-pyrazol-5-yl)benzonitrile, 90) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-5-yl)benzonitrile, 91) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(quinolin-6-yl)-1H-pyrazol-5-yl)benzonitrile, 92) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(quinolin-3-yl)-1H-pyrazol-5-yl)benzonitrile, 93) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(1-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)benzonitrile,94) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(2-fluoro-4-(2-hidroxi-2-methylpropyl)phenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 95) 4-(3-(piperazino-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 96) 4-(3-(3-(aminomethyl)piperazino-1-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 97) (S)-5-(4-cyanophenyl)-N-(1-(methylsulfonyl)piperidin-3-yl)-1-(p-tolyl)-1H-pyrazol-3-carboxamida, 98) 4-(3-(2,7-diazaespiro[3.5]nonane-7-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 99) 4-(3-(2,8-diazaespiro[4.5]decane-8-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 100) 4-(3-(octahydro-1H-pyrrolo[2,3-c]pyridino-6-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 101) 4-(3-(3,7-diazabicyclo[3.3.1]nonane-3-carbonyl)-1-(2-fluoro-4-isopropylphenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 102) 4-(3-(3-amino-8-azabicyclo[3.2.1]octane-8-carbonyl)-1-(2-fluoro-4-isopropylphenyl)-1H-pyrazol-5-yl)-2-fluorobenzonitrile,103) 4-(3-(3-amino-8-azabicyclo[3.2.1]octane-8-carbonyl)-1-(2-fluoro-4-pyrrolidin-1-yl)phenyl-1H-pyrazol-5-yl)-2-fluorobenzonitrile, 104) 4-(3-(3,7-diazabicyclo[3.3.1]nonane-3-carbonyl)-1-(p-tolyl)-1H-pyrazol-5-yl)benzonitrile, 107) (R)-5-(4-cyanophenyl)-N-(1-methylpiperidin-3-yl)-1-(p-tolyl)-1H-pyrazol-3-carboximida, 108) (S)-5-(4-cyanophenyl)-N-(1-methylpiperidin-3-yl)-1-(p-tolyl)-1H-pyrazol-3-carboximida, 109) (R)-5-(4-cyanophenyl)-N-(1-methylpirrolidin-3-yl)-1-(p-tolyl)-1H-pyrazol-3-carboximida, 110) 5-(4-cyano-3-fluorophenyl)-1-(2-fluoro-4-(pyrrolidin-1-yl)phenyl)-N-methyl-N-(piperidin3-yl)-1H-pyrazol-3-carboximida, 111) (S)-5-(4-cyano-3-fluorophenyl)-1-(2-fluoro-4-(pyrrolidin-1-yl)phenyl)-N-methyl-N-(piperidin-3-yl)-1H-pyrazol-3-carboximida, 112) (R)-5-(4-cyano-3-fluorophenyl)-1-(2-fluoro-4-(pyrrolidin-1-yl)phenyl)-N-methyl-N-(piperidin-3-yl)-1H-pyrazol-3-carboximida,113) (R)-4-(3-(3-aminopiperidine-1-carbonyl)-1-(4-cyclopropyl-2-fluorophenyl)-4-methyl-1H-pyrazol-5-yl)benzonitrile. 3 claims follow,