| Title of Invention | NOVEL OXAZOLIDINONE DERIVATIVES WITH CYCLIC AMIDOXIME OR CYCLIC AMIDRAZONE AND PHARMACEUTICAL COMPOSITIONS THEREOF |
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| Abstract | Disclosed is an oxazolidinone derivative represented by Chemical Formula 1, particularly an oxazolidinone compound with a cyclic amidoxime or cyclic amidrazone group. [Chemical Formula 1] Also disclosed is a pharmaceutical antibiotic composition including, as an effective ingredient, the oxazolidinone derivative represented by Chemical Formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof. The oxazolidinone derivative, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, and a pharmaceutically acceptable salt thereof exhibit a wide antibacterial spectrum, a low toxicity, and a strong antibacterial activity against Gram-positive and Gram-negative bacteria, suggesting that it can be used as a promising antibiotic. |
| Full Text | FORM 2 THE PATENTS ACT 1970 (39 of 1970) & The Patents Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) 1. ' NOVEL OXAZOLIDINONE DERIVATIVES WITH CYCLIC AMIDOXIME OR CYCLIC AMIDRAZONE AND PHARMACEUTICAL COMPOSITIONS THEREOF ' 2. 1. (A) LegoChem Biosciences, Inc. (B) Republic of Korea (C) Daejeon Bio Venture Town, 461-8, Jeonmin-dong, Yuseong-gu, Daejeon 305-811 Republic of Korea The following specification particularly describes the invention and the manner in which it is to be performed. ?Technical Field? The present invention relates to a novel oxazolidinone derivative represented by Chemical Formula 1, particularly to a novel oxazolidinone derivative having a cyclic amidoxime or a cyclic amidrazone group. [Chemical Formula 1] The present invention also relates to a pharmaceutical antibiotic composition comprising, as an effective ingredient, the novel oxazolidinone derivative, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof. ?Background Art? Ever since the discovery of penicillin, numerous antibiotics have been developed by pharmaceutical companies worldwide, including ß-lactam antibiotics against bacterial infections, sulfonamides, tetracyclines, aminoglycosides, macrolides, quinolones, glycopeptides, and the like. On the other hand, misuse or abuse of antibiotics incessantly created antibiotic resistant bacteria or multidrug resistant bacteria, which has been considered worldwide as a serious problem that has to be solved. Indeed, a number of scientists in the international microbiological academic community warned that as the antibiotic resistance of such bacteria becomes high, new resistant bacteria that are not affected by any currently available antibiotics might be rampant in near future. In general, bacterial pathogens are classified into Gram-positive or Gram-negative bacteria. Gram-positive bacteria, e.g. Staphylococcus, Enterococcus, Streptococcus and acid-fast bacteria, once occurring in a hospital environment, tend to develop into antibiotic resistant bacteria that are difficult to be treated. Examples of such antibiotic resistant Gram-positive bacteria include methicillin-resistant Staphylococcus (MRSA), methicillin-resistant coagulase-negative Staphylococcus (MRCNS), penicillin-resistant Streptococcus pneumoniae, multiple-resistant Enterococcus faecium, or the like. Vancomycin, a glycopeptide antibiotic, is known to be clinically effective in treating such Gram-positive antibiotic resistant bacteria. However, vancomycin has toxicity and, since the emergence of vancomycin-resistant Enterococcus (VRE) in 1990s, bacteria resistant to vancomycin and other glycopeptide-based antibiotics are emerging. In addition, for antibiotics such as ß-lactam, quinolone and macrolide used to treat infections of upper respiratory tract caused by certain Gram-negative bacteria including Haemophilus influenzae (H. influenzae) and Moraxella catarrhalis (M. catarrhalis), resistant bacteria such as quinoline-resistant Staphylococcus aureus (QRSA) are emerging. Hence, researches on new antibiotics are under way. Accordingly, in order to fundamentally solve the antibiotic resistance problem, development of antibiotics with new chemical structures and antibacterial mechanisms is urgently required. As such an antibiotic with a new chemical structure, an oxazolidinone antibiotic was first reported by DuPont in 1984 (EP 127,902), after which a variety of oxazolidinone derivatives have been reported by many pharmaceutical companies. The oxazolidinone derivatives are obtained not by fermentation but by chemical synthesis and can be administered orally. The chemical backbone of the oxazolidinone derivatives is totally different from that of the classical antibiotics. It is reported that the oxazolidinone derivatives inhibit an initial stage of protein synthesis of bacteria and they exhibit superior antibacterial activity against antibiotic-resistant bacteria, particularly Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), quinolone-resistant Staphylococcus aureus (QRSA), vancomycin-resistant Enterococcus (VRE) and multidrug-resistant Mycobacterium tuberculosis (MDRTB). One example of such oxazolidinone compounds containing an oxazolidinone ring is 3-phenyl-2-oxazolidinone derivatives having one or two substituent(s), as described in US Patent Nos. 4,948,801, 4,461,773, 4,340,606, 4,476,136, 4,250,318 and 4,128,654. Another example is 3-[(mono-substituted)phenyl]-2-oxazolidinone derivatives represented by Chemical Formula A, as described in, e.g., EP 0312000, J. Med. Chem. 32, 1673(1989), J. Med. Chem. 33, 2569 (1990), Tetrahedron Lett. 45,123(1989). [Chemical Formula A] Still another example is the compounds represented by Chemical Formula B and Chemical Formula C and synthesized by Pharmacia & Upjohn, as described in WO 93/23384, WO 95/14684 and WO 95/07271. The compound of Chemical Formula B, "linezolid", is the first commercially available oxazolidinone antibiotic and is approved by the U.S. Food and Drug Administration (FDA) and marketed under the trade name "Zyvox" for oral administration and injection. However, these compounds have some problems such such as toxicity, low in vivo efficacy and low solubility. As for linezolid, solubility in water is only about 3 mg/mL, which limits its practical use as an antibiotic for injection. [Chemical Formula B] [Chemical Formula C] Yet another example is phenyl oxazolidinone derivatives having a heterocyclic ring, such as, e.g., pyridine, thiazole, indole, oxazole, quinol, etc., at the 4-position of the phenyl group, as described in WO 93/09103. But, the substituents of the heterocyclic ring are alkyl or amino group, and the pharmaceutical efficacy is not so excellent. Still yet another example is phenyl oxazolidinone derivatives having various pyridine or phenyl derivatives at the 4-position of the phenyl group, as described in WO 01/94342. These compounds have wider antibacterial spectrum and better antibacterial activity than linezolid. They, however, have aqueous solubility of 30 µg/mL or less, and thus it is virtually impossible to use them for injection. A further example is the compounds (TR-700 and TR-701) represented by Chemical Formula D, which were developed by Dong-A Pharmaceutical (Korea) and recently licensed to Trius Therapeutics. TR-701 is a prodrug of TR-700 and the phase III clinical trial is underway. TR-701 shows higher solubility and exhibits better antibacterial activity than linezolid. However, it shows higher toxicities (cytotoxicity, MAO profile, myelosuppression, etc.) than linezolid, which may cause many limitations in practical use. [Chemical Formula D] As described above, there is still a need for a compound having superior antibacterial activity, satisfactory solubility and lower toxicity. ?Disclosure? ?Technical Problem? The inventors of the present invention have synthesized novel oxazolidinone derivatives in order to provide antibiotics having superior antibacterial activity and having higher solubility suitable for oral or injection formulations, compared with existing antibiotics. The novel oxazolidinone derivatives according to the present invention have been confirmed to have superior antibacterial activity for a significantly wide range of different types of bacteria. One of the features of the oxazolidinone derivative compounds provided by the present invention is that they have a cyclic amidoxime or cyclic amidrazone group. While oxazolidinone derivative compounds having an acyclic amidoxime or amidrazone group were known, the oxazolidinone derivative compounds having a cyclic amidoxime or cyclic amidrazone group have not been known prior to the present invention . As described in detain below, with the introduction of the cyclic amidoxime or cyclic amidrazone group, absorptivity is remarkably improved. Also, solubility in water is greatly increased as a result of formation of a salt having an adequate basicity, thereby making it possible to prepare injection formulations without using a prodrug. In addition, toxicity is significantly reduced. ?Technical Solution? Accordingly, an object of the present invention is to provide a novel oxazolidinone derivative, particularly a novel oxazolidinone compound with a cyclic amidoxime or a cyclic amidrazone group, which shows improved solubility, and a method for preparing the same. Another object of the present invention is to provide a pharmaceutical antibiotic composition comprising as an effective ingredient the novel oxazolidinone derivative, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof. The novel oxazolidinone derivative compounds and compositions according to the present invention can be used for treatment of hospital-acquired pneumonia, socially acquired pneumonia, complicated skin and skin structure infections, uncomplicated skin and skin structure infections, or infections caused by antibiotic resistance bacteria, particularly septicemia caused by vancomycin-resistant Enterococcus faecium (VRE) or linezolid-resistant Enterococcus faecalis, or for combination therapy for Gram-negative bacteria-associated diseases. ?Best Mode? Hereinafter reference will now be made in detail to various embodiments of the present invention. According to embodiments of the present invention, a novel oxazolidinone derivative, more particularly, a novel oxazolidinone compound with a cyclic amidoxime or a cyclic amidrazone group, represented by Chemical Formula 1, is provided. According to other embodiments, a pharmaceutical antibiotic composition comprising as an effective ingredient the novel oxazolidinone derivative represented by Chemical Formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof. [Chemical Formula 1] wherein, R1 represents hydrogen, a (C1-C6)alkyl or (C3-C6)cycloalkyl; Y represents –O- or –N(R2)-, wherein R2 represents hydrogen, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, -(CH2)mOC(=O)R11, -(CH2)mC(=O)R12, -(CH2)mC(=S)R12, or –SO2R13, in which (1) the alkyl of R2 may be further substituted by one or more substituent(s) selected from the group consisting of (C2-C6)alkenyl, (C2-C6)alkynyl, halogen, halo(C1-C6)alkyl, (C1-C6)alkyl(C2-C6)alkynyl, hydroxyl, (C3-C6)cycloalkyl and cyano, (2) m represents an integer from 0 to 2, and (3) R11 through R13 independently represent hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, amino, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C1-C6)alkylcarbonyl, wherein the alkyl, alkoxy, or amino of R11 through R13 may be further substituted by one or more substituent(s) selected from the group consisting of halogen, amino, hydroxyl, cyano, (C1-C6)alkyl, (C1-C6)alkylcarbonyloxy and hydroxy(C1-C6)alkyl; X1 and X2 independently represent hydrogen or fluorine; P represents –O-, -NH-, or a five-membered aromatic heterocycle with the following structure ; and Q represents hydrogen, -C(=O)R3, -C(=S)R4, -C(=O)NR5R6, -C(=S)NR5R6, or a five-membered aromatic heterocycle with a structure selected from the following structures: , wherein (1) R3 and R4 independently represent hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl, (C2-C6)alkenyl, or (C2-C6)alkynyl, (2) R5 and R6 independently represent hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl or (C2-C6)alkenyl, (3) R7 represents hydrogen, halogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl, and (4) the alkyl of R3 through R7 may be further substituted by one or more substituent(s) selected from the group consisting of hydroxyl, cyano, halogen, (C1-C6)alkylcarbonyloxy and amino. As used herein, the term "alkyl" includes linear and branched structures. For example, the term "(C1-C6)alkyl" includes all possible positional and geometrical isomers, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, and the like. The term "(C3-C6)cycloalkyl" includes all possible positional and geometrical isomers, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, and the like. The term "(C2-C6)alkenyl" includes all possible positional and geometrical isomers, such as vinyl, propenyl, 1- and 2-butenyl, pentenyl, and the like. The term "(C2-C6)alkynyl" includes all possible positional and geometrical isomers, such as acetylenyl, propargyl, 1-propynyl, 2-pentynyl, and the like. Certain embodiments of the present invention provides oxazolidinone derivatives represented by Chemical Formula 2 or 3: [Chemical Formula 2] [Chemical Formula 3] in which, R2, X1, X2, P and Q are the same as defined in Chemical Formula 1. Other certain embodiments of the present invention provide oxazolidinone derivatives represented by Chemical Formulas 4 to 9: [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8] [Chemical Formula 9] in which, R2 represents hydrogen, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, -(CH2)mOC(=O)R11, -(CH2)mC(=O)R12, -(CH2)mC(=S)R12, or –SO2R13, wherein (1) the alkyl of R2 may be further substituted by one or more substituent(s) selected from the group consisting of (C2-C6)alkenyl, (C2-C6)alkynyl, halogen, halo(C1-C6)alkyl, (C1-C6)alkyl(C2-C6)alkynyl, hydroxyl, (C3-C6)cycloalkyl and cyano, (2) m represents an integer from 0 to 2, (3) R11 through R13 independently represent hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, amino, (C3-C6)cycloalkyl, or (C1-C6)alkylcarbonyl, wherein the alkyl, alkoxy or amino of R11 through R13 may be further substituted by one or more substituent(s) selected from the group consisting of halogen, amino, hydroxyl, cyano, (C1-C6)alkyl, (C1-C6)alkylcarbonyloxy and hydroxy(C1-C6)alkyl; P represents –O-, -NH- or a five-membered aromatic heterocycle with the following structure ; and Q represents hydrogen, -C(=O)R3, -C(=S)R4, -C(=O)NR5R6, -C(=S)NR5R6, or a five-membered aromatic heterocycle with a structure selected from the following structures: , wherein (1) R3 and R4 independently represent hydrogen, (C1-C6)alkyl or (C1-C6)alkoxy, (2) R5 and R6 independently represent hydrogen or (C1-C6)alkyl, and (3) the alkyl of R3 through R6 may be further substituted by one or more substituent(s) selected from the group consisting of hydroxyl, cyano, halogen, (C1-C6)alkylcarbonyloxy and amino. The oxazolidinone derivatives according to other embodiments of the present invention may include, but not limited to, the following compounds: . The oxazolidinone derivatives according to the above and other embodiments of the present invention, which have a cyclic amidoxime or a cyclic amidrazone group, can be used in a form of prodrug, hydrate, solvate, isomer or pharmaceutically acceptable salt thereof especially in case where such a form shows improved absorption into the body or enhanced solubility. Accordingly, such a prodrug, hydrate, solvate, isomer, and pharmaceutically acceptable salt also fall within the scope of the present invention, as described below in detail. The term "pharmaceutically acceptable salt" used herein includes an acid addition salt, examples of which include methanesulfonate, ethanesulfonate, fumarate, succinate, hydrochloride, citrate, malate, tartrate and hydrobromide, phosphate, sulfate and the like. Preferably, the pharmaceutically acceptable salt may be a basic salt including, e.g., an alkali metal salt (e.g., sodium salt) or an alkaline earth metal salt (e.g., calcium or magnesium salt), an organic amine salt (e.g., triethylamine, morpholine, N-methylpiperidine, N-ethylpiperidine, dibenzylamine, N,N-dibenzylethylamine and tris-(2-hydroxyethyl)amine), or an amino acid (e.g., N-methyl-D-glutamine and lysine). The salt may include one or more cation(s) or anion(s) depending on the number of charged group(s) and the valence of the corresponding cation(s) or anion(s). A preferred pharmaceutically acceptable basic salt is a sodium salt. However, in order to facilitate release of salt during preparation, a salt less soluble in a selected solvent may be used. The oxazolidinone derivatives of the present invention may be present either in a solvated form (e.g. as a hydrate) or in a non-solvated form. The solvates of the oxazolidinone derivatives according to the present invention include all pharmaceutically active solvated forms. The oxazolidinone derivatives of the present invention may be administered in a prodrug form, which is, once administered into a human or animal, is metabolized in vivo into one of the compounds of the present invention. A prodrug may be formed by introducing an adequate group or substituent to a compound to modify or improve the physical and/or pharmacological profile of the compound. A non-limiting example of the prodrug according to the present invention may be an ester of one of the compounds of the present invention that can be hydrolyzed in vivo or a pharmaceutically acceptable salt. Various types of prodrug forms and methods for preparing the prodrug forms are known in the related art, as described, e.g., in: a) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985) and Methods in Enzymology, Vol. 42, p.309-396, edited by K. Widder, et al. (Academic press, 1985); b) A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 "Design and Application of Prodrugs", by H. Bundgaard p. 113-191 (1991); c) H. Bundgaard, Advanced Drug Delivery Reviews, 8, 1-38 (1992); d) H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77, 285 (1988); and e) N. Kakeya, et al., Chem. Pharm. Bull., 32, 692 (1984). Examples of the prodrug according to the present invention include the following compounds. As in the foregoing examples, a phosphonate or acetyl group may be attached to the hydroxyl group, so that the prodrug is matabolized to an active form after administration. Alternatively, an amino acid may be attached or a carbonate form may be prepared. The prodrug form can be used especially when the solubility or absorptivity of the active form is relatively low. The use of the prodrug may lead to the improvement of absorption, distribution, metabolism and excretion (ADME) and PK profile, in addition to the enhancement of solubility. The compounds of the present invention have a chiral center at the C-5 position of the oxazolidinone ring. Chemical Formula 1 above shows diastereomers of oxazolidinone derivative compounds of the present invention. Chemical Formula 1b shows epimers of the oxazolidinone derivative compounds of Chemical Formula 1. In general, compared to the epimers represented by Chemical Formula 1b, the oxazolidinone derivative compounds of Chemical Formula 1 exhibit better MAO profiles. [Chemical Formula 1b] Thus, in case where a mixture containing an oxazolidinone derivative (Chemical Formula 1a) and an epimer thereof (Chemical Formula 1b) is used as an antibiotic, it is preferable that the amount of the antibiotic may be controlled (increased) considering the proportion of the epimer of the mixture in order to attain a pharmacological effect substantially similar to or same as the pharmacological effect that can be attained when the oxazolidinone derivative (Chemical Formula 1a) is used alone. Further, some compounds of the present invention may have a different chiral center depending on their substituent(s). All optical isomers, diastereomers and racemic mixtures having antibacterial activity are included in the scope of the present invention. The method for preparing optically active forms (e.g., recrystallization, chiral synthesis, enzymatic resolution, biotransformation, or separation of racemic mixtures by chromatography) and methods for measurement of antibacterial activity are known in the related art. As the compounds represented by Chemical Formula 1 or the salts thereof may tautomerize, even though only one of possible tautomers is described in the chemical formulas or reaction schemes herein, the present invention encompasses all the tautomers having antibacterial activity and is not limited to the tautomer form(s) described in the chemical formulas or reaction schemes. Further, the compounds of the present invention may exhibit polymorphism. Thus, all the polymorphic compounds having antibacterial activity are included in the present invention. The oxazolidinone derivatives according to the present invention may be prepared by known methods depending on their substituents. For example, they may be prepared according to the methods exemplified by Schemes 1 to 6 below. The preparation methods described in Schemes 1 to 6 are only exemplary and may be modified without extensive difficulty by those skilled in the art to prepare compounds having the other substituents. Accordingly, methods for preparing the oxazolidinone compounds of the present invention should not be limited to the methods exemplified in Schemes 1 to 6. Unless otherwise specified, the substituents in the reaction schemes below are defined in the same manner as those defined with respect to Chemical Formula 1. As discussed above, the oxazolidinone derivatives of Chemical Formula 1 according to the present invention may be synthesized via different synthetic routes, depending on the substituents, X1, X2, Y, P and Q. Schemes 1 to 5 show examples of representative synthesis methods that can be used to prepare such derivatives in which either X1 or X2 is fluorine atom (F) and the other is hydrogen atom (H). Scheme 6 shows examples of representative synthesis methods that can be used to prepare such derivatives in which both X1 and X2 are eithr H or F. Schemes 1-4 show examples of representative synthesis methods that can be used to prepare cyclic amidrazone compounds in which Y is nitrogen atom (N-R2) and P is –NH- (Schemes 1 and 2), an aromatic heterocycle (e.g., triazole) (Scheme 3), or -O- (Scheme 4). Further, Scheme 5 shows examples of representative synthesis methods that can be used to prepare cyclic amidoxime compounds in which Y is –O-. More particularly, referring to Scheme 1, 3, 4-difluoronitrobenzene is reacted with ethanolamine to give Compound I. After protecting the alcohol and amine groups with t-butyldimethylsilyl (TBS) and tert-butyloxycarbonyl (Boc) respectively to give Compound II, the nitro group of the Compound II is reduced to amine using Pd/C to give Compound III. Benzyloxycarbonyl group (cbz) is attached using benzyl chloroformate (Cbz-Cl) to synthesize Compound IV. Compound IV is reacted with (R)-glycidyl butyrate and n-butyllithium (n-BuLi) to synthesize chiral Compound V. Compound V is reacted with methanesulfonyl chloride (Ms-Cl) to give Compound VI, and then the Compound VI is rected with sodium azide (NaN3) to give Compound VII. After converting the azide group of Compound VII into amine using Pd/C under hydrogen gas, a cbz group is attached using Cbz-Cl to synthesize Compound VIII. Compound VIII is treated with hydrochloric acid to remove the protecting groups (boc and tbs) to give Compound IX, which is reacted with methanesulfonyl chloride (Ms-Cl) to synthesize Compound X. Compound X is reacted with hydrazine to produce Compoud XI, which is then reacted with trimethyl orthoformate to produce a cyclic amidrazone Compound XII. The cbz group is removed from Compound XII to give Compound XIII. A variety of Q groups can be introduced into Compound XIII. Further, after removing the formyl group, a variety of R2 groups can be introduced. Detailed description of the repective steps is given in the Examples below. [Scheme 1] Referring to Scheme 2, in the case where Q is an aromatic heterocycle with no carbonyl group, P and Q groups are first introduced to Compound VI. A reaction with aminoisoxazole is exemplified in Scheme 2. Compound VI is reacted with aminoisoxazole with the boc protected amine group to synthesize Compound XIV. Removal of boc and tbs groups using hydrochloric acid gives Compound XV. Compound XV is mesylated to give Compound XVI, which is then reacted with hydrazine to generate Compound XVII. Compound XVII is reacted with trimethyl orthoformate to synthesize a cyclic amidrazone compound. After removing the formyl group, a variety of R2 groups are introduced. Detailed description of the repective steps is given in the Examples below. [Scheme 2] Scheme 3(1) shows the case where P is an aromatic heterocycle and Q is H and Scheme 3(2) shows the case where P is an aromatic heterocycle and Q is a substituent other than H. In Scheme 3(1), an azido compound (Compound VII) is reacted with 2,5-norbornadiene to synthesize a triazole compound (Compound XVIII). Removal of boc and tbs groups using hydrochloric acid gives Compound XIX. Compound XIX is mesylated to give Compound XX. Compound XX is treated with hydrazine followed by trimethyl orthoformate to give a cyclic amidrazone compound. In Scheme 3(2), a dichlorotosylhydrazone (Compound XXI) is prepared by reacting tosylhydrazide and acid chloride as shown. Compound XXI is reacted with Compound XIII to give a cyclic amidrazone intermediate, which after removal of formyl group is dervatized with variety of R2 groups. Detailed description of the repective steps is given in the Examples below. [Scheme 3] The case where P is oxygen atom (O) and Q is H is exemplified in Scheme 4. A compound with P being O and Q being an aromatic heterocycle can be synthesized according to Scheme 2. For a compound with Q being H, protecting the alcohol group of Compound V with benzoyl gives Compound XXII. Removal of the boc and tbs protecting groups using hydrochloric acid to give Compound XXIII. Mesylation of Compound XXIII gives Compound XXIV, which is reacted with hydrazine to give Compound XXV with the benzoyl group removed. Compound XXV is reacted with trimethyl orthoformate to synthesize a cyclic amidrazone compound. After removing the formyl group, a variety of R2 groups are introduced. Detailed description of the repective steps is given in the Examples below. [Scheme 4] Scheme 5(1) shows a synthesis method of a cyclic amidoxime compound in which Y is O and P-Q is not OH and Scheme 5(2) shows a synthesis method of a cyclic amidoxime compound in which Y is O and P-Q is OH. In Scheme 5(1), P and Q groups are introduced to Compound VI according to Schemes 1 to 4 to synthesize Compound XXVI, which is treated with hydrochloric acid to remove boc and tbs groups yielding Compound XXVII. Compound XXVII is subjected to Mitsunobu condition with hydroxyphthalimide to obtain Compound XXVIII. Removal of phthalimide using hydrazine followed by reaction with trimethyl orthoformate gives a cyclic amidoxime compound. In Scheme 5(2), the alcohol group of oxazolidinone C-5 position is protected with benzoyl group to give Compound XXIII. Mitsunobu reaction with hydroxyphthalimide gives Compound XXIX. Removal of phthalimide using hydrazine followed by reaction with trimethyl orthoformate gives a cyclic amidoxime compound. Again, the benzoyl group is removed during the hydrazine reaction. A cyclic amidoxime compound can also be obtained by reacting with trimethyl orthoformate. [Scheme 5] While Schemes 1 to 5 show the cases where either X1 or X2 is F and the other is H, Scheme 6 shows the case where both X1 and X2 is either H or F. Scheme 6 is the same as or similar to Schemes 1 to 5 except that 4-fluoronitrobenzene or 3,4,5-trifluoronitrobenzene instead of difluoronitrobenzene is used as a starting material. [Scheme 6] The compositions of the present invention can be in a adequate form for oral administration (e.g., tablet, lozenge, hard or soft capsule, aqueous or oily suspension, emulsion, dispersible powder or granule, syrup or elixir), in a form adequate for topical application (e.g., cream, ointment, gel, aqueous or oily solution or suspension), in a form adequate for ocular administration, in a form adequate for administration by inhalation (e.g., finely divided powder or liquid aerosol), in a form adequate for administration by insufflation (e.g., finely divided powder), or in a form adequate for parenteral administration (e.g., aqueous or oily sterile solution for intravenous, subcutaneous, sublingual or intramuscular injection, or rectal suppository). In addition to the compounds of the present invention, the pharmaceutical compositions of the present invention may further comprise (i.e., formulated together with) one or more of known drug(s) or may be administered in combination with one or more of known drug(s). For example, the pharmaceutical compositions may further comprise one or more of clinically useful antibacterial agents (e.g., ß-lactam, macrolide, quinolone or aminoglycoside) and/or one or more of antiinflammatory agents (e.g., antifungal triazole or amphotericin). Also, for example, the compositions may further comprise carbapenem, e.g., meropenem or imipenem, to enhance therapeutic effect. Further, for example, the compounds of the present invention may be formulated together with or administered in combination with a bactericidal/permeability increasing protein (BPI) product or an efflux pump inhibitor, in order to increase activity against Gram-negative bacteria and antibiotic resistant bacteria. The compounds of the present invention may be formulated together with or administered in combination with vitamin, e.g., vitamin B, such as vitamin B2, vitamin B6 or vitamin B12, and folic acid. Further, the compounds of the present invention may be formulated together with or administered in combination with a cyclooxygenase (COX) inhibitor, particularly COX-2 inhibitor. In addition, the compounds of the present invention may be formulated together with or administered in combination with an antibacterial agent active against Gram-positive bacteria or Gram-negative bacteria. A pharmaceutical excipient available in the art may be used to to prepare the pharmaceutical compositions of the present invention. Accordingly, the pharmaceutical compositions according to the present invention intended for oral administration may comprise, for example, one or more of coloring agent, sweetening agent, flavoring agent, and antiseptic. Preferably, the pharmaceutical composition according to the present invention for intravenous administration may comprise (for example, in order to enhance stability) at least one of a bactericide, an antioxidant, a reducing agent, and a sequestrant. The compositions for oral administration may be in the form of a hard gelatin capsule prepared by mixing the active ingredient with an inert solid diluent, e.g., calcium carbonate, calcium phosphate or kaolin, or in the form of soft gelatin capsule prepared by mixing the active ingredient with water or oil, e.g., peanut oil, liquid paraffin or olive oil. The compositions may be prepared in the form of an aqueous suspension. The aqueous suspension comprises, in addition to at least one active ingredient in the form of fine powder, a suspending agent and/or a dispersing or wetting agent. Examples of the suspending agent include, but not limited to, sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia. Examples of the the dispersing or wetting agent include, but not limited to, lecithin, a condensation product of alkylene oxide with fatty acid (e.g., polyoxyethylene stearate), condensation product of ethylene oxide with long-chain aliphatic alcohol, e.g., heptadecaethyleneoxycetanol, a condensation product of ethylene oxide with partial ester derived from fatty acid and hexitol, e.g., polyoxyethylene sorbitol monooleate, a condensation product of ethylene oxide with partial ester derived from fatty acid and hexitol anhydride, e.g., polyethylene sorbitan monooleate. The aqueous suspension may further comprise at least one of antiseptic(s) (e.g., ethyl or propyl p-hydroxybenzoate), antioxidant(s) (e.g., ascorbic acid), coloring agent(s), flavoring agent(s), and sweetening agent(s) (e.g., sucrose, saccharin or aspartame). The compositions of the present invention may be prepared in the form of an oily suspension by suspending the active ingredient in, e.g., a vegetable oil (e.g., arachis oil, olive oil, sesame oil or coconut oil) or a mineral oil (e.g., liquid paraffin). The oily suspension may further comprise a thickener, e.g., beeswax, paraffin wax or cetyl alcohol. Suitably, a sweetening agent and/or a flavoring agent may be added to provide a tasty oral administration composition. The composition may be preserved by addition of an antioxidant such as ascorbic acid. Dispersible powder or granule adequate for preparing an aqueous suspension by adding water thereto may comprise a dispersing or wetting agent, a suspending agent and one or more antiseptic(s), in addition to the active ingredient. Examples of adequate dispersing or wetting agents and suspending agents are described earlier. There may also be comprised of an additional excipient such as a sweetening agent, a flavoring agent and a coloring agent. Further information about formulations is provided in Chapter 25.2 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press, 1990. The amount of the active ingredient mixed with one or more excipient(s) to prepare a unit-dose formulation may vary, of course, depending on the subject in need thereof and the particular route of administration. For example, a formulation for oral administration to a human patient may comprise, preferably, 50 mg to 5 g of the active ingredient compound along with an adequate amount of excipient (the content may range from about 5 to about 98% based on the total weight of the composition). More preferably, a unit-dose formulation may comprise from about 200 mg to about 2 g of the active ingredient. Further information about administration route and administration regimen is provided in Chapter 25.3 in Volume 5 of Comprehensive Medicinal Chemistry (Corwin Hansch; Chairman of Editorial Board), Pergamon Press, 1990. A preferable form of the pharmaceutical composition of the present invention may be a unit-dose formulation for oral administration, for example, a tablet or capsule comprising 0.1 mg to 1 g, preferably 100 mg to 1 g, of the compound of the present invention. More preferably, a tablet or capsule may comprise 50 mg to 800 mg of the compound of the present invention. Another preferable form of the pharmaceutical compositions of the present invention may be a formulation adequate for intravenous, subcutaneous or intramuscular injection, for example, which contains 0.1% w/v to 50% w/v (1 mg/mL to 500 mg/mL) of the compound of the present invention. In an embodiment, the compositions of the present invention may be administered to a human patient intravenously, subcutaneously or intramuscularly so that the active ingredient contained in the compositions can be administered, for example, at a dose of 0.1 mg/kg to 20 mg/kg per day. Preferably, the compositions may be administered one to four times a day. In another embodiment, the compound of the present invention may be administered at a dose of 1 mg/kg to 20 mg/kg per day. A dose for intravenous, subcutaneous or intramuscular administration may be provided by bolus injection. Alternatively, a dose for intravenous administration may be continuous injection over a period of time. Also, a single-day dose for oral administration, which may be approximately equivalent to a single-day dose for parenteral administration, may be administered to each patient. Preferably, the compositions may be administered one to four times a day. The oxazolidinone derivatives of the present invention exhibit antibacterial activity against several bacteria resistant to pre-existing antibiotics, including Gram-positive bacteria such as Staphylococcus aureus, Enterococcus faecalis, etc. and Gram-negative bacteria such as Haemophilus influenzae, Moraxella catarrhalis, etc., particularly excellent antibacterial activity against linezolid-resistant Enterococcus faecalis, even when they are used in a lower concentration than the linezolid product currently marketed by Pfizer. ?Mode for Invention? The examples and experiments will now be described. However, the following examples and experiments are for illustrative purposes only and are not intended to limit the scope of the present invention. [Preparation Example 1] Preparation of Compound I After dissolving 3,4-difluoronitrobenzene (158 g, 0.99 mol) in acetonitrile (800 mL) and adding ethanolamine (117 g, 1.9 mol), the mixture was stirred for 4 hours under reflux. The reaction solution was cooled to room temperature, concentrated under reduced pressure, triturated with diethyl ether, and filtered to obtain yellow Compound I (199 g, 0.99 mol, 100%). 1H NMR (400 MHz, chloroform-d1) d 7.97 (d, 1H, J = 8.8 Hz), 7.87 (dd, 1H, J1 = 11.6 Hz, J2 = 2.4 Hz), 6.65 (t, 1H, J = 8.8 Hz), 5.10-4.87 (bs, 1H), 3.97-3.83 (m, 2H), 3.43-3.37 (m, 2H). [Preparation Example 2] Preparation of Compound II Compound I (100 g, 0.5 mol), t-butyldimethylsilyl chloride (TBS-Cl, 97 g, 0.65 mol) and imidazole (51 g, 0.75 mol) were dissolved in dichloromethane (700 mL) at 0ºC and stirred overnight after slowly heating to room temperature. The reaction solution was concentrated under reduced pressure, dissolved in ethyl acetate and washed with 0.5 N HCl, washed sequentially with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, and concentrated under reduced pressure to quantitatively obtain a compound with a tbs group attached to alcohol. This compound was dissolved in THF (500 mL) and 1.2 equivalents of Boc2O and 0.1 equivalent of 4-dimethylaminopyridine (DMAP) were added. After stirring for 3 hours at room temperature, ammonia water (30 mL) was added. After stirring further for 20 minutes, the solution was concentrated under reduced pressure. The concentrate was dissolved again in ethyl acetate, sequentially washed with 0.5 N HCl, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, and concentrated under reduced pressure to quantitatively obtain Compound II. 1H NMR (600 MHz, chloroform-d1) d 8.06-7.98 (m, 1H), 7.95 (dd, 1H, J1 = 10.2 Hz, J2 = 2.4 Hz), 7.57 (t, 1H, J = 7.8 Hz), 3.80 (t, 2H, J = 5.4 Hz), 3.73 (t, 2H, J = 4.8 Hz), 1.42 (s, 9H), 0.81 (s, 9H), 0.01 (s, 6H). [Preparation Example 3] Preparation of Compound III Compound II (92 g, 0.22 mol) was dissolved in methanol (600 mL) and stirred for 4 hours under hydrogen balloon after adding Pd/C (6 g). The reaction mixture was filtered using celite and concentrated under reduced pressure to quantitatively obtain Compound III (86 g) as a colorless oil. 1H NMR (400 MHz, chloroform-d1) d 6.99 (t, 1H, J = 12.0 Hz), 6.44-6.30 (m, 2H), 3.81-3.63 (m, 4H), 3.63-3.52 (m, 2H), 1.50 (s, 3H), 1.35 (s, 6H), 0.86 (s, 9H), 0.03 (s, 6H). [Preparation Example 4] Preparation of Compound IV Compound III (86 g, 0.22 mol) was dissolved in dichloromethane (300 mL). After adding aqueous 1 N NaOH solution (300 mL), benzyl chloroformate (Cbz-Cl, 38 mL, 0.27 mol) was slowly added dropwise while stirring. After stirring for 1 hour at room temperature, the organic layer was separated, washed twice with water, dried with anhydrous sodium sulfate, and concentrated under reduced pressure to quantitatively obtain Compound IV (116 g) as a yellow oil. 1H NMR (600 MHz, chloroform-d1) d 7.44-7.32 (m, 6H), 7.18 (t, 1H, J = 8.1 Hz), 6.96 (d, 1H, J = 8.4 Hz), 6.84-6.66 (bs, 1H), 5.20 (s, 2H), 3.82-3.63 (m, 2H), 3.63-3.58 (m, 2H), 1.51 (s, 3H), 1.35 (s, 6H), 0.86 (s, 9H), 0.02 (s, 6H). [Preparation Example 5] Preparation of Compound V Compound IV (116 g, 0.22 mol) was dissolved in THF (400 mL) and stirred for 20 minutes after slowly adding n-butyllithium (2.5 M solution in n-hexane, 90 mL, 0.23 mol) dropwise at -78ºC. After adding (R)-glycidyl butyrate (31.5 mL, 0.23 mol), followed by stirring for 3 hours while slowly heating to room temperature, the solution was adjusted to pH ~6 with aqueous ammonium chloride solution, and concentrated under reduced pressure. The concentrate was dissolved in 80% ethyl acetate/hexane solution, sequentially washed with water and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrate was separated by column chromatography using 40% ethyl acetate/hexane solution to obtain Compound V (45 g, 0.093 mol, 42%) as a colorless oil. 1H NMR (600 MHz, CDCl3) d 7.50-7.48 (m, 1H), 7.30-7.28 (m, 1H), 7.17-7.16 (m, 1H), 4.74-4.70 (m, 1H), 4.03-4.02 (m, 1H), 3.98 (m, 2H), 3.75 (m, 3H), 3.65 (m, 2H), 1.51 (s, 3H), 1.36 (s, 6H), 0.85 (s, 9H), 0.02 (s, 6H). [Preparation Example 6] Preparation of Compound VI Compound V (45 g, 0.093 mol) was dissolved in dichloromethane (300 mL) and stirred for 20 minutes after sequentially adding triethylamine (26 mL, 0.186 mol) and methanesulfonyl chloride (MsCl, 10.9 mL, 0.14 mol) dropwise at 0ºC. After heating to room temperature, followed by stirring for 1 hour, the solution was concentrated under reduced pressure. The concentrate was dissolved in ethyl acetate, sequentially washed with 0.5 N HCl, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, and concentrated under reduced pressure to obtain Compound VI (50 g, 0.089 mol, 96%) as a yellow oil. 1H NMR (400 MHz, CDCl3) d 7.46 (dd, 1H, J1 = 11.6 Hz, J2 = 2.4 Hz), 7.29 (m, 1H), 7.13 (m, 1H), 4.94-4.88 (m, 1H), 4.50-4.39 (m, 2H), 4.12 (m, 1H), 3.92 (m, 1H), 3.72 (m, 2H), 3.64-3.62 (m, 2H), 3.08 (s, 3H), 1.49 (s, 3H), 1.34 (s, 6H), 0.83 (s, 9H), 0.00 (s, 6H). [Preparation Example 7] Preparation of Compound VII Compound VI (50 g, 0.089 mol) was dissolved in DMF (200 mL) and stirred for 3 hours at 80ºC after adding NaN3 (7.16 g, 0.11 mol). The solution was cooled to room temperature, diluted with ethyl acetate, sequentially washed with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, and concentrated under reduced pressure to quantitatively obtain Compound VII (47 g, 0.089 mol) as a colorless oily solid. 1H NMR (600 MHz, CDCl3) d 7.48 (dd, J1 = 8.2 Hz, J2 = 1.4 Hz) 7.30 (m, 1H), 7.16 (m, 1H), 4.81-4.79 (m, 1H), 4.09-4.08 (m, 1H), 3.86 (m, 1H), 3.74 (m, 2H), 3.62-3.59 (m, 1H), 1.51 (s, 3H), 1.36 (s, 6H), 0.85 (s, 9H), 0.02 (s, 6H). [Preparation Example 8] Preparation of Compound VIII Compound VII (47 g, 0.089 mol) was dissolved in methanol (400 mL) and stirred for 4 hours under hydrogen balloon after adding Pd/C (3.5 g). The solution was filtered with celite and concentrated under reduced pressure. The concentrate was dissolved in dichloromethane (130 mL) and, after adding aqueous 1 N NaOH solution (130 mL), Cbz-Cl (15.5 mL, 0.11 mol) was slowly added dropwise while stirring. After stirring for 2 hours at room temperature, the organic layer was separated, washed with water and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography using 20% ethyl acetate/hexane solution to obtain Compound VIII (50.5 g, 0.082 mol, 92%) as a light yellow oil. 1H NMR (400 MHz, CDCl3) d 7.46-7.43 (m, 1H), 7.36-7.35 (m, 1H), 7.31 (s, 6H), 7.11 (m, 1H), 5.09 (s, 2H), 4.75 (m, 1H), 4.01 (t, 1H, J = 8.4 Hz), 3.76-3.50 (m, 1H), 1.49 (s, 3H), 1.34 (s, 6H), 0.83 (s, 9H), 0.01 (s, 6H). [Preparation Example 9] Preparation of Compound IX Compound VIII (50.5 g, 0.082 mol) was dissolved in dichloromethane (100 mL), stirred for 3 hours at room temperature after adding 4 N HCl solution in dioxane (130 mL), and concentrated under reduced pressure to quantitatively obtain Compound IX (36 g, 0.082 mol) as a white solid. 1H NMR (400 MHz, DMSO-d6) d 7.69 (t, 1H, J = 6.0 Hz), 7.44-7.40 (m, 1H), 7.32 (s, 6H), 7.09-7.07 (m, 1H), 6.88 (t, 1H, J = 9.2 Hz), 5.03 (s, 2H), 4.71-4.68 (m, 1H), 4.08-4.03 (m, 2H), 3.73-3.69 (m, 1H), 3.60-3.57 (m, 3H), 3.39-3.34 (m, 2H), 3.18-3.15 (m, 2H). [Preparation Example 10] Preparation of Compound XII Compound IX (36 g, 0.082 mol) was dissolved in dichloromethane (300 mL) and stirred for 10 minutes after slowly adding triethylamine (34.5 mL, 0.245 mol) and methanesulfonyl chloride (MsCl, 9.5 mL, 0.123 mol) sequentially at 0ºC dropwise. The solution was heated to room temperature, stirred for 2 hours, diluted with dichloromethane, sequentially washed with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant solid was triturated with diethyl ether solvent and filtered to obtain Compound X (30.5 g, 0.063 mol, 77%) as a white solid. Compound X (20 g, 0.042 mol) was added to ethanol (100 mL) and stirred for 2 hours at 60ºC after adding hydrazine monohydrate (H2NNH2-H2O, 50 mL). The solution was concentrated under reduced pressure to obtain Compound XI (17.4 g, 0.042 mol) as an oil. Compound XI (17.4 g, 0.042 mol) was added to acetic acid (200 mL) and refluxed for 8 hours after adding trimethyl orthoformate (100 mL). The solution was distilled under reduced pressure, dissolved in dichloromethane, sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrate was separated by column chromatography using 5% methanol/dichloromethane solution to obtain Compound XII (5.8 g, 0.013 mol, 31%) as a white solid. 1H NMR (600 MHz, CDCl3) d = 8.52 (s, 1H), 7.55-7.53 (m, 1H), 7.30-7.28 (m, 6H), 7.19-7.18 (m, 1H), 7.11-7.08 (m, 1H), 6.86 (s, 1H), 5.27 (t, J = 6 Hz, 1H), 5.08 (s, 2H), 4.77 (m, 1H), 4.03-4.00 (m, 1H), 3.97 (t, J = 4.8 Hz, 2H), 3.81-3.76 (m, 1H), 3.70 (t, J = 5.1 Hz, 2H), 3.65-3.60 (m, 1H), 3.59-3.54 (m, 1H). [Preparation Example 11] Preparation of Compound XIII Compound XII (5 g, 0.011 mol) was dissolved in methanol (100 mL) and stirred for 4 hours under hydrogen balloon after adding Pd/C (0.5 g). The solution was filtered with celite and concentrated under reduced pressure to obtain Compound XIII (3.2 g, 0.010 mol, 91%) as a oily solid. 1H NMR (600 MHz, DMSO-d6) d = 8.43 (s, 1H), 7.65-7.63 (m, 1H), 7.40-7.36 (m, 2H), 7.12 (s, 1H), 4.65-4.62 (m, 1H), 4.09-4.06 (m, 1H), 3.89-3.86 (m, 1H), 3.85 (t, J = 5.1 Hz, 2H), 3.70 (t, J = 4.8 Hz, 2H), 2.88-2.85 (m, 1H), 2.82-2.79 (m, 1H). [Preparation Example 12] Preparation of Compound XV Boc-3-aminoisoxazole (1.22g, 6.6 mmol) was dissolved in DMF (40 mL) and stirred for 30 minutes after adding 50% NaH (0.32 g, 6.6 mmol). After slowly adding Compound VI (3.6 g, 6.6 mmol) dissolved in DMF (10 mL) dropwise, the solution was stirred at 80ºC for 4 hours. The solution was cooled to room temperature, diluted with ethyl acetate, washed twice with water, dried with anhydrous sodium sulfate, and concentrated under reduced pressure to obtain Compound XIV (4.16 g, 6.4 mmol). Compound XIV (4.16 g, 6.4 mmol) was dissolved in dichloromethane (20 mL), stirred overnight at room temperature after adding 4 N HCl solution in dioxane (20 mL), concentrated under reduced pressure, and triturated with diethyl ether solvent to obtain Compound XV (2.2 g, 6.2 mmol, 94%) as a white solid. 1H NMR (600 MHz, DMSO-d6) d 8.39 (d, J = 2.2 Hz, 1H), 7.52 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.18 (dd, J1 = 8.4 Hz, J2 = 1.8 Hz, 1H), 7.10 (t, J = 9.3 Hz, 1H), 6.00 (d, J = 2.2 Hz, 1H), 4.86 (m, 1H), 4.11 (t, J = 9 Hz, 1H), 3.80-3.19 (m, 7H). [Preparation Example 13] Preparation of Compound XIX Compound VII (0.613 g, 1.2 mmol) was dissolved in dioxane (10 mL), stirred for 4 hours under reflux after adding 2,5-norbornadiene (0.6 mL, 6 mmol), and cooled to room temperature. The solution was concentrated under reduced pressure, dissolved in dichloromethane, washed with water, and dried with sodium sulfate to obtain Compound XVIII (triazole, 98%), which was treated with hydrochloric acid as in Preparation Example 9 to obtain Compound XIX (0.35 g, 1.1 mmol, 92 %). 1H NMR (600 MHz, DMSO-d6) d = 8.18 (s, 1H), 7.77 (s, 1H), 7.39 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.09-7.00 (m, 2H), 5.11 (m, 1H), 4.82 (d, J = 4.8 Hz, 2H), 4.18 (t, J = 9.0 Hz, 1H), 3.84 (m, 1H), 3.59 (t, J = 6.0 Hz, 2H), 3.19 (t, J = 6.0 Hz, 2H). [Preparation Example 14] Preparation of Compound XXVII-b Compound VI (12 g, 21 mmol) was dissolved in DMF (100 mL) and stirred at 80ºC for 3 hours after adding NaN3 (1.65 g, 26 mmol). The solution was cooled to room temperature, diluted with ethyl acetate/hexane (150 mL/30 mL), washed 3 times with distilled water (200 mL), dried with anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography using 30% ethyl acetate/hexane solution to obtain Compound VII (9.6 g, 19 mmol, 89%). Compound VII (9.6 g, 19 mmol) was dissolved in methanol (120 mL), stirred for 4 hours under hydrogen balloon after adding Pd/C (1 g), and filtered with celite to obtain an amine compound (8.6 g, 95%). The amine compound (8.6 g) was dissolved in dichloromethane (120 mL) and, after adding saturated aqueous NaHCO3 solution (40 mL) and then adding thiophosgene (1.6 mL, 21 mmol) at 0ºC, was stirred for 2 hours. The organic layer was dried with sodium sulfate, distilled under reduced pressure, dissolved in methanol (150 mL), stirred overnight under reflux, concentrated under reduced pressure, and separated by column chromatography to obtain Compound XXVI-b (2.6 g, 7.6 mmol), which was treated with hydrochloric acid as in Preparation Example 9 to quantitatively obtain Compound XXVII-b. 1H NMR (600 MHz, CDCl3) d = 7.35 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 6.99-6.89 (m, 2H), 6.70 (t, J = 9.2 Hz, 1H), 4.93 (m, 1H), 4.10-3.91 (m, 6H), 3.88-3.78 (m, 3H), 3.32 (t, J = 5.2 Hz, 2H). [Preparation Example 15] Preparation of Compound XXVII-a A hydrochloride of Compound XXVII-a (3.4 g, 9.8 mmol, 85 %) was obtained from Compound VI in a similar manner to Preparation Example 14 using Ac2O instead of thiophosgene. 1H NMR (600 MHz, DMSO-d6) d 7.69 (t, 1H, J = 6.0 Hz), 7.46 (dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.41-7.26 (m, 5H), 7.18-7.11 (m, 1H), 7.00 (t, 1H, J = 9.6 Hz), 6.21-5.73 (m, 2H), 5.03 (s, 2H), 4.74-4.66 (m, 1H), 4.07 (t, 1H, J = 9.0 Hz), 3.76-3.70 (m, 1H), 3.60 (t, 2H, J = 5.7 Hz), 3.42-3.33 (m, 2H), 3.19 (t, 2H, J = 5.7 Hz). [Preparation Example 16] Preparation of Compound XXVIII-a A hydrochloride of Compound XXV-a (1.69 g, 4.86 mmol), hydroxyphthalimide (0.83 g, 5.11 mmol), triphenylphosphine (1.34 g, 5.11 mmol) and triethylamine (0.7 mL, 4.87 mmol) were added to THF (20 mL). After slowly adding diisopropyl azodicarboxylate (DIAD, 1.15 mL, 5.84 mmol) dropwise while stirring, the solution was stirred for 3 hours at room temperature. After filtration, the filtrate was concentrated under reduced pressure and separated by column chromatography to obtain Compound XXVIII-a (1.49 g, 3.26 mmol, 88%). 1H NMR (400 MHz, CDCl3) d = 7.86 (m, 2H), 7.76 (m, 2H), 7.38 (dd, J = 8.8, 1.6 Hz, 1H), 7.00 (dd, J = 8.8, 1.6 Hz, 1H), 6.69 (t, J = 6.0 Hz, 1H), 6.13 (t, J = 4.0 Hz), 4.92 (br, s, 1H), 4.75 (m, 1H), 4.42 (t, J = 3.6 Hz, 1H), 4.00 (t, J = 6 Hz, 1H), 3.70 (m, 2H), 3.60 (m, 1H), 3.50 (br, s, 2H), 2.03 (s, 3H). LCMS: 457 (M + H+) for C22H21FN4O6. [Preparation Example 17] Preparation of Compound XXIII Compound V (26 g, 0.053 mol) was dissolved in dichloromethane (180 mL) and stirred for 10 minutes after slowly adding diisopropylethylamine (DIPEA, 13 mL, 0.079 mol) and benzoyl chloride (Bz-Cl, 7.4 mL, 0.064 mol) sequentially dropwise at 0ºC. After heating to room temperature, followed by adding a small amount of DMAP, the solution was stirred for 2 hours. The solution was concentrated under reduced pressure, dissolved in ethyl acetate, sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, and concentrated under reduced pressure to quantitatively obtain Compound XXII (31 g, 0.053 mol), which was treated with hydrochloric acid as in Preparation Example 9 to quantitatively obtain Compound XXIII. 1H NMR (600 MHz, DMSO-d6) d 7.88 (d, J = 7.8 Hz, 2H), 7.63 (t, 1H, J = 7.2 Hz), 7.46 (t, 2H, J = 7.2 Hz), 7.41 (dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.11 (d, 1H, J = 9.0 Hz), 6.88 (t, 1H, J = 9.0 Hz), 5.02 (m, 1H), 4.54-4.45 (m, 2H), 4.16 (t, 1H, J = 9.0 Hz), 3.88 (m, 1H), 3.54 (t, 2H, J = 6.0 Hz), 3.13 (t, 2H, J = 6.0 Hz). Methods for synthesizing target compounds from the intermediate prepared in Preparation Examples 1 to 17 are described in the following Examples. [Example 1] Preparation of Compound 1 Compound XIII (0.1 g, 0.31 mmol) obtained in Preparation Example 11 was dissolved in dichloromethane (3 mL), stirred for 2 hours at room temperature after sequentially adding DIPEA (0.1 mL, 0.6 mmol) and Ac2O (0.06 mL, 0.6 mmol) dropwise, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 1 (0.098 g, 0.27 mmol, 87%) as a white solid. 1H NMR (400 MHz, chloroform-d4) d = 8.54 (s, 1H), 7.59 (dd, J = 13.6, 2.4 Hz, 1H), 7.20 (dd, J = 13.6, 2.4 Hz, 1H), 7.13 (t, J = 8.8, Hz, 1H), 6.88 (s, 1H), 6.19 (t, J = 6.0 Hz, 1H), 4.81 (m, 1H), 4.05 (t, J = 8 Hz, 1H), 3.99 (t, J = 4.8 Hz, 2H), 3.80 (dd, J = 8.8, 6.8 Hz, 1H), 3.73 (t, J = 4.8 Hz, 2H), 3.69 (m, 2H), 2.03 (s, 3H). LCMS: 364 (M + H+) for C16H18FN5O4. [Example 2] Preparation of Compound 2 Compound 1 (0.7 g, 1.93 mmol), 4 N hydrochloric acid dissolved in 1,4-dioxane (3 mL, 12 mmol) and Pd/C (70 mg) were added to THF (20 mL), and stirred for 2 hours under hydrogen gas. The solution was filtered with celite and concentrated under reduced pressure to obtain Compound 2 (0.72 g, 1.93 mmol, 100%) as a white solid. 1H NMR (400 MHz, DMSO-d6) d = 8.34-8.31 (m, 2H), 7.68 (dd, J = 13.6, 2.4 Hz, 1H), 7.56 (t, J = 8.8 Hz, 1H), 7.41 (dd, J = 13.6, 2.4 Hz, 1H), 4.76 (m, 1H), 4.15 (t, J = 8.8 Hz, 1H), 3.78 (m, 3H), 3.46 (m, 2H), 3.35 (t, J = 8.4 Hz, 2H), 1.83 (s, 3H). LCMS: 336 (M + H+) for C15H18FN5O3. [Example 3] Preparation of Compound 3 Compound 2 (0.11 g, 0.34 mmol) was dissolved in methanol (3 mL), stirred for 6 hours at room temperature after adding DIPEA (0.17 mL, 1 mmol) and dimethyl sulfate (52 mg, 0.41 mmol), and separated by column chromatography to obtain Compound 3 (29 mg, 0.083 mmol, 24%) as a white solid. 1H NMR (600 MHz, chloroform-d1) d 7.52 (dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.18-7.62 (m, 1H), 7.10 (t, 1H, 8.4 Hz), 6.90 (s, 1H), 6.70 (t, 1H, J = 6.0 Hz), 4.82-4.75 (m, 1H), 4.04 (t, 1H, J = 9.0 Hz), 3.85 (t, 2H, J = 4.8 Hz), 3.82 (t, 1H, 4.8 Hz), 3.74-3.60 (m, 2H), 2.99 (t, 2H, J = 4.8 Hz), 2.79 (s, 3H), 2.02 (s, 3H). LCMS: 350 (M + H+) for C16H20F1N5O3. [Example 4] Preparation of Compound 4 Compound 2 (0.21 g, 0.63 mmol) was dissolved in DMF (3 mL), stirred for 6 hours at room temperature after adding DIPEA (0.17 mL, 1 mmol) and allyl bromide (0.1 g, 0.8 mmol), and separated by column chromatography to obtain Compound 4 (80 mg, 0.21 mmol, 33%) as a white solid. 1H NMR (600 MHz, CDCl3) d = 7.51 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.15-7.09 (m, 2H), 6.92 (s, 1H), 6.18 (br, t, 1H), 6.02 (m, 1H), 5.30-5.22 (m, 2H), 4.79 (m, 1H), 4.05 (t, J = 9 Hz, 1H), 3.82 (t, J = 4.8 Hz, 2H), 3.79-3.58 (m, 6H), 3.00 (t, J = 4.8 Hz, 2H), 2.03 (s, 3H). LCMS: 376 (M + H+) for C18H22F1N5O3. [Example 5] Preparation of Compound 5 Compound 5 (34 mg, 0.091 mmol, 43%) was obtained from Compound 2 in a similar method to the method of Example 4, using propargyl bromide. 1H NMR (600 MHz, CDCl3) d = 7.51 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.16-7.11 (m, 2H), 6.95 (s, 1H), 6.00 (br, t, 1H), 4.79 (m, 1H), 4.04 (t, J = 9 Hz, 1H), 3.85 (t, J = 4.8 Hz, 2H), 3.82 (d, J = 2.4 Hz, 2H), 3.79-3.62 (m, 3H), 3.13 (t, J = 4.8 Hz, 2H), 2.31 (t, J = 2.4 Hz, 1H), 2.03 (s, 3H). LCMS: 374 (M + H+) for C18H20F1N5O3. [Example 6] Preparation of Compound 6 Compound 2 (30 mg, 0.08 mmol), DIPEA (66 uL, 0.40 mmol) and ethyl iodide (20 uL, 0.24 mmol) were sequentially added to dichloromethane (2 mL) at 0ºC and stirred for 8 hours under reflux. The solution was concentrated under reduced pressure and separated by column chromatography to obtain Compound 6 (5 mg, 0.01 mmol, 13%) as a yellow foam. 1H NMR (400 MHz, chloroform-d4) d = 7.57 (dd, J = 15 Hz, 1H), 7.18 (s, 2H), 7.08 (s, 1H), 6.31 (t, J = 6.0 Hz, 1H), 4.83 (m, 1H), 4.07 (t, J = 8.0 Hz, 1H), 3.90 (t, J = 4.2 Hz, 2H), 3.83 (dd, J = 8.0, 7.2 Hz, 1H), 3.74-3.65 (m, 2H), 3.12 (t, J = 5.4 Hz, 3H), 3.05 (q, J = 6.6 Hz, 2H), 2.06 (s, 3H), 1.31 (t, J = 6.6 Hz, 3H). LCMS: 364 (M + H+) for C17H22FN5O3. [Example 7] Preparation of Compound 7 Compound 2 (0.1 g, 0.3 mmol) was dissolved in DMF (3 mL), heated for 6 hours at 80ºC after adding 1 equivalent of K2CO3, 2 equivalents of chloroacetonitrile and a catalytic amount of KI, and separated by column chromatography to obtain Compound 7 (107 mg, 0.287 mmol, 96%) as a white solid. 1H NMR (600 MHz, chloroform-d1) d 7.40 (dd, 1H, J1 = 13.2 Hz, J2 = 2.4 Hz), 7.01 (dd, 1H, J1 = 8.4 Hz, J2 = 1.2 Hz), 6.69 (t, 1H, J = 9.3 Hz), 6.14 (d, 1H, J = 5.4 Hz), 4.78-4.72 (m 1H), 4.40 (t, 2H, J = 5.4 Hz), 4.00 (t, 1H, J = 9.0 Hz), 3.76-3.66 (m, 2H), 3.61 (t, 1H, J = 6.0 Hz), 3.55 (t, 2H, J = 5.4 Hz), 3.03 (s, 3H), 2.03 (s, 3H). LCMS: 374 (M + H+) for C17H19FN6O3. [Example 8] Preparation of Compound 8 Compound 2 (0.1 g, 0.3 mmol) was dissolved in DMF (3 mL), for 6 hours at 200ºC after adding 1 equivalent of K2CO3 and 2 equivalents of 1,1,1-trifluoro-2-iodoethane, and separated by column chromatography to obtain Compound 8 (11 mg, 0.026 mmol, 9%) as a white solid. 1H NMR (600 MHz, chloroform-d1) d 7.52 (dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.18-7.07 (m, 2H), 6.86 (s, 1H), 6.32-6.24 (m, 1H), 4.90-4.76 (m, 1H), 4.04 (t, J = 8.7 Hz), 3.84 (t, 2H, J = 4.5 Hz), 3.81-3.76 (m, 1H), 3.62-3.52 (m, 2H), 3.24 (t, 4.5 Hz), 2.02 (s, 3H). LCMS: 418 (M + H+) for C17H19F4N5O3. [Example 9] Preparation of Compound 9 Compound 2 (150 mg, 0.40 mmol), DIPEA (200 uL, 1.20 mmol) and cyanogen bromide (63 mg, 0.60 mmol) were sequentially added to dichloromethane (2 mL) at 0ºC and stirred for 0.5 hour. The solution was concentrated under reduced pressure and separated by column chromatography to obtain Compound 9 (25 mg, 0.07 mmol, 17%) as a white solid. 1H NMR (400 MHz, chloroform-d4) d = 7.60 (dd, J = 13.2, 2.4 Hz, 1H), 7.20 (dd, J = 13.2, 2.4 Hz, 1H), 7.13 (t, J = 8.8, Hz, 1H), 6.89 (s, 1H), 4.80 (m, 1H), 4.05 (t, J = 9.2 Hz, 1H), 3.85-3.61 (m, 2H), 2.03 (s, 3H). LCMS: 361 (M + H+) for C16H17FN6O3. [Example 10] Preparation of Compound 10 Compound 2 (5 mg, 0.013 mmol), DIPEA (4 uL, 0.026 mmol) and acetyl chloride (1.5 uL, 0.02 mmol) were sequentially added to dichloromethane (2 mL) at 0ºC and stirred for 1.5 hours. After adding dichloromethane (30 mL), the solution was washed with saturated aqueous sodium bicarbonate solution (15 mL), dried with magnesium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 10 (2 mg, 0.004 mmol, 30%) as a white solid. 1H NMR (600 MHz, chloroform-d4) d = 7.57 (dd, J = 13.2, 2.4 Hz, 1H), 7.20 (dd, J = 9.6, 2.4 Hz, 1H), 7.13 (t, J = 9.6, Hz, 1H), 6.85 (s, 1H), 6.03 (t, J = 6.0 Hz, 1H), 4.80 (m, 1H), 4.06 (m, 2H), 3.79 (dd, J = 9.0, 6.6 Hz, 2H), 3.71 (m, 2H), 3.62 (m, 1H) 2.03 (s, 3H). LCMS: 378 (M + H+) for C17H20FN5O4. [Example 11] Preparation of Compound 11 Compound 2 (30 mg, 0.08 mmol), (1H-benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP, 105 mg, 0.20 mmol), cyanoacetic acid (14 mg, 0.16 mmol) and DIPEA (40 uL, 0.24 mmol) were sequentially added to DMF (2 mL) at 0ºC and stirred for 1.5 hours at room temperature. After adding dichloromethane (30 mL), the solution was washed 3 times with saturated aqueous sodium bicarbonate solution, dried with magnesium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 11 (5 mg, 0.01 mmol, 13%) as a white solid. 1H NMR (400 MHz, chloroform-d4) d = 7.61 (dd, J = 13.2, 2.8 Hz, 1H), 7.25 (dd, J = 13.2, 2.8 Hz, 1H), 7.13 (t, J = 8.8, Hz, 1H), 6.85 (s, 1H), 6.19 (t, J = 6.0 Hz, 1H), 4.81 (m, 1H), 4.07 (m, 2H), 3.85 (m, 3H), 3.75 (t, J = 6.0 Hz, 2H), 3.68 (m, 2H), 2.03 (s, 3H). LCMS: 403 (M + H+) for C18H19FN6O4. [Example 12] Preparation of Compound 12 Compound 2 (200 mg, 0.54 mmol), PyBOP (700 mg, 1.34 mmol), glycolic acid (82 mg, 1.07 mmol) and DIPEA (266 uL, 1.61 mmol) were sequentially added to DMF (2 mL) at 0ºC and stirred for 2 hours at room temperature. After adding dichloromethane (100 mL), the solution was washed 3 times with distilled water, dried with magnesium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 12 (83 mg, 0.21 mmol, 39%) as a white solid. 1H NMR (400 MHz, DMSO-d6) d = 8.25 (t, J = 6 Hz, 1H), 7.62 (dd, J = 8.8, 2.4 Hz, 1H), 7.37 (t, J = 8.8 Hz, 1H), 7.32 (dd, J = 8.8, 2.4 Hz, 1H), 7.07 (t, J = 2.0 Hz, 1H), 4.74 (m, 1H), 4.53 (t, J = 6.0 Hz, 1H), 4.32 (d, J = 6 Hz, 2H), 4.12 (t, J = 8.8 Hz, 1H), 3.89 (t, J = 4.6 Hz, 2H), 3.75-3.69 (m, 3H), 3.40 (m, 2H), 1.83 (s, 3H). LCMS: 394 (M + H+) for C17H20FN5O5. [Example 13] Preparation of Compound 13 Compound 2 (35 mg, 0.09 mmol), DIPEA (45 uL, 0.28 mmol) and cyclopropanecarbonyl chloride (13 uL, 0.14 mmol) were sequentially added to dichloromethane (3 mL) at 0ºC and stirred for 1 hour at room temperature. The solution was concentrated under reduced pressure and separated by column chromatography to obtain Compound 13 (13 mg, 0.03 mmol, 33%) as a white solid. 1H NMR (600 MHz, DMSO-d6) d = 8.25 (t, J = 6 Hz, 1H), 7.6 (d, J = 13.8 Hz, 1H), 7.39 (t, J = 9.0 Hz, 1H), 7.32 (d, J = 13.8 Hz, 1H), 7.10 (m, 1H), 4.75 (m, 1H), 4.12 (t, J = 9.0 Hz, 1H), 3.90 (s, 2H), 3.74 (t, J = 6.6 Hz, 1H), 3.70 (s, 2H), 3.42 (t, J = 5.4 Hz, 2H), 2.69 (t, J = 6.0 Hz, 1H), 1.83 (s, 3H), 0.85 (d, J = 6.0 Hz, 3H). LCMS: 404 (M + H+) for C19H22FN5O4. [Example 14] Preparation of Compound 14 Compound 2 (30 mg, 0.08 mmol), triethylamine (23 uL, 0.16 mmol) and trimethylsilyl isocyanate (63 uL, 0.40 mmol) were sequentially added to dichloromethane (3 mL) at 0ºC and stirred for 2 hours at room temperature. After adding dichloromethane (30 mL), the solution was washed twice with saturated aqueous sodium bicarbonate solution, dried with magnesium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 14 (8 mg, 0.02 mmol, 26%) as a white solid. 1H NMR (400 MHz, DMSO-d6) d = 8.26 (t, J = 6.0 Hz, 1H), 7.60 (dd, J = 15.0,2.4 Hz, 1H), 7.37-7.30 (m, 2H), 6.96 (d, J = 2.0 Hz, 1H), 6.32 (s, 2H), 4.74 (m, 1H), 4.12 (t, J = 8.8 Hz, 1H), 3.78-3.67 (m, 4H), 3.40-3.28 (m, 3H), 1.83 (s, 3H). LCMS: 379 (M + H+) for C16H19FN6O4. [Example 15] Preparation of Compound 15 Compound 15 (25 mg, 0.059 mmol, 42%) was obtained from Compound 2 in a similar method to the method of Example 6, using carbonyldiimidazole (437 mg, 2.7 mmol) and ethanolamine. 1H NMR (600 MHz, chloroform-d1) d 7.69 (s, 1H), 7.54 (dd, 1H, J1 = 13.2 Hz, J2 = 2.4 Hz), 7.16 (dd, 1H, J1 = 9.0 Hz, J2 = 1.8 Hz), 7.10-7.08 (m, 1H), 6.87 (t, 1H, J = 6.0 Hz), 6.78 (s, 1H), 6.72 (t, 1H, J = 6.0 Hz), 4.83-7.49 (m, 1H), 4.04 (t, 1H, J = 9.0 Hz), 3.95 (t, 2H, J = 4.8 Hz), 3.84-3.78 (m, 1H), 3.76 (t, 2H, J = 5.4 Hz), 3.72 (t, 2H, J = 4.8 Hz), 3.67 (dd, 2H, J1 = 6.0 Hz, J2 = 4.8 Hz), 2.03 (s, 3H). LCMS: 423 (M + H+) for C18H23FN6O5. [Example 16] Preparation of Compound 16 Compound 16 (15 mg, 0.032 mmol, 25%) was obtained from Compound 2 in a similar method to the method of Example 15, using carbonyldiimidazole and diethanolamine. 1H NMR (600 MHz, DMSO-d6) d 7.70-7.62 (m, 1H), 7.37-7.30 (m, 2H), 7.1 (s, 1H), 4.81-4.76 (m, 1H), 4.45-4.40 (m, 2H), 4.14 (t, 1H, J = 9.0 Hz), 4.01-3.94 (m, 2H), 3.82-3.78 (m, 4H), 3.55 (d, 2H, J = 4.8 Hz), 3.48-3.42 (m, 1H), 3.42-3.38 (m, 2H), 3.20-3.16 (m, 2H), 1.94 (s, 3H), 1.29 (t, 2H, J = 7.2 Hz). LCMS: 467 (M + H+) for C20H27FN6O6. [Example 17] Preparation of Compound 17 Compound 17 (31 mg, 0.075 mmol, 88%) was obtained from Compound 2 in a similar method to the method of Example 11, using difluoroacetic acid. 1H NMR (600 MHz, chloroform-d1) d 7.61 (dd, 1H, J1 = 13.2 Hz, J2 = 3.0 Hz), 7.22 (dd, 1H, J1 = 9.0 Hz, J2 = 2.4 Hz), 7.14 (t, 1H, J = 9.0 Hz), 6.90 (s, 1H), 6.77 (t, 1H, J = 53.4 Hz), 6.04 (t, 1H, J = 6.3 Hz), 4.83-4.79 (m, 1H), 4.08 (t, 2H, J = 4.8 Hz), 4.05 (t, 1H, J = 9.0 Hz), 3.88-3.80 (m, 1H), 3.78 (t, 2H, J = 4.8 Hz), 3.75-3.69 (m, 1H), 3.69-3.60 (m, 1H), 2.03 (s, 3H). LCMS: 414 (M + H+) for C17H18F3N5O4. [Example 18] Preparation of Compound 18 Compound 2 (35 mg, 0.09 mmol), DIPEA (45 uL, 0.28 mmol) and methanesulfonyl chloride (11 uL, 0.14 mmol) were sequentially added to dichloromethane (3 mL) at 0ºC and stirred for 1 hour at room temperature. The solution was concentrated under reduced pressure and separated by column chromatography to obtain Compound 18 (13 mg, 0.03 mmol, 33%) as a white solid. 1H NMR (600 MHz, DMSO-d6) d = 8.26 (t, J = 5.4 Hz, 2H), 7.61 (d, J = 13.8 Hz, 1H), 7.43 (t, J = 9.6 Hz, 1H), 7.33 (d, J = 9.6 Hz, 1H), 7.21 (s, 1H), 4.75 (m, 1H), 4.13 (t, J = 8.4 Hz, 1H), 3.84 (s, 1H), 3.74 (t, J = 8.4 Hz, 1H), 3.56 (s, 2H), 3.41 (t, J = 5.4 Hz, 2H), 2.98 (s, 3H), 1.83 (s, 3H). LCMS: 414 (M + H+) for C16H20FN5O5S. [Example 19] Preparation of Compound 19 Compound 2 (30 mg, 0.08 mmol), DIPEA (66 uL, 0.40 mmol) and methyl isothiocyanide (6 uL, 0.24 mmol) were sequentially added to dichloromethane (2 mL) at 0ºC and stirred for 12 hours. The solution was concentrated under reduced pressure and separated by column chromatography to obtain Compound 19 (17 mg, 0.03 mmol, 38%) as a white solid. 1H NMR (600 MHz, chloroform-d4) d = 7.78 (s, 1H), 7.58 (dd, J = 13.2, 2.4 Hz, 1H), 7.21 (dd, J = 13.2, 2.4 Hz, 1H), 7.13 (t, J = 8.4, Hz, 1H), 6.86 (s, 1H), 5.96 (t, J = 6.0 Hz, 1H), 4.80 (m, 1H), 4.59 (t, J = 5.4 Hz, 2H), 4.05 (t, J = 7.5 Hz, 1H), 3.81-3.77 (m, 3H), 3.71 (m, 1H), 3.65 (m, 1H), 3.20 (d, J = 4.8 Hz, 1H), 2.03 (s, 3H). LCMS: 409 (M + H+) for C17H21FN6O3S. [Example 20] Preparation of Compound 20 Compound 2 (50 mg, 0.13 mmol), triethylamine (55 uL, 0.39 mmol) and amidosulfonyl chloride (145 uL, 0.26 mmol) were sequentially added to dichloromethane (3 mL) at 0ºC and stirred for 12 hours at room temperature. After adding dichloromethane (30 mL), the solution was washed twice with saturated aqueous sodium bicarbonate solution, dried with magnesium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 20 (5 mg, 0.01 mmol, 10%) as a white solid. 1H NMR (400 MHz, DMSO-d6) d = 8.26 (t, J = 4.8 Hz, 1H) 7.60 (dd, J = 13.2, 2.4 Hz, 1H), 7.42 (t, J = 8.8 Hz, 1H), 7.32 (dd, J = 13.2, 2.4 Hz, 1H), 7.12 (s, 1H), 7.05 (s, 2H), 4.74 (m, 1H), 4.12 (t, J = 9.2 Hz, 1H), 3.81 (t, J = 5.2 Hz, 2H), 3.73 (dd, J = 9.2, 6.4 Hz, 1H), 3.50-3.38 (m, 4H), 1.83 (s, 3H). LCMS: 414 (M + H+) for C15H19FN6O5S. [Example 21] Preparation of Compound 21 Compound 2 (50 mg, 0.13 mmol), triethylamine (36 uL, 0.26 mmol) and dimethylaminosulfonyl chloride (16 uL, 0.15 mmol) were sequentially added to DMF (1 mL) at 0ºC and stirred for 12 hours at room temperature. After adding dichloromethane (30 mL), the solution was washed twice with saturated aqueous sodium bicarbonate solution (10 mL), dried with magnesium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 21 (6 mg, 0.01 mmol, 10%) as a white solid. 1H NMR (400 MHz, DMSO-d6) d = 7.62 (dd, J = 13.2, 2.4 Hz, 1H), 7.19 (dd, J = 13.2, 2.0 Hz, 1H), 7.12 (t, J = 8.8 Hz, 1H), 6.94 (s, 1H), 6.00 (t, J = 6.0 Hz, 1H), 4.80 (m, 1H), 4.05 (t, J = 8.8 Hz, 1H), 3.85 (t, J = 4.4 Hz, 2H), 3.79 (dd, J = 8.8, 6.8 Hz, 1H), 3.71-3.60 (m, 4H), 3.03 (s, 6H), 2.03 (s, 3H). LCMS: 443 (M + H+) for C17H23FN6O5. [Example 22] Preparation of Compound 22 Compound 22 (36 mg, 0.085 mmol, 78%) was obtained from Compound 2 in a similar method to the method of Example 11. 1H NMR (400 MHz, DMSO-d6) d = 8.26 (t, J = 6.0 Hz, 1H), 7.50 (d, J = 13.8 Hz, 1H), 7.37 (t, J = 9.0 Hz, 1H), 7.24 (d, J = 9.0 Hz, 1H), 5.86 (s, 1H), 5.61 (m, 1H), 4.72 (m, 1H), 4.11 (m, 1H), 3.72 (m, 1H), 3.41-3.35 (m, 2H), 3.08 (m, 2H), 2.86 (m, 2H), 1.83 (s, 3H), 1.31 (s, 3H), 1.24 (s, 3H). LCMS: 422 (M + H+) for C19H24FN5O5. [Example 23] Preparation of Compound 23 Compound 2 (30 mg, 0.08 mmol), PyBOP (105 mg, 0.20 mmol), Boc-Gly-OH (28 mg, 0.16 mmol) and DIPEA (40 uL, 0.24 mmol) were sequentially added to DMF (2 mL) 0ºC and stirred for 1.5 hours at room temperature. After adding dichloromethane (30 mL), the solution was washed 3 times with distilled water (10 mL), dried with magnesium sulfate, concentrated under reduced pressure, separated by column chromatography, and stirred for 0.5 hour after adding 4 N hydrochloric acid dissolved in 1,4-dioxane (3 mL). The product was concentrated under reduced pressure to obtain Compound 23 (10 mg, 0.02 mmol, 29%). 1H NMR (400 MHz, DMSO-d6) d = 8.29 (t, J = 6 Hz, 1H), 8.10 (s, 3H), 7.62 (dd, J = 15.0, 2.4 Hz, 1H), 7.40 (t, J = 8.8 Hz, 1H), 7.34 (dd, J = 15.0, 2.4 Hz, 1H), 7.20 (s, 1H), 4.74 (m, 1H), 4.13 (t, J = 8.8 Hz, 1H), 3.99-3.94 (m, 3H), 3.74 (t, J = 4.0 Hz, 2H), 3.42 (t, J = 4.8 Hz, 2H), 1.83 (s, 3H). LCMS: 393 (M + H+) for C17H21FN6O4. [Example 24] Preparation of Compound 24 Compound 24 (200 mg, 0.48 mmol, 34%) was obtained from Compound 2 in a similar method to the method of Example 7, using ethyl bromoacetate. 1H NMR (600 MHz, chloroform-d1) d 7.50 (dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.13 (dd, 1H, J1 = 9.0 Hz, J2 = 2.4 Hz), 7.10 (t, 1H, J = 8.4 Hz), 6.89 (s, 1H), 6.70 (t, 1H, J = 6.0 Hz), 4.82-4.79 (m, 1H), 4.25-4.21 (m, 2H), 4.04 (t, 1H, J = 9.0 Hz), 3.84 (t, 2H, J = 4.2 Hz), 3.82-3.80 (m, 1H), 3.77 (s, 2H), 3.66 (t, 2H, J = 4.2 Hz), 3.24 (t, 2H, J = 4.2 Hz), 2.02 (s, 3H). LCMS: 422 (M + H+) for C19H24FN5O5. [Example 25] Preparation of Compound 25 Compound 24 (100 mg, 0.24 mmol) was dissolved in methanol (2 mL), stirred overnight at 100ºC in a sealed tube after adding ammonia water (0.5 mL), concentrated under reduced pressure, and separated by column chromatography to obtain Compound 25 (20 mg, 0.051 mmol, 21%). 1H NMR (400 MHz, DMSO-d6) d 8.25 (t, 1H, J = 5.6 Hz), 7.56 (d, 1H, 14.0 Hz), 7.83-7.26 (m, 2H), 7.21-7.08 (m, 2H), 6.91 (s, 1H), 4.75-4.71 (m, 1H), 4.11 (t, 1H, J = 9.0 Hz), 3.82-3.69 (m, 3H), 3.50-3.40 (m, 2H), 3.31 (s, 2H), 3.03 (t, 2H, J = 4.4 Hz), 1.83 (s, 3H). LCMS: 393 (M + H+) for C17H21FN6O4. [Example 26] Preparation of Compound 26 Compound 24 (100 mg, 0.24 mmol) was dissolved in methanol (20 mL), stirred overnight at room temperature after adding hydroxylamine solution (obtained by adding 2.4 g of KOH to 2.4 g of NH2OH-HCl and then filtering) dissolved in methanol (20 mL), concentrated under reduced pressure, and separated by column chromatography to obtain Compound 26 (22 mg, 0.054 mmol, 23%). 1H NMR (600 MHz, DMSO-d6) d 8.30-8.20 (m, 1H), 7.35-7.25 (m, 1H), 7.10-7.00 (m, 1H), 6.87 (s, 1H), 5.33-5.28 (m, 1H), 4.71-7.64 (m, 1H), 4.11 (t, 2H, J = 9.0 Hz), 4.04 (t, 2H, J = 8.4 Hz), 3.17 (s, 2H), 2.91 (t, 2H, J = 6.6 Hz), 1.83 (s, 1H). LCMS: 409 (M + H+) for C17H21FN6O5. [Example 27] Preparation of Compound 27 Compound 24 (110 mg, 0.26 mmol) was dissolved in THF (10 mL) and stirred for 3 hours at room temperature after adding 2M LiBH4 solution (0.2 mL, 0.4 mmol). After adding a small amount of water, the solution was separated by column chromatography to obtain Compound 27 (24 mg, 0.063 mmol, 29%) as a light yellow solid. 1H NMR (600 MHz, chloroform-d1) d 7.54 (dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.16 (dd, 1H, J1 = 9.0 Hz, J2 = 2.4 Hz), 7.12 (t, 1H, J = 8.4 Hz), 6.90 (s, 1H), 5.98 (t, 1H, J = 6.0 Hz), 4.87 (m, 1H), 4.05 (t, 1H, J = 9.0 Hz), 3.97 (m, 2H), 3.85 (t, 2H, J = 4.2 Hz), 3.82-3.6 (m, 3H), 3.07 (t, 2H, J = 4.2 Hz), 3.00 (m, 2H), 2.04 (s, 3H). LCMS: 380 (M + H+) for C17H22FN5O4. [Example 28] Preparation of Compound 28 Compound XXVIII-a (0.22 g, 0.49 mmol) and hydrazine (monohydrate, 1 mL) were dissolved in methanol (10 mL), stirred for 2 hours under reflux, concentrated under reduced pressure, and stirred for 4 hours under reflux after adding trimethyl orthoformate (5 mL) and acetic acid (5 mL). The solution was concentrated under reduced pressure and separated by column chromatography to obtain Compound 28 (32 mg, 0.10 mmol, 20%) as a white solid. 1H NMR (400 MHz, DMSO-d6) d = 8.25 (t, J = 6 Hz, 1H), 7.60 (dd, J = 14.0, 2.4 Hz, 1H), 7.46 (s, 1H), 7.38 (t, J = 8.8 Hz, 1H), 7.31 (dd, J = 9.2, 2.0 Hz, 1H), 4.74 (m, 1H), 4.12 (t, J = 9.2 Hz, 1H), 4.04 (t, J = 3.6 Hz, 2H), 3.75-3.67 (m, 3H), 3.41 (t, J = 5.6 Hz, 2H), 1.83 (s, 3H). LCMS: 337 (M + H+) for C15H17FN4O4. [Example 29] Preparation of Compound 29 Compound 2 (100 mg, 0.27 mmol) was dissolved in chloroform (3 mL) and stirred for 30 minutes after adding saturated aqueous NaHCO3 solution (3 mL) and then adding thiophosgene (0.021 mL) at 0ºC. The organic layer was separated and ammonia water (1 mL) was added. The solution was diluted with THF (10 mL) and distilled under reduced pressure to remove the quantity of the solvent in half. After further adding ammonia water (2 mL), the solution was stirred overnight at room temperature. The solution was distilled under reduced pressure and triturated with ethyl ether to obtain Compound 29 (80 mg, 0.20 mmol, 74%) as a white solid. 1H NMR (600 MHz, DMSO-d6) d 8.27 (t, 1H, J = 4.8 Hz), 7.98 (s, 1H), 7.62 (dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.59-7.46 (m, 1H), 7.42 (t, 1H, J = 9.0 Hz), 7.34 (d, 1H, J = 9.0 Hz), 7.16 (s, 1H), 7.51-6.89 (bs, 2H), 4.79-4.69 (m, 1H), 4.37 (t, 2H, J = 4.2 Hz), 4.13 (t, 1H, J = 9.6 Hz), 3.79-3.70 (m, 3H), 3.42 (t, 2H, J = 4.8 Hz), 3.38-3.29 (m, 1H), 1.83 (s, 3H). LCMS: 395 (M + H+) for C16H19FN6O3S. [Example 30] Preparation of Compound 30 Compound 2 (100 mg, 0.27 mmol) was dissolved in chloroform (3 mL), stirred for 30 minutes after adding saturated aqueous NaHCO3 solution (3 mL) and then adding thiophosgene (0.021 mL) at 0ºC. The organic layer was separated, distilled under reduced pressure, and stirred overnight at room temperature after adding methanol (5 mL). The solution was distilled under reduced pressure and separated by column chromatography to obtain Compound 30 (31 mg, 0.20 mmol, 74%) as a white solid. 1H NMR (600 MHz, DMSO-d6) d 7.60 (dd, 1H, J1 = 13.2 Hz, J2 = 1.2 Hz), 7.25-7.18 (m, 1H), 7.16 (t, 1H, J = 8.4 Hz), 6.96 (s, 1H), 6.51 (bs, 1H), 4.86-4.79 (m, 1H), 4.64-4.54 (m, 2H), 4.19 (s, 3H), 4.06 (t, 1H, J = 9.0 Hz), 3.88-3.76 (m, 3H), 3.74-3.66 (m, 2H), 2.03 (s, 3H). LCMS: 410 (M + H+) for C17H20FN5O4S. [Example 31] Preparation of Compound 31 Compound 31 (26 mg, 0.061 mmol, 32%) was obtained from Compound 2 in a similar method to the method of Example 30, using ethanol instead of methanol. 1H NMR (600 MHz, DMSO-d6) d 7.60 (d, J = 12.0 Hz), 7.24-7.18 (m, 1H), 7.15 (t, 1H, J = 8.4 Hz), 6.97 (s, 1H), 6.32 (bs, 1H), 4.88-4.76 (m, 1H), 4.75-4.64 (m, 2H), 4.64-4.53 (m, 2H), 4.06 (t, 1H, J = 8.4 Hz), 3.88-3.77 (m, 3H), 3.74-3.60 (m, 2H), 2.03 (s, 3H), 1.46 (t, 3H, J = 6.6 Hz). LCMS: 424 (M + H+) for C18H22FN5O4S. [Example 32] Preparation of Compound 32 Compound 32 (23 mg, 0.052 mmol, 22%) was obtained from Compound 2 in a similar method to the method of Example 30, using ethylene glycol instead of methanol. 1H NMR (600 MHz, chloroform-d1) d 7.62 (dd, 1H, J1 = 12.6 Hz, J2 = 1.8 Hz), 7.23-7.19 (m, 1H), 7.18 (t, 1H, 9.0 Hz), 7.06 (s, 1H), 6.42 (t, 1H, J = 6.6 Hz), 4.96-4.86 (bs, 1H), 4.86-4.77 (m, 1H), 4.65 (t, 2H, J = 3.6 Hz), 4.59 (t, 2H, J = 4.8 Hz), 4.07 (t, 1H, 9.0 Hz), 3.98-3.89 (m, 2H), 3.88-3.79 (m, 3H), 3.72-3.65 (m, 2H), 2.03 (s, 3H). LCMS: 440 (M + H+) for C18H22FN5O5S. [Example 33] Preparation of Compound 33 Compound 33 (16 mg, 0.036 mmol, 35%) was obtained from Compound 2 in a similar method to the method of Example 30, using aminoethanol instead of methanol. 1H NMR (600 MHz, DMSO-d6) d 8.28 (t, 1H, J = 5.4 Hz), 7.67-7.58 (m, 1H), 7.43 (t, 1H, J = 9.0 Hz), 7.38-7.31 (m, 1H), 7.20 (s, 1H), 4.08 (t, 1H, J = 5.4 Hz), 4.78-4.70 (m, 1H), 4.39 (t, 2H, J = 4.8 Hz), 4.13 (t, 1H, J = 9.0 Hz), 3.81-3.75 (m, 2H), 3.58 (t, 2H, J = 4.2 Hz), 3.53 (t, 2H, J = 5.7 Hz), 3.42 (t, 2H, J = 5.4 Hz), 1.83 (s, 3H). LCMS: 439 (M + H+) for C18H23FN6O4S. [Example 34] Preparation of Compound 34 Compound 2 (50 mg, 0.13 mmol) was dissolved in ethanol (5 mL) and stirred overnight at room temperature after adding DIPEA (0.03 mL, 0.2 mmol), NaF (7 mg, 0.17 mmol) and ethyl dithioacetate (0.019 mL, 0.16 mmol). The solution was distilled under reduced pressure and separated by column chromatography to obtain Compound 34 (10 mg, 0.025 mmol, 19%) as a white solid. 1H NMR (600 MHz, CDCl3) d = 7.62 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.25-7.21 (m, 2H), 7.16 (t, J = 8.4 Hz, 1H), 6.94 (s, 1H), 5.93 (br, t, 1H), 4.81 (m, 1H), 4.73 (t, J = 5.2 Hz, 2H), 4.06 (t, J = 8.8 Hz, 1H), 3.83-3.62 (m, 5H), 2.81 (s, 3H), 2.03 (s, 3H). LCMS: 394 (M + H+) for C17H20FN5O3S. [Example 35] Preparation of Compound 35 Compound 35 (35 mg, 0.086 mmol, 65%) was obtained from Compound 2 in a similar method to the method of Example 6, using carbonyldiimidazole and ethanol. 1H NMR (600 MHz, CDCl3) d = 7.58-7.56 (m, 1H), 7.19-7.18 (m, 1H), 7.13-7.10 (m, 1H ), 6.92 (s, 1H), 6.21 (m, 1H), 4.80 (m, 1H), 4.33-4.32 (m, 2H), 4.06-4.03 (m, 1H), 3.99 (m, 2H), 3.81-3.77 (m, 3H), 3.71-3.66 (m, 2H), 2.03 (s, 3H), 1.38 (t, J = 6.3 Hz, 3H). LCMS: 407 (M + H+) for C18H22FN5O5. [Example 36] Preparation of Compound 36 Compound 36 (14 mg, 0.034 mmol, 74%) was obtained from Compound 2 in a similar method to the method of Example 11, using pyruvic acid. 1H NMR (600 MHz, DMSO-d6) d 8.27 (t, J = 6.0 Hz, 1H) 7.61 (dd, J1 = 13.2 Hz, J2 = 3.0 Hz, 1H), 7.40 (t, J = 9.0 Hz, 1H), 7.33 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 7.18 (s, 1H), 4.74 (m, 1H), 4.13 (t, J = 9 Hz, 1H), 3.90 (t, J = 4.8 Hz, 2H), 3.77-3.72 (m, 3H), 3.42-3.30 (m, 2H), 2.33 (s, 3H), 1.83 (s, 3H). LCMS: 406 (M + H+) for C18H20FN5O5. [Example 37] Preparation of Compound 37 Compound 37 (13 mg, 0.033 mmol, 65%) was obtained from Compound 2 in a similar method to the method of Example 4, using chloroacetone. 1H NMR (600 MHz, CDCl3) d = 7.52 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.15 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H), 7.11 (t, J = 8.4 Hz, 1H), 6.89 (s, 1H), 6.09 (br, t, 1H), 4.79 (m, 1H), 4.04 (t, J = 9 Hz, 1H), 3.85 (t, J = 4.8 Hz, 2H), 3.79-3.62 (m, 5H), 3.12 (t, J = 4.8 Hz, 2H), 2.26 (s, 3H), 2.03 (s, 3H). LCMS: 392 (M + H+) for C18H22FN5O4. [Example 38] Preparation of Compound 38 Compound 37 (7 mg, 0.018 mmol) was dissolved in dichloromethane (2 mL) and stirred for 2 hours at room temperature after adding 2M LiBH4 solution. After adding a small amount of water, the solution was separated by column chromatography to obtain Compound 38 (3.6 mg, 0.009 mmol, 50%) as a white solid. 1H NMR (600 MHz, CDCl3) d = 7.54 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.15 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H), 7.11 (t, J = 8.4 Hz, 1H), 6.89 (s, 1H), 6.09 (br, t, 1H), 4.79 (m, 1H), 4.04 (t, J = 9 Hz, 1H), 3.85 (t, J = 4.8 Hz, 2H), 3.79-3.62 (m, 5H), 3.12 (t, J = 4.8 Hz, 2H), 2.26 (s, 3H), 2.03 (s, 3H). LCMS: 394 (M + H+) for C18H24FN5O4. [Example 39] Preparation of Compound 39 Compound 39 (15 mg, 0.039 mmol, 74%) was obtained from Compound 2 in a similar method to the method of Example 4, using 3-chloro-2-methylpropene. 1H NMR (600 MHz, CDCl3) d = 7.51 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.15-7.09 (m, 2H), 6.91 (s, 1H), 6.06 (br, t, 1H), 4.97 (s, 1H), 4.93 (s, 1H), 4.79 (m, 1H), 4.04 (t, J = 9 Hz, 1H), 3.81 (t, J = 4.8 Hz, 2H), 3.78-3.61 (m, 3H), 3.48 (s, 2H), 2.94 (t, J = 4.8 Hz, 2H), 2.03 (s, 3H), 1.83 (s, 3H). LCMS: 390 (M + H+) for C19H24FN5O3. [Example 40] Preparation of Compound 40 Compound 40 (11 mg, 0.027 mmol, 34%) was obtained from Compound 2 in a similar method to the method of Example 4, using 2,3-dichloro-1-propene. 1H NMR (600 MHz, CDCl3) d = 7.52 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.15-7.09 (m, 2H), 6.91 (s, 1H), 6.23 (br, t, 1H), 5.49 (s, 1H), 5.42 (s, 1H), 4.79 (m, 1H), 4.04 (t, J = 9 Hz, 1H), 3.85 (t, J = 4.8 Hz, 2H), 3.79-3.62 (m, 5H), 3.08 (t, J = 4.8 Hz, 2H), 2.03 (s, 3H). LCMS: 410 (M + H+) for C18H21ClFN5O3. [Example 41] Preparation of Compound 41 Compound 2 (228 mg, 0.68 mmol), cyclobutanone (0.076 mL, 1.02 mmol) and NaBH(OAc)3 (187 mg, 0.88 mmol) were dissolved in dichloromethane (20 mL) and stirred for 2 hours at room temperature after adding acetic acid (1 mL). The solution was diluted with dichloromethane, sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, and concentrated under reduced pressure to obtain Compound 41 (200 mg, 0.51 mmol, 75%) as a white solid. 1H NMR (600 MHz, CDCl3) d = 7.51 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.15-7.09 (m, 2H), 6.95 (s, 1H), 6.09 (br, t, 1H), 4.79 (m, 1H), 4.03 (t, J = 9 Hz, 1H), 3.82 (t, J = 4.8 Hz, 2H), 3.78-3.61 (m, 3H), 3.41 (m, 1H), 2.91 (t, J = 4.8 Hz, 2H), 2.21-2.11 (m, 4H), 2.03 (s, 3H), 1.81-1.72 (m, 2H). LCMS: 390 (M + H+) for C19H24FN5O3. [Example 42] Preparation of Compound 42 Compound 42 (15 mg, 0.039 mmol, 79%) was obtained from Compound XIII in a similar method to the method of Example 11. 1H NMR (400 MHz, DMSO-d6) d = 8.64 (t, J = 5.6 Hz, 1H), 8.42 (s, 1H), 7.61 (dd, J1 = 14 Hz, J2 = 2.0 Hz, 1H), 7.38 (t, J = 8.8 Hz, 1H), 7.33 (dd, J1 = 8.8 Hz, J2 = 2.0 Hz, 1H), 7.12 (s, 1H), 4.78 (m, 1H), 4.14 (t, J = 9.2 Hz, 1H), 3.84 (t, J = 4.8 Hz, 2H), 3.75-3.47 (m, 7H). LCMS: 389 (M + H+) for C17H17FN6O4. [Example 43] Preparation of Compound 43 Compound XIII (190 mg, 0.6 mmol) and carbonyldiimidazole (143 mg, 0.9 mmol) were dissolved in dichloromethane (5 mL) and stirred for 6 hours at room temperature after adding triethylamine (0.25 mL, 1.8 mmol). After 1/3 of the solution was taken and distilled under reduced pressure, dissolved in dichloromethane (5 mL) and ethanol (10 mL), and stirred for 36 hours at room temperature. The solution was washed with distilled water, dried with magnesium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 43 (23 mg, 0.058 mmol, 29%). 1H NMR (600 MHz, DMSO-d6) d = 8.38 (s, 1H), 7.56 (dd, J1 = 14 Hz, J2 = 2.0 Hz, 1H), 7.45 (br, t, 1H), 7.35-7.28 (m, 2H), 7.01 (s, 1H), 4.69 (m, 1H), 4.10 (t, J = 9.2 Hz, 1H), 3.95 (q, J = 6.6 Hz, 2H), 3.80-3.3 (m, 7H), 1.09 (t, J = 6.6 Hz, 3H). LCMS: 394 (M + H+) for C17H20FN5O5. [Example 44] Preparation of Compound 44 Compound XIII (190 mg, 0.6 mmol) and carbonyldiimidazole (143 mg, 0.9 mmol) were dissolved in dichloromethane (5 mL) and stirred for 6 hours at room temperature after adding triethylamine (0.25 mL, 1.8 mmol). After 1/3 of the solution was taken and distilled under reduced pressure, dissolved in THF (5 mL) and ethylamine (50 mg), stirred for 36 hours at room temperature, and refluxed for 2 hours. The solution was washed with distilled water, dried with magnesium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 44 (35 mg, 0.089 mmol, 45%). 1H NMR (600 MHz, CDCl3) d = 8.53 (s, 1H), 7.59 (d, J = 13 Hz, 1H), 7.19 (d, J = 9 Hz, 1H), 7.13 (d, J = 9 Hz, 1H), 6.88 (s, 1H), 5.75 (br, s, 1H), 5.28 (br, s, 1H), 4.81 (m, 1H), 4.04 (t, J = 8.2 Hz, 1H), 3.98-3.15 (m, 9H), 1.08 (t, J = 6.6 Hz, 3H). LCMS: 393 (M + H+) for C17H21FN6O4. [Example 45] Preparation of Compound 45 Compound 45 (840 mg, 2.1 mmol, 95%) was obtained from Compound XIII in a similar method to the method of Example 11, using difluoroacetic acid. 1H NMR (400 MHz, DMSO-d6) d = 9.18 (t, J = 5.6 Hz, 1H), 8.42 (s, 1H), 7.61 (dd, J1 = 14 Hz, J2 = 2.0 Hz, 1H), 7.38 (t, J = 8.8 Hz, 1H), 7.32 (dd, J1 = 8.8 Hz, J2 = 2.0 Hz, 1H), 7.12 (s, 1H), 6.26 (t, J = 53 Hz, 1H) 4.82 (m, 1H), 4.16 (t, J = 8.8 Hz, 1H), 3.84 (t, J = 4.8 Hz, 2H), 3.80-3.53 (m, 5H). LCMS: 400 (M + H+) for C16H16F3N5O4. [Example 46] Preparation of Compound 46 Compound 46 (750 mg, 1.8 mmol, 84%) was obtained from Compound 45 in a similar method to the method of Example 2. 1H NMR (600 MHz, DMSO-d6) d 9.17-9.30 (m, 1H), 8.43-8.28 (m, 1H), 7.67 9dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.61 (t, 1H, J = 9.0 Hz), 7.44-7.36 (m, 1H), 6.27 (9t, 1H, J = 53.4 Hz), 4.85-4.80 (m, 1H), 4.19 (t, 1H, J = 9.0 Hz), 3.81-3.75 (m, 2H), 3.38-3.32 (m, 2H). LCMS: 372 (M + H+) for C15H16F3N5O3. [Example 47] Preparation of Compound 47 Compound 47 (16 mg, 0.037 mmol, 25%) was obtained from Compound 46 in a similar method to the method of Example 12. 1H NMR (600 MHz, chloroform-d1) d 7.57 (dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.21 (dd, 1H, J1 = 9.0 Hz, J2 = 2.4 Hz), 7.13 (t, 1H, J = 9.0 Hz), 6.96-6.90 (m, 1H), 6.86 (s, 1H), 5.94 (t, 1H, J = 54.0 Hz), 4.88-4.83 (m, 1H), 4.12 (t, 1H, J = 9.0 Hz), 4.06 (t, 2H, J = 5.4 Hz), 3.90-3.81 (m, 1H), 3.80-3.74 (m, 3H), 3.74-3.66 (m, 1H), 3.64 (s, 2H). LCMS: 430 (M + H+) for C17H18F3N5O5. [Example 48] Preparation of Compound 48 Compound 48 (16 mg, 0.04 mmol, 61%) was obtained from Compound 46 in a similar method to the method of Example 6. 1H NMR (600 MHz, chloroform-d1) d 7.48 (dd, 1H, J1 = 13.2 Hz, J2 = 2.4 Hz), 7.23 (t, 1H, J = 5.4 Hz), 7.16-7.08 (m, 2H), 6.94 (s, 1H), 5.94 (t, 1H, J = 54.0 Hz), 4.86-4.82 (m, 1H), 4.10 (t, 1H, J = 9.0 Hz), 3.88-3.84 (m, 1H), 3.83 (t, 2H, J = 4.8 Hz), 3.78-3.73 (m, 1H), 3.73-3.64 (m, 1H), 3.02 (t, 2H, J = 4.8 Hz), 3.00-2.94 (m, 3H), 1.23 (t, 2H, 7.2 Hz). LCMS: 400 (M + H+) for C17H20F3N5O3. [Example 49] Preparation of Compound 49 Compound 49 (15 mg, 0.037 mmol, 57%) was obtained from Compound 46 in a similar method to the method of Example 5. 1H NMR (600 MHz, CDCl3) d 7.51 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.16-7.11 (m, 2H), 6.96 (s, 1H), 6.89 (br, t, 1H), 5.94 (t, J = 54.0 Hz, 1H), 4.84 (m, 1H), 4.11 (t, J = 9.0 Hz, 1H), 3.89-3.64 (m, 7H), 3.13 (t, J = 4.8 Hz, 2H), 2.31 (t, J = 2.4 Hz, 1H). LCMS: 410 (M + H+) for C18H18F3N5O3. [Example 50] Preparation of Compound 50 Compound 50 (15 mg, 0.037 mmol, 68%) was obtained from Compound 46 in a similar method to the method of Example 7. 1H NMR (600 MHz, CDCl3) d 7.53 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.17-7.13 (m, 2H), 7.01 (br, t, 1H), 6.96 (s, 1H), 5.94 (t, J = 54.0 Hz, 1H), 4.85 (m, 1H), 4.11 (t, J = 9.0 Hz, 1H), 3.98 (s, 2H) 3.89-3.66 (m, 5H), 3.15 (t, J = 4.8 Hz, 2H). LCMS: 411 (M + H+) for C17H17F3N6O3. [Example 51] Preparation of Compound 51 Compound 51 (155 mg, 0.36 mmol, 86%) was obtained from Compound XIII in a similar method to the method of Example 11, using dichloroacetic acid. 1H NMR (400 MHz, DMSO-d6) d = 8.99 (t, J = 6.0 Hz, 1H), 8.42 (s, 1H), 7.61 (d, J = 12 Hz, 1H), 7.38 (t, J = 9.0 Hz, 1H), 7.31 (d, J = 9Hz, 1H), 7.12 (s, 1H), 6.49 (s, 1H), 4.81 (m, 1H), 4.16 (t, J = 8.8 Hz, 1H), 3.84 (t, J = 4.8 Hz, 2H), 3.74-3.66 (m, 3H), 3.55 (t, J = 5.2 Hz, 2H). LCMS: 432 (M + H+) for C16H16Cl2FN5O4. [Example 52] Preparation of Compound 52 Compound 52 (250 mg, 0.6 mmol, 92%) was obtained from Compound XIII in a similar method to the method of Example 11, using isoxazole acid. 1H NMR (400 MHz, DMSO-d6) d = 9.32 (t, J = 5.6 Hz, 1H), 8.75 (d, J = 1.2 Hz, 1H) 8.42 (s, 1H), 7.60 (dd, J1 = 14 Hz, J2 = 2.0 Hz, 1H), 7.38 (t, J = 8.8 Hz, 1H), 7.33 (dd, J1 = 8.8 Hz, J2 = 2.0 Hz, 1H), 7.11 (d, J = 1.2 Hz, 1H), 4.88 (m, 1H), 4.18 (t, J = 9.2 Hz, 1H), 3.88-3.82 (m, 3H), 3.69 (t, J = 5.2 Hz, 2H), 3.64 (t, J = 5.6 Hz, 2H). LCMS: 417 (M + H+) for C18H17FN6O5. [Example 53] Preparation of Compound 53 Compound XIII (4.5 g, 14 mmol) was dissolved in dichloromethane (75 mL) and stirred for 1 hour after adding saturated aqueous NaHCO3 solution (75 mL) and thiophosgene (1.1 mL, 14 mmol) at 0ºC. The organic layer was dried with sodium sulfate, distilled under reduced pressure, dissolved in methanol (120 mL), stirred overnight under reflux, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 53 (3.18 g, 8.05 mmol, 58%) as a white solid. 1H NMR (600 MHz, CDCl3) d = 8.55 (s, 1H), 7.58 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.21 (dd, J1 = 9.0 Hz, J2 = 2.7 Hz, 1H), 7.13 (t, J = 8.4 Hz, 1H), 6.89 (s, 1H), 6.71 (t, J = 6.3 Hz, 1H), 4.93 (m, 1H), 4.13-4.08 (m, 2H), 4.05 (m, 1H), 4.01 (s, 3H), 3.99 (t, J = 5.0 Hz, 2H), 3.90 (m, 1H), 3.74 (t, J = 5.0 Hz, 2H). LCMS: 396 (M + H+) for C16H18FN5O4S. [Example 54] Preparation of Compound 54 Compound 54 (210 mg, 0.51 mmol, 65%) was obtained from Compound XIII in a similar method to the method of Example 53, using ethanol instead of methanol. 1H NMR (600 MHz, CDCl3) d = 8.54 (s, 1H), 7.58 (dd, J1 = 14 Hz, J2 = 2.8 Hz, 1H), 7.21 (dd, J1 = 14 Hz, J2 = 3.8 Hz, 1H), 7.13 (t, J = 8.4 Hz, 1H), 6.88 (s, 1H), 6.75 (t, J = 6.3 Hz, 1H), 4.96 (m, 1H), 4.54-4.44 (m, 2H), 4.09-4.02 (m, 3H), 3.98 (t, J = 4.8 Hz, 2H), 3.92 (m, 1H), 3.73 (t, J = 4.8 Hz, 2H), 1.31 (t, J = 7 Hz, 3H). LCMS: 410 (M + H+) for C17H20FN5O4S. [Example 55] Preparation of Compound 55 Compound 55 (52 mg, 0.12 mmol, 52%) was obtained from Compound XIII in a similar method to the method of Example 53, using isopropanol instead of methanol. 1H NMR (600 MHz, CDCl3) d = 8.55 (s, 1H), 7.58 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.22 (dd, J1 = 9.0 Hz, J2 = 2.7 Hz, 1H), 7.13 (t, J = 8.4 Hz, 1H), 6.88 (s, 1H), 6.57 (t, J = 6.3 Hz, 1H), 5.54 (m, 1H), 4.93 (m, 1H), 4.12-4.06 (m, 2H), 4.02 (m, 1H), 3.99 (t, J = 4.8 Hz, 2H), 3.92 (m, 1H), 3.73 (t, J = 4.8 Hz, 2H), 1.32 (d, J = 6 Hz, 3H), 1.27 (d, J = 6 Hz, 3H). LCMS: 424 (M + H+) for C18H22FN5O4S. [Example 56] Preparation of Compound 56 Compound 56 (36 mg, 0.088 mmol, 57%) was obtained from Compound XIII in a similar method to the method of Example 53, using ethylamine instead of methanol. 1H NMR (600 MHz, CDCl3) d = 8.54 (s, 1H), 7.58 (dd, 1H, J1 = 13.2 Hz, J2 = 2.4 Hz), 7.20-7.19 (m, 1H), 7.13 (t, 1H, J = 9.0 Hz), 6.88 (s, 1H), 4.92-4.96 (m, 1H), 4.10-4.06 (m, 3H), 3.99 (t, 2H, J = 4.8 Hz), 1.44-1.43 (m,2H), 1.21 (t, 3H, J = 7.2 Hz). LCMS: 409 (M + H+) for C17H21FN6O3S. [Example 57] Preparation of Compound 57 Compound XXVII-b prepared in Preparation Example 14 was subjected to Mitsunobu reaction in a similar method to the method of Example 16. Then, Compound 57 (84 mg, 0.23 mmol, 31%) was obtained in a similar method to the method of Example 28. 1H NMR (600 MHz, CDCl3) d = 8.25 (s, 1H), 7.62 (dd, J1 = 13 Hz, J2 = 2.0 Hz, 1H), 7.30 (t, J = 9 Hz, 1H), 7.24 (dd, J1 = 9 Hz, J2 = 2.0 Hz, 1H), 6.73 (br, t, 1H), 4.94 (m, 1H), 4.21-4.04 (m, 4H), 4.01 (s, 3H), 3.90 (t, J = 4.8 Hz, 2H), 3.80 (t, J = 4.8 Hz, 2H). LCMS: 369 (M + H+) for C15H17FN4O4S. [Example 58] Preparation of Compound 58 Compound 53 (400 mg, 1.01 mmol) was dissolved in methanol (20 mL), stirred for 2 hours under hydrogen balloon after adding 4N HCl dioxane solution (2 mL) and 10% Pd/C (50 mg), filtered with celite, and distilled under reduced pressure to quantitatively obtain Compound 58 as a white solid. 1H NMR (600 MHz, CDCl3) d = 7.51 (dd, J1 = 14 Hz, J2 = 1.8 Hz, 1H), 7.16-7.10 (m, 2H), 6.89 (s, 1H), 6.78 (br, t, 1H), 4.93 (m, 1H), 4.10-3.98 (m, 6H), 3.88-3.81 (m, 3H), 3.32 (t, J = 4.8 Hz, 2H). LCMS: 368 (M + H+) for C15H18FN5O3S. [Example 59] Preparation of Compound 59 Compound 58 (150 mg, 0.41 mmol) was dissolved in dichloromethane (5 mL), stirred at room temperature for 6 hours after adding DIPEA (0.14 mL, 0.82 mmol) and acetoxyacetyl chloride (0.066 mL, 0.61 mmol) at 0ºC. The solution was distilled under reduced pressure and separated by column chromatography to obtain Compound 59 (31 mg, 0.066 mmol, 16%) as white solid. 1H NMR (600 MHz, CDCl3) d 7.58 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.22-7.11 (m, 2H), 6.83 (s, 1H), 6.69 (t, J = 6.0 Hz, 1H), 5.08 (s, 2H), 4.96 (m, 1H), 4.10-3.89 (m, 9H), 3.74 (t, J = 4.8 Hz, 2H), 2.20 (s, 3H). LCMS: 468 (M + H+) for C19H22FN5O6S. [Example 60] Preparation of Compound 60 Compound 58 (0.013 mg, 0.035 mmol) was dissolved in DMF (2 mL), stirred overnight at room temperature after adding DIPEA (0.01 mL, 0.07 mmol) and iodomethane (0.003 mL, 0.035 mmol), and separated by column chromatography to obtain Compound 60 (3.1 mg, 0.0081 mmol, 23%) as a white solid. 1H NMR (600 MHz, CDCl3) d = 7.52 (dd, J1 = 14 Hz, J2 = 2.0 Hz, 1H), 7.15 (dd, J1 = 9 Hz, J2 = 2.0 Hz, 1H), 7.11 (t, J = 9 Hz, 1H), 6.90 (s, 1H), 6.76 (br, t, 1H), 4.94 (m, 1H), 4.10-3.85 (m, 7H), 3.82 (t, J1 = 4.8 Hz, 2H), 2.99 (t, J1 = 4.8 Hz, 2H), 2.79 (s, 3H). LCMS: 382 (M + H+) for C16H20FN5O3S. [Example 61] Preparation of Compound 61 Compound 61 (15 mg, 0.038 mmol, 45%) was obtained from Compound 58 in a similar method to the method of Example 60, using iodoethane instead of iodomethane. 1H NMR (600 MHz, CDCl3) d = 7.51 (dd, J1 = 14 Hz, J2 = 1.8 Hz, 1H), 7.15 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H), 7.11 (m, 1H), 6.92 (s, 1H), 6.77 (br, t, 1H), 4.93 (m, 1H), 4.11-4.02 (m, 3H), 4.01 (s, 3H), 3.88-3.85 (m, 1H), 3.83 (t, J = 4.8 Hz, 2H), 3.02 (t, J = 4.8 Hz, 2H), 2.98-2.94 (m, 2H), 1.24 (t, J = 7.2 Hz, 3H). LCMS: 396 (M + H+) for C17H22FN5O3S. [Example 62] Preparation of Compound 62 Compound 62 (15 mg, 0.037 mmol, 67%) was obtained from Compound 58 in a similar method to the method of Example 60, using allyl bromide instead of iodomethane. 1H NMR (600 MHz, chloroform-d1) d 7.51 (dd, 1H, J1 = 13.2 Hz, J2 = 1.8 Hz), 7.15 (dd, 1H, J1 = 9.0 Hz, J2 = 2.4 Hz), 7.11 (t, 1H, 8.4 Hz), 6.92 (s, 1H), 6.68 (t, 1H, J = 6.0 Hz), 6.08-5.96 (m, 1H), 5.29 (dd, 1H, J1 = 10.2 Hz, J2 = 1.8 Hz), 5.24 (dd, 1H, J1 = 10.2 Hz, J2 = 1.8 Hz), 4.98-4.88 (m, 1H), 4.12-4.04 (m, 2H), 4.02-3.98 (m, 1H), 4.01 (s, 3H), 3.86 (dd, 1H, J1 = 9.6 Hz, J2 = 7.2 Hz), 3.82 (t, 2H, J = 4.2 Hz), 3.58 (d, 2H, J = 6.0 Hz), 3.00 (t, 2H, J = 4.8 Hz). LCMS: 408 (M + H+) for C18H22FN5O3S. [Example 63] Preparation of Compound 63 Compound 63 (36 mg, 0.089 mmol, 68%) was obtained from Compound 58 in a similar method to the method of Example 60, using propargyl bromide instead of iodomethane. 1H NMR (600 MHz, chloroform-d1) d 7.53 (dd, 1H, J1 = 13.8 Hz, J2 = 2.4 Hz), 7.16 (dd, 1H, J1 = 9.0 Hz, J2 = 2.4 Hz), 7.13 (t, 1H, 8.4 Hz), 6.96 (s, 1H), 6.69 (t, 1H, J = 6.0 Hz), 4.98-4.90 (m, 1H), 4.14-3.98 (m, 3H), 4.01 (s, 3H), 3.90-3.82 (m, 1H), 3.85 (t, 2H, J = 6.6 Hz), 3.83 (d, 2H, J = 2.4 Hz), 3.13 (t, 2H, J = 5.4 Hz), 2.31 (t, 1H, J = 2.4 Hz). LCMS: 406 (M + H+) for C18H20FN5O3S. [Example 64] Preparation of Compound 64 Compound 64 (16 mg, 0.038 mmol, 74%) was obtained from Compound 58 in a similar method to the method of Example 60, using 1-bromo-2-butyne instead of iodomethane. 1H NMR (600 MHz, CDCl3) d 7.52 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.16 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 7.12 (t, 8.4 Hz, 1H), 6.95 (s, 1H), 6.70 (t, J = 6.0 Hz, 1H), 4.94 (m, 1H), 4.13-3.75 (m, 11H), 3.12 (t, J = 5.4 Hz, 2H), 1.87 (t, J = 2.4 Hz, 3H). LCMS: 420 (M + H+) for C19H22FN5O3S. [Example 65] Preparation of Compound 65 Compound 65 (22 mg, 0.054 mmol, 64%) was obtained from Compound 58 in a similar method to the method of Example 60, using bromoacetonitrile instead of iodomethane. 1H NMR (600 MHz, CDCl3) d 7.56 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.17 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 7.14 (t, 8.4 Hz, 1H), 6.96 (s, 1H), 6.68 (t, J = 6.0 Hz, 1H), 4.95 (m, 1H), 4.12-3.86 (m, 11H), 3.15 (t, J = 5.4 Hz, 2H). LCMS: 407 (M + H+) for C17H19FN6O3S. [Example 66] Preparation of Compound 66 Compound 66 (15 mg, 0.034 mmol, 54%) was obtained from Compound 58 in a similar method to the method of Example 60, using 2,3-dichloropropene instead of iodomethane. 1H NMR (600 MHz, CDCl3) d 7.52 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.16 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 7.11 (t, 8.4 Hz, 1H), 6.92 (s, 1H), 6.73 (t, J = 6.0 Hz, 1H), 5.49 (s, 1H), 5.42 (s, 1H), 4.94 (m, 1H), 4.12-3.84 (m, 9H), 3.72 (s, 2H), 3.08 (t, J = 5.4 Hz, 2H). LCMS: 442 (M + H+) for C18H21ClFN5O3S. [Example 67] Preparation of Compound 67 Compound 67 (18 mg, 0.043 mmol, 84%) was obtained from Compound 58 in a similar method to the method of Example 41, using cyclopropanecarboxaldehyde. 1H NMR (600 MHz, CDCl3) d 7.51 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.18 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 7.11 (t, 8.4 Hz, 1H), 7.01 (t, J = 6.0 Hz, 1H), 6.91 (s, 1H), 4.95 (m, 1H), 4.12-3.83 (m, 9H), 3.13 (t, J = 4.8 Hz, 2H), 2.82 (d, J = 7.2 Hz, 2H), 1.08 (m, 1H), 0.57 (m, 2H), 0.21 (m, 2H). LCMS: 422 (M + H+) for C19H24FN5O3S. [Example 68] Preparation of Compound 68 Compound 68 (19 mg, 0.045 mmol, 76%) was obtained from Compound 58 in a similar method to the method of Example 41, using cyclobutanone. 1H NMR (600 MHz, CDCl3) d 7.51 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.16-7.09 (m, 2H), 6.95 (s, 1H), 6.64 (br, t, 1H), 4.94 (m, 1H), 4.11-3.98 (m, 6H), 3.87 (m, 1H), 3.82 (t, J = 4.8 Hz, 2H), 3.42 (m, 1H), 2.91 (t, J = 4.8 Hz, 2H), 2.23-2.12 (m, 4H), 1.81-1.73 (m, 2H). LCMS: 422 (M + H+) for C19H24FN5O3S. [Example 69] Preparation of Compound 69 Compound 69 (24 mg, 0.053 mmol, 47%) was obtained from Compound 58 in a similar method to the method of Example 60, using ethyl bromoacetate instead of iodomethane. 1H NMR (600 MHz, chloroform-d1) d 7.52 (dd, 1H, J1 = 13.2 Hz, J2 = 1.8 Hz), 7.15 (dd, 1H, J1 = 9.0 Hz, J2 = 2.4 Hz), 7.11 (t, 1H, 8.4 Hz), 6.91 (s, 1H), 6.83 (t, 1H, J = 6.6 Hz), 4.98-4.90 (m, 1H), 4.26-4.21 (m, 2H), 4.13-3.97 (m, 3H), 4.01 (s, 3H), 3.85 (t, 2H, J = 4.2 Hz), 3.78 (s, 2H), 3.24 (t, 2H, J = 4.8 Hz), 1.03 (t, 3H, J = 7.2 Hz). LCMS: 454 (M + H+) for C19H24FN5O5S. [Example 70] Preparation of Compound 70 Compound 69 (17 mg, 0.037 mmol) was dissolved in THF (2 mL) and stirred at room temperature for 3 hours after adding 2M LiBH4 solution (1 mL). After adding a small amount of water, the solution was separated by column chromatography to obtain Compound 70 (6.5 mg, 0.016 mmol, 43%) as a white solid. 1H NMR (600 MHz, chloroform-d1) d 7.53 (dd, 1H, J1 = 13.2 Hz, J2 = 1.8 Hz), 7.17 (dd, 1H, J1 = 8.4 Hz, J2 = 2.4 Hz), 7.12 (t, 1H, 9.0 Hz), 6.90 (s, 1H), 6.73 (t, 1H, J = 6.0 Hz), 4.98-4.90 (m, 1H), 4.18-4.04 (m, 2H), 4.04-3.98 (m, 1H), 4.01 (s, 3H), 3.96 (t, 2H, J = 4.8 Hz), 3.87 (dd, 1H, J1 = 9.0 Hz, J2 = 7.2 Hz), 3.84 (t, 2H, J = 4.8 Hz), 3.07 (t, 2H, J = 4.8 Hz), 3.00 (t, 2H, J = 4.8 Hz). LCMS: 412 (M + H+) for C17H22FN5O4S. [Example 71] Preparation of Compound 71 Compound 71 (84 mg, 0.19 mmol, 76%) was obtained from Compound 58 in a similar method to the method of Example 60, using bromoethyl acetate instead of iodomethane. 1H NMR (600 MHz, CDCl3) d 7.51 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.16-7.07 (m, 2H), 6.91-6.89 (m, 2H), 4.95 (m, 1H), 4.40 (t, J = 5.4 Hz, 2H) 4.13-3.86 (m, 7H), 3.83 (t, J = 4.8 Hz, 2H), 3.15 (t, J = 5.4 Hz, 2H), 3.09 (t, J = 4.8 Hz, 2H), 2.10 (s, 3H). LCMS: 454 (M + H+) for C19H24FN5O5S. [Example 72] Preparation of Compound 72 Compound 72 (54 mg, 0.12 mmol, 61%) was obtained from Compound 58 in a similar method to the method of Example 53. 1H NMR (600 MHz, DMSO-d6) d = 9.56 (t, J = 6 Hz, 1H), 7.62 (dd, J1 = 14 Hz, J2 = 2.0 Hz, 1H), 7.43 (t, J = 9 Hz, 1H), 7.34 (dd, J1 = 9 Hz, J2 = 2.0 Hz, 1H), 7.17 (s, 1H), 4.92 (m, 1H), 4.41 (br, t, 2H), 4.17 (t, J1 = 9 Hz, 1H), 3.99 (s, 3H), 3.88 (s, 3H), 3.85-3.76 (m, 5H). LCMS: 442 (M + H+) for C17H20FN5O4S2. [Example 73] Preparation of Compound 73 Compound XIII (223 mg, 0.69 mmol) and NaF (38 mg, 1.3 equivalents) were dissolved in ethanol (10 mL) and stirred overnight at room temperature after adding ethyl dithioacetate (0.1 mL, 1.2 equivalents). After distillation under reduced pressure, the mixture was dissolved in ethyl acetate, washed with brine, dried with sodium sulfate, and separated by column chromatography to obtain Compound 73 (220 mg, 0.58 mmol, 84%) as a white solid. 1H NMR (600 MHz, CDCl3) d = 8.52 (s, 1H) 7.91 (br, t, 1H), 7.56 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.17 (dd, J1 = 9.0 Hz, J2 = 2.7 Hz, 1H), 7.11 (t, J = 8.4 Hz, 1H), 6.87 (s, 1H), 4.98 (m, 1H), 4.28-4.24 (m, 1H), 4.12-4.07 (m 2H), 3.97 (t, J = 4.8 Hz, 2H), 3.86-3.84 (m, 1H), 3.71 (t, J = 4.8 Hz, 2H), 2.58 (s, 3H). LCMS: 380 (M + H+) for C16H18FN5O3S. [Example 74] Preparation of Compound 74 Compound 73 (220 mg, 0.58 mmol) was dissolved in methanol (10 mL) and stirred at room temperature for 2 hours after adding 4 M HCl dioxane solution (1 mL), and concentrated under reduced pressure to quantitatively obtain Compound 74 (240 mg) as hydrochloride salt form. 1H NMR (400 MHz, DMSO-d6) d = 10.5 (br, t, 1H), 7.70 (d, J = 14 Hz, 1H), 7.61 (t, J = 8.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 5.00 (m, 1H), 4.20 (m, 1H), 3.94-3.78 (m, 5H), 3.62 (br, t, 2H), 2.45 (s, 3H). LCMS: 352 (M + H+) for C15H18FN5O2S. [Example 75] Preparation of Compound 75 Compound 75 (35 mg, 0.090 mmol, 42%) was obtained from Compound 74 in a similar method to the method of Example 7. 1H NMR (600 MHz, CDCl3) d = 7.74 (br, t, 1H), 7.55 (dd, J1 = 14 Hz, J2 = 1.8 Hz, 1H), 7.18-7.12 (m, 2H), 6.96 (s, 1H), 5.01 (m, 1H), 4.32 (m, 1H), 4.12-4.04 (m, 2H), 3.96 (s, 2H), 3.88-3.83 (m, 3H), 3.15 (t, J = 4. Hz, 2H), 2.98-2.94 (m, 2H), 1.24 (t, J = 4.2 Hz, 2H), 2.61 (s, 3H). LCMS: 391 (M + H+) for C17H19FN6O2S. [Example 76] Preparation of Compound 76 Compound 76 (35 mg, 0.086 mmol, 36%) was obtained from Compound 74 in a similar method to the method of Example 12. 1H NMR (600 MHz, CDCl3) d = 7.80 (m, 1H), 7.56 (dd, J1 = 13 Hz, J2 = 2.4 Hz), 7.19-7.17 (m, 1H), 7.13-7.10 (m, 1H), 5.00-4.96 (m, 1H), 4.48 (d, J = 4.2 Hz, 2H), 4.29-4.25 (m, 1H), 4.10-4.07 (m, 2H), 4.05 (t, J = 4.8 Hz, 2H), 3.86-3.83 (m, 1H), 3.74 (t, J = 4.8 Hz, 2H), 3.27 (t, J = 4.8 Hz, 1H), 2.58 (s, 3H). LCMS: 410 (M + H+) for C17H20FN5O4S. [Example 77] Preparation of Compound 77 Compound 77 (350 mg, 0.84 mmol, 79%) was obtained by reacting Compound XIII with Ph2CHCH2CH2OC(S)CHF2 overnight at room temperature in the same method disclosed in Bioorg. Med. Chem. Lett. 2006, 16, 3475-3478, which is incorporated herein by reference. 1H NMR (400 MHz, CDCl3) d = 8.55 (s, 1H), 8.48 (br, t, 1H), 7.56 (dd, J1 = 14 Hz, J2 = 2.0 Hz, 1H), 7.20 (dd, J1 = 8.8 Hz, J2 = 2.0 Hz, 1H), 7.14 (t, J = 8.8 Hz, 1H), 6.89 (s, 1H), 6.22 (t, J = 56 Hz, 1H), 5.03 (m, 1H), 4.34 (m, 1H), 4.16 (t, J = 8.8 Hz, 1H), 4.06 (m, 1H), 3.99 (t, J = 4.8 Hz, 2H), 3.82-3.73 (m, 3H). LCMS: 416 (M + H+) for C16H16F3N5O3S. [Example 78] Preparation of Compound 78 Compound 77 was subjected to the same reaction as Example 74 and then to the same reaction as Example 5 to obtain Compound 78 (26 mg, 0.061 mmol, 35%). 1H NMR (600 MHz, CDCl3) d = 8.65 (br, t, 1H), 7.49 (dd, J1 = 14 Hz, J2 = 2.0 Hz, 1H), 7.14-7.13 (m, 2H), 6.96 (s, 1H), 6.22 (t, J = 56 Hz, 1H), 5.03 (m, 1H), 4.34 (m, 1H), 4.15 (t, J = 8.8 Hz, 1H), 4.04 (m, 1H), 3.86-3.78 (m, 5H), 3.14 (t, J = 4.8 Hz, 2H), 2.31 (t, J = 1.8 Hz, 1H). LCMS: 426 (M + H+) for C18H18F3N5O2S. [Example 79] Preparation of Compound 79 Compound VI prepared in Preparation Example 6 was subjected to the same reaction as Preparation Example 12, using hydroxyisoxazole instead of boc-aminoisoxazole, and then to the same reaction as Preparation Example 10 to obtain Compound 79 (53 mg, 0.14 mmol, 28%). 1H NMR (400 MHz, DMSO-d6) d = 8.71 (d, J = 2 Hz, 1H), 8.42 (s, 1H), 7.65 (dd, J1 = 14 Hz, J2 = 2.0 Hz, 1H), 7.41-7.37 (m, 2H), 7.07 (s, 1H), 6.39 (d, J = 2 Hz, 1H), 5.10 (m, 1H), 4.81 (m, 1H), 4.49 (m, 1H), 4.21 (t, J = 9.2 Hz, 1H), 3.93 (m, 1H), 3.84 (t, J = 5.6 Hz, 2H), 3.70 (t, J = 4.8 Hz, 2H). LCMS: 390 (M + H+) for C17H16FN5O5. [Example 80] Preparation of Compound 80 Compound VI was subjected to the same reaction as Preparation Example 12, using boc-aminothiazole instead of boc-aminoisoxazole and then to the same reaction as Preparation Example 10 to obtain Compound 80 (26 mg, 0.064 mmol, 16%). 1H NMR (400 MHz, CDCl3) d = 8.55 (s, 1H), 7.57 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.21 (dd, J1 = 9.0 Hz, J2 = 2.7 Hz, 1H), 7.13-7.08 (m, 2H), 6.84 (s, 1H), 6.55 (d, J = 3.6 Hz, 1H), 5.34 (br, s, 1H), 4.97 (m, 1H), 4.10 (t, J = 8.8 Hz, 1H), 3.99 (t, J = 5.4 Hz, 2H), 3.92-3.79 (m, 3H), 3.73 (t, J = 5.4 Hz, 2H). LCMS: 405 (M + H+) for C17H17FN6O3S. [Example 81] Preparation of Compound 81 Compound 81 (35 mg, 0.094 mmol, 25%) was obtained from Compound XIX in a similar method to the method of Preparation Example 10. 1H NMR (400 MHz, CDCl3) d = 8.49 (s, 1H), 7.77 (d, J = 1 Hz, 1H), 7.71 (s, 1H), 7.41 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.08-7.04 (m, 2H), 6.84 (d, J = 1 Hz, 1H), 6.86 (s, 1H), 5.06 (m, 1H), 4.78 (d, J = 4 Hz, 2H), 4.14 (t, J = 8.8 Hz, 1H), 3.94-3.64 (m, 7H). LCMS: 374 (M + H+) for C16H16FN7O3. [Example 82] Preparation of Compound 82 Compound 82 (84 mg, 0.24 mmol, 73%) was obtained from Compound 81 in a similar method to the method of Example 2. 1H NMR (400 MHz, DMSO-d6) d = 8.37 (s, 1H), 8.19 (s, 1H), 7.77 (s, 1H), 7.64-7.56 (m, 2H), 7.35 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 7.08-7.04 (m, 2H), 5.18 (m, 1H), 4.85 (d, J = 5.2 Hz, 2H), 4.27 (t, J = 9.2 Hz, 1H), 3.93 (m, 1H), 3.78 (br, t, 2H), 3.35 (br, t, 2H). LCMS: 346 (M + H+) for C15H16FN7O2. [Example 83] Preparation of Compound 83 Compound 82 (62 mg, 0.16 mmol) was dissolved in methanol (5 mL) and reacted for 2 hours at room temperature under hydrogen balloon after adding 4 M HCl dioxane solution (0.1 mL), formalin (0.2 mL) and Pd/C (6 mg). The solution was filtered with celite, dissolved in distilled water (10 mL), neutralized, extracted with dichloromethane, dried with sodium sulfate, and concentrated under reduced pressure to obtain Compound 83 (34 mg, 0.086 mmol, 54%). 1H NMR (400 MHz, CDCl3) d = 7.78 (s, 1H), 7.75 (s, 1H), 7.39-7.00 (m, 3H), 6.88 (s, 1H), 5.08 (m, 1H), 4.80 (d, J = 4.4 Hz, 2H), 4.15 (t, J = 9.2 Hz, 1H), 3.95 (m, 1H), 3.80 (t, J = 4.6 Hz, 2H), 2.98 (t, J = 4.6 Hz, 2H) 2.79 (s, 3H). LCMS: 360 (M + H+) for C16H18FN7O2. [Example 84] Preparation of Compound 84 Compound 84 (26 mg, 0.068 mmol, 74%) was obtained from Compound 82 in a similar method to the method of Example 5. 1H NMR (400 MHz, CDCl3) d = 7.79 (s, 1H), 7.76 (s, 1H), 7.39-7.03 (m, 3H), 6.94 (s, 1H), 5.08 (m, 1H), 4.80 (d, J = 3.6 Hz, 2H), 4.15 (t, J = 9.2 Hz, 1H), 3.95 (m, 1H), 3.84-3.82 (m, 4H), 3.12 (br, t, 2H), 2.34 (s, 1H). LCMS: 384 (M + H+) for C18H18FN7O2. [Example 85] Preparation of Compound 85 Compound 85 (81 mg, 0.21 mmol, 31%) was obtained from Compound XV in a similar method to the method of Preparation Example 10. 1H NMR (400 MHz, CDCl3) d = 8.49 (s, 1H), 8.02 (d, J = 2.0 Hz, 1H), 7.54 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.17 (dd, J1 = 9.0 Hz, J2 = 2.7 Hz, 1H), 7.08 (t, J = 8.4 Hz, 1H), 6.86 (s, 1H), 5.86 (d, J = 2.0 Hz, 1H), 4.93 (m, 1H), 4.06 (t, J = 8.8 Hz, 1H), 3.94 (t, J = 5.0 Hz, 2H), 3.87-3.57 (m, 5H). LCMS: 389 (M + H+) for C17H17FN6O4. [Example 86] Preparation of Compound 86 Compound 86 (35 mg, 0.097 mmol, 71%) was obtained from Compound 85 in a similar method to the method of Example 2. 1H NMR (600 MHz, DMSO-d6) d = 8.40 (s, 1H), 8.30 (s, 1H), 7.70 (d, J = 13 Hz, 1H), 7.60 (t, J = 8.4 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 6.03 (s, 1H), 5.86 (d, J = 2.0 Hz, 1H), 4.92 (m, 1H), 4.20 (t, J = 7.8 Hz, 1H), 3.89-3.36 (m, 7H). LCMS: 361 (M + H+) for C16H17FN6O3. [Example 87] Preparation of Compound 87 Compound 87 (15 mg, 0.036 mmol, 35%) was obtained from Compound 86 in a similar method to the method of Example 12. 1H NMR (600 MHz, DMSO-d6) d = 8.39 (d, J = 1.2 Hz, 1H), 7.62 (dd, J1 = 14 Hz, J2 = 2.4 Hz, 1H), 7.38-7.33 (m, 1H), 7.07 (s, 1H), 6.56 (t, J = 6 Hz, 1H), 6.00 (d, J = 1.2 Hz, 1H), 4.91-4.87 (m, 1H), 4.54-4.52 (m, 1H), 4.32 (d, J = 6.0 Hz, 2H), 4.18-4.15 (m, 1H), 3.89 (t, J = 4.8 Hz, 2H), 3.83-3.80 (m, 1H), 3.70 (t, J = 4.8 Hz, 2H), 3.46-3.43 (m, 2H). LCMS: 419 (M + H+) for C18H19FN6O5. [Example 88] Preparation of Compound 88 Compound 88 (210 mg, 0.46 mmol, 42%) was obtained from Compound 86 in a similar method to the method of Example 59. 1H NMR (600 MHz, CDCl3) d = 8.07 (d, 1H, J = 1.8 Hz), 7.58 (dd, 1H, J1 = 13.2 Hz, J2 = 3.0 Hz), 7.21 (dd, 1H J1 = 8.4 Hz, J2 = 2.4 Hz), 7.11 (t, 1H, J = 8.4 Hz), 6.82 (s, 1H), 5.88 (d, 1H, J = 1.8 Hz), 5.08 (s, 2H), 4.96-5.00 (m, 1H), 4.40 (t, 1H, J = 6.6 Hz), 4.09 (t, 1H, J = 9.0 Hz), 4.02 (t, 2H, J = 4.8 Hz), 3.77-3.78 (m, 1H), 3.74-3.76 (m, 1H), 3.66-3.62 (m, 1H). LCMS: 461 (M + H+) for C20H21FN6O6. [Example 89] Preparation of Compound 89 Compound 89 (36 mg, 0.096 mmol, 68%) was obtained from Compound 86 in a similar method to the method of Example 3. 1H NMR (600 MHz, CDCl3) d 8.07 (d, J = 1.2 Hz, 1H), 7.51 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.15 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 7.09 (t, 8.4 Hz, 1H), 6.89 (s, 1H), 5.87 (d, J = 1.2 Hz 1H), 4.97 (m, 1H), 4.42 (t, J = 6 Hz, 1H), 4.08 (t, J = 8.4 Hz, 1H), 3.87-3.60 (m, 5H), 2.98 (t, J = 4.8 Hz, 2H), 2.79 (s, 3H). LCMS: 375 (M + H+) for C17H19FN6O3. [Example 90] Preparation of Compound 90 Compound 90 (15 mg, 0.039 mmol, 45%) was obtained from Compound 86 in a similar method to the method of Example 6. 1H NMR (400 MHz, CDCl3) d = 8.07 (d, 1H, J = 1.6 Hz), 7.51 (dd, 1H, J1 = 13.6 Hz, J2 = 2.4 Hz), 7.15 (dd, 1H, J1 = 9.2 Hz, J2 = 2.4 Hz), 7.09 (t, 1H, J = 8.8 Hz), 6.91 (s, 1H), 5.87 (dd, 1H, J = 1.6 Hz), 4.99-4.93 (m, 1H), 4.40 (t, 1H, J = 6.4 Hz), 4.07 (t, 1H, J = 9.0 Hz), 3.86-3.81 (m, 3H), 3.78-3.72 (m, 1H), 3.64 (t, 1H, J = 3.2 Hz), 3.62-3.58 (m, 1H), 3.01 (t, 2H, J = 4.8 Hz), 2.95 (t, 2H, J = 7.07 Hz), 1.23 (t, 3H, J = 7.0 Hz). LCMS: 389 (M + H+) for C18H21FN6O3. [Example 91] Preparation of Compound 91 Compound 91 (25 mg, 0.063 mmol, 64%) was obtained from Compound 86 in a similar method to the method of Example 5. 1H NMR (600 MHz, CDCl3) d 8.07 (d, J = 1.8 Hz, 1H), 7.53 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.16 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 7.11 (t, 8.4 Hz, 1H), 6.95 (s, 1H), 5.87 (d, J = 1.8 Hz 1H), 4.96 (m, 1H), 4.35 (t, J = 6.6 Hz, 1H), 4.08 (t, J = 9 Hz, 1H), 3.87-3.60 (m, 7H), 3.13 (t, J = 4.8 Hz, 2H), 2.31 (t, J = 2.4 Hz, 1H). LCMS: 399 (M + H+) for C19H19¬FN6O3. [Example 92] Preparation of Compound 92 Compound 92 (240 mg, 0.75 mmol, 32%) was obtained from Compound XXIII in a similar method to the method of Preparation Example 10. 1H NMR (600 MHz, CDCl3) d = 8.55 (s, 1H), 7.61 (dd, J1 = 13 Hz, J2 = 2.4 Hz, 1H), 7.25 (dd, J1 = 9.0 Hz, J2 = 2.7 Hz, 1H), 7.14 (t, J = 8.4 Hz, 1H), 6.90 (s, 1H), 4.79 (m, 1H), 4.04-3.99 (m, 5H), 3.79-3.73 (m, 3H), 2.58 (br, s, 1H). LCMS: 323 (M + H+) for C14H15FN4O4. [Example 93] Preparation of Compound 93 Compound 93 (190 mg, 0.65 mmol, 74%) was obtained from Compound 92 in a similar method to the method of Example 2. 1H NMR (600 MHz, DMSO-d6) d = 7.73 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.60 (t, J = 9 Hz, 1H), 7.45 (dd, J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 4.75 (m, 1H), 4.11 (t, J = 9.0 Hz, 1H), 3.88 (m, 1H), 3.78 (t, J = 4.8 Hz, 2H), 3.70-3.55 (m, 2H), 3.36 (t, J = 4.8 Hz, 2H). LCMS: 295 (M + H+) for C13H15FN4O3. [Example 94] Preparation of Compound 94 Compound 93 (150 mg, 0.51 mmol) was dissolved in methanol (5 mL) and stirred for 1 hour at room temperature after adding formaldehyde (37% aqueous solution, 0.21 mL, 2.55 mmol), acetic acid (0.03 mL, 0.51 mmol), and NaBH3CN (48 mg, 0.77 mmol). The solution was distilled under reduced pressure, dissolved in dichloromethane (100 mL), sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution (brine), dried with anhydrous sodium sulfate, concentrated under reduced pressure, and separated by column chromatography to obtain Compound 94 (71 mg, 0.23 mmol, 45%). 1H NMR (600 MHz, DMSO-d6) d = 7.59 (dd, J1 = 13.8 Hz, J2 = 2.4 Hz, 1H), 7.33-7.30 (m, 2H), 6.84 (s, 1H), 5.23 (t, J = 5.4 Hz, 1H), 4.70 (m, 1H), 4.07 (t, J = 9.0 Hz, 1H), 3.82 (m, 1H), 3.71 (t, J = 4.8 Hz, 2H), 3.69-3.54 (m, 2H), 2.87 (t, J = 4.8 Hz, 2H), 2.61 (s, 3H). LCMS: 309 (M + H+) for C14H17FN4O3. [Example 95] Preparation of Compound 95 Compound 95 (300 mg, 0.86 mmol) was obtained from 4-fluoronitrobenzene in a similar method to the method of the one used in the synthesis of Compound 1, as described in Scheme 6 1H NMR (600 MHz, CDCl3) d = 8.56 (s, 1H), 7.55 (m, 2H), 7.11 (s, 1H), 7.07 (m, 2H), 6.00 (br, t, 1H), 4.79 (m, 1H), 4.07 (t, J = 9.6 Hz, 1H), 4.02 (t, J = 4.8 Hz, 2H), 3.81 (m, 1H), 3.76 (t, J = 4.8 Hz, 2H), 3.72-3.61 (m, 2H), 2.03 (s, 3H). LCMS: 346 (M + H+) for C16H19N5O4. [Example 96] Preparation of Compound 96 Compound 96 (42 mg, 0.13 mmol, 48%) was obtained from Compound 95 in a similar method to the method of Example 3. 1H NMR (600 MHz, CDCl3) d = 7.48 (d, J = 9.0 Hz, 2H), 7.22 (s, 1H), 7.02 (d, J = 9.0 Hz, 2H), 5.93 (br, t, 1H), 4.77 (m, 1H), 4.05 (t, J = 9.6 Hz, 1H), 3.81 (t, J = 4.8 Hz, 2H), 3.79-3.58 (m, 3H), 3.01 (t, J = 4.8 Hz, 2H), 2.80 (s, 3H), 2.03 (s, 3H). LCMS: 332 (M + H+) for C16H21N5O3. [Example 97] Preparation of Compound 97 Compound 97 (540 mg, 1.4 mmol) was obtained from 4-fluoronitrobenzene in a similar method to the method of the one used in the synthesis of Compound 53, as described in Scheme 6. 1H NMR (600 MHz, CDCl3) d = 8.56 (s, 1H), 7.55 (d, J = 9.0 Hz, 2H), 7.11 (s, 1H), 7.07 (d, J = 9.0 Hz, 2H), 6.69 (br, t, 1H), 4.94 (m, 1H), 4.13-4.05 (m, 3H), 4.04-3.99 (m, 5H), 3.90 (m, 1H), 3.76 (t, J = 4.8 Hz, 2H). LCMS: 378 (M + H+) for C16H19N5O4S. [Example 98] Preparation of Compound 98 Compound 98 (160 mg, 0.44 mmol, 62%) was obtained from Compound 97 in a similar method to the method of Example 60. 1H NMR (600 MHz, CDCl3) d = 7.48 (d, J = 9.0 Hz, 2H), 7.21 (s, 1H), 7.02 (d, J = 9.0 Hz, 2H), 6.69 (br, t, 1H), 4.92 (m, 1H), 4.13-4.08 (m, 2H), 4.01-3.95 (m, 4H), 3.86 (m, 1H), 3.81 (t, J = 4.8 Hz, 2H), 3.01 (t, J = 4.8 Hz, 2H), 2.80 (s, 3H). LCMS: 364 (M + H+) for C16H21N5O3S. [Example 99] Preparation of Compound 99 Compound 99 (340 mg, 0.96 mmol) was obtained from 4-fluoronitrobenzene in a similar method to the method of the one used in the synthesis of Compound 81, as described in Scheme 6. 1H NMR (600 MHz, CDCl3) d = 8.55 (s, 1H), 7.80 (d, J = 1 Hz, 1H), 7.75 (d, J = 1 Hz, 1H), 7.40 (d, J = 9.0 Hz, 2H), 7.09 (s, 1H), 7.03 (d, J = 9.0 Hz, 2H), 5.08 (m, 1H), 4.81 (d, J = 4 Hz, 2H), 4.17 (t, J = 8.4 Hz, 1H), 4.00-3.97 (m, 4H), 3.73 (t, J = 4.8 Hz, 2H). LCMS: 356 (M + H+) for C16H17N7O3. [Example 100] Preparation of Compound 100 Compound 100 (280 mg, 0.76 mmol) was obtained from 4-fluoronitrobenzene in a similar method to the method of the one used in the synthesis of Compound 85, as described in Scheme 6. 1H NMR (600 MHz, CDCl3) d = 8.55 (s, 1H), 8.06 (d, J = 1.8 Hz, 1H), 7.54 (d, J = 9 Hz, 2H), 7.10 (s, 1H), 7.06 (d, J = 9 Hz, 2H), 5.89 (d, J = 1.8 Hz, 1H), 4.96 (m, 1H), 4.10 (t, J = 9 Hz, 1H), 3.99 (t, J = 4.8 Hz, 2H), 3.89 (m, 1H), 3.75-3.72 (m, 3H), 3.62 (m, 1H). LCMS: 371 (M + H+) for C17H18N6O4. [Example 101] Preparation of Compound 101 Compound 101 (37 mg, 0.10 mmol, 68%) was obtained from Compound 100 in a similar method to the method of Example 89. 1H NMR (600 MHz, CDCl3) d = 8.07 (s, 1H), 7.48 (d, J = 9 Hz, 2H), 7.21 (s, 1H), 7.01 (d, J = 9 Hz, 2H), 5.87 (s, 1H), 4.95 (m, 1H), 4.40 (br, t, J = 6 Hz, 1H), 4.09 (t, J = 9 Hz, 1H), 3.85 (t, J = 8.4 Hz, 1H), 3.80 (t, J = 4.8 Hz, 2H), 3.89 (m, 1H), 3.76-3.59 (m, 2H), 3.00 (t, J = 4.8 Hz, 2H), 2.80 (s, 3H). LCMS: 357 (M + H+) for C17H20N6O3. [Example 102] Preparation of Compound 102 Compound XXVII-c was prepared from 4-fluoronitrobenzene in the same method as Preparation Example 14. Compound XXVII-c was then subjected to the same reaction as Example 57 to obtain Compound 102 (24 mg, 0.069 mmol, 37%), as described in Scheme 6. 1H NMR (600 MHz, CDCl3) d = 7.56 (s, 1H), 7.54 (d, J = 9 Hz, 2H), 7.06 (d, J = 9 Hz, 2H), 6.67 (br, t, 1H), 4.93 (m, 1H), 4.21 (t, J = 4.8 Hz, 2H), 4.13-4.07 (m, 3H), 4.01 (s, 3H), 3.88 (t, J = 9 Hz, 1H), 3.77 (t, J = 4.8 Hz, 2H). LCMS: 351 (M + H+) for C15H18N4O4S. [Example 103] Preparation of Compound 103 Compound 103 (350 mg, 0.90 mmol) was obtained from 3,4,5-trifluoronitrobenzene in a similar method to the method of the one used in the synthesis of Compound 81, as described in Scheme 6. 1H NMR (600 MHz, CDCl3) d = 8.54 (s, 1H), 7.77 (d, J = 1 Hz, 1H), 7.75 (d, J = 1 Hz, 1H), 7.15 (s, 1H), 7.13 (s, 1H), 6.69 (s, 1H), 5.11 (m, 1H), 4.81 (d, J = 4 Hz, 2H), 4.15 (t, J = 8.8 Hz, 1H), 4.02-3.98 (m, 3H), 3.65 (t, J = 4.8 Hz, 2H). LCMS: 392 (M + H+) for C16H15F2N7O3. [Example 104] Preparation of Compound 104 Compound 104 (23 mg, 0.061 mmol, 62%) was obtained from Compound 103 in a similar method to the method of Example 83. 1H NMR (400 MHz, CDCl3) d = 7.79 (s, 1H), 7.74 (s, 1H), 7.11 (s, 1H), 7.09 (s, 1H), 6.65 (s, 1H), 5.11 (m, 1H), 4.81 (d, J = 4 Hz, 2H), 4.16 (t, J = 9 Hz, 1H), 3.95 (m, 1H), 3.73 (t, J = 4.8 Hz, 2H), 2.99 (t, J = 4.8 Hz, 2H). LCMS: 378 (M + H+) for C16H17F2N7O2. [Example 105] Preparation of Compound 105 Compound 105 (640 mg, 1.6 mmol) was obtained from 3,4,5-trifluoronitrobenzene in a similar method to the method of the one in the synthesis of Compound 85, as described in Scheme 6. 1H NMR (400 MHz, CDCl3) d = 8.54 (s, 1H), 8.08 (d, J = 1.6 Hz, 1H), 7.29 (s, 1H), 7.27 (s, 1H), 6.71 (s, 1H), 5.89 (d, J = 1.6 Hz, 1H), 4.99 (m, 1H), 4.54 (t, J = 6.4 Hz, 1H), 4.08 (t, J = 9 Hz, 1H), 4.00 (t, J = 4.8 Hz, 2H), 3.90-3.73 (m, 2H), 3.69-3.62 (m, 3H). LCMS: 407 (M + H+) for C17H16F2N6O4. [Example 106] Preparation of Compound 106 Compound 106 (24 mg, 0.061 mmol, 74%) was obtained from Compound 105 in a similar method to the method of Example 89. 1H NMR (400 MHz, CDCl3) d = 8.06 (d, J = 1.6 Hz, 1H), 7.23 (s, 1H), 7.18 (s, 1H), 6.65 (s, 1H), 5.90 (d, J = 1.6 Hz, 1H), 4.99 (m, 1H), 4.92 (t, J = 6.4 Hz, 1H), 4.06 (t, J = 8.8 Hz, 1H), 3.89-3.61 (m, 5H), 3.00 (t, J = 4.8 Hz, 2H). LCMS: 393 (M + H+) for C17H18F2N6O3. [Test Example 1] Measurement of in vitro antibacterial activity In order to test the antibacterial activity of the oxazolidinone derivatives synthesized in Examples 1 to 107, in vitro activity test was carried out as follows. In vitro antibacterial activity of the oxazolidinone derivatives of Examples 1 to 106 was evaluated by minimum inhibitory concentration 90 (MIC90; ug/mL). The term MIC90 refers to the concentration of an antibiotic required to inhibit the growth of 90% of organisms such as bacteria subjected to the antibiotic, compared with the control group. MIC90 measurement was made according to broth microdilution method based on the CLSI standard test [Clinical and Laboratory Standards Institute Document. (2000) Methods for Dilution Antimicrobial Susceptibility Test for Bacteria that Grow Aerobically - Fifth Edition: M7-A5. CLSI, Villanova, PA]. 1) Test bacteria 14 bacterial species including methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), linezolid- and vancomycin-resistant Enterococcus faecalis (LVRE), Haemophilus influenzae and Moraxella catarrhalis (S. aureus, S. aureusMR, S. epidermidis, S. epidermidisMR, E. faecalis, E. faecalisVanA, E. faecalisVanA LR, E. faeciumVanA, E. faecium, E. coli, P. aeruginosa, K. pneumoniae, H. influenzae and M. catarrhalis) were used to measure antibacterial activity of the oxazolidinone derivatives of Examples 1 to 107. Table 1 shows MIC90 values for MRSA and LVRE, the most important two bacteria. 2) Preparation of test compounds Test compounds (Compounds 1 to 106, i.e., the oxazolidinone derivatives synthesized in Examples 1 to 106) were dissolved in DMSO at the concentration of 10240 ug/mL and subjected to two-fold serial dilution with DMSO. The test compounds in DMSO solution were further diluted 20-fold with sterile distilled water. The final concentrations of the test compounds in antibacterial incubations were from 0.0625 to 128 ug/mL. The final concentration of DMSO, which was used as an excipient, was 2.5% (v/v). Linezolid (Chemical Formula B) was used as a comparison compound. Table 1 shows the respective antibacterial activities of the test compounds. [Chemical Formula B] [Table 1] Antibacterial activity (MIC90, ug/mL) of compounds represented by Chemical Formula 1 Cpd MRSA1 LVRE2 Cpd MRSA LVRE Cpd MRSA LVRE Linezolid 2 32 36 2 8 72 0.5 2 1 1 8 37 2 8 73 0.0625 2 2 2 16 38 4 8 74 0.25 2 3 2 8 39 2 8 75 0.25 2 4 1 8 40 2 8 76 0.5 2 5 1 8 41 2 4 77 0.5 4 6 2 8 42 8 32 78 0.5 4 7 1 8 43 2 32 79 8 > 64 8 4 16 44 8 64 80 2 16 9 0.5 8 45 1 4 81 1 16 10 4 32 46 2 16 82 2 32 11 1 8 47 2 8 83 1 16 12 2 8 48 4 16 84 0.5 16 13 4 16 49 1 8 85 0.5 16 14 2 8 50 2 16 86 0.5 8 15 4 8 51 1 4 87 0.5 8 16 128 > 128 52 2 16 88 0.5 8 17 1 8 53 0.5 8 89 0.5 8 18 4 16 54 0.5 4 90 2 8 19 0.5 4 55 2 8 91 0.5 8 20 16 64 56 4 8 92 1 64 21 2 4 57 0.25 2 93 1 32 22 16 128 58 0.25 4 94 1 64 23 32 64 59 0.5 2 95 1 16 24 2 16 60 0.25 2 96 2 16 25 4 32 61 0.5 4 97 0.5 8 26 16 64 62 0.0625 2 98 1 16 27 4 64 63 0.5 4 99 2 32 28 2 16 64 2 8 100 0.5 32 29 0.5 4 65 0.5 4 101 1 32 30 1 4 66 0.5 4 102 0.25 4 31 1 8 67 0.5 4 103 0.25 16 32 8 32 68 0.25 2 104 2 32 33 2 8 69 2 8 105 0.5 16 34 0.5 4 70 1 4 106 0.5 16 35 2 8 71 0.5 4 1. methicillin-resistant Staphylococcus aureus 2. vancomycin-linezolid resistant Enterococcus faecalis As seen from Table 1, the oxazolidinone derivatives of the present invention showed potent antibacterial activity against some Gram-positive bacteria resistant to existing antibiotics, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis, at much lower concentrations when compared to the comparison compound linezolid. Although not shown in Table 1, they were also effective against various Gram-positive bacteria, including, e.g., Haemophilus influenzae, Moraxella catarrhalis. They also showed excellent antibacterial activity against linezolid-resistant Enterococcus faecalis, suggesting that they can be used as an effective antibiotic against linezolid-resistant bacteria. Accordingly, the oxazolidinone derivatives of the present invention can be used as antibiotics having a broad antibacterial spectrum against Gram-positive bacteria. [Test Example 2] Measurement of aqueous solubility Water solubilities of methanesulfonates (MSA) of representative compounds (Examples 83, 89, and 94) among the oxazolidinone derivatives of Chemical Formula 1 were measured. Linezolid of Chemical Formula B was used as a comparison compound. The results are given in Table 2. Solubility measurement was made by 1H NMR as follows. First, a methanesulfonate (100 mg) of each of the compounds was added to D2O (0.5 mL). After preparing a saturated solution by vigorous shaking for 30 minutes, the solution was filtered and 0.3 mL was taken therefrom. A reference compound solution (0.3 mL) (In this test example, DMSO diluted with D2O was used.) with an exactly known concentration was added thereto. From the 1H NMR spectrum of the solution, the integral ratio of the sample peak to the reference (DMSO) peak was calculated. The moles of the sample were calculated from the integral ratio. Then, the solubility of the sample was calculated. [Table 2] Solubility of methanesulfonate in water Compound Linezolid 83 89 94 Solubility (mg/mL) (% solubility) 3 (0.3%) 117 (12%) 129 (13%) 136 (14%) As seen from the table, the aqueous solubilities of the compounds represented by Chemical Formula 1 are greater than 10%, because the compounds can be prepared as salts. In contrast, the aqueous solubility of the linezolid is only 0.3%. That is to say, the aqueous solubilities of the compounds of the present invention are at least 50 times higher than that of linezolid. This advantage allows the development of the compounds of the present invention into antibiotics that can be administered orally or intravenously as bolus, which is not feasible for linezolid. Further, since they are effective against linezolid-resistant bacteria, as well as MRSA and VRE, they can be developed into outstanding antibiotics capable of replacing linezolid. [Test Example 3] Cytotoxicity and Monoamine Oxidase (MAO)Inhibition 1) Cytotoxicity measurement by MTT assay Cytotoxcicity was measured by MTT assay which is a qualitative, colorimetric assay that allows to assess mammalian cell survival and cell proliferation. The MTT assay measures cell respiration, using the reduction of tetrazolium salt (MTT) by the mitochondrial succinate dehrogenase of viable cells to form a blue formazan product, the amount of which is in a linear relationship with the number of living cells present in culture. In this test, Chinese hamster ovary cells (CHO-K1) purchased from ATCC (USA) were subcultured. The subcultured CHO cells were separated from the culture flask by treating with trypsin-EDTA solution, and seeded on a 96-well microplate, with 5000 cells per each well. After culturing for 24 hours in a 37oC, 5% CO2 incubator, the cells were treated with the oxazolidinone derivatives according to the present invention synthesized in the above Examples, at 7 different concentrations. After further culturing for 48 hours in a 37oC, 5% CO2 incubator, 15uL of 5 ug/mL MTT solution was added to each well. The cells were further incubated in the 37oC, 5% CO2 incubator for about 2 hours. Then, the culture medium was discarded and 100 uL of DMSO solution was added to each well. After agitating the microplate for 30 minutes, absorbance was measured at 550 nm using Spectramax plus 190 plate reader (Molecular Devices, USA). The absorbance decrease of the compound-treated groups compared to the non-treated control group is an indication of the degree of the decrease of surviving cells, which enables the measurement of the cytotoxicity of the compounds. The CC50 value, i.e., the concentration at which the cell proliferation is reduced to 50%, of the compounds according to the present invention was computed using the GraFit statistical analysis program (version 5.0.12) purchased from Erithacus Software after calculating the percentages of the absorbance at various concentrations as compared to the control group. 2) MAO inhibition Linezolid is known to act as a nonselective, reversible inhibitor of monoamine oxidases, and may possibly interact with adrenergic or serotonergic drugs. The oxazolidinone derivatives according to the present invention synthesized in the Examples were tested for inhibition of monoamine oxidase A (MAO A) and monoamine oxidase B (MAO B). MAO-GLO assay kit was purchased from Promega (USA) and MAO A and MAO B enzymes were purchased from Sigma-Aldrich (USA). From the aldehyde product resulting from the action of the MAO enzyme on the amine group of the substrate, luciferin methyl ester is produced. The luciferin detection reagent is then added to inactivate the MAO enzymes. The esterase and the luciferase included in the reagent oxidize luciferin, thereby emitting light. The light emission is detected to measure the activity of MAO. The light emission was detected using LEADseeker (Amershan Bioscience, Sweden). MAO activity was measured in the presence of the compounds according to the present invention at 3.9-500 uM and compared with the non-treated control group. Linezolid was used as a comparison compound. For the measurement of the MAO inhibition activity of the compounds represented by Chemical Formula 1, the IC50 value, i.e., the concentration of the compounds at which the enzymatic activity is inhibited by 50% (This value is related with the inhibition constant Ki), can be determined. The concentration of the inhibitor at which the rate of hydrolysis of the substrate is reduced to 50% (i.e., the IC50 value) can be determined from a log plot of the relative rate of hydrolysis (as compared to the non-inhibited control group) versus the concentration of the compounds of Chemical Formula 1. The MAO inhibition effect of the compounds of Chemical Formula 1 was measured by determining the inhibition constant Ki. Equation 1 Ki = IC50 / {1 + ([S]/Km)} In Equation 1, Km is the Michaelis-Menten constant, i.e., the concentration of the substrate at which the rate of enzymatic reaction is half of the maximum, and IC50 is the concentration of the inhibitor at which the rate of the hydrolysis of the substrate is reduced by 50%. The IC50 value was measured by plotting a log plot of the relative rate of hydrolysis (as compared to the non-inhibited control group) versus the concentration of the compounds of Chemical Formula 1. GraFit statistical analysis program (version 5.0.12) purchased from Erithacus Software was used. Cytotoxicity test and MAO inhibition test results for representative compounds among the oxazolidinone derivatives of Chemical Formula 1 are given in Table 3. Since the comparison compound linezolid exhibits significant inhibitory action against MAO enzymes and has the possibility of causing toxicity or other side effects, a lot of efforts have been made to find a compound with no MAO inhibition effect. In general, oxazolidinone-based compounds show such a strong MAO inhibition effect as to be used as MAO inhibitors. However, although the MAO inhibitor may provide a therapeutic effect for those who need it, it may result in toxicity or other side effects when it is used as an antibiotic. Accordingly, the determination of the MAO inhibition effect of oxazolidinone antibiotics is important, and one with less such effect is favored. Linezolid and TR-700 of Chemical Formula D, developed by Trius Therapeutics, were used as comparison compounds. Since TR-701 is a prodrug of TR-700, TR-700 was used. [Table 3] Cytotoxicity and MAO inhibition tests CC50 (uM) MAOA (uM) MAOB (uM) Linezolid > 130 7.9 4.3 TR-700 28 53 > 130 24 58 83 > 130 19 207 89 > 130 5.2 > 250 94 > 130 4 176 102 > 130 89 84 As seen from the table 3, TR-700 exhibits substantial amount of cytotoxic effect and potent inhibitory effect against MAO A and MAO B as well . In contrast, most of the compounds of the present invention are safe in terms of cytotoxicity and exhibit less inhibitory effect than TR-700 by 1/10. Because the compounds of the present invention exhibit high solubility and good antibacterial activity with less toxicity, they are highly promising probable as next-generation antibiotics. While the present invention has been described with respect to the specific embodiments, it will be apparent to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the following claims. ?Industrial Applicability? As described above, the novel oxazolidinone derivatives of the present invention exhibit a wide antibacterial spectrum against existing antibiotic-resistant bacteria including methicillin-resistant Staphylococcus (MRSA), a low toxicity, and a strong antibacterial activity against existing antibiotic resistant bacteria, such as Staphylococcus aureus and Enterococcus faecalis, especially an excellent antibacterial activity against linezolid-resistant Enterococcus faecalis. Therefore, they can be used as the 2nd generation oxazolidinone antibiotics. Further, the oxazolidinone derivatives with a cyclic amidoxime or cyclic amidrazone group according to the present invention can be easily formulated for oral administration or injection because they have higher solubility in water than other existing oxazolidinone compounds. WE CLAIM Claim 1 An oxazolidinone derivative represented by Chemical Formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 1] wherein, R1 represents hydrogen, a (C1-C6)alkyl or (C3-C6)cycloalkyl; Y represents –O- or –N(R2)-, wherein R2 represents hydrogen, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, -(CH2)mOC(=O)R11, -(CH2)mC(=O)R12, -(CH2)mC(=S)R12, or –SO2R13, in which (1) the alkyl of R2 may be further substituted by one or more substituent(s) selected from the group consisting of (C2-C6)alkenyl, (C2-C6)alkynyl, halogen, halo(C1-C6)alkyl, (C1-C6)alkyl(C2-C6)alkynyl, hydroxyl, (C3-C6)cycloalkyl and cyano, (2) m represents an integer from 0 to 2, and (3) R11 through R13 independently represent hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, amino, (C3-C6)cycloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, or (C1-C6)alkylcarbonyl, wherein the alkyl, alkoxy, or amino of R11 through R13 may be further substituted by one or more substituent(s) selected from the group consisting of halogen, amino, hydroxyl, cyano, (C1-C6)alkyl, (C1-C6)alkylcarbonyloxy and hydroxy(C1-C6)alkyl; X1 and X2 independently represent hydrogen or fluorine; P represents –O-, -NH-, or a five-membered aromatic heterocycle with the following structure ; and Q represents hydrogen, -C(=O)R3, -C(=S)R4, -C(=O)NR5R6, -C(=S)NR5R6, or a five-membered aromatic heterocycle with a structure selected from the following structures: , wherein (1) R3 and R4 independently represent hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl, (C2-C6)alkenyl, or (C2-C6)alkynyl, (2) R5 and R6 independently represent hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl or (C2-C6)alkenyl, (3) R7 represents hydrogen, halogen, (C1-C6)alkyl, or (C3-C6)cycloalkyl, and (4) the alkyl of R3 through R7 may be further substituted by one or more substituent(s) selected from the group consisting of hydroxyl, cyano, halogen, (C1-C6)alkylcarbonyloxy and amino. Claim 2 The oxazolidinone derivative according to claim 1, which is represented by Chemical Formula 2 or 3, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 2] [Chemical Formula 3] wherein R2, X1, X2, P and Q are the same as defined in claim 1. Claim 3 The oxazolidinone derivative according to claim 2, which is represented by Chemical Formula 4, 5, or 6, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] wherein R2 represents hydrogen, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, -(CH2)mOC(=O)R11, -(CH2)mC(=O)R12, -(CH2)mC(=S)R12, or –SO2R13, wherein (1) the alkyl of R2 may be further substituted by one or more substituent(s) selected from the group consisting of (C2-C6)alkenyl, (C2-C6)alkynyl, halogen, halo(C1-C6)alkyl, (C1-C6)alkyl(C2-C6)alkynyl, hydroxyl, (C3-C6)cycloalkyl and cyano, (2) m represents an integer from 0 to 2, (3) R11 through R13 independently represent hydrogen, (C1-C6)alkyl, (C1-C6)alkoxy, amino, (C3-C6)cycloalkyl, or (C1-C6)alkylcarbonyl, wherein the alkyl, alkoxy or amino of R11 through R13 may be further substituted by one or more substituent(s) selected from the group consisting of halogen, amino, hydroxyl, cyano, (C1-C6)alkyl, (C1-C6)alkylcarbonyloxy and hydroxy(C1-C6)alkyl; P represents –O-, -NH- or a five-membered aromatic heterocycle with the following structure ; and Q represents hydrogen, -C(=O)R3, -C(=S)R4, -C(=O)NR5R6, -C(=S)NR5R6, or a five-membered aromatic heterocycle with a structure selected from the following structures: , wherein (1) R3 and R4 independently represent hydrogen, (C1-C6)alkyl or (C1-C6)alkoxy, (2) R5 and R6 independently represent hydrogen or (C1-C6)alkyl, and (3) the alkyl of R3 through R6 may be further substituted by one or more substituent(s) selected from the group consisting of hydroxyl, cyano, halogen, (C1-C6)alkylcarbonyloxy and amino. Claim 4 The oxazolidinone derivative according to claim 2, which is represented by Chemical Formula 7, 8, or 9, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: [Chemical Formula 7] [Chemical Formula 8] [Chemical Formula 9] wherein P represents –O-, -NH-, or a five-membered aromatic heterocycle with the following structure ; Q represents hydrogen, -C(=O)R3, -C(=S)R4, -C(=O)NR5R6, -C(=S)NR5R6, or a five-membered aromatic heterocycle with a structure selected from the following structures: ; wherein (1) R3 and R4 independently represent hydrogen, (C1-C6)alkyl, or (C1-C6)alkoxy, (2) R5 and R6 independently represent hydrogen, or (C1-C6)alkyl, and (3) the alkyl of R3 through R6 may be further substituted by one or more substituent(s) selected from the group consisting of hydroxyl, cyano, halogen, (C1-C6)alkylcarbonyloxy and amino. Claim 5 The oxazolidinone derivative according to claim 3, which is selected from the following compounds, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: Claim 6 The oxazolidinone derivative according to claim 4, which is selected from the following compounds, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof: Claim 7 A pharmaceutical antibiotic composition comprising, as an effective ingredient, the oxazolidinone derivative according to any of claims 1 to 6, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt. Dated this 7th day of March 2011 |
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| Patent Number | 277200 | |||||||||||||||||||||||||||||||||
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| Indian Patent Application Number | 435/MUMNP/2011 | |||||||||||||||||||||||||||||||||
| PG Journal Number | 48/2016 | |||||||||||||||||||||||||||||||||
| Publication Date | 18-Nov-2016 | |||||||||||||||||||||||||||||||||
| Grant Date | 15-Nov-2016 | |||||||||||||||||||||||||||||||||
| Date of Filing | 07-Mar-2011 | |||||||||||||||||||||||||||||||||
| Name of Patentee | LEGOCHEM BIOSCIENCES, INC. | |||||||||||||||||||||||||||||||||
| Applicant Address | Daejeon Bio Venture Town 461-8 Jeonmin-dong Yuseong-gu Daejeon 305-811 Republic of Korea | |||||||||||||||||||||||||||||||||
Inventors:
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| PCT International Classification Number | C07D 403/08 | |||||||||||||||||||||||||||||||||
| PCT International Application Number | PCT/KR2009/005376 | |||||||||||||||||||||||||||||||||
| PCT International Filing date | 2009-09-22 | |||||||||||||||||||||||||||||||||
PCT Conventions:
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