[DESCRIPTION]

[Invention Title]

NOVEL OXAZOLIDINONE DERIVATIVE AS CETP INHIBITOR, ITS PREPARATION METHOD, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

[Technical Field]

The present invention relates to a novel oxazolidinone derivative with inhibitory activity against CETP, a preparation method thereof, and a pharmaceutical composition comprising the same.

[Background Art]

Coronary heart disease (CHD), also known as atherosclerotic heart disease, is caused by plaque being deposited and building up along the inner walls of the arteries of the heart. The risk of arteries narrowing increases with smoking, insufficient exercise, obesity, diabetes, high blood pressure, and dyslipidemia. CHD is the leading cause of death irrespective of sex and accounts for approximately 500,000 deaths in the United States every year out of 15.8 million CHD patients.

According to the guidelines of NCEP (National Cholesterol Education Program) ATP-III (Adult Treatment Panel III), management of blood cholesterol levels is very important for the prevention or improvement of CHD. NCEP classified persons with CHD history or CHD-equivalent risk factors into three groups according to the 10-year risk of CHD onset (<10%, 10-20%, >20%), and proposed criteria goals of living behavior improvement and drug treatment for reducing LDL-cholesterol levels in each group (JAMA 2001; 285: 2486- 2497, AAOHN J 2002; 50: 360-364, Vascular Medicine 2002; 7: 187-194). 3-Hydroxy-3- methylglutaryl-CoA (HMG-CoA) reductase inhibitors, such as statins, are reported to lower blood cholesterol levels by inhibiting the synthesis of cholesterol and increasing the expression of LDL receptors, and make a contribution to the treatment or prevention of cardiovascular diseases irrespective of sex and age by reducing the incidence of cardiac diseases by as high as approximately 30 % {Lancet 1994; 344: 1383-1389, Lancet 2002; 360: 7-22, Lan∞t 2004; 364: 7-22, JAMA 1999; 282: 2340-2346). However, these statin- lineage drugs are not sufficiently efficacious for the treatment or prevention of atherosclerosis-caused CHD.

Since the report that the incidence risk of CHD increases with a decrease in HDL cholesterol level (N. Engl. J. Med. 1976; 294: 293-298, Lancet. 1977; 1: 965-968, Am. J. Med. 1977; 62: 707-714), HDL cholesterol-increasing drugs such as fibrate or niacin have been developed (Vase Med 2002; 7: 187-194, JAMA 2001; 285: 2486-2497). Particularly, as HDL was revealed to have various functions including the inhibition of LDL oxidation (Free Radic. Biol. Med. 41: 1031-1040), anti-thrombotic/anti-inflammatory activity (Ore. Res. 98: 1352-1364, Arterioscler. Thromb. Vase. Biol. 15: 1987-1994), and the prevention and improvement of arteriosclerosis (Circulation. 100: 1816-1822) as well as reverse cholesterol transport, the use of HLD cholesterol-increasing drugs alone or in combination with statins has been expected as a novel therapy for CHD. However, this therapy is reported to produce a safety problem such as drug resistance, and its efficacy is, in fact, not as high as expected. Therefore, there is a need for more potent HDL cholesterol-increasing drugs.

In response to this need, CETP (cholesterylester transfer protein) inhibitors have been developed as HDL cholesterol-increasing agents with a novel mechanism. CETP is a hydrophobic glycoprotein which circulates mostly in association with HDL in blood (TallAR et al, J Lipid Res. 1993; 34: 1255-1274). This plasma protein performs a homoexchange by collecting triglycerides from very low density lipoprotein (VLDL) and LDL, and exchanges them for cholesteryl esters from HLD, thus contributing to the re-distribution of cholesterols and the remodeling of lipoproteins. Consistent with this in vivo activity of CETP, it is reported that blood HDL cholesterol levels decrease with an increase in blood CETP activity (Curr. Opin. Lipidol. 11; 4: 389-396). Also, decreased CETP activity brings about an increase in HDL cholesterol levels which, in turn, facilitate reverse cholesterol transport, resulting in a preventive arteriosclerosis effect P /jo J et al., Arterioscler Thromb Vase Biol. 2003; 23: 160-167). The suggestion of the improvement of HDL cholesterol through CETP inhibition has incited pharmaceutical companies to develop drugs for preventing or treating CHD, including anacetrapib of Merck, torcetrapib of Pfizer, and dalcetrapib of Roche. During clinical trials, torcetrapib was first to be dropped due to safety problems, followed by dalcetrapib due to its weak inhibitory activity against CETP and insufficient clinical efficacy.

Therefore, there is an urgent need for a CETP inhibitor that is safes and more potent, allowing for the development of a drug for preventing or treating CHD with excellent efficacy.

[Disclosure]

[Technical Problem]

The present invention is to provide a novel oxazolidinone derivative, a prepration method thereof, and a pharmaceutical composition comprising the same. [Technical Solution]

An aspect of the present invention provides a compound represented by the following Chemical Formula 1 , an isomer thereof, or a pharmaceutically acceptable salt [Chemical Formula 1]

wherein,

X is N, Y is N or CH;

Ri is selected from the group consisting of hydrogen, cyano, halogen, halogen- substituted or unsubstituted C1 to C6 alkyl, -NR4R5, -(0)SO ₂ R6 which is optionally substituted with C1-C4 alkyl or may not be, substituted or unsubstituted C3 to C20 cycloalkyi, substituted or unsubstituted C3 to C20 heterocyclic, substituted or unsubstituted C6 to C40 aryl, and substituted or unsubstituted C3 to C40 heteroaryl;

R_ _t and R ₅ are independently selected from the group consisting of hydrogen, C1 to C4 alkyl, and C3 to C6 cycloalkyi with a proviso that when R4 and R ₅ are independently C1 to C4 alkyl, R4 and R ₅ may be linked to each other to form a hetero cycle containing N;

the substituted C3 to C20 cycloalky or the C3 to C20 heterocyclic in Ri may be substituted with a functional radical selected from the group consisting of halogen, halogen- substituted or unsubstituted C1 to C4 alkyl, C1 to C4 hydroxyalkyl, -(CH ₂ )nCOR ₇ , and - (CH ₂ )nCO(0)R ₇ ;

the substituted C6 to C40 aryl in Ri may be substituted with a functional radical selected from the group consisting of halogen, cyano, nitryl, C1 to C4 alkyl, C1 to C4 hydroxyalkyl, and C1 to C4 alkoxy; the C3 to 40 heteroaryl in Ri may be substituted with cyano, nitryl, oxo, -NRsRg, halogen, halogen-substituted or unsubstituted C1 to C4 alkyl, C1 to C4 hydroxyalkyi, C1 to C4 alkoxy, -(CH ₂ )nCOR ₁₀ , and -(CH ₂ )nCO(O)R ₀ ;

R ₂ is selected from the group consisting of hydrogen, hydroxy-substituted or unsubstituted C1 or C6 alkyl, C3 to C7 cycloalkyi, and -(CH ₂ )nCO(O)Rn;

R ₃ is selected from the group consisting of C1 to C6 alkyl which may be substituted with substituted or unsubstituted C3 to C7 cycloalkyi or may not be, substituted or unsubstituted C3 to C7 cycloalkyi, substituted or unsubstituted C3 to C20 heterocyclic, and substituted or unsubstituted C6 to C20 spirocyclic heterocyclic;

R ₂ and R ₃ may be linked to each other to form a heterocycle containing N, said heterocycle being substituted with halogen-substituted or unsubstituted C1 to C4 alkyl or not;

the C3 to C7 cycloalkyi in R ₃ may be substituted with a functional radical selected from the group consisting of oxo, -NRi ₂ Ri ₃ , C1 to C4 hydroxyalkyi, and -(CH ₂ )nCO(O)Ri ₄ ;

the substituted C3 to C20 heterocycle and the substituted C6 to C20 spirocyclic heterocyclic in R ₃ may be independently substituted with a functional radical selected from the group consisting of oxo, C1 to C4 alkyl, C1 to C4 alkoxy, -(CH ₂ )nCO(0)Ri ₅ , -CORi ₆ , and

R ₁₆ and Ri ₇ are independently C1 to C4 alkyl or -NRi ₈ Rig;

R ₆ , R7, Rs> R9, 10, R11. R12, Ri3, Ri4, Ri5, R18 and R19 are independently hydrogen or C1 to C4 alkyl;

n is an integer of 0, 1 or 2.

Provided in accordance with another aspect of the present invention are a method for preparing the novel compound of Chemical Formula 1 , and a pharmaceutical composition with inhibitory activity against CETP, comprising the novel compound of Chemical Formula 1.

As supported in the following Example section, the compound of Chemical Formula 1 is a novel oxazolidinone derivative and is demonstrated to exhibit excellent inhibitory activity against CETP, compared to known CETP inhibitors. Thus, the compound of Chemical Formula 1 , and a pharmaceutical composition comprising the same is effectively applicable to the prevention or treatment of various diseases related to CETP activity or HDL cholesterol level, including dyslipidemia, atherosclerosis, and coronary heart disease (CHD).

Below, a detailed description will be given of a novel compound, a preparation method thereof, and a pharmaceutical composition comprising the same in accordance with embodiments of the present invention.

According to one embodiment thereof, the present invention provides a novel compound of Chemical Formula 1 exhibiting CETP inhibition activity, an isomer thereof, or a pharmaceutically acceptable salt thereof.

The compound of Chemical Formula 1 is characterized by the heterocyclic structure in which X is N and Y is N or CH. This specific heterocyclic structure may affect properties of the compound of Chemical Formula 1 such as CETP inhibition activity and safety. Accordingly, the compound of Chemical Formula 1 with such a specific heterocyclic structure can be more effectively used in preventing or treating various diseases related with CETP enzyme activity or HDL cholesterol levels, compared to those without such heterocyclic structures.

Preferable in terms of CETP inhibition activity or safety is the heterocyclic structure wherein X is N, and Y is N. In this regard, in Chemical Formula 1 , Ri is unsubstituted C3 to C20 cycloalkyi, or C3 to C40 heteroaryl substituted with C1 to C4 alkyl; R ₂ is C1 to C6 alkyl or C3 to C7 cycloalkyi, R ₃ is C3 to C7 cycloalkyi, or C1 to C6 alkyl substituted with substituted C3 to C7 cycloalkyi; R ₂ and R3 are linked to each other to form a heterocycle which may be substituted with halogen-substituted or unsubstituted C1 to C4 alkyl or may not be.

Meanwhile, the novel compounds according to the embodiment may have one or more chiral centers and may exist as racemates or individual optical isomers, all of which fall within the scope of the present invention. As used herein, the term "isomer" generally refers to compounds with the same molecular formula but different chemical structures, and the term "optical isomer" is intended to encompass any stereoisomer which may be possible for the compound of one embodiment, including the same geometrical isomers.

It is understood that in the compound of Chemical Formula 1 according to one embodiment, each substituent may be attached to a chiral center of carbon atoms. The asymmetric carbon atoms on the compound according to the embodiment may be in the form of (R)-, (S)- or (R, S)-configuration. Suitably, the compound may exist as an enantiomer taking either (R)- or (S)-configuration. Further, the compound according to one embodiment of the present invention may take the form of any possible isomer or a mixture of possible isomers, for example, a pure geometrical isomer, a diastereomer, an enantiomer, a racemate, or a mixture thereof. In addition, when the compound according to one embodiment has a double bond, substituents attached to the double bond may take E or Z configuration. Moreover, when the compound of one embodiment contains bi- substituted cycloalkyi, each substituent on the cycloalkyi moiety may take cis- or transconfiguration As used herein, the term "pharmaceutically acceptable salt" refers to any salt which possesses the same biological activity and properties of the compound of Chemical Formula 1 according to one embodiment of the present invention and which is preferable in terms of pharmaceutical, biological or other characteristics. Non-limiting examples of the salt include inorganic or organic base addition salts or acid addition salts of the compound of Chemical Formula 1. In greater detail, the existence of an amine group or a similar alkaline group on Chemical Formula 1 makes it feasible to form an acid addition salt with an organic acid or inorganic acid. Examples of the organic acid applicable to the formation of an acid addition salt include acetic acid, propionic acid, glycolic acid, pyrubic acid, oxalic acid, maleic acid, malonic acid, succinic acid, furmaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, manelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluene sulfonic acid, and salicylic acid. Among the inorganic acids useful in the present invention are hydrochloric acid, hydrobromic acid, sulfonic acid, nitric acid and phosphoric acid. With regard to other pharmaceutically acceptable salts, reference may be made to literature such as [Remington's Pharmaceutical Sciences, 20th ed., Mack Publishing Company, Easton, Pa., (1985)].

The pharmaceutically acceptable salt of the compound according to one embodiment of the present invention may be synthesized by a typical chemical method from either a compound in the form of a free base, or an alkaline or acidic residue derived therefrom. Further, a second pharmaceutically acceptable salt may be synthesized from a first pharmaceutically acceptable salt. For example, a compound in a free base form may be reacted with a stoichiometric amount of a suitable acid to give an acid addition salt of the compound of one embodiment of the present invention. In this regard, the reaction may be carried out in water, an organic solvent or a mixture thereof, for example, in a non-aqueous medium such as ether, ethyl acetate, ethanol, isopropanol or acetonitrile. Furthermore, other pharmaceutically acceptable salts may be obtained using typical reactions obvious to those skilled in the art.

Concrete examples of the compound of Chemical Formula 1 include the compounds listed in Table 1 , below, isomers thereof, and pharmaceutically acceptable salts thereof. In Table 1 , compounds 1 to 93 have heterocyclic structures in which X is N and Y is CH while compounds 94 to 131 have heterocyclic structures in which X is N and Y is N. Exhibiting excellent inhibitory activity against CETP, these compounds of Chemical Formula 1 can be effectively applied to the prevention or treatment of various diseases related with CETP enzyme activity or HDL cholesterol levels, with preference for the compounds wherein X is N and Y is N:

TABLE 1

1 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[(2-(m ethyl(tetrahydrofuran-3- yl)amino)-5-(trifluoromethyl)pyridin-3-yl)methyl]-oxazolidin -2-one

2 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{(2-[e thyl(tetrahydrofuran-3- yl)amino]-5-(trifluoromethyl)pyridin-3-yl)methyl}-oxazolidin -2-one

3 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-[( 3R, 4R)-4- ethoxytetrahydrofuran-3-yl)(methyl)amino]-5-(trifluoromethyl )pyridin-3-yl}methyl)- oxazolidin-2-one

4 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-[( 3S, 4R)-ethoxytetrahydrofuran- 3-yl)(methyl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)- oxazolidin-2-one

5 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-[( tetrahydro-2H-pyran-4- yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazolidin -2-one

(4S,5S)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( methyl)(tetrahydro-2H-pyran-4 yl)amino]-5-(trifIuoromethyl)pyridin-3-yl}methyl)-oxazolidin -2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahydro-2H

yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazoli din-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( propyl)(tetrahydro^^

yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazoli din-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)p ^

yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazoli din-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(c yclopropyl)(tetrahydro-2H- pyran-4-yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-ox azolidin-2-on

(4S,5R)-5-[3,5-bis(trifluoromethy!)phenyl]-4-methyl-3-({[2-( cyclobutyl)(tetra

pyran-4-yl)amino]-5-(trifluoro)methylpyridin-3-yl}methyl) -oxazolidin-2-one

t-butyl [3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-o xo-oxazolidin-3 yl}methyl)-5-(trifluoromethyl)pyridin-2-yl]-(tetrahydro-2H-p yran-4-yl)-carbamate

ethyl [3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-o xo-oxazolidin-3- yl}methyl)-5-(trifluoromethyl]pyridin-2-yl]-(tetrahydro-2H-p yran-4-yl)-carbamate

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-e thyl(tetrahydro-2H

yl)amino]-pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)^^

yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazoli din-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-[e thyl(tetrahydro-2H-pyran-4- yl)amino]-5-fluoropyridin-3-yl}methyl)-oxazolidin-2-one t-butyl 2-([3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- 2-oxo-oxazolidin-c yl}methyl)-5-(trifluoromethyl)pyridin-2-yl]-(tetrahydro-2H-p yran-4-yl)amino)-acetate

(4S,5R)-5-[3,5-bis(trifluoromethyl)p ^

pyran-4-yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl) -oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( oxepan-4-yl)amino]-5- (trifluoromethyl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( methyl)(oxepen-4-y^

(trifluoromethyl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(1,4- dioxaspiro[45]decan-8-yl)amino]-5-trifluoromethylpyridin-3-y l}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[ 2-(ethyl)(4-oxocy^^

5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(4- ethylaminocyclohexyl)amino]-5-(trffl^

methyl 2-(4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-meth yl-2-oxo-oxazolidin-3 yl}methyl)-5-(trifIuoromethyl)pyridin-2-yl](ethyl)amino}cycl ohexyl)acetate

(4S _J 5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2 -(ethyl)(tetrahydro-2H-^^ 4-yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazolid in-2^

(4S,5R)-5-[3,5-bis(trifluoromethyl)p ^

thiopyran-4-yl)amino]-5-(trifluoromethyl)pyridin-3-yl}met hyl)-oxazolidin-2-one

t-butyl 4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- 2-oxo-oxazolidin-3 yl}methyl)-5-(trifluoromethyl)pyridin-2-yl](ethyl)amino}pipe ridine-1-^

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[2-(ethyl)(pi peridin-4-yl)am (trifIuoromethyl)pyridin-3-yl}methyl)-4-methyloxazolidin-2-o ne

(4S,5R)-5-[3,5-bis(trifluoromethy

yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazoli din-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(1 ,1 -dimethylpiperidin-4- yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazolidin -2-one

((4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(1-propylpiperi yl)amino]-5-trifIuoromethylpyridin-3-yl}methyl)-oxazo|idin-2 -one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(1- methanesulfonylpiperidin-4-yl)amino]-5-trifluoromethylpyridi n-3-yl}m

one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(1-acetylpiper^^ yl)amino]-5-(trifluoromethyl}pyridin-3-yl}methyl)-oxazolidin -2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(1-propionylpi yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-oxazolidin -2-one

methyl 4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- 2-oxo-oxazolidin-3 yl}methyl)-5-(trifluoromethyl)pyridin-2-yl](ethyl)amino}pipe ridine-1-carboxy^

ethyl 4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- 2-oxo-oxazolidin-3 yl}methyl)-5-(trifluoromethyl)pyridin-2-yl](ethyl)amino}pipe ridine-1-carboxylate

methyl 4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- 2-oxo-oxazolidin-3 yl}methyl)-5-(trifluoromethyl)pyridin-2-yl](ethyl)amino}-N,N -dimethylpiperidine-1- carboxamide

methyl 2-(4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-meth yl-2-oxo-oxazolidin-3 yl}methyl)-5-(trifluoromethyl)pyridin-2-yl](ethyl)amino}pipe ridin-1-yl)acetate 2-(4-{[3-({(4S,5R)-5-[3,5-bis(trifluorom

yl}methyl)-5-(trifluoromethyl)pyri acid

(4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahy

yl)amino]-5-bromopyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahydro-2H-pyran-4- yl)amino]-5-(pyrrolidin-1-yl)pyridin-3-yl}methyl)-oxazolidin -2-one

methyl 2-(4-{5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methy l-2-oxo-oxazolidin-2 yl}methyl)-6-[ethyl(tetrahydro-2H-pyran-4-yl)amino]pyridin-3 -yl}piperazin-1-yl^

(4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahy

yl)amino]-5-(azetidin-1-yl)pyridin-3-yl}methyl)-oxazolidi n-2-one

(4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahydro-2H yl)amino]-5-(piperidin-1-yl)pyridin-3-yl}methyl)-oxazolidin- 2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahydro-2H-^ yl)amino]-5-phenylpyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahydro-2H-pyran-4- yl)amino]-5-(3-methylphenyl)pyridin-3-yl}methyl)-oxazolidin- 2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahydro-2H-pyran-4- yl)amino]-5-(3-fluorophenyl)pyridin-3-yl}methyl)-oxazolidin- 2-one

(4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahydro-2H-pyran-4- yl)amino]-5-(3-ethoxyphenyl)pyridin-3-yl}methyl)-oxazolidin- 2-one

(4S _! 5R)-5-[3 _> 5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-(ethy!)( tetrahydro-2H-pyran-4- yl)amino]-5-(furan-2-yl)pyridin-3-yl}methyl)-oxazolidin-2-on e

(4S,5R)-5-[3 _> 5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-(ethyl)( tetrahydro-2H-pyran-4- yl)amino]-5-(1-methyl-1 H-pyrrol-2-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahy^

yl)amino]-5-(3,5-dimethyl-isoxazol-4-yl}methyl)-oxazo!idi n-2-one

(4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(tetrahydro

yl)amino]-pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)am

(trifluoromethyl)pyridin-3-yl}methyl)-oxazolidin-2-one

5- ({4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo- ,3-oxazolidin-3-yl}methyl)-

6- [(cyclohexyl)(ethyl)amino]nicotinonitrile

5-{[(4S,5R)-5-[3,5-bis(trif]uoromethyl)ph

[(cyclohexyl)(ethyl)amino]-pyridin-3-yl methanesulfonate

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cycloh

(1 -methyl-1 H-pyrrol-2-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenylH^

5-(3,5-dimethylisoxazol-4-yl)pyridin-3-yl}methyl)-oxazoli din-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)^

(3,5-dimethylisoxazol-4-yl)pyridin-3-yl}methyl)-oxazolidi n-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amin methyl-1 H-pyrazol-5-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl-4-^^

(1 -methyl-1 H-3-(trifluoromethyl)-pyrazo

ethyl (2-{4-[5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-meth yl-2-oxo-oxazolidin-3 yl}methyl)]-6-[(cyclohexyl)(ethyl)amino]pyridin-3-yl}-1H-pyr azol-1-yl)acetate (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)am methyl-1 H-pyrazol-4-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3 ₎ 5-bis(trifluoromethyl)phenyl]-4-methy!-3-({[2-(ethyl)( cyclohexyl)amino]-5-(3- methyl-thiophen-5-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[2-(ethyl)(cy clohexyl)amino

trimethyl-1 H-pyrazol-4-yl}pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)ph^

(3,5-dimethyl-1 H-pyrazol-4-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)ami methyl-1 H-tetrazol-5-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amino]^ isobutyl-1 H-pyrazol-4-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3 _> 5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-(ethyl)( cyclohexyl)ami pyrazol-4-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amm (1 ,3-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl}methyl)-oxazolidin- 2-one

(4S ₁ 5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2 -(ethyl)(cyclohexyl)amino]-5-(3- methoxy-thiophen-2-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

5-{5-({(4S,5S)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-2 -oxo-oxazolidin-3-yl}methyl)-6 [(cyclohexyl)(ethyl)amino]pyridin-3-yl}-thiophene-2-carbonit rile

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amin (trifluoromethyl)-l H-pyrazol-4-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

ethyl 4-{5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2 -oxo-oxazolin-2 yl}methyl)-6-[(cyclohexyl)(ethyl)amino)]pyridin-3-yl}-3-meth ylisoxazole-5-carboxylate

74 ethyl 5-{5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2 -oxo-oxazolin-i yl}methyl)-6-[(cyclohexyl)(ethyl)amino)]pyridin-3-yl}-3-meth ylisoxazole-4-carboxylate

75 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amino]-5-(2- methyl-furan-5-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

76 t-butyl 2-{5-({(4S,5S)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-2 -oxo-oxazolidin-: yl}methyl)-6-[(cyclohexyl)(ethyl)amino]pyridin-3-yl}-1H-pyrr ole-1-carboxylate

77 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amino]-5- (thiophen-3-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

78 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)^

methyl-thiophen-2-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

79 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)^

methyl-thiophen-5-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

80 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)a

(thiophen-2-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

81 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)am

(thiazol-4-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

82 3-{5-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2 -oxo-oxazolidin-3-yl}methyl)-6 [(cyclohexyl)(ethyl)amino]pyridin-3-yl}-thiophene-2-carbonit rile

83 t-butyl 4-[5-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2 -oxo-oxazolidin-2 yl}methyl)-6-[cyclohexyl(ethyl)amino]pyridin-3-yl]-5-methyli soxazol-3-yl-(^rbamate

84 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amino]-5- (2,4-dimethyl-thiazol-5-yl)pyridin-3-yl}methyl)-oxazolidin-2 -one 85 (4S,5R)-5-[3,5-bis(trifluoromethy

amino-5-methyl-isoxazol-4-yl)pyridin-3-yl}methyl)-oxazolidin -2-one

86 (4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amin

methyl-thiophen-4-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

87 (4S _I 5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2 -(ethyl)(cyclohexyl)amino]-5-(3- methyl-isothioxazol-4-yl)pyridin-3-yl}methyl)-oxazolidin-2-o ne

88 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)am

(pyrrolidin-1-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

89 (4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amm

methyl-pyrrolidin-1-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

90 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)ami

ethyl-pyrrolidin-1-yl)pyridin-3-yl}methyl)-oxazolidin-2-one

91 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)ami

(3,3-difluoro-pyiTolidin-1-yl)pyridin-3-yl}methyl)-oxazolidi n-2-one

92 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexyl)amino]-5-(2- (trifluoromethyl)-pyrrolidin-1-yl)pyridin-3-yl}methyl)-oxazo lidin-2-one

93 3-[5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-^methyl-2- oxo-oxazolidin-3-yl}methyl)-6 [(cyclohexyl)(ethyl)amino]pyridin-3-yl]-1 ,2,4-oxadiazol-5(4H)-one

94 (4S,5R)-5-[3,5-bis(trifluoromethyl)phe^

dimethyl-isoxazol-4-yl)pyrazin-3-yl]methyl}-oxazolidin-2-one

95 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( methyl)(cyclohexyl)amino]-5- (3,5-dimethyl-isoxazol-4-yl)pyrazin-3-yl}methyl)-oxazolidin- 2-one

96 (4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(cyclohexy^ (3,5-dimethyl-isoxazol-4-yl)pyrazin-3-yl}methyl)-oxazolidin- 2-one

97 (4S,5R)-5-[3,5-bis(trifluoromethyl^

dimethyl-isoxazol-4-yl)pyrazin-3-yl}methyl)-4-methyloxazolid in-2-one

98 (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(3,5-dimeth ylisoxazol-4-yl)-3-(p

yl)pyrazin-2-yl]methyl}-4-methyloxazolidin-2-one

99 (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(3,5-dimeth ylisoxazol-4-yl)-3 ^

dimethylmorpholino)pyrazin-2-yl]methyl}-4-methyloxazolidin-2 -one

100 (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(3,5-dimeth ylisoxazol-4-yl)-3-[3- (trifluoromethyl)piperidin-1-yl]pyrazin-2-yl]methyl}-4-methy loxazolidin

101 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[3-(cyclopent ylmethyl)(ethyl)amino]-4- methyl6-(3,5-dimethylisoxazol-4-yl)pyrazin-3-yl}methyl)-oxaz olidin-2-one

102 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyH-met hyl-2-oxazolidi

yl}methy!)-5-(3,5-dimethyloxazol-4-yl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

103 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3- yl}methyl)-5-(pyrrolidin-1-yl)pyrazin-2-yl]{[N-(ethyl)aminom ethyl]cyclohexyl)}acete acid

104 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3^

yl}methyl)-5-(1 -methyl-1 H-pyrrol-2-yl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

105 trans-4-({[3-({(4S,5S)-5-[3 bis(triflu^^^

yl}methyl)-5-(thiophen-3-yl)pyrazin-2-yl]{[N-(ethyl)aminomet hyl]cyclohexyl)}acetic acid

106 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazoli^

yl}methyl)-5-(1 -methyl-1 H-pyrazol-5-yl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

107 trans-4-({[3-({(4S,5S>-5-[3,5-bis(trifluoromethyl)phenyl] -4-methyl-2-oxazolW

yl}methyl)-5-(1 ,3-dimethyl-l H-pyrazol-5-yl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

108 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazoiidin-3- yl}methyl)-5-(1 ,3-dimethyl-1 H-pyrazol-4-yl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

109 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3- yl}methyl)-5-(3-methoxythiophen-2-yl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

110 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifIuoromethyl)phenyl]-4- methyl-2-oxazolidin

yl}methyl)-5-(4-methylthiophen-2??-yl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

111 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidi

yl}methyl)-5-(3-methylthiophen-2-yl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

112 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3- yl}methyl)-5-(thiazol-2-yl)pyrazin-2-yl]{[N-(ethyl)aminometh yl]cyclohexyl)}^ acid

113 trans-^({[3-({(4S,5SV5-[3,5-bis(trifIuoromethyl)phenylH-meth yl-2-oxazolidin

yl}methyl)-5-(thiazol-4-yl)pyrazin-2-yl]{[N-(ethyl)aminometh yl]cyclohexyl)}aceW

114 trans^ -^S^SJ-S- S-bisitrifl^^

yl}methyl)-5-(thiophen-2-yl)pyrazin-2-yl]{[N-(ethyl)aminomet hyl]cyclohexyl)}acetic acid

115 trans-^({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-m ethyl-2-oxazol^ yl}methyl)-5-(5-acetylthiophen-2-yl)pyrazin-2-yl]{[N-(ethyl) aminomethyl]cyclohexyl)}aceti< acid

1.16 trans-4-({[3-({(4S,5S)-5-[3,5-bis(»

yl}methyl)-5-phenylpyrazin-2-yl]{[N-(ethyl)aminomethyl]cyclo hexyl)}acetic acid

117 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifIuoromethyl)phenyl]-4- methyl-2-oxazol^

yl}methyl)-5-(4-cyanophenyl)pyrazin-2-yl]{[N-(ethyl)aminomet hyl]cyclohexyl)}aceti acid

118 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)pheny -4-methyl-2-oxazolidin-3- yl}methyl)-5-(4-hydroxymethylphenyl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

119 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3- yl}methyl)-5-(pyridin-3-yl)pyrazin-2-yl]{[N-(ethyl)aminometh yl]cyclohexyl)}aceti acid

120 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidi

yl}methyl)-5-(5-fluoropyridin-3-yl)pyrazin-2-yl]{[N-(ethyl)a minomethyl]cyclohexyl)}acetic acid

121 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolid

yl}methyl)-5-(cydopropylpyrazin-2-yl)]{[N-(ethyl)aminomethyl ]cyclohexyl)}aceti acid

122 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluo^

yl}methyl)-5-(cyclobutylpyrazin-2-yl)]{[N-(ethyl)aminomethyl ]cyclohexyl)}acetic acid

123 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2 )xazoli

yl}methyl)-5-(3,5-dimethyloxazol-4-yl)pyrazin-2-yl]{[N- (propyl)aminomethyl]cyclohexyl)}acetic acid

124 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3- yl}methyl)-5-(pyrrolidin-1-yl)pyrazin-2-yl]{[N-(propyl)amino methyl]cyclohexyl)}^ acid 125 trans-4-({[3-({(4S,5S)-5-[3,5-bis^

yl}methyl)-5-(cyclohexylpyrazin-2-yl)]{[N-(propyl)am acid

126 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxaz

yl}methyl)-5-(3,5-dimethyloxazol-4-yl)pyrazin-2-yl]{[N- (methyl)aminomethyl]cyclohexyl)}acetic acid

127 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3- yl}methyl)-5-(pyrrolidin-1-yl)pyrazin-2-yl]{[N-(methyl)amino methy^ acid

128 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluorom

yl}methyl)-5-(cyclobutylpyrazin-2-yl)]{[N-(methyl)aminomethy l]cyclohexyl)}acetic acid

129 trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluorom

yl}methyl)-5-(cyclopentylpyrazin-2-yl)]{[N-(methyl)aminometh yl]cyclohexyl)}aceti acid

130 trans-4-({[3-({(4S,5S 5-[3,5-bis(trifluorome

yl}methyl)-5-(3,5-dimethyloxazol-4-yl)pyrazin-2-yl]{[N-

(ethyl)aminomethyl]cyclohexyl)}propanol

131 trans-4-({[3-({(4S,5S>5-[3,5-bis(triflu^

yl}methyl)-5-(pyrrolidin-4-yl)pyrazin-2-yl]{[N-(ethyl)aminom ethyl]cyclohexyl)}propanol

Contemplated in accordance with a furher aspect of the present invention is a method for preparing the compound of Chemical Formula 1. In one embodiment, the preparation method comprises: introducing a leaving group to a compound of Chemical Formula 2-1 to give a compound of Chemical Formula 2-2; reacting the compound of Chemical Formula 2-2 with (4S,5 )-5-[3,5-bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2- one to form a compound of Chemical Formula 3; and coupling the compound of Chemical Formula 3 with an amine group (-NR ₂ R ₃ ) to afford the compound of Chemical Formula 1 : [Chemical Formula 2-1]

[Chemical Formula 2-2]

[Chemical Formula 3]

wherein, Hal represents halogen, LG represents a leaving group selected from among halogen or methanesulfonyl, and X, Y, R-i, R ₂ and R ₃ are as defined in Chemical Formula 1.

In this preparation method, the compound of Chemical Formula 2-1 may be obtained by reducing a compound of Chemical Formula 2:

[Chemical Formula 2]

wherein, R is hydrogen or C1 to C4 alkoxy, for example, methoxy, and Hal and Ri are as defined in Chemical Formula 2-1. The prepration method described above may be summarized as illustrated following Reaction Scheme 1 :

[Reaction Scheme 1]

In this preparation method, the coupling of the amine group (-NR2R3) may be carried out in a single process using NHR2R3 as a reactant, or in a multi-step process first by using NHR ₂ or NHR ₃ as a reactant, followed by introducing R ₂ or R ₃ . This additional introduction of R ₂ or R ₃ may be achieved using alkylation or other cycloalkyi or heterocyclic coupling reactions known to those skilled in the art according to the kind of each substituent. When R ₂ is a hydroxy-containing substituent, for example, hydroxy-substituted C1 to C6 alkyl, the preparation method may further comprises protecting the hydroxy group with a protecting group such as t-butyldimethylsilyl group, and this hydroxy-protecting group may be finally removed to afford the compound of Chemical Formula 1.

In another embodiment, the method for preparing the compound of Chemical Formula 1 comprises introducing a leaving group to a compound of Chemical Formula 4-1 to give a compound of Chemical Formula 4-2; and reacting the compound of Chemical Formula 4-2 with (4S,5 ?)-5-[3,5-bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2 -one:

[Chemical Formula 4-1]

[Chemical Formula 4-2]

wherein, LG represents a leaving group selected from among halogen and sulfanyl group, and X, Y, Ri, R ₂ and R ₃ are as defined in Chemical Formula 1.

This preparation method may further comprise, prior to the formation of the compound of Chemical Formula 4-2, coupling a compound of Chemical Formula 2 with an amine group (-NR2R3) to form a compound of Chemical Formula 4; and reducing the compound of Chemical Formula 4 into the compound of Chemical Formula 4-1 :

[Chemical Formula 2]

[Chemical Formula 4]

wherein, Hal represents halogen, R is hydrogen or C1 to C4 alkoxy, and X, Y, R-i, 2 and R3 are as defined in Chemical Formula 1.

This method may be summarized as illustrated in the following Reaction Scheme 2: [Reaction Scheme 2]

1

In accordance with a further embodiment, the preparation method may further comprise, before the formation of the compound of Chemical Formula 4-2, introducing at least one of F½ and R3 to the amine group on a compound of Chemical Formula 5 to give a compound of Chemical Formula 6; performing acyl substitution on the compound of Chemical Formula 6 to form a compound of Chemical Formula 4; and reducing the compound of Chemical Formula 4 to a compound of Chemical Formula 4-1. For the acyl substitution, the halogen of the compound of Chemical Formula 6 may substituted by an aldehyde or alkylcarbonyl group:

[Chemical Formula 5]

[Chemical Formula 6]

[Chemical Formula 4] [Chemical Formula 4-1]

wherein, Hal represents halogen, R is hydrogen or C1 to C4 alkoxy, and X, Y, R-i , R2 and R ₃ are as defined in Chemical Formula 1.

This preparation method may be summarized as illustrated in the following

Reaction Scheme 3:

[Reaction Scheme 3]

1

In a still further embodiment, the preparation method may comprises, prior to the formation of the compound of Chemical Formula 4-2, coupling a compound of Chemical

Formula 2b with an amine group (-NR2R3) to give a compound of Chemical Formula 4b'; introducing Ri to the compound of Chemical Formula 4b' to form a compound of Chemical

Formula 4 (exception that Ri is hydrogen or halogen); and reducing the compound of

Chemical Formula 4 to a compound of Chemical Formula 4-1 :

[Chemical Formula 2b]

[Chemical Formula 4]

wherein, Hal represents halogen, R is hydrogen or C1 to C4 alkoxy, and X, Y, Ri, R2 and R3 are as defined in Chemical Formula 1 , with the exception that Ri is hydrogen or halogen.

This preparation method may be summarized as illustrated in the following Reaction Scheme 4, by which the compound of Chemical Formula 1 can be suitably prepared, with the exception that R is hydrogen or halogen:

[Reaction Scheme 4]

1b

In Reaction Scheme 4, Ri _b is the same as Ri except that Ri is hydrogen or halogen.

Also in the preparation methods illustrated in Reaction Schemes 2 to 4, the coupling of the amine group (-NR2R3) may be carried out in a single process using NHR2R3 as a reactant or in a multi-step process first by using NHR ₂ or NHR ₃ as a reactant, followed ·. by introducing R ₂ or R ₃ . When R ₂ is a hydroxy-containing substituent, the preparation method may further comprises protecting the hydroxy group with a protecting group such as t-butyldimethylsilyl group, and this hydroxy-protecting group may be finally removed to afford the compound of Chemical Formula 1.

According to a still further aspect thereof, the present invention provides a method for preparing the compound of Chemical Formula 1 wherein Ri is not hydrogen.

In one embodiment, this preparation method comprises introducing a leaving group to a compound of Chemical Formula 2a-1 to form a compound of Chemical Formula 2a-2; reacting the compound of Chemical Formula 2a-2 with (4S,5R)-5-[3,5- bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2-one to form a compound of Chemical Formula 3a; coupling the compound of Chemical Formula 3a with an amine group (-NR2R3) to form a compound of Chemical Formula 1a'; and introducing Ri to the compound of Chemical Formula 1a' to afford the compound of Chemical Formula 1 (with the exception that Ri is hydrogen):

[Chemical Formula 2a-1]

[Chemical Formula 2a-2]

[Chemical Formula 3a]

[Chemical Formula 1a']

Wherein, Hal represents halogen, LG represents a leaving group selected from among halogen and methanesulfonyl, and X, Y, R-i, R ₂ and R3 are as defined in Chemical Formula 1 , with the proviso that R-i is not hydrogen.

More exemplary embodiment of this preparation may be summarized as illustrated in the following Reaction Scheme 5:

[Reaction Scheme 5]

wherein R-i _a is the same as R-i, with the proviso that Ri is not hydrogen.

In the preparation method of Reaction Scheme 5, the compound of Chemical Formula 2a may be reduced to a compound of Chemical Formula 2a-1 , which is then prepared into the compound of Chemical Formula 1 a' through the steps described above. In addition, the introduction of Ri (e.g, Ri _a , but not hydrogen) to the compound of Chemical Formula 1a' may be achieved by halogenating the compound of Chemical Formula 1a' to the compound of Chemical Formula 1 b', and substituting the halogen on the compound of Chemical Formula 1b' with Ri (e.g, R _a , but not hydrogen).

In another embodiment, the method for preparing the compound of Chemical

Formula 1 wherein Ri is not hydrogen, comprises introducing a leaving group to the compound of Chemical Formula 4a-1 to give a compound of Chemical Formula 4a-2; reacting the compound of Chemical Formula 4a-2 with (4S,5R)-5-[3,5- bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2-one to form a compound of Chemical Formula 1 a'; and indroducing R-i to a compound of Chemical Formula 1a' to afford the compound of Chemical Formula 1 (with the exception that F is hydrogen):

[Chemical Formula 4a-1]

[Chemical Formula 4a-2]

[Chemical Formula 1a']

wherein, LG represents a leaving group selected from among halogen and methanesulfonyl, and X, Y, R-i, R ₂ and R ₃ are as defined in Chemical Formula 1 , with the provision that Ri is not hydrogen.

An exemplary embodiment of this preparation may be summarized as illustrated in the following Reaction Scheme 6:

[Reaction Scheme 6]

In Reaction Scheme 6, Ri _a is as defined in Reaction Scheme 5.

In the prepration method of Reaction Scheme 6, the compound of Chemical Formula 2a may be coupled with an amine group (-NR ₂ R3) to form a compound of Chemical Formula 4a which is then reduced to a compound of Chemical Formula 4a-1, which is in turn prepared into the compound of Chemical Formula 1a' through the steps described above. In addition, the introduction of Ri (e.g, Ri _a , but not hydrogen) to the compound of Chemical Formula 1a' may be achieved by halogenating the compound of Chemical Formula 1a' to the compound of Chemical Formula 1b', and substituting the halogen on the compound of Chemical Formula 1b' with Ri (e.g, Ri _a , but not hydrogen), whereby the compound of Chemical Formula 1 where Ri is not hydrogen (the compound of Chemical Formula 1a in Reaction Scheme 6) can be suitably prepared.

In accordance with another embodiment, the method for preparing the compound of Chemical Formula 1 wherein is not hydrogen, comprises: introducing a leaving group to a compound of Chemical Formula 4a-1 to give a compound of Chemical Formula 4a-2; reacting the compound of Chemical Formula 4a-2 with (4S,5R)-5-[3,5- bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2-one to form a compound of Chemical Formula 1a'; and introducing Ri to the compound of Chemical Formula 1a' to afford the compound of Chemical Formula 1 (with the exception that Ri is hydrogen.):

[Chemical Formula 4a-1]

[Chemical Formula 4a-2]

[Chemical Formula 1 a']

wherein, LG represents a leaving group selected from among halogen and methanesulfonyl, and X, Y, R-i, R ₂ and R ₃ are as defined in Chemical Formula 1 , with the provision that Ri is not hydrogen.

An exemplary embodiment of this prepration method may be summarized as illustrated in the following Reaction Scheme 7:

[Reaction Scheme 7]

In Reaction Scheme 7, Ri _a is as defined in Reaction Scheme 5.

In the preparation of Reaction Scheme 7, at least one of R ₂ and R ₃ , for example, R ₃ and optionally R ₂ which is not hydrogen, may be introduced to the amine group on the compound of Chemical Formula 5a to form a compound of Chemical Formula 6a and then, the halogen on the compound of Chemical Formula 6 may be substituted to form a compound of Chemical Formula 4a. Subsequently, the compound of Chemical Formula 4a is reduced to a compound of Chemical Formula 4a-1 which is then prepared into the compound of Chemical Formula 1 a' through the steps described above. In the preparation method of Reaction Scheme 7, the introduction of R-i (e.g, Ri _a , but not hydrogen) to the compound of Chemical Formula 1a' may be achieved by halogenating the compound of Chemical Formula 1a' to the compound of Chemical Formula 1b', and substituting the halogen on the compound of Chemical Formula 1 b' with R-i (e.g, R-i _a , but not hydrogen), whereby the compound of Chemical Formula 1 where Ri is not hydrogen (the compound of Chemical Formula 1 a in Reaction Scheme 7) can be suitably prepared.

Also, in the preparation methods illustrated in Reaction Schemes 5 to 7, the coupling of the amine group (-NR ₂ R ₃ ) may be carried out in a single process using NHR ₂ R ₃ as a reactant or in a multi-step process first by using NHR ₂ or NHR ₃ as a reactant, followed by introducing R ₂ or R ₃ . When R ₂ is a hydroxy-containing substituent, the preparation method may further comprises protecting the hydroxy group with a protecting group such as t-butyldimethylsilyl group, and this hydroxy-protecting group may be finally removed to afford the compound of Chemical Formula 1.

In accordance with still another aspect thereof, the present invention provide a method for preparing the compound of Chemical Formula 1 wherein Ri is not hydrogen.

According to one embodiment, the preparation method comprises: introducing a leaving group to a compound of Chemical Formula 4b'-1 to give a compound of Chemical Formula 4b'-2; reacting the compound of Chemical Formula 4b'-2 with (4S,5 ?)-5-[3,5- bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2-one to form a compound of Chemical Formula 1 b'; and substituting the halogen on the compound of Chemical Formula 1 b' with Ri to afford afford the compound of Chemical Formula 1 (with the exception that Ri is hydrogen.):

[Chemical Formula 4b'-1]

[Chemical Formula 4b'-2]

[Chemical Formula 1 b']

wherein Hal represents halogen, LG represents a leaving group selected from among halogen and methanesulfonyl, and X, Y, Ri, R ₂ and R ₃ are as defined in Chemical Formula 1 , with the proviso that Ri is not hydrogen nor halogen.

An exemplary embodiment of this preparation method may be summarized as illustrated in the following Reaction Scheme 8:

[Reaction Scheme 8]

In Reaction Scheme 8, R-i _b is as defined in Ri, with the provision that Ri is not hydrogen nor halogen.

In the prepration method of Reaction Scheme 8, the compound of Chemical Formula 2b may be coupled with an amine group (-NR ₂ R3) to form a compound of Chemical Formula 4b' which is then reduced to a compound of Chemical Formula 1 b', which is in turn prepared into the compound of Chemical Formula b' through the steps described above. In addition, the halogen on the compound of Chemical Formula 1 b' may be substituted by Ri (e.g, Rib but neither hydrogen nor halogen) to prepare the compound of Chemical Formula 1 where R-i is not hydrogen nor halogen (the compound of Chemical Formula 1 b in Reaction Scheme 8).

In accordance with another embodiment, the method for preparing the compound of Chemical Formula 1 wherein R is not hydrogen nor halogen, comprises: introducing a leaving group to a compound of Chemical Formula 2b-1 to give a compound of Chemical Formula 2b-2; reacting the compound of Chemical Formula 2b-2 with (4S,5f?)-5-[3,5- bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2-one to form a compound of Chemical Formula 3b'; and coupling the compound of Chemical Formula 3b' with an aming group (- NR2R3) to form a compound of Chemical Formula 1 b'; substituting the halogen on the compound of Chemical Formula 1 b' with Ri to afford the compound of Chemical Formula 1 (with the exception that Ri is hydrogen or halogen):

[Chemical Formula 2b-1]

[Chemical Formula 2b-2]

[Chemical Formula 3b']

wherein, Hal represents halogen, LG represents a leaving group selected from among halogen and methanesulfonyl, and X, Y, Ri, R ₂ and R ₃ are as defined in Chemical Formula 1 , with the provisio that, Ri is not hydrogen nor halogen.

An exemplary embodiment of this preparation method may be summarized as illustrated in the following Reaction Scheme 9:

[Reaction Scheme 9]

In Reaction Scheme 9, Rib is as defined in Reaction Scheme 8.

In this prepration method, the compound of Chemical Formula 2b may be reduced to a compound of Chemical Formula 2b-1 which is then prepared into the compound of Chemical Formula 1 b' through the steps described above. Also in this preparation method, the halogen on the compound of Chemical Formula 1 b' may be substituted by Ri (Rib, but neither hydrogen nor halogen) to produce the compound of Chemical Formula 1 wherein R-i is not hydrogen nore halogen (compound of Chemical Formula 1 b in Reaction Scheme 9).

In accordance with another embodiment, the method for preparing the compound of Chemical Formula 1 wherein Ri is not hydrogen nor halogen, comprises: introducing a leaving group to a compound of Chemical Formula 2b-1 to give a compound of Chemical Formula 2b-2; reacting the compound of Chemical Formula 2b-2 with (4S,5f?)-5-[3,5- bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2-one to form a compound of Chemical Formula 3b'; substituting the halogen on the compound of Chemical Formula 3b' with Ri to form a compound of Chemical Formula 3 (with the exception that Ri is not hydrogen nor halogen); and coupling the compound of Chemical Formula 3 with an aming group (-NR2R3) to afford a compound of Chemical Formula 1 : [Chemical Formula 2b-1]

[Chemical Formula 2b-2]

[Chemical Formula 3b']

wherein, Hal represents halogen, LG represents a leaving group selected from among halogen and methanesulfonyl, and X, Y, Ri, R ₂ and R3 are as defined in Chemical Formula 1 , with the provision that R-i is not hydrogen nor halogen.

An exemplary embodiment of this preparation method may be summarized as illustrated in the following Reaction Scheme 10: [Reaction Scheme 10]

In Reaction Scheme 10, Ri _b is as defined in Reaction Scheme 8.

In this prepration method, the compound of Chemical Formula 2b is reduced to the compound of Chemical Formula 2b-1 which is, in turn, prepared into the compound of Chemical Formula 3b' through the steps described above. Subsequently, the substitution of the halogen on the compound of Chemical Formula 3b' with R- _\ (e.g., Ri _b , but neither hydrogen nor halogen) produces the compound of Chemical Formula 3 wherein Ri is not hydrogen nor halogen (the compound of Chemical Formula 3b in Reaction Scheme 10), followed by coupling with an amine group (-NR ₂ R ₃ ) to prepare the compound of Chemical Formula 1 (the compound of Chemical Formula 1 b in Reaction Scheme 10).

Also in the preparation methods illustrated in Reaction Schemes 8 to 10, the coupling of the amine group (-NR ₂ R ₃ ) may be earned out in a single process using NHR ₂ R ₃ as a reactant or in a multi-step process first by using NHR ₂ or NHR ₃ as a reactant, followed by introducing R ₂ or R3. When R ₂ is a hydroxy-containing substituent, the preparation method may further comprises protecting the hydroxy group with a protecting group such as t-butyldimethylsilyl group, and this hydroxy-protecting group may be finally removed to afford the compound of Chemical Formula 1.

It should be noted that in the preparation methods illustrated in Reaction Schemes 1 to 10, the compound of Chemical Formula 1 (or the compound of Chemical Formula 1a or 1 b), that is, the final product may be obtained as isomers or a mixure of isomers. Hence, an additional process may be conducted to separate pure isomers. Reaction procedures and conditions for isomer sepration may follow the methods and conditions well known in the art.

As a reactant used in each prepration method, (4S,5R)-5-[3,5- bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2-one may be synthesized using a well- known method, for example, according to the disclosure of U. S. Pat. No. 7781426. The preparation method may be summarized as illustrated in the following Reaction Scheme 1 :

[Reaction Scheme 11]

In Reaction Scheme 11 , PG represents a protecting group for an amine group, and may be for example, t-Boc or Cbz.

With reference to Reaction Scheme 11 , the prepration of (4S,5R)-5-[3,5- bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2-one starts with amine-protected 2- aminopropionic acid, followed by coupling with dimethyl hydroxyl amine, a Grignard reaction, a reduction, and treatment with a base, in the order, to form an oxazolidinone ring.

In accordance with a yet further aspect thereof, the present invention addresses a pharmaceutical composition with CETP inhibition activity, comprising the compound of Chemical Formula 1 , an isomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. Exhibiting excellent inhibitory activity against CETP, the pharmaceutical composition can be effectively applied to the prevention or treatment of various CETP enzyme activity- or HDL cholesterol level-related diseases such as dyslipidemia, atherosclerosis, and coronary heart disease.

The pharmaceutical composition may take a typical drug formulation. That is, the pharmaceutical compositon may be administered in various forms such as oral or non-oral dosage forms, with preference for an oral dosage form. In this regard, the pharmaceutical composition of the present invention may be formulated in combination with a diluent or excipient such as a filler, a thickener, a binder, a humectant, a disintegrant, a surfactant, etc.

Solid preparations intended for oral administration may be in the form of tablets, pills, powders, granules, capsules, and the like. In regards to these solid agents, the active ingredient of the present invention is formulated in combination with at least one excipient such as starch, calcium carbonate, sucrose, lactose, or gelatin. In addition to a simple excipient, a lubricant such as magnesium stearate, talc, etc. may be used. Among liquid preparations intended for oral administration are suspensions, internal use solutions, emulsion, syrups, and the like. Plus a simple diluent such as water or liquid paraffin, various excipients, such as humectants, sweeteners, aromatics, preservatives, and the like may be contained in the liquid preparations. Also, the pharmaceutical composition of the present invention may be in a parenteral dosage form such as sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilizates, suppositories, and the like. Injectable propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and esters such as ethyl oleate may be suitable for the non-aqueous solvents and suspensions. The basic materials of suppositories include Witepsol, macrogol, Tween 61 , cacao butter, laurin butter, and glycerogelatin.

[Advantageous Effects]

The present invention can provide a novel compound as a potent CETP inhibitor useful for the treatment or prevention of dyslipidemia, atheriosclerosis, and coronary heart disease, a preparation method thereof, and a pharmaceutical composition comprising the same.

[Mode for Invention]

A better understanding of the present invention may be obtained through the following examples which are set forth to illustrate, but are not to be construed as limiting the present invention.

[EXAMPLE 1] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[(2- (methyl(tetrahydrofuran-3-yl)amino)-5-(trifluorornethyl)pyri din-3-yl)methyl]- oxazolidin-2-one

[Step 1] Preparation of 2-chloro-5-(trifluoromethyl)pyridin-3-yl-methane chloride

[Step 1-1] Preparation of 2-chloro-5-(trifluoromethyl)pyridine-3-carbaldehyde

To a solution of 3-bromo-2-chloro-5-(trifluoromethyl)pyridine (20.00 g, 0.077 mol) in toluene (400 ml), DMF (dimethylformaldehyde) (7.72 ml, 0.10 mol) was dropwise added at - 65°C, followed by the addition of n-BuLi (1.57M solution in hexane; 64 ml, 0.10 mol). After stirring for 30 min, the reaction was terminated with 1 N HCI, and then, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated in a vacuum to obtain 2-chloro-5- (trifluoromethyl)pyridine-3-carbaldehyde. This produce was used in the subsequent reaction without further purification.

[Step 1-2] Preparation of 2-chloro-5-(trifluoromethyl)pyridin-3-yl-methanol

To a solution of 2-chloro-5-(trifluoromethyl)pyridine-3-carbaldehyde of step 1-1 in ethanol (60 ml) was dropwise added NaBH ₄ (2.90g, 0.077 mol) while stimng for 30 min at room temperature. After the reaction was terminated with a saturated ammonium solution, extraction with ethylacetate was carried out. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography to give 2-chloro-5-(trifluoromethyl)pyr ^' idin-3-yl-methanol (12.3g, 76%). [Step 1-3] Preparation of 2-chloro-5-(trifluoromethyl)pyridin-3-yl-methane chloride

A solution of 2-chloro-5-(trifluoromethyl)pyridin-3-yl-methanol (46g, 135.0mol) of step 1-2 in DMF (300 ml) was cooled to 0°C. SOCI ₂ (thionyl chloride) (17.6g, 148mol) was dropwise added to the solution over 1 hr with stirring. The reaction mixture was diluted with acetate ethyl (200 ml), and then added with water to terminate the reaction. The organic layer thus formed was dried over Na ₂ SO , filtered, and concentrated to give 2- chloro-5-(trifluoromethyl)pyridin-3-yl-methane chloride which was then used in a subsequent reaction without further purification. [Step 2] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- oxazolidin-2-one

[Step 2-1] Preparation of (S)-benzyl 1-(A/,0-dimethylhydroxylamine)-1- oxopropan-2-yl carbamate

To a solution of Cbz-L-alanine (21.38 g, 95.78 mmol) in tetrahydrofuran (THF) (200 ml) were dropwise added HOBTDH ₂ 0 (17.60 g, 114. 93 mmol), Weinreb's aminenHCI

(12.15 g, 124.51 mmol), Hunig's base (30.95 g, 239.45 mmol), and EDCDHCI (23.87 g,

124.51 mmol) at 0°C. After being stirred at room temperature for 18 hrs, the reaction mixture was cooled to 0°C and added with 2 N HCI to terminate the reaction. After extraction with ethyl acetate, the organic layer thus formed was washed once with 1 N HCI and a saturated sodium carbonate solution, each. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in a vacuum. The concentrate was re-crystallized in hexane, and filtered at a reduced pressure to obtain the title compound (23.39 g, 92%).

¹ H NMR (400 MHz, CDCI ₃ ) δ 7.21-7.35 (m, 5H), 5.55 (m, 1 H), 5.07 (m, 2H), 4.72 (m, 1 H), 3.75 (s, 3H), 3.18 (s, 3H), 1.32 (d, J = 7.2 Hz, 3H).

[Step 2-2] Preparation of (S)-benzyl-1-[3,5-bis(trifluoromethyl)phenyl]-1- oxopropan-2-yl carbamate

To a solution of (S)-benzyl-1-(A/,0-dimethylhydroxylamine)-1-oxopropan-2-yl carbamate (1.00 g, 3.75 mmol) of step 2-1 in THF (tetrahydrofuran) (10ml) was slowly added drops of 3,5-bis(trifluoromethyl)phenyl MgBr (0.5M in THF, 18.8 mL, 9.38 mmol) at 0°C. After stirring the reaction mixture at room temperature for 2 hrs, the reaction was terminated with a saturated ammonium chloride solution, and then, the reaction mixture was extracted with ethyl acetate. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography to afford the title compound (1.2 g, 76%).

1 H NMR (400 MHz, CDCI3) δ 8.32-8.40 (m, 2H), 8.09 (brs, 1 H), 7.21-7.38 (m, 5H), 5.66 (m, 1 H), 5.34 (m, 1 H), 5.12 (s, 2H), 1.44 (d, J = 7.2 Hz, 3H). [Step 2-3] Preparation of (1 ?,2S)-benzyl-[3,5-bis(trifluoromethyl)phenyl]-1- hydroxypropan-2-yl carbamate

A solution of (S)-benzyl-1-[3,5-bis(trifluoromethyl)phenyl]-1-oxopropan-2- yl carbamate (0.3 g, 0.72 mmol), obtained in step 2-2, in toluene (5.4mL) and isopropyl alcohol (3.6ml_) was added with drops of AI(OPr/)3 (0.22 g, 1.08 mmol) at room temperature, and refluxed at 50 °C for 15 hrs with stirring. The reaction mixture was cooled to room temperature, and the reaction was terminated with 2 N HCI, followed by extraction with ethyl acetate. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was re-crystallized in hexane, and filtered at a reduced pressure to afford the title compound (0.3 g, 99%).

H NMR (400 MHz, CDCI ₃ ) δ 7.75-7.82 (m, 3H), 7.26-7.40 (m, 5H), 5.12 (s, 2H),

5.03 (brs, 1 H), 4.85 (d, J = 7.2 Hz, 1 H), 4.04 (m, 1 H), 3.24 (brs, H), 0.99 (d, J = 7.2 Hz, 3H).

[Step 2-4] Preparation of (4S,5/?)-5-[3,5-bis(trifluoromethyl)phenyl])-4-methyl- oxazolidin-2-one

A solution of (1 /?,2S)-benzyl-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxyprop an-2-yl carbamate (0.3 g, 0.71 mmol) of step 2-3 in 5 imL of isopropyl alcohol was added with drops of KOH (0.1 g, 1.78 mmol), and then stirred at room temperature for 4 hrs. The reaction was terminateion with water, followed by extraction with ethyl acetate. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was re-crystallized in hexane, and filtered at a reduced pressure to afford the title compound (0.28 g, 90%).

¹ H NMR (400 MHz, CDCI ₃ ) δ 7.88 (br s, 1 H), 7.77 (br s, 2H), 5.81 (d, J = 8.0 Hz, 1 H), 5.32 (br s, 1 H), 4.29 (m, 1 H), 0.82 (d, J = 6.4 Hz, 3H).

[Step 3] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- [(2-chloro-5-trifluoromethylpyridin-3-yl)methyl]-oxazolidin- 2-one

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyloxazolidin-2-one (46g, 147mol), obtained in step 2, in DMF (150ml) was dropwise added NaHMDS (sodium hexamethyldisilazide) (176 ml, 176 mol) at -40°C. The reaction mixture was stirred for 30 min, and slowly added with drops of a dilution of 2-chloro-5- (trifluoromethyl)pyridin-3-yl-methane chloride, obtained in step 1 , in DMF (30ml). The resulting reaction mixture was heated to room temperature, stirred for 3 hrs, diluted with ethyl acetate (200 ml), and added with water (500 ml) to terminate the reaction. The organic layer thus formed was withdrawn, washed with water (2.5 I), and filtered through silica-selite pad at a reduced pressure to afford the title compound (60g, 67%).

1 H NMR (400MHz, CDCI ₃ ) . 8.64 (s, 1 H), 8.01 (s, 1 H), 7.90 (s, 1 H), 7.82 (s, 2H), 5.76 (d, J = 8.0Hz, 1 H), 4.84 (d, J = 16.0Hz, 1 H), 4.47 (d, J = 16.4Hz, 1 H), 4.22 (m, 1 H), 083 (d, 3H). [Step 4] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- [(2-(tetrahydrofuran-3-yl)amino-5-(trifluoromethyl)pyridin-3 -yl)meth

one

Tetrahydrofuran amine (198mg, 1.92mmol) was dropwise added to (4S,5R)-5-[3,5- bis(trifluoromethyl)phenyl]-4-methyl-3-[(2-chloro-5-trifluor omethylpyridin-3-yl)met^

oxazolidin-2-one obtained in step 3. This reaction mixture was refluxed at 130°C for 4 hrs with stirring, cooled to room temperature, diluted with ethyl acetate, and then extracted with water. The organic layer thus formed was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography to afford the title compound (130 mg, 36%).

1 H NMR (400MHz, CDCI ₃ ) 8.36 (s, 1 H), 7.89 (s, 1 H), 7.71 (d, J = 2.8Hz, 2H), 7.36 (s, 1 H), 5.71 (d, J = 8.0Hz, 1 H), 4.68 (m, 2H), 4.13-3.97 (m, 4H), 3.90 (m, 2H), 3.76 (m, 2H), 2.33 (m, 1 H), 1.99 (m, 1 H), 0.88 (t, 3H), 0.80 (m, 3H).

[Step 5] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- [(2-(methyl(tetrahydrofuran-3-yl)amino)-5-(trifluoromethyl)p yridin-3-yl)methyl]- oxazolidin-2-one

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[(2- (tetrahydrofuran-3-yl)amino-5-(triflu (70mg, 0.13 mmol), obtained in step 4, in DMF (1 ml) was cooled to 0°C. This solution was stirred for 5 min in the presence of NaH (15 mg, 0.38 mmol). After addition of methyl iodide (27mg, 0.19 mmol) thereto, the reaction mixture was stirred at room temperature for 2 hrs. The reaction was terminated with a saturated ammonium solution, followed by extraction with ethyl acetate. The organic layer thus obtained was dried filtered, and concentrated in a vacuum. The residue was purified by chromatography to afford the title compound (65 mg, 90%).

¹ H NMR (400MHz, CDCI ₃ ) 8.46 (s, 1 H), 7.87 (s, 1 H), 7.77 (d, J = 2.0Hz, 1 H), 7.73 (s, 2H), 5.72 (t, J = 6.8Hz, H), 4.84 (m, 1 H), 4.34-4.24 (m, 2H), 4.01-3.85 (m, 4H), 3.75 (m, 2H), 3.63 (m, 1 H), 2.80 (s, 3H), 2.79 (s, 3H), 2.27 (m, 2H), 1.99 (m, 2H), 0.66 (m, 3H)

[EXAMPLE 2] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{(2- [ethyl(tetrahydrofuran-3-yl)amino]-5-(tri^

2-one

The title compound was prepared in the same manner as in Example 1 , with the exception that ethyl iodide, instead of the methyl iodide in step 5, was employed. 38 mg (93%).

¹ H NMR (400MHz, CDCI ₃ ) 8.51 (s, 1 H, major), 8.47 (s, 1 H, minor), 7.89 (s, 1 H, minor), 7.81 (s, 1 H, major), 7.80 (s, 1 H, minor), 7.76 (s, 2H, minor), 7.74 (s, 2H, major), 5.74 (d, 1 H, minor), 5.71 (d, 1 H, major), 4.83 (d, 1 H, minor), 4.78 (d, 1 H, major), 4.33 (m, 1 H), 4.29 (m, 1 H), 3.99 (m, 4H), 3.76 (m, 2H), 3.63 (m, 1 H, minor), 3.49 (m, 1 H, major), 3.30 (m, 3H), 2.24 (m, 1 H), 1.98 (m, 2H), 0.94 (t, 6H), 0.62 (d, 3H, major), 0.63 (d, 3H, minor).

[EXAMPLE 3] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-[( 3R, 4R)^-ethoxytetrahydrofuran-3-yl)(methyl)amino]-5-(trifIuorom ethyl)pyridin-3- yl}methyl)-oxazolidin-2-one

[Step 1] Preparation of 3-bromo-N-(4R-ethoxy-tetrahydrofuran-3-yl)-5- (trifluoromethyl)pyridine-2-amine

A solution of 2-chloro-3-bromo-5-trifluoromethyl pyridine (1.17g, 4.48mmol) in DMF (4ml) was added with drops of TEA (triethylamine) (1.24 ml, 8.96mmol) and then with (4R)- 3-ethoxy-4-tetrahydrofuranamine (824 mg, 4.93mmol), refluxed at 110°C for 5 hrs with stirring, cooled to room temperature, and quenched with water, followed by extraction with ethyl acetate. The organic layer was dried, filtered, and concentrated. The residue was purified by chromatography to afford the title compound (537mg, 34%).

¹ H NMR (400MHz, CDCI ₃ ) 8.32 (s, 1 H), 7.80 (s, 1 H), 5.41 (d, J = 6.0 Hz, H), 5.58 (t, J = 5.2Hz, 1 H), 4.11- 4.07 (m, 2H), 3.93 (d, J = 4.4 Hz, 1 H), 3.86 - 3.78 (m, 2H), 3.74 (d, J = 8.4Hz, 1 H), 3.62 (ddd, J = 7.2, 6.0, 6.0 Hz, 1 H), 1.23 (t, 3H).

[Step 2] Prepration of 3-bromo-N-(4R-ethoxy-tetrahydrofuran-3-yl)-N-methyl- 5-(trifluoromethyl)pyridine-2-amine

A solution of 3-bromo-N-(4R-ethoxy-tetrahydrofuran-3-yl)-5-

(trifluoromethyl)pyridine-2-amine (537mg), obtained in step 1 , in DMF (6ml) was added with NaH (2.0eq) and methyl iodide (1.5eq), and stirred for 1 hrs at room temperature. The reaction was terminated with an aqueous ammonium solution ermination, followed by extraction with ethyl acetate. The organic layer was dried, filtered, and concentrated. The residue was purified by chromatography to afford the title compound (470mg, 79%).

¹ H NMR (400MHz, CDCI ₃ ) 8.38 (s, 1 HO, 7.94 (d, J = 1.2Hz, 1 H), 4.57 (ddd, J = 6.8, 6.8, 4.0Hz, 1 H), 4.26-4.17 (m, H), 4.11 (dd, J = 10.0, 4.8Hz, 1 H), 3.86 (dd, J = 10.0, 4.8Hz, 1 H), 3.73 (dd, J = 10.0, 4.4Hz, 1 H), 3.49-3.39 (m, 1 H), 3.0 (s, 3H), 1.15 (t, 3H).

[Step 3] Preparation of 2-[(4R-ethoxytetrahydrofuran-3-yl)(methyl)amino]-5- (trifluoromethyl)pyridin-3-yl-methanol

A solution of 3-bromo-N-(4R-ethoxy-tetrahydrofuran-3-yl)-N-methyl-5- (trifluoromethyl)pyridine-2-amine (100mg, 0.27mmol), obtained in step 2, in DMF (30mg, 1.23mmol) and toluene (0.5ml) was added with n-BuLi (0.6ml, 1.23mmol) at -78°C, and stirred for 3 hrs. The reaction was terminated with an aqueous ammonium solution ermination, followed by extraction with ethyl acetate. The organic layer was dried, filtered, and concentrated. The concentrate was dissolved in ethanol (2ml). The reaction mixture was cooled to 0°C, and added with drops of NaBH ₄ (20 mg, 0.54 mmol). After 30 min, the reaction was terminated with a saturated aqueous ammonium solution, followed by extraction with ethyl acetate. The organic layer thus formed was dried, filtered, and concentrated in a vacuum. The residue was purified by chromatography to afford the title compound (33mg, 38%).

H NMR (400MHz, CDCI ₃ ) 8.43 (s, 1 H), 7.89 (s, 1 H), 4.73 (q, 2H), 4.25 (m, 1 H), 4.22 (m, 1 H), 4.15-4.01 (m, 2H), 3.78-3.68 (m, 2H), 3.53 (m, 2H), 2.86 (s, 3H), 1.18 (t, 3H).

[Step 4] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- ({2-[(3R,4R)-ethoxytetrahydrofuran-3-yl)(methyl)am

yl}methyl)-oxazolidin-2-one

2-[(4R-ethoxvtetrahydrofuran-3-yl)(methyl)amino]-5-(trifluor omethyl)pyridin-3-yl- methanol (33mg) obtained in step 3 was reacted with SOC (thionyl chloride) in DMF (1 ml), and then with (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]H-^e ^t hy ^| -o ^x azolidin-2-one in the same manner as in step 3 of Example 1 to afford the title compound (14.7mg, 23%).

¹ H NMR (400MHz, CDCI ₃ ) . 8.48 (s, 1 H), 7.87 (s, 1 H), 7.75-7.73 (m, 3H), 5.72 (d, 1 H), 4.91 (d, 1 H), 4.21-4.06 (m, 4H), 3.87 (m, 1 H), 3.77 (m, 1 H), 3.70 (m, 1 H), 3.50 (m, 2H), 2.87 (s, 3H), 1.14 (t, 3H), 0.65 (d, 3H).

[EXAMPLE 4] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-[( 3S, 4R)-ethoxytetrahydrofuran-3-yl)(methy^

yl}methyl)-oxazolidin-2-one

The same procedure as in Example 3 was repeated to afford the title compound (35.6mg, 57%).

H NMR (400MHz, CDCI ₃ ) 8.48 (s, 1 H), 7.87 (s, 1 H), 7.77 (s, 1 H), 7.73 (s, 2H), 5.69 (d, 1 H), 4.85 (d, 1 H), 4.35 (d, 1 H), 4.28 (m, 4H), 3.89 (m, 1 H), 3.72 (m, 2H), 3.55 (m, 2H), 2.85 (s, 3H).

[EXAMPLE 5] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2- [(tetrahydro-2H-pyran-4-yl)amino]-5-(trifl

2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[(2-ch loro-5- (trifIuoromethyl)pyridin-3-yl)methyl]-oxazolidin-2-one (500mg, 0.99mmol), obtained in step 3 of Example 1 , and TEA (270mg, 1.98mmol) were dissolved in DMF (3ml), and added with drops of tetrahydropyran amine (0.3ml, 2.96mmol). The reaction mixture was refluxed at 120°C for 48 hrs with stirring, and then cooled to the room temperature. The cooled mixture was diluted with 50 ml of acetate chloride, and washed twice with brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography to afford the title compound (368mg, 65%).

1H NMR -(400MHz, CDCI ₃ ) 8.334 (d, J = 0.8 Hz, H), 7.88 (s, 1 H), 7.70 (s, 2H), 7.34

(d, J = 4.0 Hz, 1 H), 6.17 (d, J = 8.0 Hz, 1 H), 5.69 (d, J = 8.0 Hz, 1 H), 4.64 (AB, JAB = 14.8 Hz, = 215.4, 1 H), 4.24 - 4.20 (m, 1 H), 4.11 - 4.04 (m, 2H), 4.01 - 3.98 (m, 2H), 3.58 - 3.53 (m, 2H), 2.05 - 1.68 (m, 2H), 1.68 - 1.51 (m, 2H), 0.80 (d, J = 6.0 Hz, 3H). [EXAMPLE 6] (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-

(methyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(trifluorometh yl)pyridin-3-yl}meth oxazolidin-2-one

(4S,5R)-5-[3 _J 5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-[(tetrahy dro-2H

yl)amino]-5-trifluoromethylpyridin-3-yl}methyl)-oxazolidi n-2 (214mg, 0.37mmol) of Example 5 was dissolved in DMSO (dimethyl sulfoxide) (10ml), and cooled to 0°C. The reaction mixture was added with drops of NaH (22.4 mg, 0.56mmol), and stirred for 5 min. Then, methyl iodide (68.27mg, 0.48mmol) was dropwise added. The resulting mixture was stirred for 30 min, added with brine to terminate the reaction, and diluted with 50 ml of ethyl acetate. The organic layer was washed twice with brine, dried over anhydrous magnesium sulfate. The residue was purified by chromatography to afford the title compound (190mg, 88%).

¹ H NMR (400MHz, CDCI ₃ ) 8.442 (s, 1 H), 7.88 (s, 1 H), 7.73 (s, 3H), 5.70 (d, J = 8.0Hz, 1 H), 4.82 (AB, J _AB = 15.6 Hz, Δ _AB = 222.8, 1 H), 4.26 (AB, JAB = 15.6 Hz, Δ _AB = 222.8, 1 H), 4.06 - 3.978 (m, 2H), 3.89 (dddd, J = 6.4, 13.2, 13.2 Hz, 1 H), 3.49 - 3.37 (m, 2H), 2.82 (s, 3H), 1.96 - 1.74 (m, 3H), 1.62 - 1.58 (m, 1 H), 0.63 (d, J = 6.8 Hz, 3H).

[EXAMPLE 7] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(trifluoromethyl)p yridin-3-yl}methyl)- oxazolidin-2-one

[Method 1]

The same procedure as in Example 6 was repeated, with the except that ethyl iodide, instead of methyl iodide, was reacted with (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]- 4-methyl-3-({2-[(tetrahydro-2H-pyran-4-yl)amino]-5-trifluoro methy^

oxazolidin-2-one, to afford the title compound (6mg, 15%).

[Method 2]

[Stepl] Preparation of 2-[ethyl(tetrahydro-2H-pyran-4-yl)amino]-5- (trifluoromethyl)nicotine aldehyde

2-chloro-5-trifluoromethylpyridine carbaldehyde (1.2g, 5.5mmol), obtained in step 1- 1 of Example 1 , was dissolved together with N-ethyl-N-(tetrahydro-2H-pyran-4-yl)-amine (1.3g, 16.5mmol) and K ₂ C0 ₃ (3.03g, 22mmol), in toluene (15ml), and refluxed at 130°C for 48 hrs with stirring. The reaction mixture cooled to room temperature, and added with water to terminate the reaction, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography to afford the title compound ( .1g, 50%).

¹ H NMR (400MHz, CDCI ₃ ) 8.51 (s, 1 H), 7.88 (s, 1 H), 7.79 (d, J = 2.0Hz, 1 H), 7.77 (s, 2H), 5.72 (d, J = 8.0Hz, 1 H), 4.75 (d, J = 16.0Hz, 1 H), 4.34 (d, J = 16.0Hz, 1 H), 4.00 (m, 2H), 3.46 (m, 6H), 1.86 (m, 4H), 0.93 (t, 3H), 0.63 (d, 3H).

[Step 2] Preparation of (2-[ethyl(tetrahydro-2H-pyran-4-yl)amino)-5- (trifluoromethyl)pyridin-3-yl) methanol A solution of 2-[ethyl(tetrahydro-2H-pyran-4-yl)amino]-5-(trifluoromethyl) nicotine aldehyde of step 1 (1.0g, 3.31 mmol) in methanol (10ml) was cooled to 0°C, and added with drops of NaBH (188mg, 4.96mmol). 30 min later, the reaction was terminated with a saturated aqueous ammonium solution, followed by extraction with ethyl acetate. The organic layer thus formed was dried, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (986mg, 98%).

[Step 3] Preparation of 3-(chloromethyl)-N-ethyl-N-(tetrahydro-2H-pyran-4-yl)- 5-(trifluoromethyl)pyridine-2-amine

A solution of (2-[ethyl(tetrahydro-2H-pyran-4-yl)amino)-5-(trifluoromethyl )pyridin-3- yl) methanol of step 2 (1.57g, 5.16mmol) in DMF (10ml) was added with drops of SOCI ₂ (739mg, 6.19mmol) at 0°C, and stirred at room temperature for 30 min. The reaction was terminated with water. The reaction mixture was extracted with ethyl acetate, dried, and concentrated at a reduced pressure. The residue was used in the subsequent reaction without further purification.

[Step 4] Preparation of (4S,5R)-5-[3.5-bis(trifluoromethyl)phenyl]-4-methyl-3- ({2-[ethyl(tetrahydro-2H-pyran^-yl)amino]-5-(trifluoromethyl )pyridin-3-yl}methyl)- oxazolidin-2-one

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl])-4-methyl-oxazoli din-2-one (1.78g, 5.68mmol), obtained in step 2 of Example 1 , in DMF (10ml) was added with drops of NaHMDS (5.16ml, 5.16mmol) at -40°C, and stirred for 30 min. To this mixture was slowly added a solution of 3-(chloromethyl)-N-ethyl-N-(tetrahydro-2H-pyran-4-yl)-5- (trifluoromethyl)pyridine-2-amine, obtained in step 3, in DMF (5ml), after which the reaction mixture was stirred at room temperature for 2 hrs. The reaction was terminated with a saturated aqueous ammonium solution, followed by extraction with ethyl acetate. The residue was purified by chromatography to afford the title compound ( .92g, 64%).

H NMR (400MHz, CDCI ₃ ) 8.51 (s, 1 H), 7.88 (s, 1H), 7.79 (d, J = 2.0Hz, 1H),

7.77 (s, 2H), 5.72 (d, J = 8.0Hz, 1H), 4.75 (d, J = 16.0Hz, 1 H), 4.34 (d, J = 16.0Hz, 1H), 4.00 (m, 2H), 3.46 (m, 6H), 1.86 (m, 4H), 0.93 (t, 3H), 0.63 (d, 3H).

[EXAMPLE 8] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3 (propyl)(tetrahydro-2H^yran-4-yl)amino]-5-(trifluoromethyl)p yridin-3-yl}meth oxazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that N-propyl-N-(tetrahydro-2H-pyran-4-yl)-amine (2.36g, 16.5mmol) was used instead of N-ethyl-N-(tetrahydro-2H-pyran-4-yl)-amine, to afford the title compound (2.4g, 58%).

1H NMR (400MHz, CDCI ₃ ) 8.49 (s, 1 H), 7.88 (s, 1 H), 7.77 (s, 1 H), 7.74 (s, 2H),

5.73 (d, J = 8.0Hz, 1 H), 4.75 (d, J = 16.4Hz, 1 H), 4.33 (d, J= 16.4Hz, 1 H), 4.03 (m, 3H), 3.46-3.27 (m, 4H), 3.18 (m, 1 H), 3.08 (m, 1 H), 1.92 (m, 1 H), 1.82 (m, 2H), 1.35 (m, 2H), 0.86 (s, 3H), 0.62 (d, 3H).

[EXAMPLE 9] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (butyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(trifluoromethyl)p yridin-3-yl}methyl)- oxazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that N-butyl-N-(tetrahydro-2H-pyran-4-yl)-amine was used instead of N-ethyl-N- (tetrahydro-2H-pyran-4-yl)-amine, to afford the title compound (84.6mg, 90%).

¹ H NMR (400MHz, CDCI ₃ ) 8.49 (s, 1 H), 7.88 (s, 1 H), 7.77-7.71 (m, 4H), 5073 (d, J = 8.0Hz, H), 4.74 (d, J = 16.0 Hz, 1 H), 4.32 (d, J = 16.0Hz, 1 H), 4.04 (m, 3H), 3.47-3.06 (m, 5H), 1.92-1.71 (m, 4H), 0.81 (t, 3H), 0.61 (d, J = 6.8Hz, 3H)

[EXAMPLE 10] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methy[-3-{[2- (cyclopropyl)(tetrahydro-2H-pyran^yl)amino]-5-(trifluorometh yl)pyridin-3-yl}methyl^ oxazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that N-cyclopropyl-N-(tetrahydro-2H-pyran-4-yl) -amine was used instead of N- ethyl-N-(tetrahydro-2H-pyran-4-yl)-amine, to afford the title compound (50mg, 45%).

H NMR (400MHz, CDCI ₃ ) 8.53 (s, 1 H), 7.90 (s, 1 H), 7.78 (s, 1 H), 7.75 (s, 2H), 5.73 (d, 1 H), 4.84 (d, 1 H), 4.32 (d, 1h), 4.04 (m, 2H), 3.91 (m, 1 H), 3.6 (m, 3H), 2.83 (m, 1 H), 2.13 (m, 2h), 1.89 (m, 2H), 1.78 (m 2H), 0.82 (m, 3H), 0.65 (d, 3H).

[EXAMPLE 11] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (cyclobutylj(tetrahydro-2H-pyran^yl)amino]-5-(trifluoro)meth ylpyridin-3-y^ oxazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that N-cyclobutyl-N-(tetrahydro-2H-pyran-4-yl)-amine was used instead of N-ethyl- N-(tetrahydro-2H-pyran-4-yl)-amine, to afford the title compound (22mg, 70%). ¹ H NMR (400MHz, CDCI ₃ ) 8.57 (s, 1 H), 7.89 (s, 1 H), 7.83 (s, 1 H), 7.76 (s, 2H), 5.74 (d, J = 8.0Hz, 1 H), 4.75 (d, J = 16.4Hz, 1 H), 4.50 (d, J = 16.4Hz, 1 H), 4.13 (m, 1 H), 3.97 (m, 3H), 3.34 (m, 2H), 3.08 (m, 1 H), 2.15 (m, 2H), 1.81-1.40 (m, 8H), 0.73 (d, 3H). [EXAMPLE 12] t-butyl [3-({(4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-

2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl)pyridin- 2-yl]-(tetrahydro-2H^yran-4- yl)-carbamate

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-[( tetrahydro- 2H-pyran-4-yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl) -oxazolidin-2-one (30mg, 0.09mmol), obtained in Example 5, in THF (0.5ml) was added with drops of NaHMDS (0.13ml) at -10°C, and stirred for 10 min. Then, the solution was added with (BOC) ₂ O (di-t- butyl dicarbonate) (29mg, 0.131 mmol), and stirred for 4 hrs. The reaction was terminated with water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound 13.3mg (23%).

¹ H NMR (400MHz, CDCI3) 8.46 (s, 1 H), 7.75 (s, 3H), 7.51 (s, 1 H), 5.87 (d, J = 6.0Hz, 1 H), 4.76 (m, 1 H), 4.62 (m, 1 H), 4.26 (q, 2H), 4.09 (m, 2H), 3.51 (m, 2H), 2.88 (m, 2H), 1.32-1.23 (m, 14H). [EXAMPLE 13] Ethyl [3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- 2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl]pyridin-2-y l]-(tetrahydro-2H-pyran-4- yl)-carbamate

The same procedure as in Example 12 was repeated, with the exception that diethyl pyrocarbonation was used instead of (BOC^O, to afford the title compound (11.2mg, 20%).

¹ H NMR (400MHz, CDCI ₃ ) 8.46 (s, H), 7.76 (s, 3H), 7.50 (s, 1 H), 5.95 (d, J = 6.0Hz, 1 H), 4.78 (m, 1 H), 4.62 (m, 1 H), 4.25 (m, 8H), 3.51 (m, 2H), 2.87 (m, 2H), 1.31 (m, 6H).

[EXAMPLE 14] (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- ethyl(tetrahydro-2H-pyran-4-yl)amino]-pyridin-3-yl}methyl)-o xazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that 2-chloro-pyridine carbaldehyde was used instead of 2-chloro-5- trifluoromethylpyridine carbaldehyde, to afford the title compound (15mg, 9%). ¹ H NMR (400MHz, CDCI ₃ ) 8.32 (dd, J = 4.8, 1.6Hz, 1 H), 7.87 (s, 1 H), 7.73 (s, 2H), 7.67 (d, J = 7.8Hz, 1 H), 7.05 (dd, J = 7.2, 4.8Hz, 1 H), 5.69 (d, J = 8.0Hz, 1 H), 4.73 (d, J = 16.4Hz, 1 H), 4.42 (d, J = 16.4Hz, 1 H), 3.94 (m, 3H), 3.37 (m, 3H), 3.13 (m, 2H), 1.75 (m, 2H), 1.64 (m, 2H), 0.90 (t, 3H), 0.65 (d, 3H).

[EXAMPLE 15] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- ethyl(tetrahydro-2H-pyran-3-yl)amino]-5-(trifluoromethyl)pyr idin-3-yl}methyl)- oxazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that N-ethyl-N-(tetrahydro-2H-pyran-3-yl)-amine was used instead of N-ethyl-N- (tetrahydro-2H-pyran-4-yl)-amine, to afford the title compound (70mg, 45%).

¹ H NMR (400MHz, CDCI ₃ ) 8.50 (s, 1 H), 7.87 (s, 1 H), 7.80 (m, 1 H), 7.74 (s, 2H), 5.71 (d, J = 8.4Hz, 1 H), 4.78 (m, 1 H), 4.34 (m, 1 H), 3.94-3.79 (m, 3H), 3.52-3.14 (m, 6H), 1.93-1.59 (m, 4H), 0.93 (m, 3H), 0.64 (m, 3H).

[EXAMPLE 16] (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-3-({2- [ethyl(tetrahydro-2H-pyran^yl)amino]-5-fluoropyridin-3-yl}me thyl)-oxazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that 2-chloro-5-fluoropyridine carbaldehyde was used instead of 2-chloro-5- (trifluoromethyl)pyridine carbaldehyde, to afford the title compound (100mg, 47%).

H NMR (400 MHz, CDCI ₃ ) 8.18 (d, 1 H, J = 3.2 Hz), 7.87 (s, H), 7.74 (s, 2H), 7.43- 7.40 (m, 1 H), 5.72 (d, 1 H, J = 8.0 Hz), 4.70 (d, 1 H, J = 16.4 Hz), 4.63 (d, 1 H, J = 16.4 Hz), 4.01-3.90 (m, 3H), 3.39-3.22 (m, 4H), 3.12-3.04 (m, 2H), 1.74-1.69 (m, 2H), 1.61-1.57 (m, 2H), 0.84 (t, 3H, J = 7.2 Hz), 0.67 (d, 3H, J = 6.4 Hz).

[EXAMPLE 17] t-butyl 2-([3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl)pyri din-2-yl]-(tetrahydro-2H- pyran-4-yl)amino)-acetate

The same procedure as in method 2 of Example 7, with the exception that t-butyl 2- [(tetrahydro-2H-pyran-4-yl)amino]-acetate was used instead of N-ethyl-N-cyclohexylamine, to afford the title compound (70mg, 45%).

¹ H NMR (400MHz, CDCI ₃ ) 8.42 (s, 1 H), 7.85 (s, 1 H), 7.76 (s, 2H), 5.78 (d, J = 7.8Hz, 1 H), 4.98 (d, J = 15.6Hz, 1 H), 4.36 (d, J = 15.6Hz, 1 H), 4.06-3.99 (m, 5H), 3.41 (m, 3H), 1.74 (m, 2H), 1.8 (s, 9H), 0.56 (d, 3H).

[EXAMPLE 18] (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (hydroxyethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(trifluorom ethyl)pyridin-3- yl}methyl)-oxazolidin-2-one

[Step 1 ] 2-{[2-(t-butyldimethylsiloxy)ethyl](tetrahydro-2H-pyran-4-yl )amino}-5- uoromethyhnicotine aldehyde

The same procedure as in step 1 of method 2 of Example 7 was repeated, with the exception that N-[(t-butyldimethylsiloxy)ethyl]-N-(tetrahydro-2H-pyran-4-yl )-amine was used instead of N-ethyl-N-(tetrahydro-2H-pyran-4-yl)-amine, to afford the title compound (110mg, 58%).

¹ H NMR (400MHz, CDCI ₃ ) 9.90 (s, 1 H), 8.50 (s, 1 H), 8.15 (s, 1 H), 4.04 (m, 2H), 3.71 (m, 3H), 3.39 (m, 2H), 2.03 (m, 2H), 1.77 (m, 2H), 0.82 (s, 9H), -0.05 (s, 6H).

[Step 2] Preparation of [2-{[2-(t-butyldimethylsiloxy)ethyl](tetrahydro-2H- pyran^yl)amino}-5-(trifluoromethyl)pyridin-3-yl]methyl methanesulfonate

A solution of 2-{[2-(t-butyldimethylsiloxy)ethyl](tetrahydro-2H-pyran-4-yl )amino}-5- (trifluoromethyl)nicotine aldehyde (50 mg, 0.12 mmol) of step 1 in ethanol (2ml) was added with drops of NaBH ₄ (5.2mg) at 0°C, and stirred at room temperature for 1 hr. The reaction was terminated with a saturated aqueous ammonium solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The concentrate was dissolved in 2 ml of dichloromethane, and added with TEA (14mg, 0.14mmol) and then with drops of MsCI (16mg, 0.14mmol). After stirring at room temperature for 1 hr, the reaction was terminated with water. The reaction mixture was diluted with ethyl acetate and extracted. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was used in a subsequent reaction without further purification. [Step 3] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[2-{[2-(t- butyldimethylsiloxy)ethyl](tetrahydro-2H-pyran^yl)amino}-4-m ethyl-5- (trifluoromethyl)pyridin-3-yl]methyl}-oxazolidin-2-one

[2-{[2-(t-butyldimethylsiloxy)ethyl](tetrahydro-2H-pyran-4-y l)amino}-5- (trifIuorornethyl)pyridin-3-yl]methyl methanesulfonate of step 2 and (4S,5f?)-5-[3,5- bis(trifluoromethyl)phenyl])-4-methyl-oxazolidin-2-one were used in the same manner as in step 4 of Example 3 to afford the title compound (55mg, 63%).

¹ H NMR (400MHz, CDCI ₃ ) 8.46 (s, 1H), 7.88 (s, 1 H), 7.77 (s, 1H), 7.73 (s, 2H), 5.72 (d, J = 8.0Hz, 1H), 4.75 (d, J = 16.0Hz, 1 H), 4.33 (d, J = 16.0Hz, 1H), 4.04-3.87 (m, 3H), 3.67 (m, 1 H), 3.50 (m, 2H), 3.38-3.17 (m, 6H), 1.91-1.72 (m, 4H), 0.78 (s, 9H), 0.61 (d, 3H), -0.03 (d, 3H).

[Step 4] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- ({[2-(hydroxyethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(trifl uoromethyl)pyridm yl}methyl)-oxazolidin-2-one

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[2-{[2-(t- butyldimethylsiloxy)ethyl](tetrahydro-2H-pyran-4-yl)amino}-4 -methyl-5- (trifluoromethyl)pyridin-3-yl]methyl}-oxazolidin-2-one (28mg, 0.038mmol) of step 3 in THF/H ₂ 0 (1/3, 2ml) was dropwide added TFA (22mg, 0.38mmol) at 0°C. This solution was stirred at room temperature for 1 hr, diluated with ethyl acetate, and added with water to terminate the reaction, followed by extraction. The organic layer thus formed was washed with a saturated aqueous sodium carbonate, dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure to obtain the title compound (24mg, 100%).

H NMR (400MHz, CDCI ₃ ) 8.49 (s, 1H), 7.88 (s, 1H), 7.80 (d, J = 1.6Hz, 1H), 7.74 (s, 2H), 5.75 (d, J = 8.0Hz, 1 H), 4.82 (d, J = 16.0Hz, 1 H), 4.31 (d, J = 16.0Hz, 1 H), 4.03 (m, 3H), 3.66-3.46 (m, 4H), 3.39 (m, 2H), 3.13 (m, 1 H), 1.95 (m, 2H), 1.69 (m, 2H), 0.68 (d, 3H).

[EXAMPLE 19] (4S,5R)-5-[3 ₎ 5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (oxepan^yl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl)-ox azolidin-2-one

The same procedure as in step 4 of Example 1 was repeated, with the exception that oxepane-4-amine was used instead of tetrahydrofuran-3-amine, to afford the title compound (26mg, 68%).

¹ H NMR (400MHz, CDCI ₃ ) 8.37 (s, 1 H), 8.03 (s, 1 H), 7.79 (s, 2H), 7.36 (s, 1 H), 6.13 (dd, 1 H), 5.73 (dd, 1 H), 4.70 (dd, 1 H), 4.09 (m, 3H), 3.86 (m, 4H), 2.04 (m, 2H), 1.89 (m, 2H), 1.60 (m, 2H), 0.99 (d, 3H).

[EXAMPLE 20] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (methyl)(oxepen-^yl)amino]-5-(trifluorom

The same procedure as in step 5 of Example 1 , with the exception that (4S,5R)-5- [3,5-bis(trifluoromethyl)phenylH^

3- yl}methyl)-oxazolidin-2-one was used instead of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-

4- methyl-3-[(2-(tetrahydrofuran-3-yl)amino-5-(trifIuoromethyl) pyridin-3-yl)methyl]-oxazolid 2-one, to afford the title compound (3.4mg, 28%).

H NMR (400MHz, CDCI ₃ ) 8.45 (s, 1 H), 7.89 (s, 1 H), 7.75 (s, 2H), 7.72 (m, 1 H), 5.71 (dd, 1 H), 4.84 (dd, 1 H), 4.26 (dd, 1 H), 3.83 (m, 3H), 3.66 (m, 2H), 2.83 (s, 3H), 2.07 (m, 4H), 1.84 (m, 2H), 1.02 (d, 3H).

[EXAMPLE 21] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(1,4-dioxaspiro[4.5]decan-8-yl)amino]-54ri^

oxazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that N-ethyl-N-(1 ,4-dioxaspiro[4.5]decan-8-yl)-amine was used instead of N-ethyl- N-(tetrahydro-2H-pyran-4-yl)amine, to afford the title compound (1.39g, 80%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.49 (s, 1 H), 7.87 (s, 1 H), 7.77 (s, 1 H), 7.73 (s, 2 H), 5.70 (d, 1 H, J = 8.0 Hz), 4.71 (d, 1 H, J = 15.6 Hz), 4.29 (d, 1 H, J = 15.6 Hz), 3.92 (s, 5 H), 3.49 (m, 1 H), 3.18 (m, 1 H), 3.03 (m, 1 H), 1.43-2.00 (m, 8 H), 0.90 (m, 3 H), 0.60 (m, 3 H). [EXAMPLE 22] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(4-oxocyclohexyl)amino]-5-(trifluoromethyl)pyridin-3- yl}methyl)-oxazolidin-2- one

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(1 ,4-dioxaspiro[4.5]decan-8-yl)amino]-5-trifluoromethylpyridin -3-yl}m

2-one (820mg, 1.25mmol) of Example 21 in 1 ,4-dioxene (6ml) was added with drops of 2N HCI (3 ml), refluxed at 70°C for 4 hrs with stirring, and cooled to room temperature, followed by extraction with ethyl acetate and water. The organic layer was dried, filtered, and concentrated. The residue was purified by chromatography to afford the title compound (650mg, 85%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.55 (s, 1 H), 7.90 (s, 1 H), 7.82 (s, 1 H), 7.76 (s, 2 H), 5.74 (d, 1 H, J = 8.0 Hz), 4.80 (d, 1 H, J = 16.0 Hz), 4.37 (d, 1 H, J = 16.0 Hz), 3.93 (m, 1 H), 3.62 (m, 1 H), 3.45 (m, 1 H), 3.19 (m, 1 H), 2.29-2.50 (m, 4 H), 1.90-2.21 (m, 4 H), 0.97 (m, 3 H), 0.62 (m, 3 H)

[EXAMPLE 23] (4S,5R)-5-[3,5-bis(trifluoromethyl)phe^

(ethyl)(4-ethylaminocyclohexyl)amino^

oxazolidin-2-one

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-( ethyl)(4- oxocyclohexyl)amino]-5-(trifluoromethyl)pyridin-3-yl}methyl) -oxazolid (160mg, 0.26mmol) of Example 22 in dichloromethane (10 ml) were added ethylamine hydrochloride (32mg, 0.392mmol) and NaBH(OAc) ₃ (110mg, 0.52mmol), followed by stirring at room temperature for 24 hrs. The reaction was terminated with water before extraction with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was re-crystallized in n-hexane to afford the title compound (100mg, 52%).

¹ H NMR (400MHz, CDCI ₃ ) 8.48 (s, 1 H), 7.87 (s, 1 H), 7.77 (s, 1 H), 7.73 (s, 2H), 5.70 (m, 1 H), 4.73 (m, 1 H), 4.33 (m, 1 H), 3.87 (m, 1 H), 3.50 (m, 1 H), 3.14 (m, 1 H),2.93 (m, 1 H), 2.66 (m, 2H), 2.42 (m, 1 H), 2.03 (m, 4H), 1.84-1.23 (m, 4H), 1.23 (m, 3H), 0.93 (m, 3H), 0.62 (d, 3H).

[EXAMPLE 24] methyl 2-(4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl)pyri din-2- yl](ethyl)amino}cyclohexyl)acetate

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(4-oxocyclohexyl)amino]-5-(trifluoromethyl)pyridin-3- yl}methyl)-oxazolidin-2-one (86mg, 14.0mmol) of Example 22 in THF (1ml) was added with (carmethoxymethylene)triphenylphosphorane (73mg, 0.21 mmol), and stirred at room temperature for 3 days. The reaction was terminated with water, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography and dissolved in methanol (1 ml). This solution was added with 10% Pd/C and provided with hydrogen gas from a hydrogen balloon. Stirring at room temperature for 6 hrs were followed by filtration through Celite pad. The filtrate was concentrated to afford the title compound (20mg, 30%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.50 (s, 1 H), 7.90 (s, 1 H), 7.70-7.89 (m, 3 H), 5.73 (m, 1 H), 4.72 (m, 1 H), 4.30 (m, 1 H), 4.04-4.20 (m, 4 H), 3.89 (m, 1 H), 3.42-3.61 (m, 2 H), 3.16 (m, 2 H), 2.87 (m, 1 H), 2.17 (m, 1 H), 1.40-1.90 (m, 6 H), 1.22 (m, 3 H), 0.96 (m, 3 H), 0.62 (m, 3 H)

[EXAMPLE 25] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-thiopyran-^yl)amino]-5-(trifluoromethy l)pyridin-3-yl}methyl) oxazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that N-(tetrahydro-2H-thiopyran-4-yl)-amine was used instead of N-ethyl-N- (tetrahydro-2H-pyran-4-yl)amine of step 1 to afford the title compound (450mg, 58%).

¹ H NMR (400MHz, CDCI3) 8.48 (s, 1 H), 7.87 (s, 1 H), 7.77 (s, 1 H), 7.73 (s, 2H), 4.69 (d, 1 H), 4.24 (d, 1 H), 3.88-3.48 (m, 1 H), 3.57-3.52 (m, 1 H), 3.20-3.15 (m, 1 H), 2.86- 2.83 (m, 1 H), 2.73-2.59 (m, 4H), 2.05-1.89 (m, 4H), 0.92-0.86 (m, 3H), 0.60 (d, 3H).

[EXAMPLE 26] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(1-oxidotetrahydro-2H4hiopyran-4-yl)am

yl}methyl)-oxazolidin-2-one

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-thiopyran-4-yl)amino]-5-(trifluorometh yl)pyridin-3-yl}methyl)-oxazoli 2-one (100mg, 0.16mmol) of Example 25 in dichloromethane (20 ml) was added H ₂ 0 ₂ (54mg, 0.48mmol) at 0°C. Stirring at room temperature for 4 days were followed by extraction with dichloromethane. The extract was purified by chromatography to afford the title compound (80mg, 78%).

H NMR (400MHz, CDCI ₃ ) 8.52 (s, 1 H), 7.88 (s, 1 H), 7.74 (s, 3H), 5.73 (d, 1 H), 4.76-4.70 (m, 1 H), 4.30-4.24 (m, 1 H), 3.93-3.92 (m, 1 H), 3.37-3.04 (m, 4H), 2.74-2.36 (m, 4H), 2.22-1.87 (m, 3H), 0.86 (d, 3H), 0.66-0.62 (m, 3H).

[EXAMPLE 27] t-butyl 4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl)pyri din-2- yl](ethyl)amino}piperidine-1-carboxylate

The same procedure as in method 2 of Example 7 was repeated, with the exception that t-butyl 4-(ethylamino)piperidine-1 -carboxylate was used instead of N-ethyl-N- (tetrahydro-2H-pyran-4-yl)amine, to afford the title compound (80mg, 46%).

H NMR (400MHz, CDCI ₃ ) 8.50 (s, 1 H), 7.88 (s, H), 7.79 (d, J = 2.0Hz, 1 H), 7.73 (s, 2H), 5.71 (d, J = 8.0Hz, 1 H), 4.74 (d, J = 16.0Hz, 1 H), 4.32 (d, J = 16.0Hz, H), 4. 3 (m, 2H), 3.90 (m, 1 H), 3.47 (m, 1 H), 3.17 (m, 2H), 2.71 (m, 2H), 1.76 (m, 4H), 1.43 (s, 9H), 0.93 (t, 3H), 0.63 (d, 3H).

[EXAMPLE 28] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[2-

(ethyl)(piperidin-4-yl)amino]-5-(trifluoromethyl)pyridin- 3-yl}methyl)-4- methyloxazolidin-2-one

To a solution of t-butyl 4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phe methyl-2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl)pyri din-2-yl]

carboxylate of Example 27 in dichioromethane (0.75ml) was dropwise added TFA (trifluoroacetic acid) (0.25ml, 0.36mmol). The reactiom mixture was stirred at room temperature for 2 hrs, diluted with dichioromethane, and added with water to terminate the reaction. An organic layer obtained by extraction was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure to afford the title compound (48mg, 82%).

1H NMR (400MHz, CDCI ₃ ) 8.49 (s, 1 H), 7.88 (s, 1 H), 7.78 (s, 1 H), 7.73 (s, 2H),

5.71 (d, J = 8.0Hz, 1 H), 4.74 (d, J = 16.0Hz, H), 4.32 (d, J = 16.0Hz, 1 H), 3.87 (m, 1 H), 3.54 (m, 1 H), 3.20 (m, 4H), 2.62 (m, 2H), 1.78 (m, 4H), 0.94 (t, 3H), 0.62 (d, 3H).

[EXAMPLE 29] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-met

(ethyl)(1-methylpiperidin-4-yl)amino]^

oxazolidin-2-one

To a solution of (4S,5R)-5-[3,5-l bis(trifluoromethyl)phenyl]-3-({[2-

(ethyl)(piperidin-4-yl)amino]-5-(trifluoromethyl)pyridin- 3-yl}methyl^

(35mg, 0.058mmol) of Example 28 in THF (0.5ml) were added TEA (8.8mg, 0.09mmol) and methyl iodide (12.4mg, 0.09mmol). The reaction mixture was stirred at room temperature for 2 hrs and extracted with ethyl acetate and water. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure, followed by chromatographic purification to afford the title compound (7 mg, 2%).

¹ H NMR (400MHz, CDCI ₃ ) 8.50 (s, 1 H), 7.87 (s, 1 H), 7.79 (s, 1 H), 7.74 (s, 2H), 5.73 (d, J = 8.4Hz, 1 H), 4.72 (d, J = 15.6Hz, 1 H), 4.32 (d, J = 15.6Hz, 1 H), 3.91 (m, 1 H), 3.47 (m, 1 H), 3.47 (m, 1 H), 3.21-3.00 (m, 4H), 2.34 (bs, 3H), 2.02-1.65 (m, 6H), 0.92 (t, 3H), 0.63 (d, 3H).

[EXAMPLE 30] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(1 ,1-dimethylpiperidin-4-yl)amino]-5-(trifluoromethyl)pyridin- 3-yl}methyl)- oxazolidin-2-one

The title compound was prepared in the same manner as in Example 29 and purified by chromatography (20mg, 57%).

¹ H NMR (400MHz, CDCI ₃ ) 8.49 (s, 1 H), 7.87 (s, 1 H), 7.79 (s, 2H), 7.77 (s, 2H), 5.90 (d, J = 8.0Hz, 1 H), 4.81 (d, J = 16.4Hz, 1 H), 4.44 (d, J = 16.4Hz, 1 H), 4.28 (m, 1 H), 4.02-3.71 (m, 5H), 3.46 (s, 3H), 3.37 (s, 3H), 3.26 (m, 2H), 2.44 (m, 2H), 2.17 (m, 2H), 1.03 (t, 3H), 0.53 (d, 3H).

[EXAMPLE 31] ((4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(1-propylpiperidin-4-yl)amino]-5-tri^

2-one

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[2- (ethyl)(piperidin-4-yl)amino]-5-(trifluoromethyl)pyridin-3-y l}methyl)-4-m

(70mg, 0.12mol) of Example 28 in dichloromethane (2ml) were added propionaldehyde (14mg, 0.234mmol) and NaBH(OAc) ₃ (50mg, 0.234mmol). Stirring at room temperature for 4 hrs was followed by adding water to terminate the reaction. Then, extraction was performed with dichloromethane. The organic layer thus formed was dried, and concentrated in a vacuum. The residue was purified by chromatography to afford the title compound (22mg, 29%).

¹ H NMR (400MHz, CDCI ₃ ) 8.49 (s, 1 H), 7.87 (s, 1 H), 7.77 (s, 1 H), 7.74 (s, 2H), 5.71 (d, 1 H), 4.70 (d, 1 H), 4.29 (d, H), 4.15-4.12 (m, 1 H), 3.90-3.84 (m, 1 H), 3.52-3.44 (m, 1 H), 3.22-3.14 (m, 1 H), 3.04-2.86 (m, 4H), 2.32-2.22 (m, 2H), 1.78-1.47 (m, 5H), 0.97-0.79 (m, 6H), 0.68(d, 3H).

[EXAMPLE 32] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(1-methanesulfonylpiperidin^-yl)amino]-5-trifluoromet hylpyridin-3-yl}methyl)- oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[2-(ethyl)(pi peridin-4-yl)am

(trifluoromethyl)pyridin-3-yl}methyl)-4-methyloxazolidin- 2-one of Example 28, and MsCI were used in the same manner as in step 2 of Example 18 to afford the title compound (20mg, 35%).

H NMR (400MHz, CDCI3) 8.53 (s, 1 H), 7.91 (s, 1 H), 7.80 (s, 1 H), 7.76 (s, 2H), 5.74 (d, 1 H, J = 8.0 Hz), 4.73 (d, 1 H, J = 16.0 Hz), 4.31 (d, 1 H, J = 16.0 Hz), 3.95-3.83 (m, 3H), 3.49-3.44 (m, 1 H), 3.21-3.16 (m, 2H), 2.79 (s, 3H), 2.76-2.60 (m, 2H), 1.95-1.78 (m, 4H), 0.94 (t, 3H, J = 6.8 Hz), 0.64 (d, 3H, J = 6.8 Hz).

[EXAMPLE 33] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(1-acetylpiperidin^yl)amino]-5-(tri^

oxazolidin-2-one

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[2-(ethyl)(pi peridin-4- yl)amino]-5-(trifluoromethyl)pyridin-3-yl}m (50mg, 0.084mmol) of Example 28 in dichloromethane (0.5ml) was added with TEA (13mg, 0.126mmol) and then with drops of acetyl chloride (7.9mg, O.IOmmol). The reaction mixture was stirred at room temperature for 30 min, and quenched with water, followed by extraction with dichloromethane. The organic layer thus formed was washed with a saturated aqueous sodium carbonate solution, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in a vacuum to afford the title compound (46mg, 86%).

¹ H NMR (400MHz, CDCI ₃ ) 8.51 (s, 1 H), 7.88 (s, 1 H), 7.78 (s, 1 H), 7.73 (s, 2H), 5.72 (d, J = 8.0Hz, 1 H), 4.86 (m, 2H), 4.34 (m, 1 H), 3.91 (m, 3H), 3.45-2.97 (m, 4H), 2.53 (m, 2H), 2.07 (s, 3H), 1.85-1.60 (m, 2H), 0.91 (m, 3H), 0.60 (bs, 3H).

[EXAMPLE 34] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(1-propionylpiperidin^yl)amino]-5-(trifluoromethyl)py ridin-3-yl}meth^ oxazolidin-2-one

The same procedure as in Example 33 was repeated, with the exception that propionyl chloride was used instead of acetyl chloride to afford the title compound (48mg, 90%). ¹ H NMR (400MHz, CDCI ₃ ) 8.51 (s, 1 H), 7.88 (s, 1 H), 7.78 (s, 1 H), 7.74 (s, 2H), 5.72 (d, J = 8.0Hz, 1 H), 4.72 (m, 2H), 4.30 (m, 1 H), 3.91 (m, 2H), 3.46-2.90 (m, 4H), 2.55 (m, 2H), 2.36 (m, 2H), 1.85 (m, 4H), 1.18 (m, 3H), 0.96 (m, 3H), 0.55 (m, 3H).

[EXAMPLE 35] methyl 4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl)pyri din-2- yl](ethyl)amino}piperidine-1-carboxylate

The same procedure as in Example 33, with the exception that methyl chloroformate was used instead of acetyl chloride, to afford the title compound (480mg, 65%).

¹ H NMR (400MHz, CDCI ₃ ) 8.52 (s, 1 Η), 7.90 (s, 1 H), 7.81 (d, J = 2.0Hz, 1 Η), 7.53 (s, 2Η), 5.74 (d, J = 16.0Hz, 1 H), 4.34 (d, J = 16.0Hz, 1 Η), 3.92 (m, 1 H), 3.69 (s, 3Η), 3.4 (m, 1 H), 3.19 (m, 2H), 2.79 (m, 2H), 1.80 (m, 4H), 0.94 (t, 3H), 0.64 (d, 3H).

[EXAMPLE 36] ethyl 4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolldin-3-yl}methyl)-5-(trifluoromethyl)pyri din-2- yl](ethyl)amino}piperidine-1-carboxylate

The same procedure as in Example 33 was repeated, with the exception that ethyl chloroformate was used instead of acetyl chloride, to afford the title compound (20mg, 36%).

H NMR (400 MHz, CDCI ₃ ) 8.50 (s, 1 H), 7.88 (s, 1 H), 7.78 (s, 1 H), 7.73 (s, 2H), 5.70 (d, 1 H, J = 8.0 Hz), 4.71 (d, 1 H, J = 16.0 Hz), 4.29 (d, 1 H, J = 16.0 Hz), 4.18-4.08 (m, 4H), 3.90-3.86 (m, 1 H), 3.48-3.39 (m, 1 H), 3.16-3.11 (m, 2H), 2.80-2.60 (m, 2H), 1.84-1.68 (m, 2H), 1.68-1.56 (m, 2H), 1.25-1.22 (m, 3H), 0.90 (t, 3H, J = 10.8 Hz), 0.61 (d, 3H, J = 6.4 Hz).

[EXAMPLE 37] methyl 4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl)pyri din-2-yl](ethyl)amino}- N,N-dimethylpiperidine-1-carboxamide

The same procedure as in Example 33, with the exception that dimethylcarbamic chloride was used instead of acetyl chloride, to afford the title compound (40mg, 71 %).

H NMR (400MHz, CDCI ₃ ) 8.52 (s, 1 H), 7.90 (s, 1 H), 7.80 (s, 1 H), 7.76 (s, 2H), 5.73 (d, 1 H), 4.74 (d, 1 H), 4.38 (d, 1 H), 3.92-3.89 (m, 1 H), 3.77-3.68 (m, 2H), 3.52-3.43 (m, 1 H), 3.20-3.15 (m, 2H), 2.78-2.66 (m, 4H), 2.81 (s, 6H), 1.81-1.66 (m, 4H), 0.94-0.91 (m, 3H), 0.64 (d, 3H).

[EXAMPLE 38] methyl 2-(4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl)pyri dln-2- yl](ethyl)amino}piperidin-1-yl)acetate

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[2- (ethyl)(piperidin-4-yl)amino]-5-(trifluorom

(100mg, 0.167mmol) of Example 29 in DMF (1ml) were dropwise added K ₂ C0 ₃ (46mg, 0.334mmol) and methyl bromoacetate (26mg, 0.167mmol). Stirring at room temperature for 6 hrs was followed by extraction with ethyl acetate and water. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (53mg, 47%).

H NMR (400MHz, CDCI ₃ ) 8.51 (s, 1 H), 7.89 (s, 1 H), 7.79 (s, 1 H), 7.75 (s, 2H),

5.72 (d, H, J = 8.0 Hz), 4.72 (d, H, J = 15.6 Hz), 4.31 (d, 1 H, J = 15.6 Hz), 4.13-4.11 (m, 1 H), 3.91-3.87 (m, 1 H), 3.72 (s, 2H), 3.53-3.47 (m, 1 H), 3.22-3.17 (m, 2H), 3.02-2.94 (m, 4H), 2.24-1.78 (m, 5H), 0.92 (t, 3H, J = 7.2 Hz), 0.62 (d, 3H, J = 6.8 Hz).

[EXAMPLE 39] 2-(4-{[3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-meth yl-2- oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl)pyridin-2-yl] (ethyl)amino}piperidm yl)acetic acid

To a solution of methyl 2-(4-{[3-({(4S,5R)-5-[3,5-l bis(trifluoromethyl)phenyl]-

4-methyl-2-oxo-oxazolidin-3-yl}methyl)-5-(trifluoromethyl )pyridin-2-yl](ethyl)amino}pipericlin- 1-yl)acetate (25mg, 0.037mmol) of Example 38 in THF/H ₂ O (2/1 , 0.75ml) was added LiOH (1.79mg, 0.07mmol). The reaction mixture was stirred at room temperature for 6 hrs, and neutralized with 2 N HCI, followed by extraction with ethyl acetate. The organic layer was dried, and concentrated in a vacuum. The residue was purified by chromatography to afford the title compound (10mg, 40%).

H NMR (400MHz, CDCI ₃ ) 8.51 (s, 1 H), 7.89 (s, 1 H), 7.79 (s, 1 H), 7.75 (s, 2H), 5.72 (d, 1 H, J = 8.0 Hz), 4.72 (d, 1 H, J = 15.6 Hz), 4.31 (d, 1 H, J = 15.6 Hz), 4.13-4.11 (m, 1 H), 3.91-3.87 (m, 1 H), 3.72 (s, 2H), 3.53-3.47 (m, 1 H), 3.22-3.17 (m, 2H), 3.02-2.94 (m, 4H), 2.24-1.78 (m, 5H), 0.92 (t, 3H, J = 7.2 Hz), 0.62 (d, 3H, J = 6.8 Hz).

[EXAMPLE 40] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-^yl)amino]-5^romopyridin-3-yl}me thyl)-oxazolidin-2- one

The same procedure as in method 2 of Example 7 was repeated, with the exception that 2-chloro-5-bromo-pyridine carbaldehyde, instead of 2-chloro-5- (trifluoromethyl)pyridine 3-carbaldehyde, was reacted with N-ethyl-N-(tetrahydro-2H-pyran- 4-yl)-amine, to afford the title compound (3.5g, 68%).

1H NMR (400MHz, CDCI ₃ ) 8.53 (s, 1 H), 7.90 (s, 1 H), 7.81-7.77 (m, 3H), 5.74 (d,

1 H), 4.71 (d, 1 H), 4.35 (d, 1 H), 4.14-4.09 (m, 1 H), 4.02-3.94 (m, 3H), 3.41-3.28 (m, 3H), 3.12-3.06 (m, 2H), 1.81-1.62 (m, 3H), 0.90-0.87 (m, 3H), 0.68 (d, 3H).

[EXAMPLE 41] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(pyrrolidin-1-yl)p yridin-3-yl}met^

oxazolidin-2-one

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-bromopyridin-3-yl} methyl)-oxazolidin-2-one

(100mg, 0.16mmol) of Example 40 in toluene (4 ml) were added pyrrolidine (60ul, 0.64mmol), BINAP (20mg, 0.032mmol), NatOBu (22mg, 0.22mmol), and Pd ₂ (dba) ₃ (219.8, 0.24mmol). The reaction mixture was purged with nitrogen, stirred at 100°C for 3 hrs and cooled to room temperature. Filtration through a Celite-pad filter was followed by extraction with dichloromethane. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (60mg, 60%).

¹ H NMR (400MHz, CDCI ₃ ) 7.89 (s, 1 H), 7.79-7.77 (m, 3H), 6.82 (d, 1 H), 5.68 (d, 1 H), 4.52 (d, 1 H), 4.01-3.91 (m, 3H), 3.35-3.18 (m, 6H), 3.05-3.02 (m, 2H), 2.04-2.02 (m, 3H), 1.69-1.50 (m, 6H), 0.87-0.80 (m, 3H), 0.73 (d, 3H).

[EXAMPLE 42] methyl 2-(4-{5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolidin-3-yl}methyl)-6-[ethyl(tetrahydro-2H- pyran-4- yl)amino]pyridin-3-yl}piperazin-1-yl)acetate

[Step 1] Preparation of t-butyl 4-[5-({(4S,5R)-5-[3,5- bis(trifluoromethyl)phenyl]-4-methyl-2-oxooxazolidin-3-yl}me thyl)-6-[ethyl(tetrah 2H-pyran-4-yl)amino]pyridin-3-yl]piperazine-1-carboxylate

The same procedure as in Example 41 was repeated, with the exception that 1-t- Boc-piperazine was used instead of pyrrolidine, to afford the title compound (60mg, 54%).

¹ H NMR (400MHz, CDCI ₃ ) 8.04 (s, 1 H), 7.89 (s, 1 H), 7.76 (s, 3H), 5.70 (d, 1 H), 4.67 (d, 1 H), 4.47 (d, 1H), 4.00-3.95 (m, 2H), 3.65-3.58 (m, 4H), 3.37-3.29 (m, 4H), 3.18- 3.12 (m, 6H), 1.75-1.37 (m, 12H), 1.49 (s, 9H), 0.89 (m, 3H), 0.72 (d, 3H).

[Step 2] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-

[ethyl(tetrahydro-2H-pyran-4-yl)amino]-5-(piperazin-1-yl) pyridin-3-yl}methy^ oxazolidin-2-one

A solution of t-butyl 4-[5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)ph

oxooxazolidin-3-yl}methyl)-6-[ethyl(tetrahydro-2H-pyran-4 -yl)amino]pyridin-3-yl]piperazin carboxylate (60mg, 0.08mmol) of step 1 in dichloromethane was used in the same manner as in Example 33 to afford the title compound (52mg, 100%).

¹ H NMR (400MHz, CDCI3) 8.48 (s, 1 H), 7.87 (s, 1 H), 7.77 (s, 1 H), 7.73 (s, 2H), 4.69 (d, 1 H), 4.24 (d, H), 3.88-3.48 (m, 1 H), 3.57-3.52 (m, 1 H), 3.20-3.15 (m, 1H), 2.86- 2.83 (m, 1H), 2.73-2.59 (m, 4H), 2.05-1.89 (m, 4H), 0.92-0.86 (m, 3H), 0.60 (d, 3H).

[Step 3] Preparation of methyl 2-(4-{5-({(4S,5R)-i bis(trifluoromethyl)phenyl]^methyl-2-oxo-oxazolidin-3-yl}met hyl)-6- [ethyl(tetrahydro-2H^yran^-yl)amino]pyridin-3-yl}piperazin-1 -yl)acetate

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({2-[e thyl(tetrahyd

2H-pyran-4-yl)amino]-5-(piperazin-1-yl)pyridin-3-yl}methy l)-oxazolidin-2-one of step 2 and methyl bromoacetate were used in the same manner as in Example 43 to afford the title compound (29mg, 50%).

H NMR (400MHz, CDCI3) 8.04 (s, 1 H), 7.89 (s, H), 7.76 (s, 2H), 7.23 (s, 1 H), 5.69 (d, 1 H), 4.69 (d, 1 H), 4.46 (d, 1 H), 3.99-3.61 (m, 2H), 3.81 (s, 3H), 3.37-3.24 (m, 6H), 2.77 (m, 4H), .71 -1.62 (m, 13 H), 0.86 (s, 3H), 0.72 (d, 3H).

[EXAMPLE 43] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(azetidin-1-yl)pyr idin-3-yl}meth

oxazolidin-2-one

The same procedure as in Example 41 was repeated, with the exception that azetidine was used instead of pyrrolidine, to afford the title compound (18mg, 8%).

¹ H NMR (400 MHz, CDCI ₃ ) 7.89 (s, 1 H), 7.76 (s, 2 H), 7.64 (s, 1 H), 6.73 (s, 1 H), 5.68 (d, 1 H, J = 8.0 Hz), 4.67 (d, 1 H, J = 16.0 Hz), 4.49 (d, 1 H, J = 16.0 Hz), 3.80-4.05 (m, 6 H), 3.33 (m, 2 H), 3.22 (m, 1 H), 3.03 (m, 2 H), 2.41 (m, 2 H), 1.48-1.72 (m, 5 H), 0.84 (m, 3 H), 0.67 (m, 3 H).

[EXAMPLE 44] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(piperidin-1-yl)py ridin-3-yl}met^

oxazolidin-2-one

The same procedure as in Example 41 was repeated, with the exception that piperidine was used instead of pyrrolidine, to afford the title compound (19mg, 13%).

H NMR (400 MHz, CDCI ₃ ) 8.04 (s, 1 H), 7.87 (s, 1 H), 7.74 (s, 2 H), 7.20 (s, 1 H), 5.67 (d, 1 H, J = 8.0 Hz), 4.66 (d, 1 H, J = 15.2 Hz), 4.45 (d, 1 H, J = 15.6 Hz), 3.83-4.00 (m, 3 H), 2.93-3.38 (m, 9 H), 1.48-1.78 (m, 10 H), 0.84 (t, 3 H, J = 6.8 Hz), 0.69 (d, 3 H, J = 6.4 Hz).

[EXAMPLE 45] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5^henylpyridin-3-yl} methyl)-oxazolidin-2- one

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-bromopyridin-3-yl} methyl)-oxazolidi

(100mg, 0.16mmol) of Example 40 in H ₂ 0/1 ,4-dioxane (1/2, 3ml) were added Na ₂ CO ₃ (52.15mg, 0.49mol), phenylboronic acid (30mg, 0.25mol) and Pd(PPh ₃ ) ₄ (19mg, 0.02mmol). The reaction mixture was stirred at 40°C for 24 hrs and then cooled to room temperature, followed by extraction with ethyl acetate. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (70mg, 70%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.57 (s, 1 H), 7.86 (d, 2 H, J = 1.6 Hz), 7.75 (s, 2 H), 7.56-7.57 (m, 2 H), 7.49 (t, 2 H, J = 7.6 Hz), 7.41 (s, 1 H), 5.69 (d, 1 H, J = 8.0 Hz), 4.82 (d, 1 H, J = 15.6 Hz), 4.45 (d, 1 H, J = 5.6 Hz), 4.03 (m, 1 H), 3.94 (m, 2 H), 3.42 (m, 2 H), 3.32 (m, 1 H), 3.15 (m, 2 H), 1.81 (m, 2 H), 1.69 (m, 2 H), 0.95 (m, 3 H), 0.69 (m, 3 H).

[EXAMPLE 46] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(3-methylphenyl)py ridin-3-yl}methyl)- oxazolidin-2-one

The same procedure as in Example 45 was repeated, with the exception that 2- methyltoluene boronic acid was used instead of phenyl boronic acid, to afford the title compound (80mg, 51 %).

H NMR (400 MHz, CDCI ₃ ) 8.56 (s, 1 H), 7.87 (s, 1 H), 7.83 (s, 1 H), 7.74 (s, 2 H), 7.37 (s, 3 H), 7.23 (s, 1 H), 5.68 (d, 1 H, J = 7.6 Hz), 4.82 (d, 1 H, J = 15.6 Hz), 4.44 (d, 1

H, J = 15.6 Hz), 3.87-4.05 (m, 3 H), 3.24-3.50 (m, 3 H), 3.07-3.23 (m, 2 H), 2.41 (s, 3 H),

I .52-1.90 (m, 4 H), 0.94 (m, 3 H), 0.69 (m, 3 H).

[EXAMPLE 47] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-^yl)amino]-5-(3-fluorophenyl)pyr idin-3-yl}methyl)- oxazolidin-2-one

The same procedure as in Example 45 was repeated, with the exception that 3- fluorophenyl boronic acid wa used instead of phenyl boronic acid, to afford the title compound (79mg, 50%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.52 (s, 1 H), 7.86 (s, 1 H), 7.80 (s, 1 H), 7.73 (s, 3 H), 7.44 (m, 1 H), 7.31 (s, 1 H), 7.08 (m, 1 H), 5.68 (d, 1 H, J = 7.6 Hz), 4.79 (d, 1 H, J = 15.6 Hz), 4.41 (d, 1 H, J = 15.2 Hz), 3.83-4.02 (m, 3 H), 3.22-3.50 (m, 3 H), 3.16 (m, 2 H), 1.60-1.89 (m, 4 H), 0.93 (m, 3 H), 0.68 (m, 3 H). [EXAMPLE 48] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-

(ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(3-ethoxyphenyl )pyridin-3-yl}methy oxazolidin-2-one

The same procedure as in Example 45 was repeated, with the exception that 3- ethoxyphenylboronic acid was used instead of phenyl boronic acid, to afford the title compound (75.9mg, 71 %).

¹ H NMR (400 MHz, CDCI ₃ ) 8.56 (s, 1 H), 7.88 (s, 1 H), 7.83 (s, 1 H), 7.75 (s, 2 H), 7.49 (m, 1 H), 7.03-7.16 (m, 2 H), 6.93 (m, 1 H), 5.69 (d, 1 H, J = 7.2 Hz), 4.82 (d, 1 H, J = 15.6 Hz), 4.43 (d, 1 H, J = 15.6 Hz), 3.86-4.16 (m, 5 H), 3.26-3.50 (m, 3 H), 3.08-3.26 (m, 2 H), 1.40-1.90 (m, 4 H), 1.25 (m, 3 H), 0.91 (m, 3 H), 0.68 (m, 3 H)

[EXAMPLE 49] (4S,5R)-5-[3,5-bis(trifluoromethyl)ph

(ethyl)(tetrahydro-2H^yran-4-yl)amino]-5-(furan-2-yl)pyri din-3-yl}methyl)-oxazolidin 2-one

The same procedure as in Example 45 was repeated, with the exception that 1- furanyl boronic acid was used instead of phenyl boronic acid, to afford the title compound (33.8mg, 34%).

H NMR (400 MHz, CDCI ₃ ) 8.62 (s, 1 H), 7.84-7.92 (m, 2 H), 7.74 (s, 2 H), 7.50 (s, 1 H), 6.66 (d, 1 H, J = 2.8 Hz), 6.49 (s, 1 H), 5.70 (d, 1 H, J = 8.4 Hz), 4.76 (d, 1 H, J = 16.4 Hz), 4.40 (d, 1 H, J = 15.6 Hz), 3.89-4.02 (m, 3 H), 3.24-3.42 (m, 3 H), 3.05-3.21 (m, 2 H), 1.50-1.82 (m, 4 H), 0.90 (m, 3 H), 0.66 (m, 3 H).

[EXAMPLE 50] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H^yran-^yl)amino]-5-(1-methyl-1H^yiTol-2 -yl)pyridin-3- yl}methyl)-oxazolidin-2-one

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-

(ethyl )(tetrahydro-2H-pyran-4-yl)amino]-5-bromopyridin-3-yl}methyl )-oxazolidin-2-one (100mg, 0.16mmol) of Example 40 in toluene (4ml) were dropwise added 1-methyl-2- (tributylstannyl)-l H-pyrrole (90mg, 0.24mmol) and P(PPh ₃ ) ₄ (23mg, 0.02mmol). The reaction mixture was stirred at 100°C for 24 hrs and cooled to room temperature, followed by extraction with ethyl acetate and water. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (33.8mg, 34%).

1H NMR (400 MHz, CDCI ₃ ) 8.41 (s, 1 H), 7.89 (s, 1 H), 7.75 (s, 2 H), 7.68 (s, 1

H), 6.78 (s, 1 H), 6.21-6.29 (m, 2 H), 5.70 (d, 1 H, J = 7.6 Hz), 4.79 (d, 1 H, J = 16.0 Hz), 4.41 (d, 1 H, J = 16.8 Hz), 3.89-4.03 (m, 3 H), 3.70 (s, 3 H), 3.26-3.43 (m, 3 H), 3.07-3.23 (m, 2 H), 1.62-1.86 (m, 4 H), 0.95 (m, 3 H), 0.68 (m, 3 H).

[EXAMPLE 51] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran-4-yl)amino]-5-(3,5-dimethyl-isox azol-4-yl}methyl)- oxazolidin-2-one

The same procedure as in Example 45 was repeated, with the exception that 3,5- dimethyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)isoxazole was used instead of phenyl boronic acid, to afford the title compound (18mg, 17%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.24 (s, 1 H), 7.87 (s, 1 H), 7.67 (s, 2 H), 7.58 (s, 1 H), 5.68 (d, 1 H, J = 8.4 Hz), 4.74 (d, 1 H, J = 15.6 Hz), 4.40 (d, 1 H, J = 15.6 Hz), 3.84-4.03 (m, 3 H), 3.24-3.42 (m, 4 H), 3.14 (m, 1 H), 2.44 (s, 3 H), 2.29 (s, 3 H), 1.49-2.88 (m, 4 H), 0.92 (m, 3 H), 0.67 (m, 3 H). [EXAMPLE 52] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(tetrahydro-2H-pyran^yl)amino]-pyridin-3-yl}methyl)-o xazolidin-2-one

The same procedure as in method 2 of Example 7 was repeated, with the exception that 2-chloronicotine aldehyde was used instead of 2-chloro-5- (trifluoromethyl)pyridine carbaldehyde, to afford the title compound (15mg, 9%).

¹ H NMR (400MHz, CDCI ₃ ) 8.31 (dd, 1 H), 7.88 (s, 1 H), 7.75 (s, 2H), 7.66 (d, 1 H), 7.00 (dd, 1 H), 5.69 (d, 1 H), 4.71 (d, 1 H), 4.39 (d, 1 H), 3.92 (m, 1 H), 3.50 (m, 1 H), 3.11 (m, 1 H), 2.74 (m, 1 H), .86-1.05 (m, 10H), 0.90 (t, 3H), 0.65 (d, 3H).

[EXAMPLE 53] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(trifluorom

The same procedure as in method 2 of Example 7 was repeated, with the exception that N-ethyl-N-cyclohexylamine was used instead of N-ethyl-N-(tetrahydropyran- 4-yl)amine, to afford the title compound (160mg, 32%). ¹ H NMR (400 MHz, CDCI ₃ ) 8.47 (s, 1 H), 7.87 (s, 1 H), 7.76 (s, 2 H), 7.24 (s, 1 H), 5.69 (d, 1 H, J = 8.0 Hz), 4.70 (d, 1 H, J = 15.6 Hz), 4.27 (d, 1 H, J = 15.6 Hz), 3.84 (m, 1 H), 3.55 (m, 1 H), 3.15 (m, 1 H), 2.82 (m, 1 H), 1.38-1.81 (m, 6 H), 1.00-1.36 (m, 4 H), 0.92 (m, 3 H), 0.80 (m, 3 H)

[EXAMPLE 54] 5-({4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo - 1,3-oxazolidin-3-yl}methyl)-6-[(cyclohexyl)(ethyl)amino]nico tinonitri

[Step 1] Preparation of methyl 5-bromo-2-[cyclohexyl(ethyl)amino]nicotinate

To a solution of methyl 2-chloro-5-bromo nicotinate (100g, 399mol) in toluene (400ml, 1 M) was dropwise added N-ethyl-N-cyclohexyl amine (62.2g, 489mol) at room temperature. The reaction mixture was refluxed at 140°C for 6 hrs and futher added with drops of N-ethyl-N-cyclohexyl amine (62.2g, 489mol). Again, the rection mixture was refluxed for 20 hrs, cooled to the room temperature, diluted with ethyl acetate, and then washed with water, ammonium chloride and 2N HCI. Concentration in a vacuum afforded the title compound (130g, 95.5%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.21 (s, 1 H), 7.88 (s, 1 H), 3.86 (s, 3 H), 3.41 (m, 2 H), 3.34 (m, 1 H), 1.78 (m, 2 H), 1.46-1.69 (m, 4 H), 1.18-1.29 (m, 4 H), 1.80 (t, 3 H, J = 6.8 Hz)

[Step 2] Preparation of {5-bromo-2-[cyclohexyl(ethyl)amino]pyridin-3- yl}methanol

A solution of methyl 5-bromo-2-[cyclohexyl(ethyl)amino]nicotinate (226g, 662mol) of step 1 in tetrahydrofuran (700ml, 0.9M) was cooled to 0°C, and slowly added with drops of LAH (25g, 662mol). The reaction mixture was stirred for 30 min, diluted with ethyl acetate, and added with drops of Na ₂ S0 ₄ decahydrate (430g). Stirring at room temperature for 24 hrs was followed by filtration in a vacuum. Concentration at a reduced pressure afforded the title compound (201 g, 97%).

H NMR (400 MHz, CDCI ₃ ) 8.33 (d, 1 H, J = 2.4 Hz), 7.65 (s, 1 H, J = 2.4 Hz), 4.69 (s, 2 H), 3.22 (m, 2 H), 2.92 (m, 1 H), 1.69-1.83 (m, 3 H), 1.62 (m, 1 H), 1.30-1.50 (m, 2 H), .08-1.30 (m, 4 H), 0.92 (t, 3 H, J = 7.2 Hz)

[Step 3] Preparation of 5-bromo-3-(chloromethyl)-N-cyclohexyl-N- ethylpyridine-2-amine

A solution of {5-bromo-2-[cyclohexyl(ethyl)amino]pyridin-3-yl}methanol (46g, 135mol) of step 2 in DMF (300ml) was cooled to 0°C, and slowly added with drops of SOCI ₂ (17.6g, 148mol) with stirring for 1 hr. The reaction solution was diluted with ethyl acetate (200ml) before quenching with water. The organic layer thus formed was dried over anhydrous Na ₂ S0 ₄ , and concentrated in a vacuum to give 5-bromo-3-(chloromethyl)-N- cyclohexyl-N-ethylpyridine-2-amine which was immediately used in a subsequent reaction without further purification.

[Step 4] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- ({5-bromo-2-[cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxa zolidin-2-on

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl-4- methyloxazolidin-2-one (46g, 147mol) in DMF (150ml) was dropwise added NaHMDS (176ml, 176mol) at -40°C. The reaction mixture was stirred for 30 min, and slowly added with drops of a dilution of 5-bromo-3-(chloromethyl)-N-cyclohexyl-N-ethylpyrid ^' ine-2-amine of step 3 in DMF (30ml). The resulting reaction mixture was heated to room temperature, stirred for 3 hrs, and diluted with ethyl acetate (200ml) before quenching with water (500ml). The organic layer was withdrawn, washed with water (1.5L), and filtered through a silica- selite pad in a vacuum to afford the title compound (60g, 67%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.31 (s, 1 H), 7.89 (s, 1 H), 7.76 (s, 2 H), 7.74 (s, 1 H), 5.73 (d, 1 H, J = 8.0 Hz), 4.68 (d, 1 H, J = 16.0 Hz), 4.30 (d, 1 H, J = 16.0 Hz), 3.93 (m, 1 H), 3.44 (m, 1 H), 3.03 (m, 1 H), 2.68 (m, 1 H), 1.44- .86 (m, 5 H), 1.02-1.44 (m, 5 H), 0.86 (t, 3 H, J = 6.8 Hz), 0.66 (d, 3 H, J = 6.4 Hz). [Step 5] Preparation of 5-({4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- 2-oxo-1,3-oxazolidin-3-yl}methyl)-6-[(cyclohexyl)(ethyl)amin o]nicotinonitri

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2-

[cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2 -one (500mg, 0.82mmol) of step 4 in DMF (3ml) was added with CuCN (147mg, 1.64mmol) and Cul (232mg, 1.23mmol), and then refluxed for 24 hrs with stirring. The resulting reaction mixture was cooled to room temperature and extracted with ethyl acetate and water. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (200mg, 44%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.47 (s, 1 H), 7.90 (s, 1 H), 7.79 (s, 1 H), 7.76 (s, 2 H), 5.75 (d, 1 H, J = 8.0 Hz), 4.75 (d, 1 H, J = 15.6 Hz), 4.13 (d, 1 H, J = 16.4 Hz), 3.84 (m, 1 H), 3.62 (m, 1 H), 3.17 (m, 1 H), 2.98 (m, 1 H), 1.72-1.90 (m, 2 H), 1.42-1.71 (m, 4 H), 1.02-1.40 (m, 4 H), 0.96 (t, 3 H, J = 6.4 Hz), 0.63 (d, 3 H, J = 6.0 Hz).

[EXAMPLE 55] 5-{[(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-ox o- oxazolidin-3-yl]methyl}-6-[(cyclohexyl)(ethyl)amino]^yridin- 3-yl methanesulfonate

[Step 1] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl3- ({2-[cyclohexyl(ethyl)amino]-5-hydroxypyridin-3^

solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2-

[cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2 -one (500mg, 0.8mmol) of step 3 of Example 54 in 1 ,4-dioxane/H ₂ 0 (1/1 , 8ml) were added Pd ₂ (dba) ₃ (90mg, 0.08mmol), KOH (135mg, 2.4mmol) and 2-di-i-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopro pyl-1 ,1'- biphenyl (100mg, 0.16mmol). The reaction mixture was refluxed at 100°C for 3 hrs with stirring, and then cooled to room temperature. Extraction was performd with dichloromethane and water. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (200mg, 45%).

H NMR (400 MHz, CDCI ₃ ) . 8.03 (d, 1H), 7.87 (s, 1 H), 7.72 (s, 2H), 7.25 (m, 1 H), 5.84 (d, 1H), 4.68 (d, 1H), 4.46 (d, 1H), 4.0 (m, 1 H), 3.37 (m, 1 H), 3.03 (m, 1 H), 2.64 (m, H), .79 (m, 4H), .41 (m, 2H), 1.28 (m, 4H), 0.86 (t, 3H), 0.73 (d, 3H). [Step 2] Preparation of 5-{[(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- 2-oxo-oxazolidin-3-yl]methyl}-6-[(cyclohexyl)(ethyl)amino]-p yridin-3-yl

methanesulfonate

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl3-({2-[cy clohexyl(ethyl)^ hydroxypyridin-3-yl}methyl)-oxazolidin-2-one of step 1 and MsCI were used in the same manner as in Example 32 to afford the title compound (18mg, 12%).

H NMR (400 MHz, CDCI ₃ ) . 8.21 (s, 1 H), 7.88 (s, 1 H), 7.56 (s, 2 H), 7.59 (s, 1 H), 5.74 (d, 1 H, J = 8.4 Hz), 4.73 (d, 1 H, J = 16.0 Hz), 4.29 (d, 1 H, J = 16.0 Hz), 3.90 (m, 1 H), 3.50 (m, 1 H), 3.34 (s, 3 H), 3.07 (m, 1 H), 2.74 (m, 1 H), 1.06-1.84 (m, 10 H), 0.90 (t, 3 H, J = 7.0 Hz), 0.62 (d, 3 H, J = 6.8 Hz).

[EXAMPLE 56] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyW-yl)amino]-5-(1-methyl-1H-pyrrol-2-yl)pyri din-3-yl}meth

oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl) >xazoliclin-2-one and 1 -methyl-2-

(tributylstannyl)-l H-pyrrole (137mg, 0.37mmol) were used in the same manner as in Example 50 to afford the title compound (45mg, 30%).

H NMR (400 MHz, CDCI ₃ ) 8.37 (s, 1 H), 7.87 (s, 1 H), 7.74 (s, 2 H), 7.66 (s, 1 H), 6.77 (s, 1 H), 6.24 (m, 2 H), 5.68 (d, 1 H, J = 7.6 Hz), 4.74 (m, 1 H), 4.38 (m, 1 H), 3.90 (m, 1 H), 3.69 (s, 3 H), 3.54 (m, 1 H), 3.06 (m, 1 H), 2.76 (m, 1 H), 1.50-1.92 (m, 5 H), 1.06-1.50 (m, 5 H), 0.93 (m, 3 H), 0.66 (m, 3 H)

[EXAMPLE 57] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (methyl)(cyclohexyl-^yl)amino]-5-(3,5-dimethylisoxazol^yl)py ridin-3-yl}methyl)- oxazolidin-2-one

The same procedure as in Example 53 was repeated, with the exception that N-methyl-N-cyclohexylamine was used instead of N-ethyl-N-(tetrahydropyran-4- yl)amine, to afford 5-bromo-2-[cyclohexyl(methyl)amino]nicotine aldehyde. This compound was reacted with 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-isoxazole in the same procedure as in Example 56, with the exception that DME/H ₂ 0 (2/1) was used instead of 1 ,4-dioxane/H ₂ O, to afford the title compound (85mg, 42%).

¹ H NMR (400MHz, CDCI ₃ ) 8.18 (s, 1 H), 7.88 (s, 1 H), 7.73 (s, 2H), 7.53 (s, 1 H), 5.68 (d, 1 H), 4.78 (d, 1 H), 4.33 (d, 1 H), 3.92 (m, 1 H), 3.00 (m, 1 H), 2.79 (s, 3H), 2.44 (s, 3H), 2.29 (s, 3H), .83-1. 3 (m, 10H), 0.70 (d, 3H). [EXAMPLE 58] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3,5-dimethylisoxazol-^yl)pyridi n-3-yl}methyl)- oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5 -bromo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, obtained in step 4 of Example 54, and 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-isoxazole were used in the same manner as in Example 56 to afford the title compound (85mg, 42%).

H NMR (400 MHz, CDCI ₃ ) 8.21 (s, 1 H), 7.88 (s, 1 H), 7.74 (s, 2 H), 7.57 (s, 1 H), 5.68 (d, 1 H, J = 8.0 Hz), 4.73 (d, 1 H, J = 15.6 Hz), 4.37 (d, 1 H, J = 15.6 Hz), 3.94 (m, 1 H), 3.52 (m, 1 H), 3.1 (m, 1 H), 2.78 (m, 1 H), 2.50 (s, 3 H), 2.31 (s, 3 H), 1.50-1.90 (m, 4 H), 1.43 (m, 2 H), 1.25 (m, 2 H), 1. 2 (m, 2 H), 0.95 (t, 3 H, J = 7.2 Hz), 0.70 (d, 3 H, J = 6.8 Hz).

[EXAMPLE 59] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(1-methyM

2-one

(4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, obtained in step 4 of Example 54, and 1-methyl-2-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole were used in the same manner as in Example 50 to afford the title compound (300mg, 90%).

H NMR (400 MHz, CDCI ₃ ) 8.37 (s, 1 H), 7.88 (s, 1 H), 7.74 (s, 2 H), 7.69 (s, 1 H), 7.55 (s, 1 H), 6.34 (s, 1 H), 5.69 (d, 1 H, J = 8.0 Hz), 4.76 (d, 1 H, J = 15.6 Hz), 4.35 (d, 1 H, J = 16,0 Hz), 3.92 (s, 4 H), 3.58 (m, 1 H), 3.11 (m, 1 H), 2.80 (m, 1 H), 1.40-1.92 (m, 6 H), 1.04-1.40 (m, 4 H), 0.97 (m, 3 H), 0.88 (m, 3 H).

[EXAMPLE 60] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl-4-yl)amino]-5-(1-methyl-1H-3-(trifluorome thyl)-pyrazol-5-yl)

3-yl}methyl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 1-methyl-3-trifluoromethyl-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H- pyrazole were used in the same manner as in Example 45 to afford the title compound (160mg, 50%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.34 (s, 1 H), 7.89 (s, 1 H), 7.74 (s, 2 H), 7.68 (s, 1 H), 6.57 (s, 1 H), 5.70 (d, 1 H, J = 7.6 Hz), 4.74 (d, 1 H, J = 16.4 Hz), 4.34 (d, 1 H, J = 15.6 Hz), 2.85-4.00 (m, 4 H), 3.56 (m, 1 H), 3.16 (m, 1 H), 2.84 (m, 1 H), 1.40-1.90 (m, 6 H), 1.03-1.39 (m, 4 H), 0.98 (m, 3 H), 0.97 (m, 3 H), 0.68 (m, 3 H).

[EXAMPLE 61] ethyl (2-{4-[5-({(4S,5R)-5-[3,5-bis(trifluoro

methyl-2-oxo-oxazolidin-3-yl}methyl)]-6-[(cyclohexyl)(eth yl)amino]pyridin

pyrazol-1-yl)acetate

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and methyl 3-(4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazol-1 -yl)- propionate were used in the same manner as in Example 45 to afford the title compound (15mg, 5%).

H NMR (400 MHz, CDCI ₃ ) 8.46 (s, 1 H), 7.87 (s, 1 H), 7.82 (s, 1 H), 7.71-7.45 (m, 4 H), 5.70 (d, 1 H, J = 8.4 Hz), 4.97 (s, 2 H), 4.75 (d, 1 H, J = 15.6 Hz), 4.38 (d, 1 H, J = 15.2 Hz), 4.28 (t, 2 H, J = 7.2 Hz), 3.89 (m, 1 H), 3.53 (m, 1 H), 3.05 (m, 1 H), 2.72 (m, 1 H), 1.08-1.91 (m, 13 H), 0.92 (t, 3 H, J = 7.2 Hz), 0.69 (d, 3 H, J = 6.4 Hz). [EXAMPLE 62] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(1 -methyl-1 ^

2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 1-methyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole were used in the same manner as in Example 50 to afford the title compound (100mg, 50%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.43 (s, 1 H), 7.88 (s, 1 H), 7.74 (s, 3 H), 7.69 (s, 1 H), 7.62 (s, 1 H), 5.67 (d, 1 H, J = 8.0 Hz), 4.72 (d, 1 H, J = 16.4 Hz), 4.39 (d, 1 H, J = 15.6 Hz), 3.97 (s, 3 H), 3.92 (m, 1 H), 3.51 (m, 1 H), 3.06 (m, 1 H), 2.74 (m, 1 H), 1.31 ~1.90 (m, 6 H), 1.04-1.31 (m, 4 H), 0.92 (m, 3 H), 0.68 (m, 3 H).

[EXAMPLE 63] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3-methyl-thiophen-5-yl)pyridin- 3-yl}methyl)-oxaz one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 3-methyl-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-thiophene were used in the same manner as in Example 50 to afford the title compound (50mg, 25%).

H NMR (400 MHz, CDCI ₃ ) 8.52 (s, 1 H), 7.87 (s, 1 H), 7.75 (s, 3 H), 7.09 (s, 1

H), 6.89 (s, 1 H), 5.71 (d, 1 H, J = 8.4 Hz), 4.75 (d, 1 H, J = 16.0 Hz), 4.35 (d, 1 H, J = 16.0 Hz), 3.90 (m, 1 H), 3.53 (m, 1 H), 3.06 (m, 1 H), 2.70 (m, 1 H), 2.04 (s, 3 H), 1.09-1.80 (m, 10 H), 0.91 (m, 3 H), 0.67 (m, 3 H). [EXAMPLE 64] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[2-

(ethyl)(cyclohexyl)amino]-5-(1,3,5-trim

oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 1 ,3,5-trimethyl-4-(4,4,5,5-tetramethyl- ,3,2-dioxaborolan-2-yl)-1 H-pyrazole were used in the same manner as in Example 45 to afford the title compound (30mg, 8%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.21 (s, 1 H), 7.88 (s, 1 H), 7.74 (s, 2 H), 7.53 (s, 1 H), 5.66 (d, 1 H, J = 7.6 Hz), 4.74 (d, 1 H, J = 15.6 Hz), 4.38 (d, 1 H, J = 15.2 Hz), 3.94 (m, 1 H), 3.80 (s, 3 H), 3.51 (m, 1 H), 3.08 (m, 1 H), 2.76 (m, 1 H), 2.27 (s, 6 H), 1.03-1.92 (m, 10 H), 0.94 (m, 3 H), 0.69 (m, 3 H). [EXAMPLE 65] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl-4-yl)amino]-5-(3,5-dimethyl-1 H-pyrazol-4-yl)pyridin-3-yl}methyl)- oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole-1- carboxylate were used in the same manner as in Example 50 to afford the title compound (42mg, 35%).

H NMR (400MHz, CDCI ₃ ) 8.25 (s, 1 H), 7.88 (s, 1 H), 7.74 (s, 2H), 7.58 (s, 1 H), 5.83 (bs, 1 H), 5.68 (d, 1 H), 4.77 (d, 1 H), 4.41 (d, 1 H), 3.94 (m, 1 H), 3.52 (m, 1 H), 3.08 (m, 1 H), 2.76 (m, 1 H), 2.33 (s, 6H), 1.87-1.13 (m, 0H), 1.02 (m, 3H), 0.71 (m, 3H).

[EXAMPLE 66] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(1-methyM

2-one

[Step 1] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({2- [cyclohexyl(ethyl)amino]^-methyl-5-(4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2- yl)pyridin-3-yl}methyl)-oxazolidin-2-one

To a solution (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e (1.Og, 1.64mmol), prepared in step 4 of Example 54, in toluene (4ml) were dropwise added Pd(dppf)CI (134mg, 0.164mmol), KOAc (483mg, 4.92mmol), and 4,4,4 ^, ,4',5,5,5 ^, ,5'-octamethyl-2,2'-bi(1 ,3,2- dioxaborolane) (500mg, 1.97mmol). The reaction mixture was refluxed at 100°C for 5 hrs with stirring, and then cooled to room temperature, followed by extraction with dichloromethane. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford a dioxaborolane compound (750mg, 70%).

1H NMR (400MHz, CDCI ₃ ) 8.61 (s, 1 H), 7.95 (s, 1H), 7.87 (s, 1 H), 7.75 (s, 2H),

5.70 (d, H), 4.78 (d, 1H), 4.28 (d, H), 3.83 (m, 1H), 3.59 (m, 1H), 3.08 (m, 1H), 2.78 (m, 1 H), 1.95 (m, 5H), 1.34 (m, 5H), 1.24 (s, 12H), 0.92 (t, 3H), 0.64 (d, 3H). [Step 2] Preparation of (4S,5R)-5-[3,5-bis(trifIuoromethyl)phenyl]-4-methyl-3- ({[2-(ethyl)(cyclohexyl)amino]-5-(1-methyl-1H-tetrazol-5-yl) pyridin-3-yl}^

oxazolidin-2-one

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({2- [cyclohexyl(ethyl)amino]-4-methyl-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)p yl}methyl)-oxazolidin-2-one (200mg, 0.30mmol) of step 1 in DME/H20 (2/1 , 4.5ml) was added with drops of 1-methyl-5-iodo-tetrazole (90mg, 0.46mmol), K ₂ CO ₃ (82mg, 0.6mmol), and Pd(PPh ₃ ) ₄ (50mg, 0.03mmol), and refluxed at 90°C for 62 hrs with stirring. Cooling to room temperature was followed by extraction with ethyl acetate. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (17mg, 9%).

H NMR (400MHz, CDCI ₃ ) 8.63 (d, 1H), 8.04 (d, h), 7.88 (s, 1 H), 7.75 (s, 2H), 5.76 (d, 1 H), 4.84 (d, 1 H), 4.28 (d, 1H), 4.22 (s, 3H), 3.95 (m, 1H), 3.67 (m 1 H), 3.19 (m, 1 H), 2.94 (m, 1H), 1.87 (m, 1 H), 1.79 (m, 1H), 1.67 (m, 4H), 1.34 (m, 4H), 1.00 (t, 3H), 0.68 (d, 3H).

[EXAMPLE 67] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(1-isobutyl-1H^yrazol-4-yl)pyrid in-3-yl}methyl)- oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2-

[cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2 -one, prepared in step 4 of Example 54, and 1-isobutyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole were used in the same manner as in Example 45 to afford the title compound (60mg, 28%).

¹ H NMR (400MHz, CDCI ₃ ) 8.46 (d, 1 H), 7.87 (s, 1 H), 7.77 (s, 1 H), 7.74 (s, 2H), 7.71 (d, 1 H), 7.62 (s, 1 H), 5.69 (d, 1 H), 4.75 (d, 1 H), 4.41 (d, 1 H), 4.41 (d, 1 H), 3.97 (m, 3H), 3.53 (m, 1 H), 3.08 (m, 1 H), 2.71 (m, 1 H), 2.28 (m, 1 H), 2.17-1.24 (m, 10H), 0.96 (m, 12H), 0.70 (d, 3H).

[EXAMPLE 68] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(1H-pyrazol^yl)pyridin-3-yl}meth yl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 1 H-pyrazol-4-yl boronic acid were used in the same manner as in Example 45 to afford the title compound (50mg, 25%).

¹ H NMR (400MHz, CDCI ₃ ) 8.49 (d, 1 H), 7.87 (s, 2H), 7.74 (s, 3H), 7.63 (s, 1 H), 6.37 (bs, 1 H), 5.69 (d, 1 H), 4.77 (d, 1 H), 4.42 (d, 1H), 3.93 (m, 1 H), 3.54 (m, 1H), 3.09 (m, 1 H), 2.73 (m, 1 H), 1.88-1.50 (m, 6H), 1.40 (m, 2H), 1.14 (m, 2H), 0.94 (t, 3H), 0.70 (d, 3H).

[EXAMPLE 69] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(1,3-dimethyl-1H-pyrazol^yl)pyri din-3-yl}methyl)- oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 1 ,3-dimethyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole were used in the same manner as in Example 45 to afford the title compound (56mg, 54%).

H NMR (400MHz, CDC ) 8.36 (s, 1 H), 7.88 (s, 1 H), 7.74 (s, 2H), 7.64 (s, 1 H), 7.45 (s, 1H), 4.75 (d, 1H), 4.41 (d, 1H), 3.90 (s, 3H), 3.50 (m, 1H), 3.06 (m, 1H), 2.73 (m, 1 H), 2.41 (m, 3H), .93-1.13 (m, 10H), 093 (m, 3H), 0.70 (d, 3H).

[EXAMPLE 70] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3-methoxy hiophen-2-yl)pyridin-3-yl}methyl)-oxazolidin 2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 3-methoxy-2-(4,4,5,5-tetramethyl-1 ,3,2-dioxoborolan-2-yl)-thiophene were used in the same manner as in Example 45 to afford the title compound (55mg, 55%).

¹ H NMR (400MHz, CDCI ₃ ) 8.64 (d, 1 H), 8.00 (s, 1 H), 7.87 (s, 1 H), 7.76 (s, 2H), 7.20 (d, 1H), 6.96 (d, 1H), 5.69 (d, 1 H), 4.79 (d, 1 H), 4.36 (d, 1H), 3.94 (m, 4H), 3.56 (m, 1 H), 3.07 (m, 1 H), 2.75 (m, 1 H), 1.87-1.33 (m, 7H), 1.14 (m, 3H), 0.94 (m, 3H), 0.68 (d, 3H).

[EXAMPLE 71] 5-{5-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2 - oxo-oxazolidin-3-yl}methyl)-6-[(cyclohexyl)(ethyl)amino]pyri din-3-yl}-thiophene-2- carbonitrile

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 2-cyano-5-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)-thio phene were used in the same manner as in Example 45 to afford the title compound (78mg, 76%). ¹ H NMR (400MHz, CDCI ₃ ) 8.52 (d, 1H), 7.88 (s, 1 H), 7.80 (d, 1H), 7.74 (s, 2H), 7.62 (d, 1H), 7.24 (d, 1 H), 5.70 (d, 1 H), 4.76 (d, 1 H), 4.34 (d, 1 H), 3.92 (m, 1H), 3.58 (m, 1 H), 3.58 (m, 1 H), 3.15 (m, 1 H), 2.84 (m, 1 H), 1.84 (m, 2H), 1.64 (m, 2H), 1.49 (m, 2H), 1.30 (m, 2H), 1.20 (m, 2H), 0.96 (t, 3H), 0.68 (d, 1 H).

[EXAMPLE 72] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3-(trifluorom

oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 3-(trifluoromethyl)-4-(4,4,5,5-tetramethyl- ,3,2-dioxaborolan-2-yl)-1 H-pyrazole were used in the same manner as in Example 45 to afford the title compound (40mg, 8%).

¹ H NMR (400MHz, CDCI ₃ ) 8.32 (s, 1H), 7.88 (s, 1H), 7.75 (s, 3H), 7.72 (d, H), 5.72 (d, 1H), 4.78 (d, H), 4.37 (d, H), 3.94 (m, 1H), 3.57 (m, H), 3.12 (m, 1H), 2.78 (m, 1 H), 1.87-1.00 (m, 10H), 0.96 (t, 3H), 0.67 (d, 3H).

[EXAMPLE 73] ethyl 4-{5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolin-3-yl}methyl)-6-[(cyclohexyl)(ethyl)ami no)]pyridin-3-yl}-3- methylisoxazole-5-carboxylate

The same procedure as in Example 66 was repeated, with the exception that ethyl 4-bromo-3-methylisoxazole-5-carboxylate was used instead of 1-methyl-5-iodo- tetrazole, to afford the title compound (30mg, 14%).

¹ H NMR (400MHz, CDCI ₃ ) 8.69 (d, 1 H), 8.30 (d, 1 H), 7.87 (s, 1 H), 7.81 (s, 2H), 5.98 (d, 1 H), 7.87 (d, 1 H), 4.36 (q, 2H), 4.23 (d, 1 H), 4.15 (m, 1 H), 3.73 (m, 1 H), 3.11 (m, 1 H), 2.96 (m, 1 H), 2.52 (s, 3H), 1.94 (m, 1 H), 1.69 (m 9H), 1.40 (t, 3H), 0.98 (t, 3H), 0.65 (d, 3H).

[EXAMPLE 74] ethyl 5-{5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolin-3-yl}methyl)-6-[(cyclohexyl)(ethyl)ami no)]pyridin-3-yl}-3- methylisoxazole-4-carboxylate

The same procedure as in Example 66 was repeated, with the exception that ethyl 5-bromo-3-methylisoxazole-4-carboxylate was used instead of 1-methyl-5-iodo- tetrazole, to afford the title compound (15mg, 15%).

H NMR (400MHz, CDCI ₃ ) 8.69 (d, 1 H), 7.88 (s, 2H), 7.82 (s, 1 H), 7.75 (s, 1 H), 5.69 (d, 1 H), 4.71 (d, 1 H), 4.42 (m, 2H), 4.15 (m, 1 H), 3.92 (m, 1 H), 3.70 (m, 1 H), 3.50 (m, 1 H), 2.40 (s, 3H), 1.82 (m, 10H), 1.43 (t, 3H), 0.94 (t, 3H), 0.66 (d, 3H).

[EXAMPLE 75] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(2-methyl-fura^

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cycloh8xyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 5-methyl-2-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-furan were used in the same manner as in Example 45 to afford the title compound (30mg, 15%).

¹ H NMR (400MHz, CDCI ₃ ) 8.56 (d, 1 H), 7.87 (s, 1 H), 7.83 (d, 1 H), 7.75 (s, 2H), 6.54 (d, 1 H), 6.08 (d, 1 H), 5.71 (d, 1 H), 4.78 (d, 1 H), 4.39 (d, 1 H), 3.90 (m, 1 H), 3.55 (m, 1 H), 3.07 (m, 1 H), 2.73 (m, 1 H), 1.82-1.05 (m, 10H), 0.93 (t, 3H), 0.68 (d, 3H).

[EXAMPLE 76] t-butyl 2-{5-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolidin-3-yl}methyl)-6-[(cyclohexyl)(ethyl)a mino]pyridin-3-yl}-1H- pyrrole-1 -carboxylate

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br orno-2-

[cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2 -one, prepared in step 4 of Example 54, and t-butyl 2-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrrole-1-carboxylate were used in the same manner as in Example 45 to afford the title compound (350mg, 47%).

H NMR (400MHz, CDCI ₃ ) 8.27 (s, 1 H), 7.87 (s, 1 H), 7.75 (s, 2H), 7.72 (s, 1H), 7.38 (m, 1H), 6.26 (m, 1H), 5.77 (d, 1 H), 4.88 (d, H), 4.32 (d, 1H), 3.99 (m, 1H), 3.62 (m, 1 H), 3.05 (m, 1 H), 2.73 (m, 1 H), 1.90 (m, 10H), 1.48 (s, 9H), 097 (t, 3H), 0.68 (d, 3H). [EXAMPLE 77] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2-

(ethyl)(cyclohexyl)amino]-5-(thiophen-3-y ^

The same procedure as in Example 66 was repeated, with the exception that thiophene-3-boronic acid was used instead of 1-methyl-5-iodo-tetrazole, to afford the title compound (130mg, 64%).

H NMR (400MHz, CDCI ₃ ) 8.56 (s, 1H), 7.87 (s, 1 H), 7.82 (s, 1 H), 7.74 (s, 2H), 7.46 (m, 2H), 7.37 (d, 1H), 5.69 (d, 1H), 4.79 (d, 1H), 4.40 (d, 1H), 3.91 (m, 1H), 3.57 (m, 1 H), 3.09 (m, 1 H), 2.78 (m, 1 H), 1.89-1.06 (m, 10H), 0.95 (t, 3H), 0.69 (d, 3H).

[EXAMPLE 78] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3-methyl-thto

one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- thiophene were used in the same manner as in Example 45 to afford the title compound (110mg, 53%).

¹ H NMR (400MHz, CDCI ₃ ) 8.41 (d, 1 H), 7.88 (s, 1 H), 7.75 (s, 2H), 7.71 (s, 1 H), 7.26 (d, 1H), 6.97 (d, 1H), 5.70 (d, H), 4.79 (d, 1 H), 4.38 (d, 1H), 3.94 (m, 1H), 3.58 (m, 1 H), 3. 1 (m, H), 2.78 (m, H), 2.35 (s, 3H), .72- .07 (m, 10H), 0.96 (t, 3H), 0.70 (d, 3H).

[EXAMPLE 79] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(2-methyl^hiophen-5-yl)pyridin-3 -yl}methyl)-oxa^ one

(4S,5R)-5-[3 _I 5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-bromo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 2-methyl-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-thiophenyl were used in the same manner as in Example 45 to afford the title compound (30mg, 42%)-§r

¹ H NMR (400MHz, CDCI ₃ ) 8.52 (d, 1 H), 7.87 (s, 1 H), 7.77 (d, 1 H), 7.75 (s, 2H),

7.09 (s, 1 H), 6.89 (s, 1 H), 5.70 (d, 1 H), 4.78 (d, 1 H), 4.37 (d, 1 H), 3.93 (m, 1 H), 3.58 (m, 1 H),

3.10 (m, 1 H), 2.78 (m, 1 H), 1.89-1.02 (m, 10H), 0.94 (t, 3H), 0.68 (d, 3H).

[EXAMPLE 80] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(thiophen-2-yl)pyridin-3-yl}meth yl)-oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and tributyl(thiophen-2-yl)stannane were used in the same manner as in Example 50 to afford the title compound (33mg, 16%). 2 ¹ H NMR (400MHz, CDCI ₃ ) 8.56 (d, 1 H), 7.87 (s, 1 H), 7.81 (d, 1 H), 7.75 (d, 2H), 7.33 (d, 1 H), 7.29 (d, 1 H), 7.13 (t, 1 H), 5.70 (d, 1 H), 4.78 (d, 1H), 4.38 (d, 1H), 3.94 (m, 1H), 3.57 (m, 1H), 3.12 (m, 1H), 2.79 (m, 1H), 1.89-1.069 (m, 10H), 0.95 (t,3H), 0.69 (d, 3H).

[EXAMPLE 81] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(thiazol-4-yl)pyridin-3-yl}methy l)-oxazolidin-2-one

The same procedure as in Example 66 was repeated, with the exception that 4-bromothiazole was used instead of 1 -methyl-5-iodo-tetrazole, to afford the title compound (85mg, 45%). ¹ H NMR (400MHz, CDCI ₃ ) 8.91 (d, 1H), 8.83 (d, 1H), 8.17 (d, 1H), 7.87 (s, 1H), 7.75 (s, 2H), 7.54 (d, 1H), 5.72 (d, 1H), 4.82 (d, 1H), 4.40 (d, 1H), 3.94 (m, 1H), 3.59 (m, 1H), 3.12 (m, 1H), 2.83 (m, 1H), 1.90 (m, 4H), 1.46 (m, 2H), 1.34 (m,2H), 1.16 (m, 2H), 0.96 (t, 3H), 0.68 (d, 3H).

[EXAMPLE 82] 3-{5-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2 - oxo-oxazolidin-3-yl}methyl)-6-[(cyclohexyl)(ethyl)amino]pyri din-3-yl}-thioph

carbonitrile

The same procedure as in Example 66 was repeated, with the exception that 3-bromo-2-cyanothiophene was used instead of 1-methyl-5-iodo-tetrazole, to afford the title compound (80mg, 38%).

¹ H NMR (400MHz, CDCI ₃ ) 8.45 (s, 1 H), 8.07 (s, 1 H), 7.86 (s, 1 H), 7.81 (s, 2H), 7.68 (d, 1 H), 7.30 (d, 1 H), 6.06 (d, 1 H), 4.88 (d, 1 H), 4.32 (d, 1H), 4.12 (m, 1 H), 3.65 (m, 1 H), 3.06 (m, 1 H), 2.85 (m, 1 H), 1.95-1.13 (m, 10H), 1.11 (m, 3H), 0.67 (d, 3H).

[EXAMPLE 83] t-butyl 4-[5-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxo-oxazolidin-3-yl}methyl)-6-[cyclohexyl(ethyl)ami no]pyridin-3-yl]-5- methylisoxazol-3-yl-carbamate

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and t-butyl 5-methyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-isoxazol-3-yl- carboxylate were used in the same manner as in Example 45 to afford the title compound (50mg, 16%).

¹ H NMR (400MHz, CDCI ₃ ) 8.35 (d, 1 H), 7.88 (s, 1 H), 7.75 (s, 2H), 7.65 (d, 1 H), 5.70 (d, 1 H), 4.76 (d, 1 H), 4.37 (d, 1 H), 3.96 (m, 1 H), 3.57 (m, H), 3.15 (m, 1 H), 2.81 (m, 1 H), 2.07 (s, 3H), 2.48 (s, 3H), 1.89-1.07 (m, 10H), 0.96 (t, 3H), 0.69 (d, 3H).

[EXAMPLE 84] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(2,4-dimethyl-thiazol-5-yl)pyrid in-3-yl}methyl)-ox

2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 2,4-dimethyl-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-thiazole were used in the same manner as in Example 45 to afford the title compound (70mg, 33%).

H NMR (400MHz, CDCI ₃ ) 8.35 (d, 1 H), 7.88 (s, 1 H), 7.75 (s, 2H), 7.65 (d, 1 H), 5.70 (d, 1H), 4.76 (d, 1H), 4.37 (d, 1H), 3.96 (m, 1 H), 3.57 (m, 1 H), 3.15 (m, 1 H), 2.81 (m, 1 H), 2.07 (s, 3H), 2.48 (s, 3H), 1.89-1.07 (m, 0H), 0.96 (t, 3H), 0.69 (d, 3H).

[EXAMPLE 85] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3-amino-5-methyi-isoxazol-4-yl) pyridin-3-yl}meth oxazolidin-2-one

t-Butyl 4-[5-({(4S,5S)-5-[3 _> 5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-oxazolidi n-3- yl}methyl)-6-[cyclohexyl(ethyl)amino]pyridin-3-yl]-5-methyli soxazol-3-yl-carbamate of Example 83 was used in the same manner as in Example 28 to afford the title compound (30mg, 50%).

H NMR (400MHz, CDCI ₃ ) 8.28 (d, 1H), 7.89 (s, 1H), 7.75 (s, 2H), 7.65 (d, 1H), 5.72 (d, 1H), 4.74 (d, 1H), 4.37 (d, 1H), 3.99 (m, 4H), 3.56 (m, 1H), 3.13 (m, 1H), 2.79 (m, 1 H), 2.39 (s, 1 H), 1.89-1.04 (m, 10H), 0.96 (t, 3H), 0.72 (d, 3H).

[EXAMPLE 86] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3-methyl-^

one

The same procedure as in Example 66 was repeated, with the exception that 3-bromo-4-methylthiophene was used instead of 1-methyl-5-iodo-tetrazole to afford the title compound (40mg, 19%).

¹ H NMR (400MHz, CDCI ₃ ) 8.36 (d, 1H), 7.87 (s, 1H), 7.74 (s, 1H), 7.68 (d, 1H), 7.25 (d, 1H), 7.08 (d, 1H), 5.69 (d, 1H), 4.78 (d, 1H), 4.40 (d, 1H), 3.94 (m, 1H), 3.57 (m, 1H), 3.11 (m, 1H),2.77(m, 1H), 2.31 (s, 3H), 1.90-1.01 (m, 10H),0.96(t, 3H), 0.70 (d, 3H).

[EXAMPLE 87] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3-methyl-isothioxazol-4-yl)pyri din-3-yl}methyl)- oxazolidin-2-one

The same procedure as in Example 66 was repeated, with the exception that 4-bromo-3-methylisothiazole was used instead of 1-methyl-5-iodo-tetrazole to afford the title compound (70mg, 34%).

¹ H NMR (400MHz, CDCI ₃ ) 8.53 (s, 1 H), 8.35 (d, 1 H), 7.88 (s, 1 H), 7.74 (s, 2H), 7.69 (d, 1 H), 5.69 (d, 1 H), 4.78 (d, 1 H), 4.40 (d, 1 H), 3.97 (m, 1 H), 3.57 (m, 1 H), 3.16 (m, H), 2.82 (m, H), 2.58 (s, 3H), 1.90-1.08 (m, 10H), 0.97 (t, 3H), 0.71 (d, 3H).

[EXAMPLE 88] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(pyrrolidin-1-yl)pyridin-3-yl}me thyl)-oxazolidin

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and pyrrolidine were used in the same manner as in Example 41 to afford the title compound (60mg, 60%).

¹ H NMR (400 MHz, CDCI ₃ ) 7.88 (s, 1 H), 7.76 (s, 3 H), 6.84 (s, 1 H), 5.66 (d, 1 H, J = 7.6 Hz), 4.67 (d, 1 H, J = 15.2 Hz), 4.49 (d, 1 H, J = 16.0 Hz), 3.97 (m, 1 H), 3.28 (s, 4 H), 3.00 (m, 1 H), 2.64 (m, 1 H), 2.03 (s, 4 H), 1.60-1.83 (m, 5 H), 0.98-1.38 (m, 6 H), 0.84 (m, 3 H), 0.72 (m, 3 H).

[EXAMPLE 89] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(2-methyl^yrrolidin-1-yl)pyridin -3-yl}methyl)-oxa

2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 2-methyl pyrrolidine were used in the same manner as in Example 41 to afford the title compound ( 0mg, 50%).

¹ H NMR (400 MHz, CDCI ₃ ) 7.87 (s, 1 H), 7.76-7.78 (m, 3 H), 6.85 (s, 1 H), 5.68 (m, 1 H), 4.67 (d, 1 H, J = 15.6 Hz), 4.49 (m, 1 H), 3.98 (m, 1 H), 3.85 (m, 1 H), 3.43 (m, 1 H), 3.30 (m, 1 H), 3.13 (m, 1 H), 3.00 (m, 1 H), 2.64 (m, 1 H), 1.02-2.07 (m, 14 H), 1.18 (d, 3 H, J = 7.2 Hz), 0.85 (m, 3 H), 0.73 (d, 3 H, J = 6.0 Hz)

[EXAM PLE 90] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(2-ethyl^yrrolidin-1-yl)pyridin- 3-yl}methyl)-ox

one

The same procedure as in Example 88 was repeated, with the exception that 2-ethyl pyrrolidine was used instead of pyrrolidine, to afford the title compound (30mg, 15%).

¹ H NMR (400MHz, CDCI ₃ ) 7.88 (s, 1 H), 7.76 (s, 3H), 6.84 (s, 1 H), 5.69 (dd, 1 H), 4.69 (d, 1 H), 4.50 (dd, 1 H), 3.99 (m, 1 H), 3.54 (m, 1 H), 3.43 (m, 1 H), 3.30 (m, 1 H), 3.11 (m, 1 H), 3.01 (m, 1 H), 2.64 (m, 1 H), 2.00 (m, 4H), 1.85 (m, 6H), 1.32 (m, 4H), 0.96 (m, 3H), 0.87 (t, 3H), 0.74 (d, 3H).

[EXAMPLE 91] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3,3-difluoro^

oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2- [cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2-on e, prepared in step 4 of Example 54, and 3,3-difluoro pyrrolidine were used in the same manner as in Example 41 to afford the title compound (110mg, 50%). ¹ H NMR (400MHz, CDCI ₃ ) 7.88 (s, 1 H), 7.76 (m, 3H), 6.90 (d, 1 H), 5.68 (d, 1 H), 4.68 (d, 1 H), 4.50 (d, 1 H), 3.99 (m, 1 H), 3.70 (t, 2H), 3.55 (m, 2H), 3.36 (m, 1 H), 3.05(m, 1 H), 2.66 (m, 1 H), 2.56 (m, 2H), 1.83 (m, 6H), 1.42-1.00 (m, 4H), 0.88 (t, 3H), 0.73 (d, 3H).

[EXAMPLE 92] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(2-(trifluorom

oxazolidin-2-one

The same procedure as in Example 88 was repeated, with the exception that 2-trifluoromethyl pyrrolidine was used instead of pyrrolidine to afford the title compound (140mg, 70%).

¹ H NMR (400MHz, CDCI ₃ ) 7.94 (d, 1 H, major), 7.91 (d, 1 H, minor), 7.88 (s, 1 H), 7.76 (s, 2H), 7.75 (s, 1 H), 5.70 (d, 1 H, major), 5.64 (d, 1 H, minor), 4.72 (m, 1 H), 4.50 (m, 1 H), 4.20 (m, 1 H), 4.04 (m, 1 H), 3.92 (m, 1 H, minor), 3.72 (m, 1 H), 3.41 (m, 1 H, minor), 3.31 (m, 2H), 3.11 (m, 1 H), 2.98 (m, 1 H, minor), 2.67 (m, 1 H), 2.29 (m, 4H), 1.82 (m, 5H), 1.44 (m, 5H), 0.91 (m, 3H), 0.69 (d, 3H).

[EXAMPLE 93] 3-[5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2 - oxo-oxazolidin-3-yl}methyl)-6-[(cyclohexyl)(ethyl)amino]pyri din-3-yl]-1,2,4-oxa

5(H)-one

[Step 1] Preparation of (Z)-5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxooxazolidin-3-yl}methyl)-6-[cyclohexyl(ethyl)amin o]-N'- hydroxynicotinamide

To a solution of 5-({4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo -1 ,3- oxazolidin-3-yl}methyl)-6-[(cyclohexyl)(ethyl)amino]nicotino nitrile (200mg, 0.36mmol) of Example 54 in IPA (2ml) was added 20 equivalents of a 50% ammonia solution. Stirring at 80°C for 24 hrs was followed by extraction with ethyl acetate. The organic layer thus formed was dried, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (110mg, 45%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.51 (s, 1 H), 7.88 (s, 2 H), 7.77 (s, 2 H), 5.78 (d, 1 H, J = 7.6 Hz), 4.93 (s, 2 H), 4.77 (d, 1 H, J = 15.6 Hz), 4.27 (d, 1 H, J = 15.2 Hz), 3.86 (m, 1 H), 3.56 (m, 1 H), 3.04 (m, 1 H), 2.78 (m, 1 H), 1.60-1.88 (m, 6 H), 1.26 (m, 2 H), 1.10 (m, 2 H), 0.90 (m, 3 H), 0.64 (m, 3 H).

[Step 2] Preparation of 3-[5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxooxazolidin-3-yl}methyl)-6-[cyclohexyl(ethyl)amin o]pyridin-3-yl]^ oxadiazol-5(4H)-one

To a solution of (Z)-5-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl- 2- oxooxazolidin-3-yl}methyl)-6-[cyclohexyl(ethyl)amino]-N'-hyd roxynicotinami^ of step 1 in dichloromethane (2m)l was dropwise added CDI (carbonyl diimidazole) (61.6mg, 0.38mmol), followed by stirring at 80 ^° C for 2 hrs. The reaction mixture ws cooled to room temperature, and quenched with water. Extraction was performed with dichloromethane.

The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated at a reduced pressure. The residue was purified by chromatography to afford the title compound (71 mg, 62%).

¹ H NMR (400 MHz, CDCI ₃ ) 8.61 (s, 1 H), 7.89 (s, 2 H), 7.76 (s, 2 H), 5.73 (d, 1 H,

J = 8.4 Hz), 5.23 (s, 1 H), 4.75 (d, 1 H, J = 14.8 Hz), 4.26 (d, 1 H, J = 14.2 Hz), 3.90 (m, 1 H),

3.59 (m, 1 H), 3.12 (m, 1 H), 2.85 (m, 1 H), 1.51-1.84 (m, 6 H), 1.26 (m, 2 H), 1.23 (m, 2 H), 0.94 (m, 3 H), 0.65 (d, 3 H, J = 6.4 Hz).

[EXAMPLE 94] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2- (cyclohexylamino)-5-(3,5-dimethyl-isoxazol-4-yl)pyrazin-3-yl ]methyl}-oxazolidin-2-one

Preparation of (3-chloropyrazin-2-yl)methanol

To a solution of 3-chloropyrazine-2-carbaldehyde (700mg, 4.91 mmol) in methanol (10ml) was dropwise NaBH ₄ (223mg, 5.89mmol). The reaction mixture was stirred at room temperature for 1 hr, and the reaction was terminated with a saturated aqueous ammonium solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in a vacuum.

[Step 2] Preparation of 2-chloro-3-(chloromethyl)pyrazine

To (3-chloropyrazin-2-yl)methanol of step 1 was dropwise added a solution of SOCI ₂ (700mg, 5.89mmol) in DMF (10ml) at 0°C. Stirring at 0°C for 30 min was followed by extraction with ethyl acetate. The organic layer was washed with a saturated NaHC03 solution, dried over anhydrous magnesium sulfate, filtered, and concentrated in a vacuum. The residue was used in a subsequent step without further purification.

[Step 3] Preparation of (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]- 4-methyl- 3-[(3-chloropyrazin-2-yl)methyl]-oxazolidin-2-one

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyloxazolidi n-2-one (1.84g, 5.89mmol) in DMF (10ml) was dropwise added NaHMDS (5.4ml, 5.4mmol) at - 40°C. After being stirred for 30 min, the reaction mixture was slowly added with drops of a dilution of 2-chloro-3-(chloromethyl)pyrazine, obtained in step 2, in DMF (10ml). The resulting reaction mixture was warmed to room temperature, stirred for 3 hrs, diluted with ethyl acetate (200ml), and quenched with water (200ml). The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated in a vacuum. The residue was purified by chromatography to afford the title compound (900mg, 35%).

H NMR (400MHz, CDCI ₃ ) 8.51 (d, 1 H), 8.36 (d, 1 H), 7.90 (s, 1 H), 7.83 (s, 2H), 5.85 (d, 1 H), 5.05 (d, 1 H), 4.50 (d, 1 H), 4.45 (m, 1 H), 0.81 (d, 3H).

[Step 4] Preparation of (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- {[3-(cyclohexylamino)pyrazin-2-yl]methyl}-oxazolidin-2-one

To (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]- 4-methyl-3-[(3-chloropyrazin-2- yl)methyl]-oxazolidin-2-one (910mg, 2.07mmol) of step 3 was added cyclohexylamine (1 ml, 8.28mmol), and the reaction mixture was stirred at 100°C for 4 hrs. After cooling, chromatographic purification afforded the title compound (650mg, 75%).

¹ H NMR (400MHz, CDCI ₃ ) 7.97 (s, 1 H), 7.87 (s, 1 H), 7.70 (s, 2H), 7.60 (d, 1 H), 5.82 (d, 1 H), 5.69 (d, 1 H), 4.68 (d, 1 H), 4.32 (d, 1 H), 4.14 (m, 1 H), 3.89 (m, 1 H), 2.03 (m, 2H), 1.76 (m, 2H), 1.61 -1.24 (m, 6H), 0.79 (d, 3H).

[Step 5] Preparation of (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- {[6-bromo-3-(cyclohexylamino)pyrazin-2-yl]methyl}-oxazolidin -2-one

To a solution of (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[3- (cyclohexylamino)pyrazin-2-yl]methyl}-oxazolidin-2-one (300mg, 0.6mmol) of step 4 in DMF (3ml) was dropwise added NBS (N-bromo succinic imide) (128mg, 0.72mmol) at 0°C. The reaction mixture was stirred for 2 hrs and quenched with water. Extraction afforded afforded the title compound (370mg, 92%).

¹ H NMR (400MHz, CDCI ₃ ) 8.06 (s, 1 H), 7.90 (s, 1 H), 7.72 (s, 2H), 6.01 (d, 1 H), 5.73 (d, 1 H), 4.63 (d, 1 H), 4.32 (d, 1 H), 4.23 (m, 1 H), 3.85 (m, 1 H), 2.06 (m, 10H), 0.83 (d, 3H).

[Step 6] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- {[2-(cyclohexylamino)-5-(3,5-dimethyl-isoxazol^yl)pyrazin-3- yl]methyl}-oxazolidin-2- one

(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[6-br omo-3- (cyclohexylamino)pyrazin-2-yl]methyl}-oxazolidin-2-one and 3,5-dimethyl-4-(4,4,5,5- tetramethyl-1 ,3 _> 2-dioxaborolan-2-yl)-isoxazole were used in the same manner as in Example 45 to afford the title compound (340mg, 72%).

H NMR (400MHz, CDCI ₃ ) . 8.06 (s, 1 H), 7.90 (s, 1 H), 7.72 (s, 2H), 6.02 (bd, 1 H), 5.73 (d, 1 H), 475 (d, 1 H), 4.35 (d, 1 H), 4.22 (m, 1 H), 3.94 (m, 1 H), 2.50 (s, 3H), 2.36 (s, 3H), 2.10 (m, 2H), 1.83 (m, 2H), 1.68 (m, 2H), 1.49 (m, 4H), 0.88 (d, 3H).

[EXAMPLE 95] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (methyl)(cyclohexyl)amino]-5-(3,5-dim

oxazolidin-2-one

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-{[2-(c yclohexylamino)-5-(3,5- dimethyl-isoxazol-4-yl)pyrazin-3-yl]methyl}-oxazolidin-2-one of Example 94, and methyl iodide were used in the same manner as in Example 6 to afford the title compound (5mg, 4%).

¹ H NMR (400MHz, CDCI ₃ ) 8.20 (s, 1 H), 7.89 (s, 1 H), 7.74 (2H), 5.69 (d, 1 H), 5.01 (d, 1 H), 4.24 (d, H), 4.18 (m, 1 H), 3.32 (m, 1 H), 2.85 (s, 3H), 2.61 (s, 3H), 2.47 (s; 3H), 1.89-1.12 (m, 10H), 0.74 (d, 3H).

[EXAMPLE 96] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({[2- (ethyl)(cyclohexyl)amino]-5-(3,5-dimethyl-isoxazol-^yl)pyraz in-3-yl}methyl)- oxazolidin-2-one

[Method 1]

[Step 1] Preparation of 6-bromo-3-[cyclohexyl(ethyl)amino]pyrazine-2- carbaldehyde

To a solution of 2,5-dibromopyrazine carbaldehyde (300mg, 1.13mmol) in toluene (6ml) were dropwise added K2CO3 (314mg, 2.26mmol) and N-ethyl-N-cyclohexylamine (0.26ml, 1.69mmol). The reaction mixture was stirred at 60°C for 10 min and then cooled to room temperature. After concentration in a vacuum, the residue was purified by chromatography to afford the title compound (80mg, 23%).

¹ H NMR (400MHz, CDCI ₃ ) 9.85 (s, 1 H), 8.18 (s, 1 H) ,3.87 (m 1 H), 3.58 (m 2H), 1.88 (m, 2H), 1.68 (m, 4H), 1.36 (m 2H), 1.03 (t, 3H). [Step 2] Preparation of {6-bromo-3-[cyclohexyl(ethyl)amino]pyrazin-2- yl}methanol

To a solution of 6-bromo-3-[cyclohexyl(ethyl)amino]pyrazine-2-carbaldehyde (80mg, 0.26mmol) of step 1 in methanol (1 ml) was dropwise added NaBH ₄ (30mg, 0.79mmol). The reaction mixture was stirred at room temperature for 30 min, and extracted with ethyl acetate. The extract was purified by chromatography to afford the title compound (40mg, 50%).

¹ H NMR (400MHz, CDCI ₃ ) 8.23 (s, 1 H), 4.64 (s, 2H), 3.31 (q, 2H), 3.07 (m, 1 H), 1.81-1.42 (m, 8H), 1.17 (m, 2H), 1.03 (t, 3H).

[Step 3] Preparation of 5-bromo-3-(chloromethyl)-N-cyclohexyl-N- ethylpyrazine-2-amine

To a solution of {6-bromo-3-[cyclohexyl(ethyl)amino]pyrazin-2-yl}methanol (40mg, 0.127mmol) in DMF (1 ml) was dropwise added SOCI ₂ (18mg, 0.153mmol). The reaction mixture was stirred at room temperature for 30 min, quenched with water, and then extracted with ethyl acetate. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated in a vacuum. The concentrate was used in a subsequent step without further purification. [Step 4] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({6-bromo- 3-[cyclohexyl(ethyl)amino]pyrazin-2-yl}methylH-methyl-oxazol idin-2-one

The same procedure as in step 4 of Example 54 was repeated, with the exception that 5-bromo-3-(chloromethyl)-N-cyclohexyl-N-ethylpyrazine-2-amin e was used instead of 5- bromo-3-(chloromethyl)-N-cyclohexyl-N-ethylpyridine-2-amine, to afford the title compound (150mg, 80%).

H NMR (400MHz, CDCI ₃ ) 8.23 (s, 1 H), 7.89 (s, 1 H), 7.79 (s, 1 H), 5.82 (d, 1 H), 4.91 (d, 1 H), 4.28 (m, 1 H), 4.21 (d, 1 H), 3.42 (m, 1 H), 3.23 (m, 1 H), 3.03 (m, 1 H), 1.83 (m, 10H), 0.96 (t, 3H), 0.72 (d, 3H).

[Step 5] Preparation of (4S,5R)-5-[3,5-bis(trif1uoromethyl)phenyl]-4-methyl-3- ({[2-(ethyl)(cyclohexyl)amino]-5-(3,5-dimethyl-isoxazol-4-yl )pyrazin-3-yl}methyl)- oxazolidin-2-one

The same procedure as in Example 58 was repeated, with the exception that (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({6-bromo-3- [cyclohexyl(ethyl)amino]pyrazin-2-yl}methyl)-4-methyl-oxazol idin-2-one was used instead of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-({5-br omo-2-

[cyclohexyl(ethyl)amino]pyridin-3-yl}methyl)-oxazolidin-2 -one, to afford the title compound (30mg, 70%) H NMR (400MHz, CDCI ₃ ) H NMR (400MHz, CDCI ₃ ) 8.27 (s,

1 H), 7.89 (s, 1 H), 7.74 (s, 2H), 5.69 (d, 1 H), 4.96 (d, 1 H), 4.14 (m, 1 H), 3.54 (m, 1 H), 3.22 (m, 1 H), 3.04 (m, 1 H), 2.64 (s, 3H), 2.50 (m, 3H), 1.91-1.45 (m, 10H), 1.00 (t, 3H), 0.72 (d, 3H). [Method 2]

[Step 1] Preparation of methyl 6-bromo-3-[cyclohexyl(ethyl)amino]pyrazine- 2-carboxylate

To a solution of methyl 2,5-dibromo pyrazine carboxylate (40g, 135mmol) in toluene (300ml) were dropwise added K ₂ CO ₃ (28g, 202mmol) and N-ethyl-N- cyclohexylamine (35g, 270mmol). The reaction mixture was refluxed at 120°C for 3 with stirring, and then cooled to room temperature. After extraction with ethyl acetate, the organic layer thus formed was washed with 2N HCI and further with water. Then, the organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated in a vacuum to afford the title compound (46g, 99%).

¹ H NMR (400MHz, CDCI ₃ ) 8.15 (s, 1 H), 3.92 (s, 3H), 3.50 (, 3H), 1.81 (m, 4H), 1.66 (m, 2H), 1.57 (m, 2H), 1.28 (m 2H), 1.12 (t, 3H). [Step 2] Preparation of methyl 3-[cyclohexyl(ethyl)amino]-6-(3,5- dimethylisoxazol-4-yl)pyrazine-2-carboxylate

Methyl 6-bromo-3-[cyclohexyl(ethyl)amino]pyrazine-2-carboxylate of step 1 and

3,5-dimethyl-4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-isoxazole were used in the same manner as in Example 45 to afford the title compound (33g, 68%).

H NMR (400MHz, CDCI ₃ ) 8.15 (s, 1 H), 3.96 (s, 3H), 3.54 (m, 3H), 2.49 (s, 3H), 2.39 (s, 3H), 1.85 (m, 4H), 1.67 (m, 2H), 1.59 (m, 2H), 1.31 (m, 2H), 1.16 (t, 3H).

[Step 3] Preparation of {6-bromo-3-[cyclohexyl(ethyl)amino]pyrazin-2- yl}methanol

To a solution of methyl 3-[cyclohexyl(ethyl)amino]-6-(3,5-dimethylisoxazol-4- yl)pyrazine-2-carboxylate (4.0g, 11.16mmol) of step 2 in ethylether (50ml) were dropwise methanol (1 ml) and 2M LiBH ₄ (12.3ml, 24.6mmol) at 0°C. One hour later, methanol (1 ml) and LiBH ₄ (12.3ml, 24.6mmol) were added again. The reaction mixture was also added with methanol (30ml) and then with NaBH ₄ (422mg, 11.26mmol), and stirred for 30 min at room temperature. The reaction was terminated with a saturated aqueous ammonium solution, followed by extraction with ethyl acetate. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated in a vacuum. The residue was purified by chromatography to afford the title compound (2.5g, 68%).

¹ H NMR (400MHz, CDCI ₃ ) 8.18 (s, 1 H), 4.71 (s, 2H), 4.34 (s, 1 H, exchanable proton), 3.39 (q, 2H), 3.19 (m, 1 H), 2.58 (s, 3H), 2.44 (s, 3H), 1.81 (m, 4H), 1.68 (m, 4H), 1.31 (m, 2H), 1.03 (t, 3H).

[Step 4] Preparation of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3- ({[2-(ethyl)(cyclohexyl)amino]-5-(3,5-dim

oxazolidin-2-one

{6-Bromo-3-[cyclohexyl(ethyl)amino]pyrazin-2-yl}methanol of Step 3 was used in the same manner as in steps 3 and 4 of Example 7, with the exception that {3- [cyclohexyl(ethyl)amino]-6-(3,5-dimethylisoxazol-4-yl)pyrazi n-2-yl}methanol was used instead of (2-[ethyl(tetrahydro-2H-pyran-4-yl)amino)-5-(trifluoromethyl )pyridin-3-yl) methanol, to afford the title compound (5.0g, 70%).

¹ H NMR (400MHz, CDCI ₃ ) 8.27 (s, 1 H), 7.89 (s, 1 H), 7.74 (s, 2H), 5.69 (d, 1 H), 4.96 (d, 1 H), 4.14 (m, 1 H), 3.54 (m, 1 H), 3.22 (m, H), 3.04 (m, 1 H), 2.64 (s, 3H), 2.50 (m, 3H), 1.91-1.45 (m, 10H), 1.00 (t, 3H), 0.72 (d, 3H).

[EXAMPLE 97] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[2-

(cyclopropyl)(cyclohexyl)amino]-5-(3,5-dimethyl-isoxazol- 4-yl)pyrazin-3-yl}methyl)-^ methyloxazolidin-2-one

The same procedure as in method 1 of Example 96 was repeated, with the exception that N-cyclopropyl-N-cyclohexylamine was used instead of N-ethyl-N- cyclohexylamine, to afford the title compound (32mg, 70%).

H NMR (400MHz, CDCI ₃ ) 8.28 (s, 1 H), 7.89 (s, 1 H), 7.78 (s, 2H), 5.80 (d, 1 H), 4.95 (d, 1 H), 4.33 (m, 1 H), 4.18 (m, 1 H), 3.10 (m, 1 H), 2.74 (m, 1 H), 1.81-1.13 (m, 14H), 0.74 (d, 3H). [EXAMPLE 98] (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(3,5- dimethylisoxazol^yl)-3-(piperidin-1-yl)pyra

The same procedure as in method 2 of Example 96 was repeated, with the exception that piperidine was used instead of N-ethyl-N-cyclohexylamine, to afford the title compound (520mg, 74%).

¹ H NMR (400MHz, CDCI ₃ ) 8.24 (s, 1 H), 7.89 (s, 1 H), 7.75 (s, 2H), 5.71 (d, 1 H), 5.03 (d, 1 H), 4.29 (d, 1 H), 4.23 (m, 1 H), 3.24 (m, 2H), 3.16 (m, 2H), 2.60 (s, 3H), 2.46 (s, 3H), 1.80 (m, 6H), 0.77 (d, 3H).

[EXAMPLE 99] (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(3,5- dimethylisoxazo -yl)-3-(2,6-dimethylmorpholino)pyrazin-2-yl]methyl}-4- methyloxazolidin-2-one

The same procedure as in method 2 of Example 96 was repeated, with the exception that 2,6-dimethylmorpholine was used instead of N-ethyl-N-cyclohexylamine to afford the title compound (510mg, 71 %).

¹ H NMR (400MHz, CDCI ₃ ) 8.26 (s, 1 H), 7.90 (s, 1 H), 7.75 (s, 2H), 5.72 (d, 1 H), 5.05 (d, 1 H), 4.27 (m, 2H), 3.94 (m, 1 H), 3.83 (m, 1 H), 3.43 (dd, 2H), 2.84 (m, 1 H), 2.68 (m, 3H), 2.46 (s, 3H), 1.27 (d, 6H), 0.73 (d, 3H).

[EXAMPLE 100] (4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[6-(3,5- dimethylisoxazoM-yl)-3-[3-(trifluoromethyl)piperidin-1-yl]py razin-2-yl]meth

methyloxazolidin-2-one

The same procedure as in method 2 of Example 96 was repeated, with the exception that 3-(2,2,2-trifluoromethyl)piperidine was used instead of N-ethyl-N- cyclohexylamine, to afford the title compound (50mg, 48%).

H NMR (400MHz, CDCI ₃ ) 8.29 (s, 1 H), 8.28 (s, 1 H), 7.75 (s, 2H), 5.71 (d, 1 H), 5.03 (d, 1 H), 4.29 (m, 2H), 3.75 (m, 1 H), 3.48 (m, 1 H), 3.05 (m, 2H), 2.82 (m, 1 H), 2.63 (m, 8H), 2.13 (m, 2H), 1.94 (m, 2H), 1.61 (m, 8H), 0.79 (m, 6H),

[EXAMPLE 101] (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({[3-

(cyclopentylmethyl)(ethyl)amino]^methyl6-(3,5-dimethyliso xazoW-yl)pyrazin yl}methyl)-oxazolidin-2-one

The same procedure as in step 2 of Example 96 was repeated, with the exception that N-(cyclopentylmethyl)ethaneamine was used instead of N-ethyl-N-cyclohexylamine, to afford the title compound (100mg, 30%).

H NMR (400MHz, CDCI ₃ ) 8.24 (s, 1 H), 7.89 (s, H), 7.74 (s, 2H), 5.70 (d, 1 H), 4.99 (d, 1 H), 4.30 (d, 1 H), 4.18 (m, 1 H), 3.40 (m, 2H), 3.12 (m, 1 H), 2.62 (s, 3H), 2.48 (s, 3H), 2.14 (m, 1 H), 1.68 (m, 8H), 1.17 (t, 3H), 0.73 (d, 3H).

[EXAMPLE 102] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(3,5-dimethyloxazol-4-yl) pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

[Stepl] Preparation of ethyl trans-4-({[3-({(4S,5S)-5-[3,5- bis(trifluoromethyl)phenyl]-4-methyl-2-oxazolidin-3-yl}methy l)-5-br^

yl]{[N-(ethyl)aminomethyl]cyclohexyl)}acetate

The same procedure as in method 2 of Example 96 was repeated, with the exception that ethyl trans-{4-[(N-ethylamino)methyl]cyclohexyl}acetate was used instead of N-ethyl-N-cyclohexylamine, to afford the title compound ethyl trans-4-({[3-({(4S,5S)-5-[3,5- bis(trifluoromethyl)phenyl]-4-methyl-2-oxazolidin-3-yl}methy l)-5-bromo-pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetate (120mg, 77%).

¹ H NMR (400 MHz, CDCI ₃ ): 8.16 (s, 1 H), 7.87 (s, 1 H), 7.77 (s, 2H), 5.78 (d, 1 H, J = 8.4 Hz), 4.87 (d, 1 H, J = 16.8 Hz), 4.31-4.27 (m, 1 H), 4.15-4.05 (m, 3H), 3.23-3.01 (m, 4H), 2.11 (d, 2H, J = 6.8 Hz), 1.73-1.71 (m, 5H), 1.46-1.38 (m, 1 H), 1.21 (t, 3H, J = 7.2 Hz), 1.10 (t, 3H, J = 7.2 Hz), 0.91-0.88 (m, 4H), 0.70 (d, 3H, J = 6.8 Hz).

[Step2] Preparation of ethyl trans-4-({[3-({(4S,5S)-5-[3,5- bis(trifluoromethyl)phenyl]-4-methyl-2-oxazolidin-3-yl}methy l)-5-(3,5-dimethyloxazol- 4-yl)pyrazin-2-yl]{[N-(ethyl)aminomethyl]cyclohexyl)}acetate

The title compound ethyl trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(3,5-dimethyloxazol-4-yl) pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetate (66mg, 49%) were prepared in the same as in Example 58.

¹ H NMR (600 MHz, CDCI ₃ ): 8.23 (s, 1 H), 7.89 (s, 1 H), 7.74 (s, 2H), 5.68 (d, 1 H, J = 8.4 Hz), 4.96 (d, 1 H, J = 16.8 Hz), 4.26 (d, 1 H, J = 16.8 Hz), 4.18-4.16 (m, 1 H), 4.11-4.07 (m, 2H), 3.34-3.22 (m, 3H), 3.34-3.01 (m, 1 H), 2.62 (s, 3H), 2.48 (s, 3H), 2.14 (d, 2H, J = 6.6 Hz), 1.78-1.71 (m, 5H), 1.52-1.48 (m, 1 H), 1.23 (t, 3H, J = 7.2 Hz), 1.14 (t, 3H, J = 7.2 Hz), 0.97-0.84 (m, 4H), 0.71 (d, 3H, J = 6.6 Hz).

[Step 3] Preparation of trans-4-({[3-({(4S,5S)-5-[3,5- bis(trifluoromethyl)phenyl]-4-methyl-2-oxazolidin-3-yl}methy l)-5-(3,5-dim

4-yl)pyrazin-2-yl]{[N-(ethyl)aminomethyl]cyclohexyl)}acet ic acid

To a solution of ethyl trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(3,5-dimethyloxazol-4-yl) pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetate (18mg) of step 2 in ethanol (2ml_) was dropwise added 4N NaOH (0.8ml_), followed by stirring at room temperature for 6 hrs. After neutralization with 2N HCI, the reaction mixture was extracted with ethyl acetate, and the organic layer was dried and concentrated in a vacuum. The residue was purified through a column to afford the title compound (50mg, 50%).

H NMR (600 MHz, CDCI ₃ ): 8.23 (s, 1 H), 7.89 (s, 1 H), 7.74 (s, 2H), 5.68 (d, 1 H, J = 8.4 Hz), 4.96 (d, 1 H, J = 16.8 Hz), 4.26 (d, 1 H, J = 16.8 Hz), 4.18-4.16 (m, 1 H), 3.34-3.22 (m, 3H), 3.34-3.01 (m, 1 H), 2.62 (s, 3H), 2.48 (s, 3H), 2.14 (d, 2H, J = 6.6 Hz), 1.78-1.71 (m, 5H), 1.52-1.48 (m, 1 H), 1.14 (t, 3H, J = 7.2 Hz), 0.97-0.84 (m, 4H), 0.71 (d, 3H, J = 6.6 Hz).

[EXAMPLE 103] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(pyrrolidin-1-yl)pyrazin- 2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

[Stepl] Preparation of ethyl trans-4-({[3-({(4S,5S)-5-[3,5- bis(trifluoromethyl)phenyl]-4 nethyl-2<>xaz

yl)pyrazin-2-yl]{[N-(ethyl)aminomethyl]cyclohexyl)}acetat e

Ethyl trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin 3-yl}methyl)-5-(3,5-dimethyloxazol-4-yl)pyrazin-2-yl]{[N-

(ethyl)aminomethyl]cyclohexyl)}acetate of step 2 of Example 102 was used in the same manner as in Example 88 to afford the title compound ethyl trans-4-({[3-({(4S,5S)-5-[3,5- bis(trifluoromethyl)phenyl]-4-methyl-2-oxazolidin-3-yl}methy l)-5-(pyrrolidin-1-yl)pyrazin-2- yl]{[N-(ethyl)aminomethyl]cyclohexyl)}acetate (35mg, 51 %).

¹ H NMR (600 MHz, CDCI ₃ ): 7.88 (s, 1 H), 7.77 (s, 1 H), 7.60 (s, 2H), 5.73 (d, 1 H, J = 8.4 Hz), 4.82 (d, 1 H, J = 16.8 Hz), 4.36-4.30 (m, 2H), 4.10-4.07 (m, 2H), 3.51-3.42 (m, 4H), 2.96-2.88 (m, 3H), 2.74-2.71 (m, 1 H), 2.12 (d, 2H, J = 6.6 Hz), 2.04-2.01 (m, 4H), 1.82-1.70 (m, 4H), 1.30-1.25 (m, 1 H), 1.22 (t, 3H, J = 7.2 Hz), 0.97 (t, 3H, J = 7.2 Hz), 0.96-0.85 (m, 4H), 0.73 (d, 3H, J = 6.0 Hz). [Step 2] Preparation of trans-4-({[3-({(4S,5S)-5-[3,5- bis(trifluoromethyl)phenyl]^-methyl-2-oxazolidin-3-yl}methyl )-5-(pyrrolW

yl)pyrazin-2-yl]{[N-(ethyl)aminomethyl]cyclohexyl)}acetic acid

The compound of step 1 was used in the same manner as in step 3 of Example 102 to afford the title compound (15mg, 98%).

¹ H NMR (600 MHz, CDCI ₃ ): 7.88 (s, 1 H), 7.77(s, 1 H), 7.61 (s, 2H), 5.73 (d, 1 H, J = 9.0 Hz), 4.83 (d, 1 H, J = 17.4 Hz), 4.36-4.30 (m, 2H), 3.51-3.44 (m, 4H), 3.00-2.85 (m, 3H), 2.71-2.78 (m, 1 H), 2.17 (d, 2H, J = 7.2 Hz), 2.04-2.01 (m, 4H), 1.82-1.69 (m, 5H), 0.98-0.85 (m, 7H), 0.73 (d, 3H, J = 6.0 Hz).

[EXAMPLE 104] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(1-meth^

(ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (23mg, 98%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600MHz, CDCI3): 8.45 (s, 1 H), 7.88 (s, 1 H), 7.73 (s, 2H), 6.76 (s, 1 H), 6.61-6.60 (m, 1 H), 6.21-6.20 (m, 1 H), 5.66 (d, 1 H, J = 8.4 Hz), 4.92 (d, 1 H, J = 17.4 Hz), 4.31 (d, 1 H, J = 16.2 Hz), 4.14-4.09 (m, 1 H), 3.96 (s, 3H), 3.35-3.12 (m, 3H), 3.11-2.88 (m, 1 H), 2.18 (d, 2H, J = 7.2 Hz), 1.78-1.63 (m, 5H), 1.48-1.42 (m, 1 H), 1.10 (t, 3H, J = 7.2 Hz), 0.98-0.84 (m, 4H), 0.67 (d, 3H, J = 6.6 Hz). ^* C0 ₂ H was not observed.

[EXAMPLE 105] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(thiophen-3-yl)pyrazin-2- yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (60mg, 78%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used. ¹ H NMR (600MHz, CDCI3): 8.50 (s, 1 H), 7.88 (s, 1 H), 7.82-7.81 (m, 1 H), 7.76 (s, 2H), 7.62-7.61 (m, 1 H), 7.43-7.42 (m, 1 H), 5.74 (d, 1 H, J = 9.0 Hz), 4.97 (d, 1 H, J = 16.8 Hz), 4.27-4.21 (m, 2H), 3.35-3.19 (m, 3H), 3.02-2.98 (m, 1 H), 2.18 (d, 2H, J = 6.6 Hz), 1.78- 1.65 (m, 5H), 1.52-1.45 (m, 1 H), 1.12 (t, 3H, J = 7.2 Hz), 0.98-0.87 (m, 4H), 0.72 (d, 3H, J = 6.6 Hz).

[EXAMPLE 106] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(1-methyl-1H-pyrazol-5-yl )pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (32mg, 84%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600MHz, CDCI3): 8.45 (s, 1 H), 7.89 (s, 1 H), 7.73 (s, 2H), 7.53 (d, 1 H, J = 1.8 Hz), 7.59 (d, 1 H, J = 1.8 Hz), 5.68 (d, 1 H, J = 9.0 Hz), 4.98 (d, 1 H, J = 16.2 Hz), 4.19 (s, 3H), 4.17-4.12 (m, 1 H)„ 3.41-3.22 (m, 3H), 3.03-3.02 (m, 1 H), 2.19 (d, 2H, J = 7.2 Hz), 1.79- 1.75 (m, 5H), 1.52-1.45 (m, H), 1. 5 (t, 3H, J = 7.2 Hz), 0.99-0.85 (m, 4H), 0.69 (d, 3H, J = 6.6 Hz).

[EXAMPLE 107] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(1 ,3-dimethyl-1 H-pyrazol-5-yl)pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (60mg, 96%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

1H NMR (400MHz, CDCI3): 8.39 (s, 1 H), 7.87 (s, 1 H), 7.71 (s, 2H), 6.35 (s, 1 H),

5.65 (d, 1 H, J = 8.0 Hz), 4.95 (d, 1 H, J = 16.8 Hz), 4.23 (d, 1 H, J = 16.8 Hz), 4.10-4.04 (m, 6H), 3.39-3.18 (m, 3H), 3.00-2.95 (m, 1 H), 2.30 (s, 3H), 2.11 (d, 2H, J = 6.0 Hz), 1.79-1.68 (m, 5H), 1.52-1.45 (m, 1 H), 1.22-1.16 (m, 3H), 1.13 (t, 3H, J = 6.8 Hz), 0.98-0.85 (m, 4H), 0.67 (d, 3H, J = 6.4 Hz).

[EXAMPLE 108] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-^

(ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (34mg, 89%) was prepared in the same manner as in Example

102, with the exception that the different reactant was used.

¹ H NMR (400MHz, CDCI3): 8.39 (s, 1 H), 7.87 (s, 1 H), 7.71 (s, 2H), 6.35 (s, 1 H), 5.65 (d, 1 H, J = 8.0 Hz), 4.95 (d, 1 H, J = 16.8 Hz), 4.23 (d, 1 H, J = 16.8 Hz), 4.10-4.04 (m, 6H), 3.39-3.18 (m, 3H), 3.00-2.95 (m, 1 H), 2.30 (s, 3H), 2.11 (d, 2H, J = 6.0 Hz), 1.79-1.68 (m, 5H), 1.52-1.45 (m, 1 H), 1.22-1.16 (m, 3H), 1.13 (t, 3H, J = 6.8 Hz), 0.98-0.85 (m, 4H), 0.67 (d, 3H, J = 6.4 Hz). ¹ H NMR (600MHz, CDCI3): 8.32 (s, 1 H), 7.88 (s, 1 H), 7.74 (s, 2H), 7.73 (s, 1 H), 5.69 (d, 1 H, J = 8.4 Hz), 4.94 (d, H, J = 16.8 Hz), 4.28 (d, 1 H, J = 16.8 Hz), 4.17-4.12 (m, 1 H), 3.90 (s, 3H), 3.31-3.13 (m, 3H), 2.95-2.92 (m, 1 H), 2.31 (s, 3H), 2.18 (d, 2H, J = 7.2 Hz), 1.78-1.70 (m, 5H), 1.48-1.42 (m, 1 H), 1.10 (t, 3H, J = 7.2 Hz), 0.97-0.85 (m, 4H), 0.69 (d, 3H, J = 6.6 Hz).

[EXAMPLE 109] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(3-methoxythiophen-2-yl)p yrazin

(ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (110mg, 95%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600MHz, CDCI3): 8.90 (s, 1 H), 7.88 (s, 1 H), 7.80 (s, 2H), 7.26 (s, 1 H), 6.94 (d, 1 H, J = 5.4 Hz), 5.88 (d, 1 H, J = 8.4 Hz), 4.95 (d, 1 H, J = 16.2 Hz), 4.43-4.38 (m, 2H), 4.20 (d, 1 H, J = 17.4 Hz), 3.99 (s, 3H), 3.28-3.16 (m, 3H), 3.02-2.99 (m, 1 H), 2.18 (d, 2H, J = 7.2 Hz), 1.79-1.69 (m, 5H), 1.48-1.42 (m, 1 H), 1.11 (t, 3H, J = 7.2 Hz), 0.96-0.84 (m, 4H), 0.74 (d, 3H, J = 6.6 Hz). [EXAMPLE 110] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(4-methylthiophen-???yl)p yrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (140mg, 95%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600MHz, CDCI3): 8.47 (s, 1 H), 7.88 (s, 1 H), 7.80 (s, 2H), 7.31 (s, 1 H), 6.95 (s, 1 H), 5.87 (d, 1 H, J = 8.4 Hz), 4.97 (d, 1 H, J = 17.4 Hz), 4.43-4.40 (m, 1 H), 4.20 (d, 1 H, J = 16.2 Hz), 3.28-3.21 (m, 3H), 3.07-3.04 (m, 1 H), 2.31 (s, 3H), 2.19 (d, 2H, J = 7.2 Hz), 1.79-1.70 (m, 5H), 1.48-1.45 (m, 1 H), 1.13 (t, 3H, J = 6.6 Hz), 0.93-0.88 (m, 4H), 0.75 (d, 3H, J = 6.6 Hz).

[EXAMPLE 111] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(3-methylthiophen-2-yl)py razin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (35mg, 99%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

1 H NMR (600MHz, CDCI3): 8.45 (s, 1 H), 7.88 (s, 1 H), 7.79 (s, 2Η), 7.27 (s, 1 H), 6.94-6.93 (m, 1 H), 5.87 (d, 1 H, J = 8.4 Hz), 4.98 (d, 1 H, J = 16.8 Hz), 4.45-4.42 (m, 1 H), 4.21 (d, 1 H, J = 17.4 Hz), 3.30-3.23 (m, 3H), 3.08-3.05 (m, 1 H), 2.52 (s, 3H), 2.19 (d, 2H, J = 6.6 Hz), 1.78-1.71 (m, 5H), 1.52-1.48 (m, 1 H), 1.14 (t, 3H, J = 6.6 Hz), 0.96-0.91 (m, 4H), 0.75 (d, 3H, J = 6.6 Hz).

[EXAMPLE 112] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(thiazol-2-yl)pyrazin-2-y l]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (70mg, 93%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

H NMR (600MHz, CDCI3): 8.92 (s, 1 H), 7.89 (m, 2H), 7.79 (s, 2H), 7.38 (s, 1 H),

5.84 (d, 1 H, J = 7.8 Hz), 4.97 (d, 1 H, J = 17.4 Hz), 4.35-4.33 (m, 1 H), 4.22 (d, 1 H, J = 16.2 Hz), 3.39-3.32 (m, 3H), 3.18-3.15 (m, 1 H), 2.19 (d, 2H, J = 7.2 Hz), 1.79-1.60 (m, 5H), 1.58- 1.52 (m, H), 1.18 (t, 3H, J = 6.6 Hz), 0.98-0.91 (m, 4H), 0.76 (d, 3H, J = 6.6 Hz).

[EXAMPLE 113] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(thiazol-4-yl)pyrazin-2-y l]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (160mg, 95%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600MHz, CDCI3): 8.95-8.91 (m, 2H), 7.95-7.79 (m, 2H), 7.75 (s, 2H), 5.73 (d, 1 H, J = 8.4 Hz), 4.97 (d, 1 H, J = 16.8 Hz), 4.28 (d, 1 H, J = 16.2 Hz), 4.15-4.10 (m, 1 H), 3.40-3.24 (m, 3H), 3.05-3.01 (m, 1 H), 2.17 (d, 2H, J = 7.2 Hz), 1.78-1.68 (m, 5H), 1.52-1.48 (m, 1 H), 1.14 (t, 3H, J = 7.2 Hz), 0.95-0.86 (m, 4H), 0.70 (d, 3H, J = 6.6 Hz).

[EXAMPLE 114] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(thiophen-2-yl)pyrazin-2- yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (110mg, 88%) was prepared in the same manner Example 102, with the exception that the different reactant was used.

¹ H NMR (600 MHz, CDCI ₃ ): 8.50(s, 1 H), 7.86(s, 1 H), 7.78(s, 2H), 7.49(dd, J 4.2 Hz), 7.34(d, 1 H, J = 4.8 Hz), 7.10(dd, 1 H, J = 4.2, 4.8 Hz), 5.86(d, 1 H, J = 8.4 Hz), 4.95(d, 1 H, J = 17.4 Hz), 4.43~4.38(m, 1 H), 4.19(d, 1 H, J = 17.4 Hz), 3.27~3.19(m, 3H), 3.06~3.02(m, 1 H), 2.16(d, 2H, J = 7.2 Hz), 1.77~1.68(m, 5H), 1.51~1.43(m, 1 H), 1..12(t, 3H, J = 7.2 Hz), 0.95~0.86(m, 4H), 0.74(d, 3H, J = 6.6 Hz)

[EXAMPLE 115] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(5-acetylthiophen-2-yl)py razin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (109mg, 90%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

H NMR (400 MHz, CDCI ₃ ): 8.50(s, 1 H), 7.86(s, 1 H), 7.78(s, 2H), 7.66(d, 1 H, J = 4.0 Hz), 7.46(d, 1 H, J = 4.0 Hz), 5.85(d, 1 H, J = 8.4 Hz), 4.96(d, 1 H, J = 16.4 Hz), 4.50~4.45(m, 1 H), 4.15(d, 1 H, J = 16.4 Hz), 3.33~3.14(m, 4H), 2.55(s, 3H), 2.15(d, 2H, J = 6.8 Hz), 1.76-1.64(m, 5H), 1.54~1.45(m, 1 H), 1.15(t, 3H, J = 6.8 Hz), 0.77(d, 3H, J = 6.8 Hz).

[EXAMPLE 116] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-phenylpyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (112mg, 78%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600MHz, CDCI ₃ ): 8.60(s, 1 H), 7.95(d, 2H, J = 7.8 Hz), 7.86(s, 1 H), 7.74(s, 2H), 7.46(t, 2H, J = 7.8 Hz), 7.38(t, 1 H, J = 7.8 Hz), 5.72(d, 1 H, J = 9.0 Hz), 4.99(d, 1 H, J = 16.8 Hz), 4.26(d, 1 H, J = 16.2 Hz), 4.25~4.22(m, 1 H), 3.33-3.21 (m, 3H), 3.05-3.01 (m, H), 2.16(d, 2H, J = 6.6 Hz), 1.78~1.63(m, 5H), 1.52-1.45(m, 1 H), 1.12(t, 3H, J = 6.6 Hz), 0.96~0.85(m, 4H), 0.71 (d, 3H, J = 6.6 Hz)

[EXAMPLE 117] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(4-cyanophenyl)pyrazin-2- yl]{[N- (ethyl)aminometh l]cyclohexyl)}acetic acid

The title compound (70mg, 45%) was prepared in the same manner as in Example 02, with the exception that the different reactant was used. ¹ H NMR (600MHz, CDCI3): 8.62 (s, 1 H), 8.07-8.06 (m, 2H), 7.89 (s, 1 H), 7.76-7.74 (m, 4H), 5.71 (d, 1 H, J = 7.8 Hz), 4.98 (d, 1 H, J = 16.2 Hz), 4.26 (d, 1 H, J = 16.2 Hz), 4.16- 4.11 (m, 1 H), 3.40-3.30 (m, 3H), 3.14-3.11 (m, 1 H), 2.19 (d, 2H, J = 6.6 Hz), 1.77-1.66 (m, 5H), .54-1.50 (m, 1 H), 1.17 (t, 3H, J = 6.6 Hz), 0.98-0.83 (m, 4H), 0.72 (d, 3H, J = 6.0 Hz).

[EXAMPLE 118] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(4-hydroxymethylphenyl)py razin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (25mg, 16%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600MHz, CDCI3): 8.61 (s, H), 7.97 (d, 2H, J = 8.4 Hz), 7.88 (s, 1 H), 7.75 (s, 2H), 7.48 (d, 2H, J = 8.4 Hz), 5.73 (d, 1 H, J = 8.4 Hz), 5.00 (d, H, J = 16.2 Hz), 4.77 (s, 2H), 4.29-4.22 (m, 2H), 3.36-3.24 (m, 3H), 3.07-3.03 (m, 1 H), 2.19 (d, 2H, J = 7.2 Hz), 1.82- 1.69 (m, 5H), 1.52-1.48 (m, 1 H), 1.15 (t, 3H, J = 7.2 Hz), 0.99-0.87 (m, 4H), 0.73 (d, 3H, J = 6.0 Hz).

[EXAMPLE 119] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(pyridin-3-yl)pyrazin-2-y l]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (140mg, 88%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

H NMR (600MHz, CDCI3): 9.23 (s, 1H), 8.61 (m, 2H), 8.27 (d, 1H, J = 7.8 Hz), 7.88 (s, 1H), 7.77 (s, 2H), 7.46-7.43 (m, 1H), 5.80 (d, 1H, J = 8.4 Hz), 5.01 (d, 1H, J = 16.2 Hz), 4.33-4.19 (m, 2H), 3.37-3.27 (m, 3H), 3.13-3.10 (m, 1H), 2.18 (d, 2H, J = 7.2 Hz), 1.82- 1.68 (m, 5H), 1.56-1.50 (m, 1H), 1.17 (t, 3H, J = 6.6 Hz), 0.98-0.84 (m, 4H), 0.74 (d, 3H, J = 6.6 Hz).

*C0 ₂ H was not observed.

[EXAMPLE 120] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(5-fluoropyridin-3-yl)pyr azin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (140mg, 91%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600MHz, CDCI3): 9.01 (s, 1H), 8.60 (s, 1H), 8.47 (s, 1H), 7.95 (d, 1 H, J = 9.0 Hz), 7.88 (s, 1H), 7.76 (s, 2H), 5.76 (d, 1H, J = 8.4 Hz), 5.00 (d, 1 H, J = 16.2 Hz), 4.27- 4.23 (m, 2H), 3.38-3.33 (m, 3H), 3.17-3.13 (m, 1H), 2.19 (d, 2H, J = 7.2 Hz), 1.82-1.68 (m, 5H), 1.54-1.50 (m, 1H), 1.18 (t, 3H, J = 6.6 Hz), 0.97-0.87 (m, 4H), 0.75 (d, 3H, J = 6.6 Hz).

[EXAMPLE 121] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(cyclopropylpyrazin-2-yl) ]{[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (60mg, 91 %) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

H NMR (400MHz, CDCI3): 8.07 (s, 1H), 7.87 (s, 1H), 7.75 (s, 2H), 5.70 (d, 1H, J = 8.4 Hz), 4.83 (d, 1H, J = 16.8 Hz), 4.21-4.09 (m, 2H), 3.18-3.03 (m, 3H), 2.92-2.87 (m, 1 H), 2.16 (d, 2H, J = 6.8 Hz), 2.03-1.97 (m, 1 H), 1.75-1.68 (m, 5H), 1.41-1.32 (m, 1H), 1.06-0.87 (m, 11H), 0.67 (d, 3H, J = 6.4 Hz).

[EXAMPLE 122] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(cyclobutylpyrazin-2-yl)] {[N- (ethyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (100mg, 90%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600 MHz, CDCI ₃ ): 7.96(s, H), 7.87(s, 1H), 7.75(s, 2H), 5.75(d, 1H, J = 8.4 Hz), 4.92(d, 1H, J = 16.2 Hz), 4.28~4.24(m, H), 4.23(d, H, J = 16.8 Hz), 3.66~3.57(m, 1H), 3.20~3.09(m, 3H), 2.95~2.91(m, 1H), 2.32~2.27(m, 4H), 2.15(d, 2H, J = 7.2 Hz), 2.08~2.03(m, 1H), 1.96~1.88(m, 1H), 1.79~1.62(m, 5H), 1.41-1.33(m, 1H), 1.23~1.18(m, 1 H), .06(t, 3H, J = 6.6 Hz), 0.95~0.80(m, 4H), 0.70(d, 3H, J = 6.6 Hz)

[EXAMPLE 123] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(3,5-dimethyloxazol-4-yl) pyrazin-2-yl]{[N- (propyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (35mg, 98%) was prepared in the same manner as in Example 02, with the exception that the different reactant was used.

H NMR (400 MHz, CDCI ₃ ): 8.20 (s, 1H), 7.87 (s, H), 7.72 (s, 2H), 5.65 (d, 1H, J = 8.4 Hz), 4.94 (d, 1H, J = 16.8 Hz), 4.23 (d, 1 H, J = 16.4 Hz), 4.17-4.07 (m, 1H), 3.32-3.02 (m, 4H), 2.60 (s, 3H), 2.46 (s, 3H), 2.17 (d, 2H, J = 7.2 Hz), 1.78-1.48 (m, 9H), 0.92-0.81 (m, 7H), 0.99 (d, 3H, J = 6.8 Hz).

[EXAMPLE 124] ΐΓ3η8-4-({[3-({(48,58)-5-[3,5^Ϊ5(ΙΐΊΑυθΓθΓηβ� � γΙ)ρίιβηγΙ]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(pyrrolidin-1-yl)pyrazin- 2-yl]{[N- (propyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (90mg, 98%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600 MHz, CDCI ₃ ): 7.88 (s, 1 H), 7.77 (s, 2H), 7.59 (s, 1H), 5.74 (d, 1H, J = 7.2 Hz), 4.81 (d, 1H, J = 16.8 Hz), 4.37-4.30 (m, 2H), 3.57-3.43 (m, 4H), 2.92-2.17(m, 4H), 2.11 (d, 2H, J = 6.6 Hz), 2.05-1.98 (m, 4H), 1.78-1.61 (m, 5H), 1.48-1.38 (m, 2H), 1.26-1.21 (m, 1 H), 0.94-0.82 (m, 7H), 0.64 (d, 3H, J = 7.2 Hz).

[EXAMPLE 125] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifIuoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(cyclohexylpyrazin-2-yl)] {[N- (propyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (80mg, 99%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (600MHz, CDCI3): 8.08 (s, 1H), 7.89 (s, 1H), 7.77 (s, 2H), 5.71 (d, 1 H, J = 7.8 Hz), 4.85 (d, H, J = 16.2 Hz), 4.21-4.14 (m, 2H), 3.21-2.94 (m, 4H), 2.18 (d, 2H, J = 6.0 Hz), 2.04-2.01 (m, 1H), 1.77-1.65 (m, 5H), 1.58-1.38 (m, 3H), 1.01-0.82 (m, 11H), 0.68 (d, 3H, J = 4.8 Hz).

[EXAMPLE 126] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(3,5-dimethyloxazol-4-yl) pyrazin-2-yl]{[N- (methyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (70mg, 99%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (400 MHz, CDCI ₃ ): 8.17(s, 1H), 7.87(s, 1H), 7.72(s, 2H), 5.66(d, 1H, J = 8.4 Hz), 5.00(d, 1H, J = 16.8 Hz), 4.23(d, 1H, J = 16.0 Hz), 3.26~3.06(m, 2H), 2.94(s, 3H), 2.58(s, 3H), 2.44(s, 3H), 2.20(d, 2H, J = 7.2 Hz), 1.82-1.58(m, 6H), 1.03~0.88(m, 4H), 0.71 (d, 3H, J = 6.4 Hz)

[EXAMPLE 127] trans-4-({[3-({(4S _> 5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(pyrrolidin-1-yl)pyrazin- 2-yl]{[N- (methyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (70mg, 92%) was prepared in the same manner as in Example 02, with the exception that the different reactant was used.

¹ H NMR (400 MHz, CDCI ₃ ): 7.87 (s, 1 H), 7.76 (s, 2H), 7.55 (s, 1 H), 5.72 (d, 1 H, J = 8.8 Hz), 4.82 (d, 1 H, J = 17.2 Hz), 4.36-4.28 (m, 2H), 3.52-3.38 (m, 4H), 2.86-2.78 (m, 1 H), 2.74-2.66 (m, 1 H), 2.59 (s, 3H), 2.18 (d, 2H, J = 6.8 Hz), 2.04-1.98 (m, 4H), 1.86-1.72 (m, 5H), 1.42-1.36 (m, 1 H), 0.98-0.84 (m, 4H), 0.73 (d, 3H, J = 6.4 Hz).

[EXAMPLE 128] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(cyclobutylpyrazin-2-yl)] {[N- (methyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (60mg, 92%) was prepared in the same manner as in Example 102, with the exception that the different reactant was used.

¹ H NMR (400 MHz, CDCI ₃ ): 7.93(s, 1H), 7.87(s, 1 H), 7.75(s, 2H), 5.75(d, 1H, J = 8.0 Hz), 4.96(d, 1H, J = 16.8 Hz), 4.30~4.24(m, 2H), 3.62~3.57(m, 1H), 3.12~3.07(m, 1H), 3.00~2.93(m, 1H), 2.83(s, 3H), 2.32~2.26(m, 3H), 2.19(d, 2 _. H, J = 6.4 Hz), 2.11~1.99(m, 1H), 1.96~1.89(m, 1H), 1.81~1.50(m, 7H), 1.00~0.82(m, 4H), 0.72(d, 3H, J = 6.8 Hz)

[EXAMPLE 129] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(cyclopentylpyrazin-2-yl) ]{[N- (methyl)aminomethyl]cyclohexyl)}acetic acid

The title compound (50mg, 79%) was prepared from the same manner as in Example 102, with the exception that trans-{4-[(N-methylamino)methyl]cyclohexyl}acetatein and a different reactant were used.

¹ H NMR (400 MHz, CDCI ₃ ): 7.97(s, 1H), 7.86(s, 1H), 7.74(s, 2H), 5.71 (d, 1H, J = 8.0 Hz), 4.93(d, 1H, J = 16.8 Hz), 4.23-4.17(m, 2H), 3.15~3.05(m, 2H), 2.98~2.83(m, 1H), 2.81 (s, 3H), 2.18(d, 2H, J = 6.8 Hz), 2.08-1.97(m, 2H), 1.83~1.56(m, 12H), 1.00~0.85(m, 4H), 0.70(d, 3H, J = 6.8 Hz).

[EXAMPLE 130] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(3,5-dimethyloxazol-4-yl) pyrazin-2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}propanol

A solution of trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2- oxazolidin-3-yl}methyl)-5-(3,5-dimethyloxazol-4-yl)pyrazin-2 -yl]{[N-

(ethyl)aminomethyl]cyclohexyl)}acetic acid (100mg, 0.14mmol), prepared in Example 102, in THF (2mL) was cooled to 0°C and slowly added with drops of LAH (11mg, 0.28mmol). Then, the solution was stirred for 1 hr, added with drops of sodium sulfate decahydrate, and stirred again for 6 hrs. The reaction mixture was filterd through a celite-pad, concentrated in a vacuum, and purified through a column to afford the title compound (25mg, 26%).

¹ H NMR (600MHz, CDCI3): 8.23 (s, 1H), 7.89 (s, 1H), 7.74 (s, 2H), 5.68 (d, 1H, J = 9.0 Hz), 4.97 (d, H, J = 16.8 Hz), 4.27 (d, 1H, J = 16.8 Hz), 4.18-4.15 (m, 1H), 3.69-3.65 (m, 2H), 3.33-3.21 (m, 3H), 3.04-3.00 (m, 1H), 2.62 (s, 3H), 2.48 (s, 3H), 1.78-1.74 (m, 5H), 1.45-1.30 (m, 3H), 1.14 (t, 3H, J = 7.2 Hz), 0.94-0.83 (m, 4H), 0.71 (d, 3H, J = 6.6 Hz).

[EXAMPLE 131] trans-4-({[3-({(4S,5S)-5-[3,5-bis(trifluoromethyl)phenyl]-4- methyl-2-oxazolidin-3-yl}methyl)-5-(pyrrolidin-4-yl)pyrazin- 2-yl]{[N- (ethyl)aminomethyl]cyclohexyl)}propanol

The title compound (70mg, 51 %) was prepared in the same manner as in Example 102, with the exception that the the compound of Example 103 was used as a reactant.

H NMR (600MHz, CDCI3): 7.88 (s, 1 H), 7.77 (s, 2H), 7.60 (s, 1 H), 5.73 (d, 1 H, J = 9.0 Hz), 4.83 (d, 1 H, J = 17.4 Hz), 4.35 (d, 1 H, J = 16.8 Hz), 4.33-4.30 (m, 1 H), 3.65 (t, 2H, J = 6.6 Hz), 3.52-3.40 (m, 4H), 2.97-2.90 (m, 3H), 2.74-2.71 (m, 1 H), 2.05-2.02 (m, 4H), 1.82- 1.70 (m, 5H), 1.44-1.25 (m, 3H), 0.97 (t, 3H, J = 7.2 Hz), 0.90-0.81 (m, 4H), 0.73 (d, 3H, J = 7.2 Hz).

[TEST EXAMPLE 1] In Vivo Assay for Inhibitory Activity against CETP in Human Blood

A CETP activity kit (#RB-CETP) was purchased from Roar Biochemical, Inc. A donor and an acceptor (each, 4 ul), a 10x assay buffer (177ul), and each of dilutions of test compounds in dimethylsulfoxide (DMSO, Sigma-Aldrich) (0.01 nM ~ ΙΟΟΟΟηΜ) were added to each well of black round-bottom 96-well plates (Corning #3792). Plasma samples from healthy men were diluted in the assay buffer (1 :10 = plasma: assay buffer), and added to each well. The plates were sealed with a sealing film (Sigma-Aldrich, #Z369659), and incubated in a 37 ^° C incubator microplate shaker (#SLST-3, Seolin Bio) for 3 hrs. After removal of the sealing film, fluorescence was read on Spectra Max Gemini EM (Molecular devices) with an excitation wavelength of 465 nm and an emission wavelength of 535 nm. Measurements were calculated according to the following formula. Calculated value = (Fluorescence Intensity with both compound and plasma -

Fluorescence Intensity with compound but without plasma)/(Fluorescence Intensity with plasma but without compound - Fluorescence Intensity with neither compound nor plasma)

From the calculated value, a sigmoidal curve (y=start+(end-start)x ⁿ /k ⁿ +x ⁿ ) was drawn using Origin Software (OriginLab Corporation, ver. 8.0724) to obtain IC ₅ o values. IC ₅₀ values of the compounds of the Examples are summarized in Table 2, below. As their IC ₅ o values were measured to be less than 10μΜ, particularly, below 0.5μΜ, the compounds exhibited excellent inhibitory activity against CEPT. TABLE 2 In vivo Inhibition of CETP Activity in Human Plasma

10 0.060 77 0.0021

11 0.317 78 0.0177

14 0.098 79 0.0243

15 0.010 80 0.022

16 0.075 81 0.0265

17 0.379 82 0.2459

18 0.091 84 0.0297

20 0.059 85 0.0319

21 0.114 86 0.0304

22 0.010 87 0.0056

23 0.0444 88 0.0107

24 0.1854 89 0.007

25 0.108 90 0.0118

26 0.100 91 0.0267

27 0.430 92 0.048

29 0.54 95 0.0038

31 0.108 96 0.002

32 0.410 97 0.01161

33 0.0399 98 0.00261

34 0.062 99 0.0831

35 0.020 100 0.0156

36 0.220 101 0.00345

37 0.498 102 0.00065 38 0.0193 103 0.00326

39 0.492 104 0.0038

40 0.0198 105 0.0008

41 0.0024 106 0.0303

43 0.0079 107 0.0370

44 0.0570 108 0.0459

45 0.0269 109 0.00384

46 0.0280 110 0.05617

47 0.0450 111 0.00311

48 0.133 112 0.03744

49 0.0237 113 0.01604

50 0.0111 114 0.0103

51 0.0127 116 0.00629

52 0.0734 117 0.01172

53 0.0052 119 0.07816

54 0.019 120 0.02475

55 0.0111 121 0.00388

56 0.0109 122 0.00468

57 0.0167 123 0.00719

58 0.0027 124 0.00713

59 0.0057 125 0.04027

60 0.0347 126 0.0170

62 0.1507 127 0.043 63 0.0189 128 0.0239

64 0.0293 129 0.03401

65 0.2235 130 0.00886

66 0.0463 131 0.00498

68 0.3336

ITEST EXAMPLE 21 Effect on CETP Activity in Hamster Administered with Single Dose

Each of the compounds of the Examples was orally administered at a dose of 100 mg/kg to three 7-week-old male Golden Syrian hamsters per group. Blood samples were taken from the retro-orbital plexus before administration and 0.5, 1 , 2, 4, 6, 8, and 24 hrs after administration, and measured for blood CETP activity using a Roar CETP activity assay kit (Cat#: RB-CETP, Roar Biomedical Inc.).

As shown in Table 3, compounds of Examples 50, 56, 58, 77, 87, 88, 89, 96, 103, 105, 124 and 125 inhibited CETP activity by 45-72% to the maximum, compared to pre- treatment.

TABLE 3: Inhibition of CETP Activity in Hamsters Administered with Single Dose

87 59

88 45

89 53

96 56

103 52

105 72

124 52

125 56

[TEST EXAMPLE 31 Assay for Blood Lipid Level and Drug Concentration in

Hamster Administered with Multiple Doses

Each of the compounds of Examples 58, 96, 103 and 125 was orally administered at a dose of 10 mg/kg to 10 7-week-old male Golden Syrian Hamsters per group, every day for two weeks. Two hours after the final administration, blood samples were taken from the hamsters which then underwent an autopsy to analyze blood lipid levels and drug concentrations in blood and tissues (adipose tissues and liver)

As shown in Table 4, the compounds of the Examples effectively increased HDL levels.

TABLE 4: Effect of Compounds on Blood HDL-C Level in Multi-Dosed Hamsters 96 48

103 47

125 27

In addition, as is understood from data of Table 5, compounds of Examples 58 and 96 were detected at low levels in blood and liver tissues, but at high levels in adipose tissues, showing a liphophilic distribution mode. In most animal species, fats are known as a main organ expressing CETP. Particularly, there is a correlation of CETP expression between fat and blood in humans and hamsters (Atherosclerosis, 1998; 139: 369-376, J Lipid Res. 34: 845-852). The compounds with lipophilicity are considered to effectively inhibit CETP in adipose tissues after CETP is generated from adipose tissues, and thus, can effectively improve HDL-C, as shown in Table 4, in spite of their low blood concentrations.

TABLE 5: Concentrations of Drug in Blood and Tissues of Hamsters Administered with Multiple Doses