KR101657596B1 - 4,5-dihydro-1h-pyrazole derivatives or salts thereof and pharmaceutical composition comprising the same - Google Patents

Abstract

The present invention provides a 4,5-dihydro-1H-pyrazole derivative or a pharmaceutically acceptable salt thereof, a process for preparing the same, and a pharmaceutical composition containing the same. The 4,5-dihydro-1H-pyrazole derivative or a pharmaceutically acceptable salt thereof effectively increases the LXR transcriptional activity and is useful for prevention and treatment of cholesterol metabolism including cholesterol gallstone, hyperlipidemia, coronary and atherosclerosis, Can be usefully applied.

Description

4,5-DIHYDRO-1H-PYRAZOLE DERIVATIVES OR SALTS THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a 4,5-dihydro-1H-pyrazole derivative or a salt thereof,

The present invention relates to a 4,5-dihydro-1H-pyrazole derivative or a pharmaceutically acceptable salt thereof, a process for preparing the same, and a pharmaceutical composition containing the same.

Nuclear receptors are receptors in the nucleus of the cell. A total of 48 human nuclear receptors are known and are involved in various transcription programs in vivo. Nuclear receptors are usually present as heterodimers or homodimer complexes and are inactive by corepressors. An endogenous ligand or an artificial ligand, which is caused by external stimuli or changes in the body, separates the secondary inhibitory substance, invokes a coactivator and binds to the receptor, and transcription factors (McKenna, NJ et al., Endocrinol. 2009, 23: 740-746). In addition, posttranslational modifications such as acetylation, phosphorylation, ubiquitination and the like play an important role in regulating the activity of nuclear receptors.

Liver X receptor (LXR), a nuclear receptor, is a transcription factor involved in the regulation of cholesterol homeostasis in the body and is activated by the endogenous ligand oxysterols. Oxysterol is an oxidized form of cholesterol, formed by metabolism of cholesterol in the body (Lehmann, et al. J. Biol. Chem. 1997, 272 (6): 3137-3140). LXR has two types of alpha and beta, and the homology of the lignad binding domain (LBD) of the two receptors is about 77%. LXRα is mainly present in the liver, and LXRβ is present throughout the body (Willy, et al. Gene Dev. 1995, 9 (9): 1033-1045). LXR promotes cholesterol release through reverse cholesterol transport (RCT) from peripheral to liver. Two RCTs (cholesterol transporters) play an important role in the RCT, with the ATP-binding casette transporter A1 and the ATP-binding casette transporter G1 of the macrophage playing an important role, while the LXR ligands Activating RCT by increasing gene expression of ABC-A1 / G1 (J Clin Invest 2006, 116 (3): 607-614).

Overexpression of ABC-A1 in apoE knockout mice, a model of atherosclerotic disease, resulted in a 66% reduction in intravascular atherosclerotic lesions (Singaraja, et al. J Clin Invest 2002, 110 (1) 42). Knockout of the LXRα gene results in the loss of normal cholesterol-regulating ability, resulting in an increase in blood LDL, a decrease in HDL, and a decrease in the expression of lipid-related genes (Peet et al. Cell 1998, 93 : 693-704). Double knockout of LXR alpha / beta resulted in a decrease in cholesterol transporter expression, an increase in lipid accumulation in macrophages, an increase in the induction of arteriosclerosis, and a decrease in HDL in humans, (Tangirala et al., PNAS 2002, 99 (18): 11896-11901). It has also been reported that the gene expression of ABC-A1 and ABC-G1 is dramatically increased when synthetic LXR ligands are treated in peripheral blood monocytes (PBMC) of humans (Diblasio-Smith et al. J Transl Med 2008, 6 (59): 1-15). When the correlation between ABC-A1 / G1 expression and plasma drug concentration was measured after a single dose of synthetic LXR ligand in healthy normal subjects, the expression of ABC-A1 / G1 was found to increase in proportion to the blood drug concentration (Katz et al. J Clin Pharmacol 2009, 49: 643-649).

Thus, ligands that increase LXR transcriptional activity are expected to be useful for the prevention and treatment of cholesterol metabolism including cholesterol gallstones, cholesterol gallstones, hyperlipidemia, coronary and atherosclerosis, and the like.

The present inventors have discovered that 4,5-dihydro-1H-pyrazole derivatives or pharmaceutically acceptable salts thereof are useful for preventing or treating cholesterol metabolism by increasing LXR transcriptional activity.

Accordingly, it is an object of the present invention to provide the 4,5-dihydro-1H-pyrazole derivative or a pharmaceutically acceptable salt thereof, a process for producing the same, and a pharmaceutical composition containing the same.

According to one aspect of the present invention there is provided a 4,5-dihydro-1H-pyrazole derivative or a pharmaceutically acceptable salt thereof.

According to another aspect of the present invention there is provided a process for the manufacture of said compound or a pharmaceutically acceptable salt thereof.

According to still another aspect of the present invention there is provided a pharmaceutical composition for preventing or treating cholesterol metabolism including cholesterol gallstone, hyperlipidemia, or coronary and atherosclerosis, comprising the compound or a pharmaceutically acceptable salt thereof as an active ingredient do.

The compounds according to the invention, i.e. 4,5-dihydro-lH-pyrazole derivatives or their pharmaceutically acceptable salts, effectively increase LXR transcriptional activity. Accordingly, the 4,5-dihydro-1H-pyrazole derivative or a pharmaceutically acceptable salt thereof can be usefully used for the prevention and treatment of cholesterol metabolism including cholesterol gallstone, hyperlipidemia, coronary atherosclerosis and the like.

The term " alkyl " refers to an aliphatic hydrocarbon radical, including both linear and branched hydrocarbon radicals. For example, C ₁ -C ₆ alkyl is an aliphatic hydrocarbon group having from 1 to 6 carbon atoms, methyl, ethyl, propyl, n - butyl, n - pentyl, n - hexyl, isopropyl, isobutyl, sec - butyl, tert -Butyl, neopentyl, isopentyl and the like.

The term " alkoxy ", unless otherwise defined, means a radical in which the hydrogen atom of the hydroxy group is substituted with an alkyl, for example C ₁ -C ₆ alkoxy is methoxy, ethoxy, propoxy, n- , n-pentyloxy, isopropoxy, sec -butoxy, tert -butoxy, neopentyloxy, isopentyloxy and the like.

The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof.

Wherein,

L and L 'are, independently of each other, - (CH ₂ ) _n -, n is 0, 1, 2, or 3,

Ring X and Ring Y are independently of each other C ₃ -C ₆ cycloalkyl, aryl, heteroaryl, or a heterocyclic ring,

R ₁ And R < ₃ > are independently of each other hydrogen or halogen,

R ₂ And R < ₄ > are, independently of each other, hydrogen; halogen; C ₁ -C ₅ alkyl optionally one or more optionally substituted with halogen; C ₁ -C ₅ alkoxy; An aryl group; A heteroaryl group; Or a heterocyclic group,

;

; -OR; -COR; -CO₂R; -OC(=O)R; -OCO₂R; -OC(=O)NRR'; -NR''C(=O)R'''; -NR''C(=O)OR'''; -NR''SO₂R'''; -CONR''R'''; 및 -NR''R'''로 이루어진 군으로부터 하나 이상 선택된 치환기로 선택적으로 치환될 수 있고,R ₂ And R ₄ are, independently of each other, an aryl group, a heteroaryl group or a heterocyclic group, the aryl group, the heteroaryl group or the heterocyclic group may be substituted with halogen; Hydroxy; Cyano; Azaido; C ₁ -C ₅ alkyl optionally substituted with one or more selected substituents from the group consisting of halogen, hydroxy, and hydroxyimino; C ₂ -C ₆ alkenyl; C ₂ -C ₆ alkynyl; C ₃ -C ₆ cycloalkyl; Aryl; Heteroaryl; Heterocyclic; -SO ₃ H; -SO ₂ R; -SOR; -SR;

;

; -OR; -COR; -CO ₂ R; -OC (= O) R; -OCO ₂ R; -OC (= O) NRR ';-NR'C (= O) R ''';-NR'C (= O) OR ''';-NR''SO ₂ R '''; -CONR '' R '''; And < RTI ID = 0.0 > -NR " R '

Wherein R and R 'are independently from each other hydrogen; C ₁ -C ₅ alkyl optionally substituted with one or more selected substituents from the group consisting of halogen, hydroxy and C ₃ -C ₆ cycloalkyl; C ₃ -C ₆ cycloalkyl; One or more aryl optionally substituted with halogen; Aralkyl; Heteroaryl ; Or heterocyclic,

R " and R "'are independently from each other hydrogen; C ₁ -C ₅ alkyl optionally substituted with one or more selected substituents from the group consisting of halogen and hydroxy; C ₃ -C ₆ cycloalkyl; Or an aryl group,

p is 0, 1, 2, 3, 4, or 5,

R ₅ is CF ₂ CF ₃ or C (CF ₃ ) ₂ OH.

In one embodiment, R ₅ may be a C (CF _{3) 2} OH, wherein the compounds according to the invention has the structure of formula (1a) below.

<Formula 1a>

Wherein ring X, ring Y, L, L ', R ₁ , R ₂ , R ₃ , and R ₄ are as defined above.

In another embodiment of the present invention, ring Y can be benzene, wherein the compound according to the present invention has the structure:

&Lt; EMI ID =

In the formula, the rings X, L, L ', R ₁ , R ₂ , R ₃ , R ₄ , and R ₅ are as defined above.

In another embodiment of the present invention, ring Y can be pyridine, wherein the compound according to the present invention has the structure:

&Lt; Formula 1c >

In the formula, the rings X, L, L ', R ₁ , R ₂ , R ₃ , R ₄ , and R ₅ are as defined above.

In another embodiment of the present invention, ring Y can be a thiophene, wherein the compound according to the invention has the structure:

<Formula 1d>

In the formula, the rings X, L, L ', R ₁ , R ₂ , R ₃ , R ₄ , and R ₅ are as defined above.

Preferably, in the compounds of the present invention or pharmaceutically acceptable salts thereof, n is 0,

Ring X is benzene,

Ring Y is benzene, pyridine, or thiophene,

R ₁ And R &lt; ₃ &gt; are independently of each other hydrogen or halogen,

R ₂ is halogen; Phenyl; Pyridinyl; 1,2,3,6-tetrahydropyridinyl; Or piperazinyl,

When R ₂ is phenyl, pyridinyl, 1,2,3,6-tetrahydropyridinyl, or a piperazinyl group, the phenyl, pyridinyl, 1,2,3,6-tetrahydropyridinyl, or piperazine C ₁ -C ₅ alkylthio; C ₁ -C ₅ alkylsulfonyl; C ₃ -C ₆ cycloalkylsulfonyl; And C _{1 to} C ₅ alkoxycarbonyl, which may be optionally substituted with one or more groups selected from the group consisting of

R ₄ is halogen; A phenyl group; A heteroaryl group selected from the group consisting of furanyl, pyridinyl, pyrimidinyl, indolyl, benzofuranyl, benzothiophenyl, and quinolinyl; Or a heterocyclic group selected from the group consisting of 1,2,3,6-tetrahydropyridinyl, piperidinyl, piperazinyl, 1,1-dioxo-thiomorpholinyl and homopiperazinyl,

; 및

로 이루어진 군으로부터 하나 이상 선택된 치환기로 선택적으로 치환될 수 있고(식 중, R'' 및 R'''는, 서로 독립적으로, 수소, 하이드록시로 하나 이상 선택적으로 치환된 C₁∼C₅ 알킬, 또는 C₃∼C₆ 사이클로알킬이고, p는 0, 1, 2, 또는 3 이다),When R ₄ is a phenyl group, the phenyl group may be substituted with halogen; Hydroxy; Cyano; C ₁ -C ₅ alkyl optionally substituted with one or more substituents selected from the group consisting of halogen and hydroxy; C ₁ -C ₅ alkoxy optionally substituted by one or more halogen; C ₁ -C ₅ alkylthio; C ₁ -C ₅ alkylsulfonyl; C ₁ -C ₅ alkylsulfinyl; C ₁ -C ₅ alkylcarbonyl; Hydroxycarbonyl; Triazolyl; Tetrazolyl; -NR'R ''';-NR''SO ₂ R ''';-NR'C (= O) R ''';

; And

, Wherein R "and R '" are independently of each other hydrogen, C ₁ -C ₅ alkyl optionally substituted by one or more substituents selected from hydroxy, , Or C ₃ -C ₆ cycloalkyl and p is 0, 1, 2, or 3,

When R ₄ is a heteroaryl group or a heterocyclic group, the heteroaryl group or the heterocyclic group may be substituted with halogen; Cyano; C ₁ -C ₅ alkyl optionally one or more optionally substituted with halogen; C ₁ -C ₅ alkoxy; Formyl; C ₁ -C ₅ alkylthio; C ₁ -C ₅ alkylsulfonyl optionally substituted by one or more halogen; C ₃ -C ₆ cycloalkylsulfonyl; Benzenesulfonyl; Pyrrolidin-1-yl-sulfonyl; Mono or di-C ₁ -C ₅ alkylaminosulfonyl; C ₁ -C ₅ alkylcarbonyl optionally substituted with hydroxy; C ₃ -C ₆ cycloalkylcarbonyl; C ₃ -C ₆ cycloalkyl-C ₁ -C ₅ alkylcarbonyl; Benzoyl optionally substituted with halogen; Benzylcarbonyl; Thiophenecarbonyl; C ₁ -C ₅ alkoxycarbonyl; Hydroxycarbonyl; Mono or di-C ₁ -C ₅ alkylaminocarbonyl; Amino; C ₃ -C ₆ cycloalkylsulfonylamino; C ₁ -C ₅ alkoxycarbonylamino; Tetrazolyl, &lt; / RTI &gt; and &lt; RTI ID = 0.0 &gt;

R ₅ is C (CF ₃ ) ₂ OH.

In a preferred embodiment of the present invention, R &lt; ₃ &gt; may be hydrogen, wherein the compound according to the present invention has the structure of formula (Ie).

<Formula 1e>

Wherein ring X, ring Y, R ₁ , R ₂ , and R ₄ are as defined above, and n is 0.

In a preferred embodiment of the invention R &lt; ₃ &gt; is halogen; The ring X and the ring Y may be benzene, and the compound according to the present invention has a structure represented by the following formula (1f).

&Lt; Formula 1f >

Wherein R ₁ , R ₂ , and R ₄ are as defined above, R ₃ is halogen, and n is 0.

In a preferred embodiment of the invention R &lt; ₃ &gt; is hydrogen; R &lt; ₄ &gt; is halogen; Ring X and ring Y are benzene; R ₂ can be phenyl, pyridinyl, 1,2,3,6-tetrahydropyridinyl, or piperazine, and wherein the phenyl, pyridinyl, 1,2,3,6-tetrahydropyridinyl, or piperazine C ₁ -C ₅ alkylthio; C ₁ -C ₅ alkylsulfonyl; C ₃ -C ₆ cycloalkylsulfonyl; And C _{1 to} C ₅ alkoxycarbonyl.

The compound of formula (I) or a salt thereof may have a substituent including an asymmetric atom. In this case, the compound of formula (1) or a salt thereof may exist as an optical isomer such as (R), (S), or racemic have. Accordingly, unless otherwise indicated, the compound of Formula 1 or its salt includes all optical isomers such as (R), (S), or racemic (RS).

The compound of formula (I) of the present invention may be in the form of a pharmaceutically acceptable salt. The salts may be formed with conventional acid addition salts such as salts derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid or phosphoric acid and organic acids such as citric acid, lactic acid, tartaric acid, maleic acid, fumaric acid, formic acid, propionic acid, oxalic acid, Salts derived from organic acids such as benzoic acid, gluconic acid, methanesulfonic acid, glycolic acid, succinic acid, 4-toluenesulfonic acid, glutamic acid or aspartic acid. The salt may also be in the form of a conventional metal salt, for example, an alkali metal salt such as lithium, sodium, or potassium; Alkaline earth metal salts such as calcium or magnesium salts; Or chromium salts.

The compound of formula (I) or a pharmaceutically acceptable salt thereof according to the present invention can be prepared according to the following exemplary reaction scheme. It will be apparent to those skilled in the art that in the following reaction scheme, the order of the reactions can be changed according to the order of introduction of ring X, ring Y, R ₁ , R ₂ , R ₃ , and R ₄ .

The compound of formula (I) or a pharmaceutically acceptable salt thereof according to the present invention can be prepared according to the following reaction scheme (1).

<Reaction Scheme 1>

In the above reaction formula, ring X, ring Y, L, R ₁ , R ₂ , R ₃ , and R ₄ are the same as defined above, Hal is halogen, and PG ₁ is a carboxyl protecting group. R is hydrogen or a C ₁ ~C ₅ alkyl; Or they may form a ring of 5 or 5 rings containing boron and oxygen, and the ring may be substituted with C ₁ -C ₅ alkyl.

Aldehyde derivatives of compound 1 are commercially available. Compound 1 can be converted to Compound 2 (i.e., acid or sodium salt, potassium salt) by reacting Compound 1 with pyruvic acid. The reaction of the compound 1 with pyruvic acid can be carried out according to a known method (Meng, Qinghua; Zhu, Lufeng; Zhang, Zhaoguo; Journal of Organic Chemistry , 73, 7209-7212, 2008).

The compound 2 can be converted to the ester derivative Compound 3 by reacting with an alkyl alcohol or an alkyl halide in the presence of an acid or a base. At this time, the available carboxyl protecting group (PG ₁ ) may preferably be a C ₁ -C ₆ alkyl group such as methyl, ethyl, isobutyl, tert-butyl and the like.

Compound 3 or Compound 9 can be converted to Compound 5 or Compound 11 by condensation with Compound 4 or a hydrazine derivative of Compound 10. The hydrazine derivatives of Compound 4 or Compound 10 are commercially available. The condensation can be carried out according to known methods (Srivastava, Brijesh Kumar, Joharapurkar, Amit, Raval, Saurin, Patel, Jayendra Z .; Soni, Rina, Raval, Preeti, Gite, Archana, Goswami, Amitgiri, Sadhwani, Nisha, Gandhi, Neha, Patel, Harilal, et al. Journal of Medicinal Chemistry , 50, 5951-5966, 2007).

The compound 5 or compound 11 mono and di-CF ₃ using a commercially available CF ₃ TMS Can be converted to Compound 6 or Compound 12, respectively, via a base addition reaction. The addition reaction can be carried out according to a known method (Yoshikazu Kawano; Nobuya Kaneko; Teruaki Mukaiyama; Bull . Chem . Soc . Jpn . , 79, 1133-1145, 2006).

Compound 6 or Compound 12 can be converted to Compound 8 or Compound 14 by reacting with Compound 7 or a boronic acid derivative of Compound 13. The reaction can be carried out according to an arylation reaction such as a Suzuki coupling reaction and a Buchwald-Hartwig cross-coupling reaction using an amine (Barbara Czako and Laszlo Kurti; STRATEGIC APPLICATIONS of NAMED REACTIONS in ORGANIC SYNTHESIS , 2005 ).

If desired, the compound 8 or compound 14 may also be used as an intermediate in the preparation of other compounds of the present invention. For example, an oxidation reaction, a reduction reaction, an addition reaction, a protective reaction, Other compounds of the present invention having moieties such as sulfinyl, sulfonyl, amine, alcohol, carboxylic acid, carboxamide, sulfonamide, oxime and the like can also be prepared by carrying out a deprotection reaction, an amide coupling reaction and the like.

The compound of formula (I) or a pharmaceutically acceptable salt thereof according to the present invention can also be prepared according to the following reaction formula (2).

<Reaction Scheme 2>

In the above reaction formula, ring X, ring Y, L, R ₁ , R ₂ , R ₃ , and R ₄ are the same as defined above, and PG ₁ is a carboxyl protecting group.

The compound 15 can be converted to the compound 16 by deprotection. The deprotection reaction can be carried out using an aqueous solution of an inorganic base such as sodium hydroxide, lithium hydroxide or potassium hydroxide in a mixed solvent of distilled water or a polar solvent such as tetrahydrofuran or alcohol and water. Further, the deprotection reaction can be carried out, for example, at room temperature to 80 ° C.

The compound 16 can be converted to an acyl halide derivative of compound 17 by reacting with thionyl chloride. Further, the compound 17 can be converted to the compound 18 through a di-CF ₃ group addition reaction using CF ₃ TMS. The addition reaction can be carried out according to known methods (Babadzhanova, LA; Kirij, NV; Yagupolskii, Yu L.; Tyrra, W .; Naumann, D .; Tetrahedron , 61, 1813-1820, 2005).

If desired, the compound 18 may also be used as an intermediate in the preparation of other compounds of the present invention. For example, a Suzuki coupling reaction as defined in Scheme 1 above for Compound 18, Buchwald-Hartwig An amine, an alcohol, a carboxylic acid, a carboxylic acid, a sulfonic acid, a sulfonic acid, a sulfonic acid, a sulfonic acid, a sulfonic acid, a sulfonic acid, a sulfonic acid, a sulfonic acid, or a salt thereof by performing cross coupling, oxidation reaction, reduction reaction, addition reaction, protection reaction, deprotection reaction, amide coupling reaction, Other compounds of the present invention having moieties such as carboxamide, sulfonamide, oxime, and the like may also be prepared.

The compound of formula (I) or a pharmaceutically acceptable salt thereof according to the present invention can also be prepared according to the following reaction formula (3).

<Reaction Scheme 3>

In the above reaction formula, ring X, ring Y, L, R ₁ , R ₂ , R ₃ , and R ₄ are as defined above, and Het is a heterocyclic group. R ₆ is C ₃ -C ₆ cycloalkylsulfonyl; Mono or di-C ₁ -C ₅ alkylaminosulfonyl; C ₁ -C ₅ alkylcarbonyl; C ₁ -C ₅ alkoxycarbonyl; And mono or di-C ₁ -C ₅ alkylaminocarbonyl.

The compound 19 or the compound 22 can be converted to the compound 20 or the compound 23 through the deprotection reaction. The deprotection reaction is carried out in an organic solvent such as dichloromethane, dioxane, ethyl acetate or the like using trifluoroacetic acid or a saturated hydrochloric acid solution (for example, a saturated hydrochloric acid solution in ethyl acetate) at room temperature for 1 hour to 24 hours &Lt; / RTI &gt; The deprotection reaction can be carried out according to known methods (Theodora W. Greene; Peter GM Wuts; Protective groups in organic synthesis 3 rd Ed ., 1999).

The compound 20 or the compound 23 is reacted with an acyl halide, a sulfonyl chloride, an isocyanate, an isothiocyanate or the like which is a nucleophilic reagent in an organic solvent such as dichloromethane, tetrahydrofuran and N, N-dimethylformamide Can be converted to compounds 21 or 24, respectively, of the amide, sulfonamide, urea and thyourea structures.

The present invention provides a pharmaceutical composition for preventing and treating cholesterol metabolism comprising a therapeutically effective amount of the compound of formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient, And atherosclerosis, and the like.

The pharmaceutical composition may contain a pharmaceutically acceptable carrier such as an excipient, a disintegrant, a sweetening agent, a lubricant or a flavoring agent, and may be formulated into tablets, capsules, powders, granules and suspensions, Oral preparations such as emulsions or syrups; Or an injectable preparation for parenteral administration. The formulations can be formulated in a variety of forms, for example, single-dose or multi-dose dosage forms.

The pharmaceutical composition of the present invention may contain an excipient such as lactose, corn starch, a lubricant such as magnesium stearate, an emulsifier, a suspending agent, a stabilizer, and an isotonic agent. If desired, sweetening and / or flavoring agents may be added.

The compositions of the present invention may be administered orally, parenterally, including intravenously, intraperitoneally, subcutaneously, rectally, and topically. Thus, the composition of the present invention can be formulated into various forms such as tablets, capsules, aqueous solutions or suspensions. In the case of oral tablets, a carrier such as lactose, corn starch, and a lubricant such as magnesium stearate may be usually added. In the case of capsules for oral administration, lactose and / or dried corn starch may be used as a diluent. If an oral aqueous suspension is required, the active ingredient may be combined with an emulsifying agent and / or a suspending agent. If desired, certain sweetening and / or flavoring agents may be added. For intramuscular, intraperitoneal, subcutaneous and intravenous administration, sterile solutions of the active ingredient are usually prepared and the pH of the solution should be suitably adjusted and buffered. For intravenous administration, the total concentration of solutes should be adjusted to give the formulation isotonicity. The composition according to the present invention may be in the form of an aqueous solution comprising a pharmaceutically acceptable carrier such as a saline solution having a pH of 7.4. The solution can be introduced into the intramuscular blood stream of the patient by local bolus injection.

The pharmaceutical compositions according to the present invention may be administered in a therapeutically effective amount. Accordingly, the compound of formula (I) or a pharmaceutically acceptable salt thereof contained in the pharmaceutical composition may be administered to a patient in an effective amount of about 50 mg / kg to about 500 mg / kg per day. Of course, the dose may vary depending on the patient's age, weight, susceptibility, symptoms, or drug efficacy.

Hereinafter, the present invention will be described in more detail through examples and test examples. However, these examples and test examples are illustrative of the present invention, and the present invention is not limited thereto.

Analysis of the compounds prepared in the following Reference Examples and Examples was carried out as follows: Nuclear magnetic resonance (NMR) spectral analysis was performed on a Bruker 400 MHz spectrometer and chemical shifts were carried out in ppm Column chromatography was performed on silica gel (Merck, 70-230 mesh or ZEOCHEM, ZEOprep 60-200 mu m) (WC Still, J. Org . Chem . , 1978 (43), 2923-2925). The abbreviations used in the following Reference Examples and Examples are as follows: Methyl is Me, ethyl is Et, phenyl is Ph, tert-butyloxycarbonyl is BOC, N- (3-dimethylaminopropyl) N'-ethylcarbodiimide is EDAC, 1-hydroxybenzotriazole is HOBT, (trifluoromethyl) trimethylsilane is CF ₃ TMS, tetrabutylammonium fluoride is TBAF, tetramethylammonium fluoride is TMAF , TBAA for tetrabutylammonium acetate, DMP for Dess-Martin periodinane, and BAST for bis (2-methoxyethyl) aminosulfur trifluoride. In addition, the starting materials of the respective examples were synthesized according to the literature as known compounds or purchased from Sigma Aldrich or TCI.

Reference Example 1. Preparation of 5- (3-bromo-phenyl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy- methyl] -4,5-dihydro- 1H-pyrazole

Step 1. Potassium salt of 4- (3-bromo-phenyl) -2-oxo-3-

To a solution of 3-bromobenzaldehyde (22.0 mL, 189.0 mmol) and pyruvic acid (15.8 mL, 227.0 mmol) in 100.0 mL of methanol was added slowly a solution of potassium hydroxide (19.0 g, 340.0 mmol) dissolved in 100.0 mL of methanol at 0 After that, the mixture was stirred at room temperature for 16 hours. The reaction precipitate was filtered off and washed with diethyl ether to give 47.0 g of the title compound as a yellow solid.

^{1 H NMR (400 MHz, DMSO} -d 6) 7.87 (s, 1H), 7.66 (d, 1H), 7.58 (d, 1H), 7.40-7.34 (m, 2H), 6.82 (d, 1H)

Step 2. 4- (3-Bromo-phenyl) -2-oxo-3-butenoic acid methyl ester

(41.0 g, 140.0 mmol) and methyl iodide (15.0 mL, 238.0 mmol) prepared in Step 1 were dissolved in N, N-dimethylformamide Was added to 200.0 mL of dimethylformamide, and the mixture was stirred at 75 占 폚 for 4 hours. Distilled water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/8) to obtain 10.0 g of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.82-7.77 (m, 2H), 7.60-7.54 (m, 2H), 7.37 (d, 1H), 7.31 (t, 1H), 3.95 (s, 3H)

Step 3. 5- (3-Bromo-phenyl) -l- (2-chloro-phenyl) -4,5-dihydro- lH- pyrazole-

3-butenoic acid methyl ester (10.0 g, 37.2 mmol) and 2-chlorophenylhydrazine hydrochloride (7.3 g, 40.9 mmol) prepared in Step 2 were dissolved in acetic acid 150.0 mL, and the mixture was stirred at 125 DEG C for 4 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with saturated aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 11.0 g of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.33-7.23 (m, 4H), 7.13-7.05 (m, 3H), 6.99 (t, 1H), 5.84 (dd, 1H), 3.90 (s, 3H), 3.70 (dd, 1 H), 3.27 (dd, 1 H)

Step 4. Synthesis of 5- (3-bromo-phenyl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy- methyl] -4,5-dihydro-1H - pyrazole

Pyrazole-3-carboxylic acid methyl ester (210.0 mg, 0.53 mmol), prepared in step 3, was added to a solution of 5- (3-bromo-phenyl) _{, CF 3 TMS (316.0 uL,} 2.13 mmol), molecular sieves (4, 100.0 mg) was added slowly was added to toluene 4.0 mL under a nitrogen condition, TBAF (1.0 M, in tetrahydrofuran, 106.0 uL, 0.11 mmol) at room temperature Lt; / RTI &gt; for 2 h. CF ₃ TMS (158.0 uL, 1.06 mmol) and TBAF (1.0 M in tetrahydrofuran, 30.0 uL, 0.03 mmol) were added at room temperature and the mixture was stirred at 45 ° C for 48 hours. The reaction mixture was filtered through a pad of celite, dichloromethane was added to the filtrate, washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 130.0 mg of the title compound as a brown liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.34-7.26 (m, 3H), 7.17-7.06 (m, 4H), 7.00 (t, 1H), 5.81 (dd, 1H), 4.90 (s, 1H), 3.63 (dd, 1 H), 3.18 (dd, 1 H)

Reference Example 2. Synthesis of 5- (4-bromo-phenyl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy- methyl] -4,5-dihydro- 1H-pyrazole

Step 1. Potassium salt of 4- (4-bromo-phenyl) -2-oxo-3-

To a solution of 4-bromobenzaldehyde (35.0 g, 189.0 mmol) and pyruvic acid (15.8 mL, 227.0 mmol) in 100.0 mL of methanol was added slowly a solution of potassium hydroxide (19.0 g, 340.0 mmol) dissolved in 100.0 mL of methanol at 0 After that, the mixture was stirred at room temperature for 16 hours. The reaction precipitate was filtered off and washed with diethyl ether to give 48.0 g of the title compound as a pale yellow solid.

¹ H NMR (400 MHz, DMSO-d ₆ ) 7.61-7.58 (m, 4 H), 7.37 (d,

Step 2. Preparation of 4- (4-bromo-phenyl) -2-oxo-3-butenoic acid methyl ester

(48.0 g, 164.0 mmol) and methyl iodide (20.0 mL, 327.0 mmol) prepared in Step 1 were dissolved in N, N-dimethylformamide Was added to 250.0 mL of dimethylformamide, and the mixture was stirred at 75 占 폚 for 4 hours. Distilled water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 13.5 g of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.81 (d, 1H), 7.57 (d, 2H), 7.50 (d, 2H), 7.37 (d, 1H), 3.94 (s, 3H)

Step 3. 5- (4-Bromo-phenyl) -l- (2-chloro-phenyl) -4,5-dihydro- lH- pyrazole-

3-butenoic acid methyl ester (13.5 g, 50.2 mmol) and 2-chlorophenylhydrazine hydrochloride (9.9 g, 55.2 mmol) prepared in Step 2 were dissolved in acetic acid 200.0 mL, and the mixture was stirred at 125 DEG C for 4 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 18.9 g of the title compound as a brown liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.33-7.26 (m, 3H), 7.21 (d, 1H), 7.09 (t, 1H), 7.03 (d, 2H), 6.96 (t, 1H), 5.87 (dd , 3.90 (s, 3H), 3.70 (dd, 1 H), 3.25 (dd,

Step 4. Preparation of 5- (4-bromo-phenyl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy- methyl] -4,5-dihydro-lH - pyrazole

Pyrazole-3-carboxylic acid methyl ester (3.0 g, 7.6 mmol), prepared in step 3, was added to a solution of 5- (4-bromo-phenyl) , TBAF (1.0 M, 1.5 mL in tetrahydrofuran, 30.5 mmol) was added slowly to 50.0 mL of toluene under a nitrogen atmosphere, and CF ₃ TMS (4.5 mL, 30.5 mmol) and molecular sieves (4 and 1.0 g) Lt; / RTI &gt; for 2 h. CF ₃ TMS (2.3 mL, 15.3 mmol) and TBAF (1.0 M in tetrahydrofuran, 0.38 mL, 0.38 mmol) were added at room temperature and stirred at 45 ° C for 16 hours. The reaction mixture was filtered through a pad of celite, dichloromethane was added to the filtrate, washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/8) to obtain 890.0 mg of the title compound as a brown liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.35 (d, 2H), 7.25 (d, 1H), 7.16-7.08 (m, 2H), 7.03-6.97 (m, 3H), 5.84 (dd, 1H), 4.88 (s, 1 H), 3.63 (dd, 1 H), 3.16 (dd, 1 H)

Reference Example 3. Synthesis of 4- (3'-ethoxy-biphenyl-4-yl) -2-oxo-3-

Step 1. Preparation of 3'-ethoxy-biphenyl-4-carbaldehyde

4-bromo-benzaldehyde (4.0 g, 21.6 mmol), ethoxy-phenylboronic acid to 3- (4.0 g, 21.6 mmol) , 2N aqueous sodium carbonate solution (216.0 mL, 216.0 mmol), Pd (dppf) Cl 2 (1.6 g, 2.2 mmol) were added to 216.0 mL of N, N-dimethylformamide, and the mixture was stirred at 80 占 폚 for 3 hours. The reaction mixture was filtered through a pad of celite, distilled water was added to the obtained filtrate, and the mixture was extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 4.6 g of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 10.05 (s, 1H), 7.94 (d, 2H), 7.74 (d, 2H), 7.38 (t, 1H), 7.20 (d, 1H), 7.16 (s, 1H ), 6.95 (d, IH), 4.10 (q, 2H), 1.45 (t, 3H)

Step 2. Preparation of 4- (3'-ethoxy-biphenyl-4-yl) -2-oxo-

Ethyl 4-carbaldehyde (4.6 g, 20.1 mmol) and pyruvic acid (1.7 mL, 24.1 mmol) prepared in Step 1 were added to 15.0 mL of methanol and dissolved in 15.0 mL of methanol at 0 & A solution of potassium (2.0 g, 36.2 mmol) was slowly added thereto, followed by stirring at room temperature for 7 hours. The reaction precipitate was filtered off, acidified with a 1N aqueous hydrochloric acid solution, and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 2.5 g of the title compound as a brown liquid.

¹ H NMR (400 MHz, CDCl ₃ ) 8.19 (d, 1 H), 7.76 (d, 2H), 7.70-7.62 (m, 3H), 7.36 2H), 1.46 (t, 3H), &lt; RTI ID = 0.0 &

Step 3. Preparation of 4- (3'-ethoxy-biphenyl-4-yl) -2-oxo-3-

Acetyl chloride (2.0 mL, 28.7 mmol) was slowly added to 10.0 mL of methanol at 0 ° C and stirred. 4-yl) -2-oxo-3-butenoic acid (2.5 g, 8.4 mmol) prepared in Step 2 was dissolved in 10.0 mL of methanol and added to the reaction mixture at room temperature , And the mixture was stirred at room temperature for 1 hour and then at 80 ° C for 16 hours. The precipitate formed at room temperature was filtered to obtain 1.0 g of the title compound as a yellow solid.

¹ H NMR (400 MHz, CDCl ₃ ) 7.92 (d, 1 H), 7.72-7.64 (m, 4H), 7.44-7.35 (d, IH), 4.11 (q, 2H), 3.95 (s, 3H), 1.45

Chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro- 5-dihydro-lH-pyrazole

Step 1. Preparation of 4- (4-bromo-2-fluoro-phenyl) -2-oxo-3-

Pyruvic acid (1.9 mL, 27.1 mmol) was dissolved in 2.5 mL of ethanol, and the solution was added to 74.0 mL of a 0.5 M aqueous sodium hydroxide solution. The mixture was stirred at room temperature for 10 minutes. 4-Bromo-2-fluorobenzaldehyde (5.0 g, 24.6 mmol) was dissolved in 22.5 mL of ethanol and slowly added to the reaction mixture at room temperature for 1 hour, followed by stirring at room temperature for 18 hours. The resulting precipitate was filtered off, washed with ethyl acetate, acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 5.5 g of the title compound as a yellow solid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.90 (d, 1H), 7.76 (t, 1H), 7.53-7.47 (m, 3H)

Step 2. 4- (4-Bromo-2-fluoro-phenyl) -2-oxo-3-butenoic acid methyl ester

Acetyl chloride (4.8 mL, 68.5 mmol) was slowly added to methanol (28.0 mL) at 0 ° C and stirred. 2-oxo-3-butenoic acid (5.5 g, 20.1 mmol) prepared in Step 2 was dissolved in 5.0 mL of methanol, added to the reaction mixture at room temperature, The mixture was stirred at room temperature for 1 hour and then at 80 ° C for 16 hours. The precipitate formed at room temperature was filtered to obtain 4.7 g of the title compound as a yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.93 (d, 1H), 7.52 (t, 1H), 7.44 (s, 1H), 7.35 (m, 2H), 3.94 (s, 3H)

Step 3. 5- (4-Bromo-2-fluoro-phenyl) -l- (2-chloro-phenyl) -4,5-dihydro- lH- pyrazole-

(2.0 g, 7.0 mmol), 2-chlorophenylhydrazine hydrochloride (1.4 g, 7.7 mmol) prepared in Step 2 and 4- (4-bromo-2-fluoro- mmol) were added to 25.0 mL of acetic acid, and the mixture was stirred at 80 ° C for 2 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 3.0 g of the title compound as a black liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.36 (d, 1H), 7.25 (d, 1H), 7.12-7.09 (m, 3H), 6.99 (t, 1H), 3.95 (s, 3H), 3.63 (dd , &Lt; / RTI &gt; 1H), 3.22 (dd, 1H)

Step 4. Preparation of 5- (4-bromo-2-fluoro-phenyl) -l- (2- chloro-phenyl) -4,5-dihydro- lH- pyrazole-

(2-chloro-phenyl) -4,5-dihydro-lH-pyrazole-3-carboxylic acid methyl ester (3.0 g, 7.0 mmol) and potassium hydroxide aqueous solution (790.9 mg, 14.1 mmol) dissolved in 47.0 mL of distilled water were added to 47.0 mL of methanol, followed by stirring at 70 DEG C for 2 hours. The reaction mixture was concentrated under reduced pressure to remove methanol. The resulting residue was washed with diethyl ether, acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 2.5 g of the title compound as a white solid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.37 (d, 1H), 7.26-7.14 (m, 5H), 7.03 (t, 1H), 3.68 (dd, 1H), 3.20 (dd, 1H)

Step 5. Preparation of 5- (4-bromo-2-fluoro-phenyl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) - dihydro-lH-pyrazole

Pyrazole-3-carboxylic acid (2.5 g, 0.35 mmol) prepared in step 4, (5-chloro-phenyl) 6.3 mmol) was added to 30.0 mL of thionyl chloride, and the mixture was stirred at 100 DEG C for 2 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was concentrated with toluene under reduced pressure for 3 times to obtain a dark brown liquid 5- (4-bromo-2-fluoro-phenyl) , 5-dihydro-lH-pyrazole-3-carbonyl chloride.

The dark brown liquid 5- (4-bromo-2-fluoro-phenyl) -l- (2-chloro-phenyl) -4,5- dihydro- lH- pyrazole- 3- carbonyl chloride, TMAF (1.3 g, 13.7 mmol) was added to 100.0 mL of 1,2-dimethoxyethane, CF ₃ TMS (2.0 mL, 13.7 mmol) was slowly added to the reaction mixture at -78 ° C under nitrogen, And stirred for 2 hours. The reaction mixture was quenched with a 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 2.5 g of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.37-7.28 (m, 2H), 7.25-7.12 (m, 4H), 7.02 (t, 1H), 6.06 (dd, 1H), 4.86 (s, 1H), 3.62 (dd, 1 H), 3.13 (dd, 1 H)

Reference Example 5. 5- (6-Bromo-pyridin-3-yl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) - dihydro-lH-pyrazole

Step 1. 4- (6-Bromo-pyridin-3-yl) -2-oxo-3-butenoic acid methyl ester

Pyruvic acid (412.0 uL, 5.9 mmol) was dissolved in 0.6 mL of ethanol, and the solution was added to 16 mL of a 0.5 M aqueous sodium hydroxide solution. The mixture was stirred at room temperature for 10 minutes. 6-Bromo-3-pyridinecarbaldehyde (1.0 g, 5.4 mmol) was dissolved in 5.4 mL of ethanol and slowly added to the reaction mixture at room temperature for 1 hour, followed by stirring at room temperature for 18 hours. The resulting reaction precipitate was filtered and washed with diethyl ether to obtain 1.3 g of 4- (6-bromo-pyridin-3-yl) -2-oxo-3-butenoic acid sodium salt as a pale yellow solid.

3-yl) -2-oxo-3-butenoic acid sodium salt (900.0 mg, 3.2 mmol) and methyl iodide (400.0 mL, 6.47 mmol) were dissolved in N , N-dimethylformamide (20.0 mL), and the mixture was stirred at 75 占 폚 for 3 hours. Distilled water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 615.0 mg of the title compound as a light yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 8.58 (s, 1H), 7.82 (d, 2H), 7.57 (d, 1H), 7.45 (d, 1H), 3.96 (s, 3H)

Step 2. Preparation of 5- (6-bromo-pyridin-3-yl) -l- (2-chloro-phenyl) -4,5-dihydro- lH- pyrazole-

3-yl) -2-oxo-3-butenoic acid methyl ester (615.0 mg, 2.3 mmol) and 2-chlorophenylhydrazine hydrochloride (450.0 mg, 2.5 mmol ) Was added to 10.0 mL of acetic acid, and the mixture was stirred at 125 DEG C for 3 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 650.0 mg of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.21 (s, 1H), 7.46 (d, 1H), 7.32 (d, 1H), 7.25 (d, 1H), 7.19 (d, 1H), 7.13 (t, 1H ), 7.02 (t, IH), 5.92 (dd, IH), 3.91 (s, 3H)

Step 3. 5- (6-Bromo-pyridin-3-yl) -l- (2-chloro-phenyl) -4,5-dihydro- lH- pyrazole-

(2-chloro-phenyl) -4,5-dihydro-lH-pyrazole-3-carboxylic acid methyl ester (650.0 mg, , 1.7 mmol) and potassium hydroxide aqueous solution (185.0 mg, 3.3 mmol) dissolved in 10.0 mL of distilled water were added to 10.0 mL of methanol, followed by stirring at 70 DEG C for 2 hours. The reaction mixture was concentrated under reduced pressure to remove methanol. The resulting residue was washed with diethyl ether, acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 455.0 g of the title compound as a light yellow solid.

^{1 H NMR (400 MHz, CD} 3 OD) 8.22 (s, 1H), 7.48 (d, 1H), 7.29-7.20 (m, 3H), 7.15 (t, 1H), 7.06 (t, 1H), 6.00 ( dd, 1 H), 3.77 (dd, 1 H), 3.27 (dd, 1 H)

Methyl-4-tert-butoxycarbonylamino-lH-pyrrolo [2,3-c] Dihydro-lH-pyrazole

Pyrazole-3-carboxylic acid (450.0 mg, 1.2 &lt; RTI ID = 0.0 &gt; mmol) was added to 5.0 mL of thionyl chloride, and the mixture was stirred at 100 DEG C for 2 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was concentrated with toluene three times under reduced pressure to give 5- (6-bromo-pyridin-3-yl) 5-dihydro-lH-pyrazole-3-carbonyl chloride.

This dark brown liquid of 5- (6-bromo-pyridin-3-yl) -1- (2-chloro-phenyl) -4,5-dihydro-lH- pyrazole-3-carbonyl chloride, TMAF 242.0 mg, 2.6 mmol) was added to 10.0 mL of 1,2-dimethoxyethane, CF ₃ TMS (385.0 uL, 2.6 mmol) was slowly added to the reaction mixture under nitrogen at -78 ° C, Lt; / RTI &gt; The reaction mixture was quenched with a 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 500.0 mg of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.21 (s, 1H), 7.43 (d, 1H), 7.27 (d, 1H), 7.21-7.11 (m, 3H), 7.02 (t, 1H), 5.90 (dd , 4.97 (s, IH), 3.68 (dd, IH), 3.17 (dd, IH)

Reference Example 6 Preparation of 5- (4-bromo-3-fluoro-phenyl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

Step 1. Preparation of 4- (4-bromo-3-fluoro-phenyl) -2-oxo-3-

Pyruvic acid (1.9 mL, 27.1 mmol) was dissolved in 6.0 mL of ethanol, and the solution was added to 74.0 mL of a 0.5 M aqueous sodium hydroxide solution. The mixture was stirred at room temperature for 5 minutes. 4-Bromo-3-fluorobenzaldehyde (5.0 g, 24.6 mmol) was dissolved in 20.0 mL of ethanol and slowly added to the reaction mixture at room temperature for 1 hour, followed by stirring at room temperature for 18 hours. The resulting precipitate was filtered off, washed with ethyl acetate, acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 3.2 g of the title compound as a yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 8.02 (d, 1H), 7.65 (t, 1H), 7.57 (d, 1H), 7.43 (d, 1H), 7.34 (d, 1H)

Step 2. 4- (4-Bromo-3-fluoro-phenyl) -2-oxo-3-butenoic acid methyl ester

Acetyl chloride (2.9 mL, 41.0 mmol) was slowly added to 15.0 mL of methanol at 0 ° C and stirred. 3-butenoic acid (3.2 g, 11.7 mmol) prepared in Step 1 was dissolved in 5.0 mL of methanol, added to the reaction mixture at room temperature, The mixture was stirred at room temperature for 1 hour and then at 80 ° C for 16 hours. The precipitate formed at room temperature was filtered to obtain 1.1 g of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.77 (d, 1H), 7.62 (t, 1H), 7.39 (s, 1H), 7.36 (d, 1H), 7.29 (d, 1H), 3.95 (s, 3H )

Step 3. 5- (4-Bromo-3-fluoro-phenyl) -l- (2-chloro-phenyl) -4,5-dihydro- lH- pyrazole-

3-butenoic acid methyl ester (665.0 mg, 2.3 mmol), 2-chlorophenylhydrazine hydrochloride (455.0 mg, 2.6 mmol) were added to 10.0 mL of acetic acid, and the mixture was stirred at 125 DEG C for 3 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 835.0 mg of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.38 (t, 1H), 7.32 (d, 1H), 7.24 (d, 1H), 7.12 (t, 1H), 7.00 (t, 1H), 6.94 (d, 1H ), 6.84 (d, IH), 5.86 (dd, IH), 3.90 (s,

Step 4. 5- (4-Bromo-3-fluoro-phenyl) -l- (2-chloro-phenyl) -4,5-dihydro- lH- pyrazole-

(2-chloro-phenyl) -4,5-dihydro-1H-pyrazole-3-carboxylic acid methyl ester (830.0 mg, 2.0 mmol) and potassium hydroxide aqueous solution (226.0 mg, 4.0 mmol) dissolved in 10.0 mL of distilled water were added to 10.0 mL of methanol, followed by stirring at 70 ° C for 4 hours. The reaction mixture was concentrated under reduced pressure to remove methanol. The resulting residue was washed with diethyl ether, acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 820.0 mg of the title compound as a light yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.41 (t, 1H), 7.29-7.26 (m, 2H), 7.15 (t, 1H), 7.05 (t, 1H), 6.95 (d, 1H), 6.86 (d , 5.94 (dd, 1 H), 3.74 (dd, 1 H), 3.28 (dd,

Step 5. Synthesis of 5- (4-bromo-3-fluoro-phenyl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) - dihydro-lH-pyrazole

(2-chloro-phenyl) -4,5-dihydro-lH-pyrazole-3-carboxylic acid (820.0 mg, 2.1 mmol) was added to 7.0 mL of thionyl chloride, and the mixture was stirred at 100 DEG C for 2 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was concentrated with toluene under reduced pressure for 3 times to obtain a dark brown liquid 5- (4-bromo-3-fluoro-phenyl) , 5-dihydro-lH-pyrazole-3-carbonyl chloride.

The dark brown liquid 5- (4-bromo-3-fluoro-phenyl) -l- (2-chloro-phenyl) -4,5-dihydro- lH- pyrazole- 3- carbonyl chloride, TMAF (420.0 mg, 4.5 mmol) was added to 10.0 mL of 1,2-dimethoxyethane, and CF ₃ TMS (670.0 uL, 4.5 mmol) was slowly added to the reaction mixture at -78 ° C under nitrogen. And stirred for 2 hours. The reaction mixture was quenched with a 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 940.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.40 (t, 1H), 7.28 (d, 1H), 7.19-7.10 (m, 2H), 7.04-7.00 (m, 1H), 6.93 (d, 1H), 6.83 (d, IH), 5.83 (dd, IH), 4.84 (s, IH), 3.65

Reference Example 7. Preparation of 5- (4-bromo-phenyl) -l- (2,4-difluoro-phenyl) -3- [di- (trifluoromethyl) - dihydro-lH-pyrazole

Step 1. 5- (4-Bromo-phenyl) -l- (2,4-difluoro-phenyl) -4,5-dihydro-lH- pyrazole-

3-butenoic acid methyl ester (50.0 g, 185.8 mmol), 2,4-difluorophenylhydrazine hydrochloride (prepared according to the procedure described in Step 2 of Reference Example 2, 36.9 g, 204.4 mmol) were added to 600.0 mL of acetic acid, and the mixture was stirred at 125 DEG C for 3 hours. The reaction mixture was concentrated under reduced pressure, and ethyl acetate was added thereto, followed by washing with a saturated aqueous solution of sodium hydrogencarbonate, drying over anhydrous magnesium sulfate and concentration under reduced pressure to obtain 5- (4-bromo-phenyl) , 4-difluoro-phenyl) -4,5-dihydro-lH-pyrazole-3-carboxylic acid methyl ester.

The above yellow liquid 5- (4-bromo-phenyl) -l- (2,4-difluoro-phenyl) -4,5-dihydro- lH- pyrazole- 3- carboxylic acid methyl ester (73.4 g, 185.8 mmol), potassium hydroxide aqueous solution (20.9 g, 371.6 mmol) dissolved in 400.0 mL of distilled water was added to 400.0 mL of methanol, and the mixture was stirred at 70 DEG C for 4 hours. The reaction mixture was concentrated under reduced pressure to remove methanol. The resulting residue was washed with diethyl ether, acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 70.0 g of the title compound as a yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.46-7.38 (m, 3H), 7.03 (d, 2H), 6.79-6.66 (m, 2H), 5.65 (dd, 1H), 3.69 (dd, 1H), 3.19 (dd, 1 H)

Step 2. Synthesis of 5- (4-bromo-phenyl) -l- (2,4-difluoro-phenyl) -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole

Pyrazole-3-carboxylic acid (10.0 g, 26.2 &lt; RTI ID = 0.0 &gt; mmol) was added to 100.0 mL of thionyl chloride, and the mixture was stirred at 100 DEG C for 2 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was concentrated with toluene under reduced pressure for 3 times to obtain 5- (4-bromo-phenyl) -1- (2,4-difluoro- 5-dihydro-lH-pyrazole-3-carbonyl chloride.

The dark brown liquid 5- (4-bromo-phenyl) -l- (2,4-difluoro-phenyl) -4,5-dihydro-lH- pyrazole- 3-carbonyl chloride, TMAF 5.4 g, 57.7 mmol) was added to 80.0 mL of 1,2-dimethoxyethane, and CF ₃ TMS (8.5 mL, 57.7 mmol) was slowly added to the reaction mixture under nitrogen at -78 ° C. Lt; / RTI &gt; The reaction mixture was quenched with a 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/10) to obtain 7.0 g of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 2H), 7.22 (q, 1H), 7.01 (d, 2H), 6.77-6.68 (m, 2H), 5.52 (dd, 1H), 4.81 (s , 3.61 (dd, 1 H), 3.10 (dd, 1 H)

Reference Example 8. Preparation of 5- (5-bromo-thiophen-2-yl) -1- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

Step 1. Preparation of 4- (5-bromo-thiophen-2-yl) -2-oxo-

The pyruvic acid (10.0 mL, 143.9 mmol) was dissolved in 13.0 mL of ethanol, and the solution was added to 393.0 mL of a 0.5 M aqueous sodium hydroxide solution. The mixture was stirred at room temperature for 5 minutes. 5-Bromo-thiophene-2-carbaldehyde (25.0 g, 130.9 mmol) was dissolved in 112.0 mL of ethanol and slowly added to the reaction mixture at room temperature for 1 hour, followed by stirring at room temperature for 18 hours. The resulting precipitate was filtered off, washed with ethyl acetate, acidified with 3N aqueous hydrochloric acid, and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 25.0 g of the title compound as a yellow solid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.89 (d, 1H), 7.33 (s, 1H), 7.19 (s, 1H), 7.05 (d, 1H)

Step 2. Preparation of 4- (5-bromo-thiophen-2-yl) -2-oxo-3-

Acetyl chloride (23.0 mL, 325.6 mmol) was slowly added to 100.0 mL of methanol at 0 ° C and stirred. 3-butenoic acid (25.0 g, 95.8 mmol) prepared in Step 1 was dissolved in 25.0 mL of methanol and added to the reaction mixture at 0 ° C. , And the mixture was stirred at room temperature for 1 hour and then at 80 ° C for 3 hours. The precipitate formed at room temperature was filtered to obtain 23.6 g of the title compound as a yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.86 (d, 1H), 7.26 (s, 1H), 7.17 (s, 1H), 7.06 (d, 1H), 3.93 (s, 3H)

Step 3. Preparation of 5- (5-bromo-thiophen-2-yl) -l- (2-chloro-phenyl) -4,5-dihydro-lH- pyrazole-

3-butenoic acid methyl ester (19.9 mg, 72.2 mmol) and 2-chlorophenylhydrazine hydrochloride (14.2 g, 79.4 mmol) prepared in Step 2, mmol) were added to 250.0 mL of acetic acid, and the mixture was stirred at 125 DEG C for 3 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/6) to obtain 18.9 g of the title compound as a pale yellow liquid.

¹ H NMR (400 MHz, CDCl ₃ ) 7.40-7.22 (m, 2H), 7.20-7.00 (m, 2H), 6.72 (s, (s, 3H), 3.65 (dd, IH), 3.44 (dd, IH)

Step 4. Preparation of 5- (5-bromo-thiophen-2-yl) -l- (2-chloro-phenyl) -4,5-dihydro-lH- pyrazole-

(5-Bromo-thiophen-2-yl) -l- (2-chloro-phenyl) -4,5-dihydro-lH- pyrazole-3- carboxylic acid methyl ester prepared in step 3 g, 47.3 mmol) and potassium hydroxide aqueous solution (5.3 g, 94.6 mmol) dissolved in 200.0 mL of distilled water was added to 200.0 mL of methanol, followed by stirring at 80 DEG C for 12 hours. The reaction mixture was concentrated under reduced pressure to remove methanol. The resulting residue was washed with diethyl ether, acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 18.1 g of the title compound as a light yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.38-7.22 (m, 2H), 7.20-7.00 (m, 2H), 6.72 (s, 1H), 6.60 (s, 1H), 6.16 (dd, 1H), 3.68 (dd, 1 H), 3.42 (dd, 1 H)

Step 5. Synthesis of 5- (5-bromo-thiophen-2-yl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) - dihydro-lH-pyrazole

(5-bromo-thiophen-2-yl) -l- (2-chloro-phenyl) -4,5-dihydro- lH- pyrazole- 3-carboxylic acid (18.1 g, 46.9 mmol) was added to 200.0 mL of thionyl chloride, and the mixture was stirred at 100 DEG C for 2 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was concentrated with toluene three times under reduced pressure to obtain a dark brown liquid 5- (5-bromo-thiophen-2-yl) , 5-dihydro-lH-pyrazole-3-carbonyl chloride.

The above dark brown liquid 5- (5-bromo-thiophen-2-yl) -1- (2-chloro-phenyl) -4,5- dihydro- lH- pyrazole- 3-carbonyl chloride, TMAF (9.6 g, 103.1 mmol) was added to 200.0 mL of 1,2-dimethoxyethane, and CF ₃ TMS (15.3 mL, 103.1 mmol) was slowly added to the reaction mixture at -78 ° C under nitrogen. And stirred for 3 hours. The reaction mixture was quenched with a 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/8) to obtain 19.0 g of the title compound as a brown liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.30 (dd, 1H), 7.22-7.00 (m, 3H), 6.70 (s, 1H), 6.57 (s, 1H), 6.13 (dd, 1H), 4.84 (s , 3.60 (dd, 1 H), 3.30 (dd, 1 H)

Reference Example 9: l- (4-Bromo-phenyl) -5- (2-chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy- methyl] -4,5- 1H-pyrazole

Step 1. Preparation of 4- (2-chloro-phenyl) -2-oxo-3-butenoic acid

Pyruvic acid (13.6 mL, 195.3 mmol) was dissolved in 20.0 mL of ethanol, and the solution was added to 533.0 mL of 0.5 M aqueous sodium hydroxide solution. The mixture was stirred at room temperature for 5 minutes. 2-Chlorobenzaldehyde (20.0 mL, 177.6 mmol) was dissolved in 155.0 mL of ethanol and slowly added to the reaction mixture at room temperature for 1 hour, followed by stirring at room temperature for 18 hours. The resulting precipitate was filtered, washed with ethyl acetate, acidified with a 6N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 34.5 g of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.53 (d, 1H), 7.81 (d, 1H), 7.59 (d, 1H), 7.47 (d, 1H), 7.42 (dd, 1H), 7.35 (dd, 1H )

Step 2. Preparation of 4- (2-chloro-phenyl) -2-oxo-3-butenoic acid methyl ester

Acetyl chloride (19.4 mL, 274.4 mmol) was slowly added to 120.0 mL of methanol at 0 占 폚 and stirred. To the reaction mixture was added 4- (2-chloro-phenyl) -2-oxo-3-butenoic acid (17.0 g, 80.7 mmol) prepared in Step 1 in 80.0 mL of methanol and the mixture was stirred at room temperature for 1 hour Then, the mixture was stirred at 80 DEG C for 16 hours. The reaction mixture was concentrated under reduced pressure, and ethyl acetate was added thereto. The mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/8) to obtain 7.2 g of the title compound as a yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 8.32 (d, 1H), 7.76 (d, 1H), 7.46 (d, 1H), 7.40-7.30 (m, 3H), 3.95 (s, 3H)

Step 3. l- (4-Bromo-phenyl) -5- (2-chloro-phenyl) -4,5-dihydro- lH-pyrazole-

(4.9 g, 21.9 mmol) and 4-bromophenylhydrazine hydrochloride (5.0 g, 22.4 mmol) prepared in Step 2 were dissolved in acetic acid 50.0 mL, and the mixture was stirred at 125 DEG C for 3 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The yellow liquid residue was crystallized from diethyl ether to give 5.3 g of the title compound as a white solid.

¹ H NMR (400 MHz, CDCl ₃ ) 7.44 (d, 1 H), 7.31 (d, 2H), 7.23 (dd, ), 5.76 (dd, 1 H), 3.87 (s, 3 H), 3.82

Step 4. l- (4-Bromo-phenyl) -5- (2-chloro-phenyl) -4,5-dihydro-lH- pyrazole-

5-dihydro-lH-pyrazole-3-carboxylic acid methyl ester (5.3 g, 13.5 mmol), prepared in step 3, , Potassium hydroxide aqueous solution (2.0 g, 35.6 mmol) dissolved in 25.0 mL of distilled water was added to 25.0 mL of methanol, and the mixture was stirred at 100 DEG C for 12 hours. The reaction mixture was concentrated under reduced pressure to remove methanol. The resulting residue was washed with diethyl ether, acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 5.4 g of the title compound as a white solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.20-6.98 (m, 3H), 6.97-6.60 (m, 5H), 5.40-5.20 (m, 1H), 3.70-3.45 (m, 1H), 2.80-2.55 ( m, 1H)

Step 5. l- (4-Bromo-phenyl) -5- (2-chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy- methyl] -4,5-dihydro-1H - pyrazole

Pyrazole-3-carboxylic acid (5.4 g, 14.3 mmol) prepared in Step 4 was added to a solution of cyano-4-hydroxy-2- Was added to 50.0 mL of onyl chloride, and the mixture was stirred at 100 DEG C for 2 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was concentrated with toluene under reduced pressure for 3 times to obtain a dark brown liquid 1- (4-bromo-phenyl) -5- (2-chloro-phenyl) -LH-pyrazole-3-carbonyl chloride.

This dark brown liquid of l- (4-bromo-phenyl) -5- (2-chloro-phenyl) -4,5-dihydro-lH- pyrazole-3- carbonyl chloride, TMAF (2.9 g, 31.4 mmol) was added to 70.0 mL of 1,2-dimethoxyethane, CF ₃ TMS (4.7 mL, 31.4 mmol) was slowly added to the reaction mixture under nitrogen at -78 ° C, and the mixture was stirred at -50 ° C for 2 hours . The reaction mixture was quenched with a 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/10) to obtain 5.5 g of the title compound as a yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.45 (d, 1H), 7.32-7.18 (m, 4H), 7.07 (d, 1H), 6.77 (d, 2H), 5.81 (dd, 1H), 4.76 (s , &Lt; / RTI &gt; 1H), 3.77 (dd, 1H), 2.91

Chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- 1H-pyrazole

Step 1. l- (3-Bromo-phenyl) -5- (2-chloro-phenyl) -4,5-dihydro-lH-pyrazole-

(1.4 g, 6.0 mmol) and 3-bromophenylhydrazine hydrochloride (1.4 g, 6.1 mmol) prepared in Step 2 of Reference Example 9 and 4- (2-chloro-phenyl) ) Were added to 20.0 mL of acetic acid, and the mixture was stirred at 125 DEG C for 3 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The yellow liquid residue was crystallized from methanol to obtain 1.2 g of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.46-7.40 (m, 2H), 7.26-7.15 (m, 2H), 7.05-7.01 (m, 3H), 6.77-63.73 (m, 1H), 5.76 (dd, 1H), 3.88 (s, 3H), 3.82 (dd,

Step 2. Synthesis of l- (3-bromo-phenyl) -5- (2-chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy- methyl] -4,5-dihydro-1H - pyrazole

(2-chloro-phenyl) -4,5-dihydro-lH-pyrazole-3-carboxylic acid methyl ester (1.2 g, 3.1 mmol) , TBAA (94.0 mg, 0.3 mmol ), CF 3 TMS (1.4 mL, 9.4 mmol) was added to at 0 ℃ in 10.0 mL dichloromethane, and the mixture was stirred at 0 ℃ for 20 minutes. After completion of the reaction, CF ₃ TMS (1.4 mL, 9.4 mmol) was added at room temperature, and the mixture was stirred at room temperature for 10 minutes. After the reaction mixture was quenched with a 6N aqueous hydrochloric acid solution, the organic solvent layer was separated, TBAA (471.0 mg, 1.6 mmol) was added, and the mixture was stirred at room temperature for 10 minutes. The reaction mixture was quenched with a 1N aqueous hydrochloric acid solution, washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/10) to obtain 1.3 g of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.46 (d, 1H), 7.30-7.20 (m, 3H), 7.09-7.00 (m, 3H), 6.62 (d, 1H), 5.82 (dd, 1H), 4.78 (s, 1 H), 3.78 (dd, 1 H), 2.92 (dd, 1 H)

Example 1. Synthesis of 5- (2'-acetyl-biphenyl-3-yl) -1- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; (8.0 mg, 0.05 mmol), Pd (dppf) Cl ₂ (2.0 mg, cat.) And 0.5 mL of a 2N aqueous sodium carbonate solution (20.0 mg, 0.04 mmol) Was added to 0.5 mL of N, N-dimethylformamide, and the mixture was stirred at 80 DEG C for 16 hours. Ethyl acetate was added to the reaction mixture, which was then washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 5.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.53-7.39 (m, 6H), 7.20-7.06 (m, 5H), 6.95 (t, 1H), 5.96 (dd, 1H), 4.92 (s, 1H), 3.70 (dd, 1 H), 3.29 (dd, 1 H), 1.66 (s, 3 H)

Examples 2 to 7

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; Dihydro-1H-pyrazole was used in place of 2-acetylphenylboronic acid, and boronic acid corresponding to Examples 2 to 7 was used instead of 2-acetylphenylboronic acid. Respectively.

Example 2. Preparation of 5- (3'-Acetyl-biphenyl-3-yl) -1- (2- chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.03 (s, 1H), 7.93 (d, 1H), 7.64 (d, 1H), 7.53 (t, 1H), 7.44 (d, 1H), 7.38 (s, 1H ), 7.39-7.26 (m, 2H), 7.18 (t, 2H), 7.10 (t, 1H), 3.29 (dd, 1 H), 2.65 (s, 3 H)

Example 3. Preparation of 5- (4'-Acetyl-biphenyl-3-yl) -1- (2- chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.01 (d, 2H), 7.53 (d, 2H), 7.44 (d, 1H), 7.39 (s, 1H), 7.32 (t, 1H), 7.28-7.26 (m (Dd, 1H), 7.18 (d, 2H), 7.09 (t, 1H), 6.97 1H), 2.64 (s, 3H)

Example 4. Preparation of l- (2-chloro-phenyl) -5- (2'-methoxy-biphenyl-3-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.36-7.22 (m, 5H), 7.15 (t, 2H), 7.10-7.06 (m, 2H), 7.02-6.95 (m, 3H), 5.89 (dd, 1H) , 4.93 (s, 1H), 3.76 (s, 3H), 3.64 (dd,

Example 5. Preparation of l- (2-chloro-phenyl) -5- (4'-methoxy-biphenyl-3-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.40-7.33 (m, 4H), 7.27-7.23 (m, 2H), 7.17 (d, 1H), 7.08 (t, 2H), 6.97-6.94 (m, 3H) , 5.93 (dd, 1 H), 4.94 (s, 1 H), 3.85 (s, 3 H), 3.67

Example 6. Preparation of l- (2-chloro-phenyl) -5- [4 '- (methylsulfonyl) -biphenyl-3-yl] -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.99 (d, 2H), 7.61 (d, 2H), 7.43 (d, 1H), 7.37-7.32 (m, 2H), 7.27 (d, 1H), 7.23-7.17 (m, 2H), 7.10 (t, IH), 6.97 (t, IH), 5.98 (dd, IH), 4.91 s, 3H)

Example 7. Preparation of l- (2-chloro-phenyl) -5- [3 '-( methylsulfanyl) -biphenyl-3-yl] -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.40-7.14 (m, 11H), 6.96 (t, 1H), 5.94 (dd, 1H), 4.92 (s, 1H), 3.68 (dd, 1H), 3.28 (dd , &Lt; / RTI &gt; 1H), 2.53 (s, 3H)

Example 8. Preparation of l- (2-chloro-phenyl) -5- [3 '-( 1 -hydroxy- 1 -methyl- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) -3- Dihydro-1H-pyrazole (39.0 mg, 0.07 mmol) was added to 1.0 mL of tetrahydrofuran, and then methylmagnesium chloride (3.0 M, 120.0 uL in tetrahydrofuran, 0.36 mmol) was slowly added thereto, and the mixture was stirred at -78 ° C for 5 hours. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution at O &lt; 0 &gt; C and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/3) to obtain 20.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.58 (s, 1H), 7.48-7.25 (m, 7H), 7.18-7.12 (m, 2H), 7.07 (t, 1H), 6.95 (t, 1H), 5.94 (d, 1H), 4.97 (s, 1H), 3.67 (dd,

Example 9 l- (2-Chloro-phenyl) -5- [4 '- (1 -hydroxy- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) -3- Dihydro-1H-pyrazole (25.0 mg, 0.05 mmol) was added to 1.0 mL of tetrahydrofuran, and then methylmagnesium chloride (77.0 uL, 0.23 mmol in 3.0 M tetrahydrofuran, ) Was added slowly and the mixture was stirred at -78 ° C for 5 hours. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution at O &lt; 0 &gt; C and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/3) to obtain 20.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.54 (d, 2H), 7.44-7.37 (m, 4H), 7.26 (d, 2H), 7.18-7.05 (m, 3H), 6.95 (t, 1H), 5.93 (s, 1H), 1.62 (s, 1H), 3.67 (dd,

Example 10 l- (2-Chloro-phenyl) -5- [3- (l-BOC-l, 2,3,6-tetrahydropyridin- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; (1.1 g, 2.2 mmol), tert-butyl 4- (4,4,5,5-tetramethyl-l, 3,2-dioxaborolan- (805.5 mg, 2.6 mmol), potassium carbonate (900.0 mg, 6.5 mmol) and Pd (dppf) Cl ₂ (159.0 mg, 0.20 mmol) were added to a 1,4-dioxane Was added to a mixed solvent of 35.0 mL of dioxane and 9.0 mL of distilled water, stirred for 15 minutes, and then stirred at 90 DEG C for 16 hours. Ethyl acetate was added to the reaction mixture, which was then washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/4) to obtain 820.0 mg of the title compound as a white solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.06 (m, 6H), 7.03 (d, 1H), 6.96 (t, 1H), 5.92 (br, 1H), 5.89 (dd, 1H), 4.96 (s 2H), 1.49 (s, 9H), 2.40 (br, 2H)

Example 11. l- (2-Chloro-phenyl) -5- [3- (l, 2,3,6-tetrahydropyridin-4- yl) -phenyl] -3- [di- (trifluoromethyl ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole trifluoroacetic acid salt

(2-chloro-phenyl) -5- [3- (1-BOC-1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole (350.0 mg, 0.58 mmol) and triflu or o acetic acid (444.0 uL, 5.79 mmol) were dissolved in dichloromethane mL) at 0 &lt; 0 &gt; C, and then stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 400.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.36 (d, 1H), 7.29 (d, 1H), 7.24-7.20 (m, 3H), 7.15-7.09 (m, 2H), 6.93 (t, 1H), 2H), 3.43 (br, 2H), 3.33 (dd, 1H), 2.69 (d, (m, 2H)

Example 12. Preparation of 5- [3- (1-acetyl-1,2,3,6-tetrahydropyridin-4-yl) -phenyl] Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(2-chloro-phenyl) -5- [3- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [ (11.0 mg, 0.02 mmol), acetyl chloride (1.5 uL, 0.02 mmol) and triethylamine (7.5 uL, 0.025 mmol) in dichloromethane , 0.05 mmol) were added to 0.5 mL of dichloromethane, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 3.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 5.94 (d, 1H), 5.98 (dd, 1H), 4.96 (s, 1H), 4.15 (d, 2H), 3.72 (dt 2H), 2.14 (d, 3H), 2.43 (d, 2H), 3.68-3.62 (dd,

Examples 13 to 35

(2-chloro-phenyl) -5- [3- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [ -Methyl] -4,5-dihydro-1H-pyrazole trifluoroacetic acid salt was used in place of acetyl chloride, and the sulfonyl chloride or acyl chloride corresponding to Examples 13 to 35 was used , The compounds of Examples 13 to 35 were respectively prepared in the same manner as in Example 12. [

Example 13 5- [3- (l-Butyryl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.18-7.04 (m, 6H), 6.96 (t, 1H), 5.94 (d, 1H), 5.88 (dd, 1H), 4.96 (s 2H), 3.72 (dt, 2H), 3.64 (dd, 1H), 3.22 (dd, 1.66 (m, 2 H), 1.02 (m, 3 H)

Example 14. l- (2-Chloro-phenyl) -5- [3- (l-isobutyryl- l, 2,3,6-tetrahydropyridin-4- yl) -phenyl] - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.18-7.04 (m, 6H), 6.96 (t, 1H), 5.94 (d, 1H), 5.88 (dd, 1H), 4.94 (s , 4.18 (d, 2H), 3.74 (dt, 2H), 3.64 (dd, 1H), 3.23 (dd, 1H), 2.88-2.79 m, 6H)

Example 15 l- (2-Chloro-phenyl) -5- [3- (1-pentanoyl-l, 2,3,6- tetrahydropyridin- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.18-7.04 (m, 6H), 6.96 (t, 1H), 5.94 (d, 1H), 5.88 (dd, 1H), 4.96 (s 2H), 3.71 (dd, 2H), 3.63 (dd, 2H) 1.62 (m 2H), 1.42-1.37 (m, 2H), 1.26 (t, 3H)

Example 16 l- (2-Chloro-phenyl) -5- {3- [l- (3-methyl-butyryl) -1,2,3,6-tetrahydropyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.18-7.04 (m, 6H), 6.96 (t, 1H), 5.94 (d, 1H), 5.88 (dd, 1H), 4.96 (s , 4.16 (d, 2H), 3.73 (dt, 2H), 3.64 (dd, IH), 3.22 m, 1 H), 0.99 (dt, 6 H)

Example 17. l- (2-Chloro-phenyl) -5- {3- [l- (2,2- dimethyl- propionyl) - l, 2,3,6-tetrahydropyridin- ] -Phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.18-7.04 (m, 6H), 6.96 (t, 1H), 5.97 (s, 1H), 5.88 (dd, 1H), 4.95 (s 2H), 3.32 (s, 2H), 3.32 (s, 2H), 3.64 (d,

Example 18. l- (2-Chloro-phenyl) -5- [3- (1-cyclopentanecarbonyl-l, 2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.18-7.04 (m, 6H), 6.96 (t, 1H), 5.95 (d, 1H), 5.88 (dd, 1H), 4.94 (s , 4.18 (d, 2H), 3.76 (dt, 2H), 3.64 (dd, IH), 3.23 (dd, IH), 2.98-2.90 m, 4H), 1.74 (m, 2H), 1.60 (m, 4H)

Example 19. l- (2-Chloro-phenyl) -5- [3- (1-cyclohexanecarbonyl-l, 2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.18-7.04 (m, 6H), 6.96 (t, 1H), 5.95 (d, 1H), 5.88 (dd, 1H), 4.94 (s 2H), 3.64 (dd, 1H), 3.21 (dd, 1H), 2.58-2.34 1.24 (m, 12H)

Example 20 l- (2-Chloro-phenyl) -5- {3- [l- (2-cyclopentyl-acetyl) - 1,2,3,6-tetrahydropyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.18-7.04 (m, 6H), 6.96 (t, 1H), 5.94 (d, 1H), 5.88 (dd, 1H), 4.94 (br 2H), 2.63 (d, 2H), 3.73 (dd, 2H), 3.63 (dd, 1H), 1.85 (m, 2H), 1.56 (m, 6H), 1.18

Example 21. l- (2-Chloro-phenyl) -5- {3- [l- (3-cyclopentyl- propionyl) - l, 2,3,6-tetrahydropyridin- Phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.18-7.04 (m, 6H), 6.96 (t, 1H), 5.94 (d, 1H), 5.88 (dd, 1H), 4.13 (d 2H), 3.73 (dt, 2H), 3.63 (dd, IH), 3.22 (dd, 1.50 (m, 10 H), 1.11 (m, 2 H)

Example 22. l- (2-Chloro-phenyl) -5- {3- [l- (thiophene-2- carbonyl) - l, 2,3,6-tetrahydropyridin-4- } -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.48 (d, 1H), 7.37 (d, 1H), 7.24-7.06 (m, 7H), 6.96 (t, 1H), 5.95 (s, 1H), 5.88 (dd 2H), 3.64 (dd, 1H), 3.22 (dd, 1H), 2.52 (s, 2H)

Example 23. 5- [3- (1-Benzoyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.48 (s, 5H), 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.05 (s, 1H), 5.88 (dd, 1H), 4.99 (br 2H), 3.64 (d, 2H), 3.64 (dd, 1H), 3.60 (s,

Example 24. l- (2-Chloro-phenyl) -5- [3- (l-phenylacetyl-l, 2,3,6-tetrahydropyridin- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.48 (s, 5H), 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.05 (s, 1H), 5.88 (dd, 1H), 4.99 (br 2H), 3.64 (d, 2H), 3.64 (dd, 1H), 3.60 (s,

Example 25. 5- {3- [l- (4-Chloro-benzoyl) -l, 2,3,6-tetrahydropyridin-4-yl] -phenyl} 3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (s, 3H), 7.26-7.23 (m, 2H), 7.19-7.06 (m, 5H), 6.96 (t, 1H), 6.03 (br, 1H), 5.87 (dd, 1H), 4.92 (s, 1H), 4.35 (br, 1H), 3.99 d, 2H)

Example 26. l- (2-Chloro-phenyl) -5- [3- (l-methanesulfonyl-l, 2,3,6-tetrahydropyridin- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 5.95 (s, 1H), 5.89 (dd, 1H), 4.90 (s, 1H), 3.94 (s 2H), 3.66 (dd, 1 H), 3.49 (t, 2H), 3.22 (dd,

Example 27. l- (2-Chloro-phenyl) -5- [3- (l-ethanesulfonyl-l, 2,3,6-tetrahydropyridin- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.20-7.06 (m, 6H), 6.96 (t, 1H), 5.95 (s, 1H), 5.89 (dd, 1H), 4.91 (s 2H), 3.64 (dd, 1H), 3.53 (t, 2H), 3.21 (dd, 3H)

Example 28. l- (2-Chloro-phenyl) -5- {3- [1- (propane- 1 -sulfonyl) - 1,2,3,6-tetrahydropyridin-4- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.20-7.06 (m, 6H), 6.96 (t, 1H), 5.94 (s, 1H), 5.89 (dd, 1H), 4.92 (s (Dd, 2H), 3.97 (s, 2H), 3.64 (dd, 2H), 1.06 (t, 3H)

Example 29. l- (2-Chloro-phenyl) -5- {3- [1- (propane- 2- sulfonyl) -l, 2,3,6- tetrahydropyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.20-7.06 (m, 6H), 6.96 (t, 1H), 5.94 (s, 1H), 5.89 (dd, 1H), 4.91 (s 2H), 1.87 (m, 2H), 4.02 (s, 2H), 3.64 (dd, 2H), 1.37 (d, 6H)

Example 30. l- (2-Chloro-phenyl) -5- {3- [l- (2- methyl- propane- l- sulfonyl) - l, 2,3,6-tetrahydropyridin- ] -Phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.20-7.06 (m, 6H), 6.96 (t, 1H), 5.95 (s, 1H), 5.89 (dd, 1H), 4.91 (s 2H), 2.32 (m, 2H), 3.95 (s, 2H), 3.64 (d, 1H), 1.87 (m, 2H), 1.12 (d, 6H)

Example 31. l- (2-Chloro-phenyl) -5- [3- (1-trifluoromethanesulfonyl-l, 2,3,6-tetrahydropyridin-4- - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.20-7.06 (m, 6H), 6.96 (t, 1H), 5.92 (s, 1H), 5.90 (dd, 1H), 4.90 (s 2H), 3.71 (s, 2H), 3.65 (dd, 1H), 3.22

Example 32. l- (2-Chloro-phenyl) -5- [3- (1-cyclopropanesulfonyl-l, 2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.20-7.06 (m, 6H), 6.96 (t, 1H), 5.95 (s, 1H), 5.89 (dd, 1H), 4.92 (s 2H), 2.31 (m, IH), 1.22 (m, IH), 4.00 (s, 2H), 3.65 (dd, 2H), 1.00 (m, 2H)

Example 33. l- (2-Chloro-phenyl) -5- [3- (1-cyclopentanesulfonyl- 1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.20-7.06 (m, 6H), 6.96 (t, 1H), 5.94 (s, 1H), 5.88 (dd, 1H), 4.92 (s , 2.50 (s, 2H), 2.04 (m, IH), 4.00 (s, 2H), 3.65 (dd, 1.98 (m, 4H), 1.76 (m, 2H), 1.62 (m, 2H)

Example 34. l- (2-Chloro-phenyl) -5- [3- (1-cyclohexanesulfonyl- 1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.20-7.06 (m, 6H), 6.96 (t, 1H), 5.94 (s, 1H), 5.88 (dd, 1H), 4.92 (s 1H), 2.47 (s, 2H), 2.12 (d, 1H), 4.01 (s, 2H), 3.64 (dd, 2H), 1.88 (d, 2H), 1.71 (d, 2H), 1.55-1.21 (m, 6H)

Example 35. l- (2-Chloro-phenyl) -5- [3- (1-dimethylsulfamoyl- l, 2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.19-7.06 (m, 6H), 6.96 (t, 1H), 4.91 (s, 1H), 3.91 (s, 2H), 3.64 (dd 2H), 2.46 (s, 3H), 2.48 (s, 3H)

Example 36. Preparation of 5- (2'-Acetyl-biphenyl-4-yl) -1- (2- chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; 5-dihydro -1H- pyrazole (50.0 mg, 0.10 mmol), 2- acetyl-phenylboronic acid (21.0 mg, 0.13 mmol), Pd (PPh 3) 4 (4.0 mg, cat.) and 2N sodium carbonate 0.5 mL N, N-dimethylformamide (0.5 mL), and the mixture was stirred at 80 占 폚 for 2 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/3) to obtain 10.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.50-7.12 (m, 10H), 7.03 (t, 1H), 6.94 (t, 1H), 5.95 (dd, 1H), 4.93 (s, 1H), 3.70 (dd , &Lt; / RTI &gt; 1H), 3.33 (dd,

Examples 37 to 90

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; Dihydro-1H-pyrazole was used in place of 2-acetylphenylboronic acid and boronic acid corresponding to Example 37 to 90 was used in place of 2-acetylphenylboronic acid, Respectively.

Example 37. 5- (3'-Acetyl-biphenyl-4-yl) -1- (2- chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.10 (s, 1H), 7.91 (d, 1H), 7.73 (d, 1H), 7.58-7.48 (m, 3H), 7.35 (t, 1H), 7.28-7.23 (m, 1H), 7.20 (d, 1H), 7.12-7.05 (m, 2H), 6.97 3.25 (dd, 1 H), 2.63 (s, 3 H)

Example 38. Preparation of 5- (4'-Acetyl-biphenyl-4-yl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.06 (d, 2H), 7.73 (d, 2H), 7.52-7.33 (m, 4H), 7.14-6.98 (m, 4H), 5.84 (dd, 1H), 4.88 (s, 1 H), 3.64 (dd, 1 H), 3.16 (dd,

Example 39. l- (2-Chloro-phenyl) -5- (2'-methoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.40 (d, 2H), 7.36-7.22 (m, 3H), 7.20-7.16 (m, 3H), 7.10 (t, 1H), 7.00-6.93 (m, 3H) , 5.88 (dd, 1 H), 4.95 (s, 1 H), 3.77 (s, 3 H), 3.64

Example 40. l- (2-Chloro-phenyl) -5- (3'-methoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.44 (d, 2H), 7.33-7.17 (m, 5H), 7.08 (d, 2H), 7.02 (s, 1H), 6.97 (t, 1H), 6.87 (d 3H), 3.65 (dd, IH), 3.24 (dd, IH)

Example 41. l- (2-Chloro-phenyl) -5- (4'-methoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (d, 2H), 7.40 (d, 2H), 7.26 (m, 1H), 7.19 (d, 3H), 7.09 (t, 1H), 6.98-6.91 (m 3H), 3.65 (dd, IH), 3.24 (dd, IH)

Example 42. l- (2-chloro-phenyl) -5- [2 '-( methylsulfanyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.36-6.98 (m, 12H), 5.88 (dd, 1H), 4.94 (s, 1H), 3.65 (dd, 1H), 3.30 (dd, 1H), 2.27 (s , 3H)

Example 43. l- (2-chloro-phenyl) -5- [3 '-( methylsulfanyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43-6.97 (m, 12H), 5.92 (dd, 1H), 4.94 (s, 1H), 3.64 (dd, 1H), 3.24 (dd, 1H), 2.51 (s , 3H)

Example 44. l- (2-chloro-phenyl) -5- [4 '-( methylsulfanyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) -hydroxy- ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 2H), 7.35 (d, 2H), 7.28-7.09 (m, 5H), 7.03-6.96 (m, 3H), 5.91 (dd, 1H), 4.94 (d, IH), 3.65 (dd, IH), 3.23 (dd,

Example 45. l- (2-chloro-phenyl) -5- [4 '- (methanesulfonyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.97 (d, 2H), 7.68 (d, 2H), 7.59 (d, 1H), 7.47 (d, 2H), 7.27 (d, 2H), 7.20 (d, 1H 1H), 3.96 (s, 1H), 3.68 (dd, 1H), 3.23 (dd,

Example 46. l- (2-Chloro-phenyl) -5- (2 ', 3'-dimethoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.39 (d, 2H), 7.27-7.25 (m, 1H), 7.18 (d, 2H), 7.14 (d, 1H), 7.06 (t, 2H), 6.97-6.82 (m, 3H), 5.88 (dd, IH), 4.94 (s, IH), 3.88 (s, 3H), 3.66 (dd,

Example 47. l- (2-Chloro-phenyl) -5- (2 ', 4'-dimethoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.37 (d, 2H), 7.29-7.26 (m, 1H), 7.18-7.07 (m, 5H), 6.97 (t, 1H), 6.55-6.51 (m, 2H) , 5.87 (s, 3H), 3.62 (dd, 1H), 3.24 (sd, 1H)

Example 48. l- (2-Chloro-phenyl) -5- (2 ', 5'- dimethoxy- biphenyl- 4- yl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.40 (d, 2H), 7.29-7.26 (m, 1H), 7.20-7.16 (m, 2H), 7.10 (t, 1H), 6.98 (t, 1H), 6.92 (S, 3H), 3.69 (s, 3H), 3.63 (dd, 1H), 3.25 (dd,

Example 49. l- (2-Chloro-phenyl) -5- (2 ', 6'-dimethoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 1H), 7.34 (d, 1H), 7.30-7.22 (m, 2H), 7.20-7.06 (m, 3H), 7.03-6.96 (m, 2H) , 6.61 (d, 2H), 5.82 (dd, IH), 4.95 (s, IH), 3.65

Example 50. l- (2-Chloro-phenyl) -5- (3 ', 4'- dimethoxy- biphenyl- 4- yl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.41 (d, 2H), 7.27 (d, 1H), 7.20 (d, 3H), 7.11-7.04 (m, 2H), 7.01 (s, 1H), 6.97 (t , 3.90 (s, 3H), 3.65 (dd, 1H), 3.29 (dd, 1H)

Example 51. l- (2-Chloro-phenyl) -5- (3 ', 5'- dimethoxy- biphenyl- 4- yl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (d, 2H), 7.27 (d, 1H), 7.22-7.17 (m, 3H), 7.09 (t, 1H), 6.97 (t, 1H), 6.62 (s 2H), 6.44 (s, 1H), 5.91 (dd, 1H), 4.93 (s,

Example 52. Preparation of 5- (2'-chloro-biphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (d, 1H), 7.35 (d, 1H), 7.31-7.20 (m, 6H), 7.16-7.06 (m, 2H), 7.03-6.96 (m, 2H) , 5.89 (dd, IH), 4.93 (s, IH), 3.66 (dd, IH), 3.29

Example 53. 5- (3'-Chloro-biphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.48 (s, 1H), 7.42 (d, 2H), 7.38-7.17 (m, 7H), 7.10 (t, 1H), 6.97 (t, 1H), 5.92 (dd , 4.92 (s, 1 H), 3.67 (dd, 1 H), 3.23 (dd,

Example 54. Preparation of 5- (4'-chloro-biphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43-7.35 (m, 6H), 7.27-7.17 (m, 4H), 7.10 (t, 1H), 6.97 (t, 1H), 5.92 (dd, 1H), 4.92 (s, 1 H), 3.66 (dd, 1 H), 3.23 (dd, 1 H)

Example 55. l- (2-Chloro-phenyl) -5- (2'-fluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 2H), 7.36-7.08 (m, 9H), 6.98 (t, 1H), 5.91 (dd, 1H), 4.93 (s, 1H), 3.65 (dd , &Lt; / RTI &gt; 1H), 3.25 (dd, 1H)

Example 56. l- (2-Chloro-phenyl) -5- (3'-fluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (d, 2H), 7.38-7.32 (m, 1H), 7.28-7.17 (m, 6H), 7.10 (t, 1H), 7.03-6.95 (m, 2H) , 5.92 (dd, IH), 4.93 (s, IH), 3.66 (dd, IH), 3.24

Example 57. l- (2-Chloro-phenyl) -5- (4'-fluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.47-7.43 (m, 2H), 7.39 (d, 2H), 7.28-7.17 (m, 4H), 7.11-7.06 (m, 3H), 6.97 (t, 1H) , 5.92 (dd, 1 H), 4.93 (s, 1 H), 3.66 (dd,

Example 58. l- (2-Chloro-phenyl) -5- [2 '-( trifluoromethyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.69 (d, 1H), 7.51 (t, 1H), 7.44 (t, 1H), 7.34 (d, 1H), 7.28-7.26 (m, 2H), 7.21-7.09 (d, 1H), 3.67 (dd, 1H), 3.32 (dd, 1H)

Example 59. l- (2-Chloro-phenyl) -5- [3 '-( trifluoromethyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.73 (s, 1H), 7.67 (d, 1H), 7.59-7.41 (m, 5H), 7.27-7.24 (m, 2H), 7.20 (d, 1H), 7.11 (d, 1H), 6.98 (t, 1H), 5.95 (dd,

Example 60. l- (2-Chloro-phenyl) -5- [4 '-( trifluoromethyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.65 (d, 2H), 7.59 (d, 2H), 7.46 (d, 2H), 7.28-7.24 (m, 3H), 7.20 (d, 1H), 7.10 (t (Dd, 1H), 6.98 (t, 1H), 5.94 (dd,

Example 61. l- (2-Chloro-phenyl) -5- [3 '-( trifluoromethoxy) -biphenyl-4-yl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.44-7.42 (m, 4H), 7.33 (s, 1H), 7.28-7.18 (m, 5H), 7.10 (t, 1H), 6.97 (t, 1H), 5.94 (dd, 1 H), 4.93 (s, 1 H), 3.67 (dd, 1 H), 3.24

Example 62. l- (2-Chloro-phenyl) -5- (2'-methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.35 (d, 1H), 7.28-7.08 (m, 9H), 7.03-6.97 (m, 2H), 5.88 (dd, 1H), 4.93 (s, 1H), 3.66 (dd, 1 H), 3.30 (dd, 1 H), 2.12 (s, 3 H)

Example 63. l- (2-Chloro-phenyl) -5- (3'-methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.43 (d, 2H), 7.36-6.94 (m, 10H), 5.91 (dd, , &Lt; / RTI &gt; 1H), 2.38 (s, 3H)

Example 64. l- (2-Chloro-phenyl) -5- (4'-methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.44-7.33 (m, 4H), 7.21-6.96 (m, 8H), 5.90 (dd, 1H), 4.93 (s, 1H), 3.66 (dd, 1H), 3.24 (dd, 1 H), 2.37 (s, 3 H)

Example 65. l- (2-Chloro-phenyl) -5- (2 ' -isopropoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) 4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.38 (d, 2H), 7.35 (d, 1H), 7.26-7.21 (m, 3H), 7.15 (d, 2H), 7.09-6.93 (m, 4H), 5.89 (dd, 1H), 4.95 (s, 1H), 4.32-4.25 (m, 1H), 3.65

Example 66. l- (2-Chloro-phenyl) -5- (3 ' -isopropoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) 4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (d, 2H), 7.31-7.26 (m, 2H), 7.21-7.16 (m, 3H), 7.11-6.95 (m, 4H), 6.85 (d, 1H) , 5.91 (dd, 1 H), 4.93 (s, 1 H), 4.62 - 4.55 (m,

Example 67. l- (2-Chloro-phenyl) -5- (4'-isopropoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) 4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.40 (t, 4H), 7.25 (d, 1H), 7.18 (d, 3H), 7.08 (t, 1H), 6.96 (t, 1H), 6.90 (d, 2H ), 5.90 (dd, IH), 4.94 (s, IH), 4.58-4.53 (m, IH), 3.64 (dd,

Example 68. l- (2-Chloro-phenyl) -5- (3'-ethoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (d, 2H), 7.31-7.16 (m, 5H), 7.11-7.06 (m, 2H), 7.02 (s, 1H), 6.96 (t, 1H), 6.85 (d, 1H), 5.91 (dd, IH), 4.93 (s, IH), 4.06 (q, 2H), 3.65

Example 69. l- (2-Chloro-phenyl) -5- (3'-hydroxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 2H), 7.28-7.16 (m, 5H), 7.11-7.06 (m, 2H), 6.98-6.95 (m, 2H), 6.79 (d, 1H) , 5.91 (dd, 1 H), 4.93 (s, 1 H), 4.77

Example 70. l- (3-Amino-biphenyl-4-yl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.41 (d, 2H), 7.25 (d, 1H), 7.20-7.15 (m, 4H), 7.08 (t, 1H), 6.96 (t, 1H), 6.89 (d 2H), 3.65 (dd, IH), 3.24 (dd, IH) 1H)

Example 71. l- (2-Chloro-phenyl) -5- (4'-dimethylamino-biphenyl-4-yl) -3- [di- (trifluoromethyl) 4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.48-7.38 (m, 5H), 7.25 (d, 1H), 7.16 (d, 2H), 7.08 (t, 1H), 6.95 (t, 1H), 6.75 (d 2H), 5.88 (dd, IH), 4.95 (s, IH), 3.63 (dd, IH), 3.24

Example 72. l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy- -Methyl] -4,5-dihydro-lH-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.29-7.26 (m, 4H), 7.20-7.07 (m, 4H), 7.00-6.97 , 4.93 (s, 1H), 3.82 (s, 3H), 3.65 (dd,

Example 73. l- (3-chloro-4'-fluoro-biphenyl-4-yl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.52 (d, 1H), 7.51-7.32 (m, 3H), 7.26-7.08 (m, 6H), 6.98 (t, 1H), 5.93 (dd, 1H), 4.92 (s, 1 H), 3.66 (dd, 1 H), 3.22 (dd, 1 H)

Example 74. l- (5-chloro-2'-methoxy-biphenyl-4-yl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.37 (d, 2H), 7.29-7.16 (m, 6H), 7.10 (t, 1H), 6.98 (t, 1H), 6.86 (d, 1H), 5.89 (dd 3H), 3.64 (dd, IH), 3.24 (dd, IH)

Example 75. l- (4-tert-Butyl-biphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) 4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.45-7.40 (m, 5H), 7.25 (d, 1H), 7.20-6.93 (m, 6H), 5.90 (dd, 1H), 4.94 (s, 1H), 3.65 (dd, 1 H), 3.26 (dd, 1 H), 1.33 (s, 9 H)

Example 76. l- (2-Chloro-phenyl) -5- (4-furan-3-yl-phenyl) -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.66 (s, 1H), 7.44 (s, 1H), 7.33 (d, 2H), 7.25 (d, 2H), 7.18-7.13 (m, 2H), 7.09 (t 1H), 3.96 (dd, 1H), 3.22 (dd, 1H), 6.96 (s,

Example 77. l- (2-Chloro-phenyl) -5- (4-pyrimidin-5-yl-phenyl) -3- [di- (trifluoromethyl) - dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 9.18 (s, 1H), 8.87 (s, 2H), 7.45 (d, 2H), 7.31 (d, 2H), 7.27 (d, 1H), 7.20 (d, 1H ), 7.12 (t, IH), 6.99 (t, IH), 5.96 (dd, IH), 4.94

Example 78. l- (2-Chloro-phenyl) -5- (4-quinolin-3-yl-phenyl) -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 9.08 (s, 1H), 8.23 (s, 1H), 8.12 (d, 1H), 7.85 (d, 1H), 7.72 (t, 1H), 7.59-7.56 (m (D, 1H), 3.97 (d, 1H), 3.98 (s, 3H), 7.33-7.21 dd, 1 H)

Example 79. l- (2-Chloro-phenyl) -5- [4- (6-methoxy-pyridin- 3- yl) -phenyl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 8.29 (s, 1 H), 7.70 (dd, 1 H), 7.38 (d, 2H), 7.28-7.18 (s, 3H), 3.67 (dd, 1H), 3.23 (dd, 1H)

Example 80. l- (2-Chloro-phenyl) -5- [4- (2- fluoro-pyridin-3- yl) -phenyl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.17 (d, 1H), 7.79 (t, 1H), 7.44 (d, 2H), 7.29-7.22 (m, 4H), 7.19 (d, 1H), 7.11 (t (D, 1H), 6.99 (d, 1H), 5.93 (dd,

Example 81. 5- (4-benzofuran-2-yl-phenyl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy- - dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.71 (d, 2H), 7.55 (d, 1H), 7.47 (d, 1H), 7.26-7.17 (m, 6H), 7.09 (t, 1H), 6.96 (s (Dd, 2H), 5.92 (dd, IH), 4.93

Example 82. l- (2-Chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] Dihydro-lH-pyrazole &lt; / RTI &gt;

^{1 H NMR (400 MHz, CDCl} 3) 7.80 (d, 1H), 7.74 (d, 1H), 7.57 (d, 2H), 7.48 (s, 1H), 7.36-7.18 (m, 5H), 7.11 (t 1H), 3.63 (dd, IH), 3.23 (dd, IH)

Example 83. 5- (3'-Carboxy-biphenyl-4-yl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 1 H NMR (CDCl 3) 8.24 (s, 1H), 8.26 (d, 1H), 7.74 (d, 1H), 7.53-7.47 (m, 3H), 7.28-7.23 (m, 3H), 7.20 (d, IH), 7.10 (t, IH), 6.97 (t, IH), 5.94 (dd,

Example 84. Preparation of 5- (4'-carboxy-biphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.13 (d, 2H), 7.60 (d, 2H), 7.50 (d, 2H), 7.27-7.25 (m, 3H), 7.20 (d, 1H), 7.10 (t (Dd, 1H), 6.97 (t, 1H), 5.94

Example 85. Preparation of 5- (4'-amino-biphenyl-4-yl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.36 (d, 2H), 7.30 (d, 2H), 7.24 (d, 1H), 7.17-7.14 (m, 3H), 7.06 (t, 1H), 6.93 (t , 6.68 (d, 2H), 5.87 (dd, 1H), 3.62

Example 86. l- (2-Chloro-phenyl) -5- (2'-ethoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.41 (d, 2H), 7.28-7.15 (m, 6H), 7.08 (t, 1H), 6.99-6.91 (m, 3H), 5.88 (dd, 1H), 4.94 (s, 1 H), 3.96 (q, 2H), 3.64 (dd,

Example 87. l- (2-Chloro-phenyl) -5- (4'-ethoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.41 (t, 4H), 7.26 (s, 1H), 7.18 (d, 3H), 7.09 (t, 1H), 6.96 (t, 1H), 6.91 (d, 2H 2H), 3.64 (dd, 1H), 3.24 (dd, 1H), 1.27 (t, 3H)

Example 88. l- (2-Chloro-phenyl) -5- (4'-isopropyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (d, 4H), 7.29-7.15 (m, 6H), 7.08 (t, 1H), 6.96 (t, 1H), 5.89 (dd, 1H), 4.93 (s , 3.65 (dd, 1 H), 3.24 (dd, 1 H), 2.94-2.91

Example 89. l- (2-chloro-phenyl) -5- (4'-fluoro-2'-methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.28-7.03 (m, 8H), 7.00-6.85 (m, 3H), 5.89 (dd, 1H), 4.93 (s, 1H), 3.66 (dd, 1H), 3.29 (dd, 1 H), 2.10 (s, 3 H)

Example 90. l- (2-chloro-phenyl) -5- (2'-fluoro-4'- methyl- biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.39 (d, 2H), 7.28-7.07 (m, 6H), 7.00-6.91 (m, 3H), 5.89 (dd, 1H), 4.93 (s, 1H), 3.64 (dd, 1 H), 3.23 (dd, 1 H), 2.36 (s, 3 H)

Example 91. l- (2-chloro-phenyl) -5- [4- (6-methylsulfanyl-pyridin-3- yl) -phenyl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

Step 1. l- (2-Chloro-phenyl) -5- [4- (4,4,5,5-tetramethyl-l, - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; (3.65 g, 14.35 mmol), Pd (dppf) Cl ₂ (0.29 g, 0.36 mmol), dppf (0.20 g, g, 0.36 mmol) and potassium acetate (3.52 g, 35.88 mmol) were added to 30 mL of 1,4-dioxane and the mixture was stirred at 80 ° C for 3 hours. The reaction mixture was filtered through a pad of celite, distilled water was added to the obtained filtrate, and the mixture was extracted three times with diethyl ether. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/100) to obtain 3.5 g of the title compound as a white liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.65 (d, 2H), 7.23 (d, 1H), 7.22-7.13 (m, 3H), 7.07 (dd, 1H), 6.95 (dd, 1H), 5.89 (dd (S, 1H), 4.92 (s, 1H), 3.63 (dd,

Step 2. Synthesis of l- (2-chloro-phenyl) -5- [4- (6-methylsulfanyl-pyridin-3- yl) -phenyl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

5-Bromo-2-was added to the Mo (methylthio) pyridine (14.0 mg, 0.07 mmol) 1,2- dimethoxy ethane was added to _{1.5 mL Pd (PPh 3) 4} (8.4 mg, cat.) In. To the reaction mixture was added 1- (2-chloro-phenyl) -5- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolane- Dihydro-1H-pyrazole (25.0 mg, 0.05 mmol), ethanol 183.0 uL, 2N (2-ethoxyphenyl) 183.0 [mu] L of sodium carbonate was added thereto, followed by stirring at 88 [deg.] C for 2 hours. Distilled water was added to the reaction mixture and extracted twice with diethyl ether. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 8.0 mg of the title compound as a white liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.58 (s, 1H), 7.60 (d, 1H), 7.40 (d, 2H), 7.28-7.18 (m, 5H), 7.10 (t, 1H), 6.97 (t (S, 3H), 3.40 (dd, 2H), 3.40 (dd,

Examples 92 to 128

To a solution of 1- (2-chloro-phenyl) -5- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan- ) - phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole, The compounds of Examples 92 to 128 were each prepared in the same manner as in Step 2 of Example 91, except that the substituted aryl bromide corresponding to Examples 92 to 128 was used instead of pyridine.

Example 92. l- (2-Chloro-phenyl) -5- [4- (6-cyano-pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.87 (s, 1H), 7.90 (d, 1H), 7.72 (d, 1H), 7.47 (d, 2H), 7.31 (d, 2H), 7.28 (d, 1H ), 7.20 (d, 1H), 7.11 (t, IH), 6.98 (t, IH), 5.96 (dd,

Example 93. l- (2-Chloro-phenyl) -5- [4- (6-fluoro-pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.32 (s, 1H), 7.87 (t, 1H), 7.39 (d, 2H), 7.28-7.25 (m, 3H), 7.20 (d, 1H), 7.10 (t 1H), 3.67 (dd, IH), 3.22 (dd, IH)

Example 94. l- (2-Chloro-phenyl) -5- [4- (6-ethoxy-pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.27 (s, 1H), 7.69 (d, 1H), 7.37 (d, 2H), 7.25-7.17 (m, 4H), 7.10 (t, 1H), 6.97 (t (D, 1H), 6.74 (d, 1H), 5.90 (dd, 1H), 4.92 3H)

Example 95. l- (2-Chloro-phenyl) -5- [4- (6-methoxy-4-methyl- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.86 (s, 1H), 7.28-7.11 (m, 7H), 7.08 (t, 1H), 6.97 (t, 1H), 6.60 (s, 1H), 5.89 (dd (S, 3H), 3.92 (s, 3H), 3.65 (dd,

Example 96. l- (2-Chloro-phenyl) -5- [4- (2-methyl-pyridin- ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.47 (d, 1H), 7.40 (d, 1H), 7.27 (d, 1H), 7.23-7.11 (m, 6H), 7.08 (t, 1H), 6.97 (t (D, 1H), 5.90 (dd, IH), 5.17 (s, IH), 3.68 (dd,

Example 97. l- (2-Chloro-phenyl) -5- [4- (4-methyl-pyridin- ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.40 (d, 1H), 8.30 (s, 1H), 7.28-7.22 (m, 3H), 7.15 (d, 4H), 7.08 (t, 1H), 6.97 (t (S, 3H), 3.40 (dd, IH), 5.89 (d,

Example 98. l- (2-Chloro-phenyl) -5- [4- (6-trifluoromethyl-pyridin-3- yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.84 (s, 1H), 7.94 (d, 1H), 7.71 (d, 1H), 7.30 (d, 2H), 7.29 (d, 2H), 7.25 (m, 1H ), 7.20 (d, 2H), 7.11 (t, IH), 6.98 (t, IH), 5.95 (dd,

Example 99. l- (2-Chloro-phenyl) -5- [4- (5-methoxycarbonyl-pyridin-3- yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 9.18 (s, 1H), 8.90 (s, 1H), 8.38 (s, 1H), 7.47 (d, 2H), 7.28 (d, 2H), 7.25 (m, 1H ), 7.20 (d, IH), 7.10 (t, IH), 6.97 (t, IH), 5.95 (dd, , 3.23 (dd, 1 H)

Example 100. l- (2-Chloro-phenyl) -5- [4- (5-formyl-6-methoxy-pyridin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 10.44 (s, 1H), 8.51 (s, 1H), 8.22 (s, 1H), 7.41 (d, 2H), 7.26 (d, 2H), 7.19 (d, 1H ), 7.08 (t, IH), 6.97 (t, IH), 5.93 (dd, IH), 4.92 (s,

Example 101. l- (2-Chloro-phenyl) -5- [4- (2- cyano-pyridin- 3- yl) -phenyl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.69 (d, 1H), 7.75 (d, 1H), 7.53 (t, 1H), 7.33 (d, 2H), 7.28 (d, 2H), 7.26 (d, 1H ), 7.16 (d, IH), 7.11 (t, IH), 6.99 (t, IH), 5.92 (dd,

Example 102. l- (2-Chloro-phenyl) -5- [4- (5-fluoro-pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.61 (s, 1H), 8.47 (s, 1H), 7.49 (d, 1H), 7.43 (d, 2H), 7.27 (d, 2H), 7.26 (m, 1H ), 7.19 (d, 1H), 7.10 (t, IH), 6.97 (t, IH), 5.95 (dd,

Example 103. l- (2-Chloro-phenyl) -5- [4- (5-methyl-pyridin- ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.55 (s, 1H), 8.39 (s, 1H), 7.58 (s, 1H), 7.42 (d, 2H), 7.27 (m, 1H), 7.25 (d, 2H ), 7.19 (d, IH), 7.09 (t, IH), 6.97 (t, IH), 5.92 (dd, , 2.36 (s, 3 H)

Example 104. l- (2-Chloro-phenyl) -5- [4- (6-fluoro-4- methyl-pyridin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.92 (s, 1H), 7.28-7.22 (m, 3H), 7.18-7.08 (m, 4H), 6.99 (t, 1H), 6.81 (s, 1H), 5.94 (dd, 1 H), 5.01 (s, 1 H), 3.69 (dd,

Example 105. l- (2-chloro-phenyl) -5- (2'-isopropyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.33-7.26 (m, 3H), 7.22-7.03 (t, 8H), 6.98 (t, 1H), 5.90 (dd, 1H), 5.01 (s, 1H), 3.68 (dd, 1 H), 3.34 (dd, 1 H), 2.78-2.72 (m,

Example 106. l- (2-Chloro-phenyl) -5- (3'-isopropyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.45 (d, 2H), 7.35-7.31 (m, 3H), 7.16-7.17 (m, 5H), 7.09 (t, 1H), 6.96 (t, 1H), 5.92 (dd, 1H), 4.95 (s, 1H), 3.66 (dd, 1H), 3.24

Example 107. l- (2-Chloro-phenyl) -5- (4'-isopropyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (m, 3H), 7.26-7.15 (m, 6H), 7.07 (t, 1H), 6.97 (t, 1H), 5.90 (dd, 1H), 4.95 (s (D, 1H), 3.65 (dd, 1H), 3.24

Example 108. l- (2-Chloro-phenyl) -5- [4- (3-methyl-pyridin- ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.47 (d, 1H), 7.54 (d, 1H), 7.39 (d, 2H), 7.26-7.22 (m, 3H), 7.18-7.13 (m, 2H), 7.08 (t, 1H), 6.96 (t, IH), 5.92 (dd, IH), 4.96

Example 109. l- (2-Chloro-phenyl) -5- [4- (6-methyl-pyridin- ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.84 (d, 2H), 7.59 (t, 1H), 7.42 (d, 1H), 7.26-7.18 (m, 4H), 7.08-7.05 (m, 2H), 6.94 (d, IH), 5.94 (dd, IH), 4.93 (s, IH), 3.66 (dd,

Example 110. l- (2-Chloro-phenyl) -5- [4- (pyridin-3- yl) -phenyl] -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.75 (s, 1H), 8.57 (s, 1H), 7.79 (d, 1H), 7.44 (d, 2H), 7.33 (t, 1H), 7.28-7.25 (m (Dd, 1H), 7.20 (d, 1H), 7.20 (d,

Example 111. l- (2-Chloro-phenyl) -5- [4- (5-cyano-pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.94 (s, 1H), 8.83 (s, 1H), 8.04 (s, 1H), 7.44 (d, 2H), 7.33-7.26 (m, 3H), 7.20 (d 1H), 3.69 (dd, 1 H), 3.22 (dd, 1 H), 7.12 (t,

Example 112. l- (2-chloro-phenyl) -5- [4- (2-methoxy-pyrimidin- 5- yl) -phenyl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.63 (s, 2H), 7.37 (d, 2H), 7.28-7.25 (m, 3H), 7.19 (d, 1H), 7.11 (t, 1H), 6.98 (t 3H), 3.67 (dd, IH), 3.22 (dd, IH)

Example 113. l- (2-Chloro-phenyl) -5- [4- (2,4-dimethoxy-pyrimidin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.18 (s, 1H), 7.37 (d, 2H), 7.29-7.17 (m, 4H), 7.09 (t, 1H), 6.99 (t, 1H), 5.89 (dd 3H), 3.64 (dd, IH), 3.22 (dd, IH)

Example 114. l- (2-Chloro-phenyl) -5- [4- (2- chloro-pyrimidin- 5- yl) -phenyl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.46 (s, 2H), 7.32 (d, 2H), 7.29-7.17 (m, 4H), 7.10 (t, 1H), 6.96 (t, 1H), 5.90 (dd , 4.93 (s, IH), 3.65 (dd, IH), 3.21 (dd, IH)

Example 115. l- (2-Chloro-phenyl) -5- {4 '- [(2-hydroxy-ethyl) -methanesulfonyl-amino] (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.53 (d, 2H), 7.45-7.38 (m, 5H), 7.27-7.22 (m, 2H), 7.18 (d, 1H), 7.09 (dd, 1H), 6.97 (dd, 1H), 5.92 (dd, IH), 4.96 (brs, IH), 3.86 (t, 2H), 3.71-3.62 (m, 3H), 3.24 1.94 (brs, 1 H)

Example 116. l- (2-Chloro-phenyl) -5- {3 '- [(2-hydroxy- ethyl) -methyl-sulfamoyl] Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.97 (s, IH), 7.81 (d, IH), 7.73 (dd, IH), 7.62-7.52 (m, 3H), 7.21 (d, IH), 7.11 (dd, IH), 6.98 (dd, IH), 5.95 3.68 (dd, 1 H), 3.26-3.17 (m, 3H), 2.85 (s, 3H), 2.02 (brs,

Example 117. l- (2-chloro-phenyl) -5- {4 '- [(2-hydroxy-ethyl) -methyl- sulfamoyl] Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.88-7.80 (m, 2H), 7.64 (d, 2H), 7.46 (d, 2H), 7.28-7.25 (m, 3H), 7.20 (d, 1H), 7.10 (dd, IH), 6.97 (dd, IH), 5.94 (dd, IH), 4.96 (brs, 3.17 (m, 2 H), 2.85 (s, 3 H), 2.05 (brs, 1 H)

Example 118. l- (2-Chloro-phenyl) -5- (3 ' -dimethylsulfamoyl-biphenyl-4- yl) -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole &lt; / RTI &gt;

^{1 H NMR (400 MHz, CDCl} 3) 7.89 (s, 1H), 7.72 (d, 2H), 7.57 (dd, 1H), 7.46 (d, 2H), 7.28-7.25 (m, 3H), 7.20 (d (Dd, IH), 3.73 (dd, IH), 3.69 (dd, 6H)

Example 119. l- (2-Chloro-phenyl) -5- (4'-dimethylsulfamoyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole &lt; / RTI &gt;

^{1 H NMR (400 MHz, CDCl} 3) 7.80 (d, 2H), 7.65 (d, 2H), 7.47 (d, 2H), 7.28-7.25 (m, 3H), 7.20 (d, 1H), 7.10 (dd (Dd, IH), 6.72 (dd, IH), 5.94 (dd, IH), 4.91 (brs,

Example 120. 5- {3 '- [3- (N-BOC-N-methyl-amino) -propane- 1 -sulfonyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.01 (s, 1H), 7.92 (d, 2H), 7.67 (dd, 1H), 7.47 (d, 2H), 7.28-7.25 (m, 3H), 7.20 (d (M, 3H), 3.18 (dd, IH), 7.11 (dd, IH), 6.98 3H), 1.96-1.92 (m, 2H), 1.41 (s, 9H)

Example 121. Preparation of 5- (4'- [3- (N-BOC-N-methyl-amino) -propane- 1 -sulfonyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.91 (d, 2H), 7.67 (d, 2H), 7.47 (d, 2H), 7.28-7.25 (m, 3H), 7.20 (d, 1H), 7.11 (dd (M, 2H), 6.98 (dd, IH), 5.95 (dd, IH), 4.94 (brs, 2.80 (s, 3H), 1.98-1.92 (m, 2H), 1.41 (s, 9H)

Example 122. l- (2-chloro-phenyl) -5- {4- [6- (methyl- sulfonyl) -pyridin- 2- yl] -phenyl} -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.98 (d, 2H), 7.94-7.89 (m, 3H), 7.30-7.24 (m, 3H), 7.20 (d, 1H), 7.10 (t, 1H), 6.97 (s, 3H), 3.24 (dd, 1 H), 3.95 (d,

Example 123. l- (2-Chloro-phenyl) -5- {4- [5- (methyl- sulfonyl) -pyridin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 9.09 (s, 1H), 9.00 (s, 1H), 8.30 (s, 1H) 7.49 (d, 2H), 7.31 (d, 2H), 7.27 (d, 1H) , 7.21 (d, IH), 7.10 (t, IH), 6.98 (t, IH), 5.97 (dd, IH), 4.96 3.13 (s, 3 H)

Example 124. l- (2-Chloro-phenyl) -5- [2 ', 5'-difluoro-4' - (lH-1,2,4- triazol- l-yl) Yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.74 (s, 1H), 8.13 (s, 1H), 7.77 (dd, 1H), 7.43 (d, 2H), 7.32-7.26 (m, 4H), 7.20 (d (Dd, IH), 7.99 (t, IH), 6.99 (t, IH), 5.94

Example 125. l- (2-Chloro-phenyl) -5- [2 ', 6'-difluoro-4' - (methylsulfonyl) Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.56 (d, 2H), 7.34 (d, 2H), 7.30-7.26 , 3.10 (s, 3H), 3.14 (d, 2H)

Example 126. l- (2-Chloro-phenyl) -5- [4- (5- (methylsulfonyl) -pyridin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 9.15 (s, 1H), 8.23 (d, 1H), 7.93 (d, 2H), 7.82 (d, 1H), 7.31 (d, 2H), 7.25 (d, 1H ), 7.20 (d, IH), 7.09 (t, IH), 6.98 (t, IH), 5.96 (dd, , 3.12 (s, 3H)

Example 127. l- (2-chloro-phenyl) -5- [4 '-( methylsulfonyl) -2 '-( trifluoromethyl) Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.28 (s, 1H), 8.09 (d, 1H), 7.45 (d, 1H), 7.27 (d, 1H), 7.26-7.21 (m, 2H), 7.16-7.09 (m, 4H), 7.00 (t, IH), 5.90 (dd, IH), 4.93 (s, IH), 3.68 (dd,

Example 128. l- (2-Chloro-phenyl) -5- [3 ' - cyano-4 '-( methylsulfonyl) ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.21 (d, 1H), 8.00 (s, 1H), 7.89 (d, 1H), 7.47 (d, 2H), 7.32 (d, 2H), 7.27 (d, 1H ), 7.20 (d, 1H), 7.30 (t, 1H), 7.00 (t, , 3.24 (dd, 1 H)

Example 129. l- (2-chloro-phenyl) -5- [4- (l-BOC-l, 2,3,6-tetrahydropyridin- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; (1801.0 mg, 3.59 mmol), tert-butyl 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan- (1332.1 mg, 0.13 mmol), Pd (dppf) Cl ₂ (262.7 mg, cat.) And potassium carbonate (1448.6 mg, 10.77 mmol) were added to a 1,4-dioxane Was added to a mixed solvent of dioxane (57.6 mL) and water (14.4 mL), and the mixture was stirred at 90 DEG C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/6) to obtain 1.46 g of the title compound as a white solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.06 (m, 7H), 6.95 (t, 1H), 5.97 (br, 1H), 5.86 (dd, 1H), 4.97 (s, 1H), 4.02 (br 2H), 3.70-3.49 (m, 3H), 3.18 (dd,

Example 130. l- (2-Chloro-phenyl) -5- [4- (1,2,3,6-tetrahydropyridin-4- yl) -phenyl] -3- [di- (trifluoromethyl ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole trifluoroacetic acid salt

The title compound was obtained as white crystals from 1- (2-chloro-phenyl) -5- [4- (1-BOC-1,2,3,6-tetrahydropyridin-4-yl) (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole (350.0 mg, 0.58 mmol) and trifluoroacetic acid (444.0 uL, 5.79 mmol) Methane (5.0 mL), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain 400.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 9.68 (br, 2H), 7.26-7.11 (m, 6H), 7.07 (t, 1H), 6.95 (t, 1H), 5.90 (s, 1H), 5.86 (dd 2H), 3.64 (br, 2H), 3.64 (brd, 2H)

Example 131. l- (2-Chloro-phenyl) -5- [4- (l-acetyl- 1,2,3,6-tetrahydropyridin- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

The title compound was prepared from 1- (2-chloro-phenyl) -5- [4- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [ (15.0 mg, 0.02 mmol), triethylamine (9.3 uL, 0.07 mmol) and acetyl chloride (3.6 uL, 0.35 mmol) in dichloromethane , 0.03 mmol) were added to 1.0 mL of dichloromethane at 0 ° C, and the mixture was stirred at room temperature for 2 hours. Distilled water was added to the reaction mixture and extracted twice with dichloromethane. The extract was washed with 1N hydrochloric acid, saturated sodium carbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/3) to obtain 4.9 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 5.99 (d, 1H), 5.86 (dd, 1H), 4.94 (s, 1H), 4.14 (d (D, 2H), 3.68 (dt, 2H), 3.62 (dd,

Examples 132 to 155

The title compound was prepared from 1- (2-chloro-phenyl) -5- [4- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [ Dimethyl-methyl] -4,5-dihydro-1H-pyrazole trifluoroacetic acid salt was used instead of acetyl chloride and acyl chloride or sulfonyl chloride corresponding to Examples 132 to 155 was used , The compounds of Examples 132 to 155 were prepared in the same manner as in Example 131, respectively.

Example 132. l- (2-Chloro-phenyl) -5- [4- (l-butyryl- l, 2,3,6-tetrahydropyridin- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (d, 1H), 5.86 (dd, 1H), 4.91 (s, 1H), 4.14 (d 2H), 1.67 (m, 2H), 0.97 (m, 2H), 3.66 (dt, 2H), 3.62 (dd, 3H)

Example 133. l- (2-Chloro-phenyl) -5- {4- [l- (2-methyl- propionyl) -l, 2,3,6-tetrahydropyridin-4- } -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.94 (t, 1H), 6.02 (d, 1H), 5.87 (dd, 1H), 4.93 (s, 1H), 4.17 (d 2H), 3.71 (d, 2H), 3.64 (dd, 1H), 3.18 (dd,

Example 134. l- (2-Chloro-phenyl) -5- [4- (1-pentanoyl- l, 2,3,6- tetrahydropyridin- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (d, 1H), 5.86 (dd, 1H), 4.94 (s, 1H), 4.14 (d 2H), 1.63 (m, 2H), 1.63 (m, 2H), 3.63 (d, 2H), 0.93 (m, 3H)

Example 135. l- (2-Chloro-phenyl) -5- {4- [l- (3-methyl-butyryl) -1,2,3,6-tetrahydropyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (d, 1H), 5.87 (dd, 1H), 4.93 (s, 1H), 4.15 (d (D, 2H), 3.71 (dt, 2H), 3.64 (dd, 1H), 3.18 6H)

Example 136. l- (2-Chloro-phenyl) -5- {4- [l- (2,2- dimethyl- propionyl) - l, 2,3,6-tetrahydropyridin- ] -Phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.03 (s, 1H), 5.86 (dd, 1H), 4.93 (s, 1H), 4.21 (s (D, 2H), 3.79 (d, 2H), 3.62 (dd,

Example 137. l- (2-Chloro-phenyl) -5- [4- (1-cyclopentylcarbonyl- 1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.02 (d, 1H), 5.86 (dd, 1H), 4.94 (s, 1H), 4.17 (d 2H), 3.73 (dt, 2H), 3.63 (dd, IH), 3.18 (dd, IH), 2.94 1.25 (m, 2H)

Example 138. l- (2-Chloro-phenyl) -5- [4- (1-cyclohexylcarbonyl- 1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.02 (d, 1H), 5.86 (dd, 1H), 4.94 (s, 1H), 4.15 (d 2H), 3.73 (dt, 2H), 3.63 (dd, IH), 3.18 (dd, IH), 2.48 (d, 2H), 1.80-1.69

Example 139. l- (2-Chloro-phenyl) -5- [4- (1-cyclopentyl-acetyl- 1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (d, 1H), 5.87 (dd, 1H), 4.94 (s, 1H), 4.14 (d 2H), 3.73 (dt, 2H), 3.63 (dd, 1H), 3.18 (dd, 2H), 1.61 (br, 4 [Eta]), 1.17 (br, 2H)

Example 140. l- (2-Chloro-phenyl) -5- [4- (1-cyclopentyl-propionyl- l, 2,3,6-tetrahydropyridin- - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (d, 1H), 5.87 (dd, 1H), 4.94 (s, 1H), 4.14 (d 2H), 3.72 (dt, 2H), 3.63 (dd, 1H), 3.19 (dd, 1.10 (br, 2H)

Example 141. l- (2-Chloro-phenyl) -5- {4- [l- (2- thiophenecarbonyl) - 1,2,3,6-tetrahydropyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.45 (d, 1H), 7.34 (d, 1H), 7.24-7.06 (m, 7H), 6.96 (t, 1H), 5.89 (s, 1H), 5.87 (dd 2H), 3.62 (dd, 1H), 3.19 (dd, 1H), 2.55 (d, 2H)

Example 142. l- (2-Chloro-phenyl) -5- [4- (l-benzoyl- l, 2,3,6-tetrahydropyridin- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (s, 5H), 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.11 (br, 1H), 5.87 (dd, 1H), 4.93 (s , 3.18 (br, IH), 3.92 (br, IH), 3.92 (br, IH), 3.62 (dd, )

Example 143. l- (2-Chloro-phenyl) -5- [4- (l-phenylacetyl- l, 2,3,6-tetrahydropyridin- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.34-7.06 (m, 12H), 6.96 (t, 1H), 6.01-5.88 (d, 1H), 5.85 (dd, 1H), 4.92 (s, 1H), 4.23 (m, 2H), 3.17 (dd, IH), 2.34 (d, 2H)

Example 144. l- (2-Chloro-phenyl) -5- {4- [l- (4-chlorobenzoyl) - 1,2,3,6-tetrahydropyridin-4- yl] -phenyl} -3 - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.41 (s, 4H), 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.09 (br, 1H), 5.87 (dd, 1H), 4.94 (s (Br, d, 2H), 3.62 (dd, 1H), 3.32-4.04 (brd, 2H)

Example 145. l- (2-Chloro-phenyl) -5- [4- (l-methanesulfonyl-l, 2,3,6-tetrahydropyridin- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.01 (br, 1H), 5.87 (dd, 1H), 4.92 (s, 1H), 3.92 (br 2H), 3.63 (dd, 1 H), 3.46 (t, 2H), 3.18 (dd,

Example 146. l- (2-Chloro-phenyl) -5- [4- (l-ethanesulfonyl-l, 2,3,6-tetrahydropyridin- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (s, 1H), 5.87 (dd, 1H), 4.92 (s, 1H), 3.96 (s 2H), 3.62 (dd, 1H), 3.51 (t, 2H), 3.18 (dd,

Example 147. l- (2-chloro-phenyl) -5- {4- [1- (propane- 1 -sulfonyl) - 1,2,3,6-tetrahydropyridin-4- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (s, 1H), 5.87 (dd, 1H), 4.91 (s, 1H), 3.96 (s 2H), 1.86 (m, 2H), 1.05 (t, 2H), 3.63 (dd, 3H)

Example 148. l- (2-Chloro-phenyl) -5- {4- [1- (propane-2- sulfonyl) -l, 2,3,6- tetrahydropyridin-4- 3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (s, 1H), 5.87 (dd, 1H), 4.91 (s, 1H), 4.00 (s (D, 2H), 3.62 (dd, 1H), 3.55 (t, 2H), 3.22

Example 149. l- (2-Chloro-phenyl) -5- {4- [l- (2- methyl- propane- l- sulfonyl) - l, 2,3,6-tetrahydropyridin- ] -Phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (s, 1H), 5.87 (dd, 1H), 4.91 (s, 1H), 3.94 (s 2H), 3.60 (d, 1H), 3.46 (t, 2H), 3.18 (dd,

Example 150. l- (2-Chloro-phenyl) -5- [4- (l-trifluoromethanesulfonyl- l, 2,3,6-tetrahydropyridin-4- - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 5.97 (s, 1H), 5.88 (dd, 1H), 4.91 (s, 1H), 4.14 (br 2H), 3.67 (br, 2H), 3.63 (dd, IH), 3.18

Example 151. l- (2-Chloro-phenyl) -5- [4- (1-cyclopropanesulfonyl- l, 2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.01 (br, 1H), 5.88 (dd, 1H), 4.93 (s, 1H), 3.98 (s 2H), 3.65 (d, 1H), 3.51 (t, 2H), 3.18 (dd, 2H)

Example 152. l- (2-chloro-phenyl) -5- {4- [1- (N, N- dimethylsulfamoyl) -l, 2,3,6- tetrahydropyridin- Phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.01 (br, 1H), 5.87 (dd, 1H), 4.91 (s, 1H), 3.89 (s 2H), 3.65 (dd, IH), 3.44 (t, 2H), 3.18 (dd,

Example 153. l- (2-Chloro-phenyl) -5- [4- (1-cyclopentanesulfonyl- 1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (br, 1H), 5.88 (dd, 1H), 4.91 (s, 1H), 3.99 (s 2H), 3.60 (d, 1H), 3.52 (t, 2H), 3.49 (m, 1H), 3.18 (dd, 2H), 1.60 (m, 2H)

Example 154. l- (2-Chloro-phenyl) -5- [4- (1-cyclohexanesulfonyl- 1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24-7.06 (m, 7H), 6.96 (t, 1H), 6.00 (s, 1H), 5.87 (dd, 1H), 4.91 (s, 1H), 3.99 (s 2H), 2.10 (m, 2H), 1.88 (m, 2H), 3.62 (dd, 2H), 1.68 (m, 2H), 1.30 (m, 4H)

Example 155. l- (2-Chloro-phenyl) -5- {4- [1- (pyrrolidine- 1 -sulfonyl) - l, 2,3,6- tetrahydropyridin- Phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.20 (m, 3H), 7.19-7.06 (m, 4H), 6.95 (dd, 1H), 6.00 (brs, 1H), 6.87 (dd, 1H), 4.93 (d, 1H), 3.90-3.86 (m, 2H), 3.62 (dd, , 2H), 1.94-1.87 (m, 4H)

Example 156. 5- (3'-Acetaminobiphenyl-4-yl) -1- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) -3- Pyridine (2.2 uL, 0.02 mmol) and acetyl chloride (1.4 uL, 0.02 mmol) were added to 0.3 mL of dichloromethane at 0 &lt; 0 &Lt; / RTI &gt; for 2 h. Distilled water was added to the reaction mixture and extracted twice with dichloromethane. The extract was washed with 1N hydrochloric acid, saturated sodium carbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to give the title compound (1.9 mg) as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.71 (s, 1H), 7.43 (d, 2H), 7.40-7.31 (m, 2H), 7.25-7.17 (m, 5H), 7.08 (t, 1H), 6.96 (d, IH), 5.91 (dd, IH), 4.96 (s, IH), 3.65

Examples 157 to 164

(Trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) -3- Dihydro-1H-pyrazole was used in place of acetyl chloride and acyl chloride or sulfonyl chloride corresponding to Example 157 to Example 164 was used in place of acetyl chloride. 164 were prepared.

Example 157. 5- (3'-Butyrylaminobiphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.79 (s, 1H), 7.43 (d, 2H), 7.36-7.31 (m, 2H), 7.25-7.14 (m, 5H), 7.08 (t, 1H), 6.96 (t, 1H), 5.91 (dd, 1H), 4.95 (s, 1H), 3.66 (dd, 1H), 3.24 t, 3H)

Example 158. 5- (3'-isobutyrylaminobiphenyl-4-yl) -1- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.84 (s, 1H), 7.44 (d, 2H), 7.31 (m, 2H), 7.25-7.17 (m, 5H), 7.08 (t, 1H), 6.96 (t (D, 1H), 5.91 (dd, IH), 4.95 (s, IH), 3.66 (dd,

Example 159. 5- [3 '-( 2,2-Dimethyl-propionyl) -aminobiphenyl-4-yl] Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.84 (s, 1 H), 7.45 (d, 2H), 7.35 (m, 3H), 7.25-7.17 (D, 1H), 5.91 (dd, 1H), 4.95 (s,

Example 160. Preparation of 5- (3'-ethanesulfonyl-aminobiphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole &lt; / RTI &gt;

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 2H), 7.37 (d, 2H), 7.31-7.21 (m, 4H), 7.18-7.08 (m, 3H), 6.97 (t, 1H), 6.38 (s, 1H), 5.93 (dd, 1H), 4.93 (s, 1H), 3.66 (dd,

Example 161. Preparation of 5- [3 '-( propane-l-sulfonyl) -aminobiphenyl-4-yl1- (2- chloro- phenyl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 2H), 7.36 (t, 2H), 7.31-7.18 (m, 5H), 7.12 (t, 2H), 6.97 (t, 1H), 6.38 (s 2H), 1.87 (m, 2H), 1.02 (t, &lt; RTI ID = 0.0 & 3H)

Example 162. Preparation of 5- [3 '- (2-methyl-propane-l-sulfonyl) -aminobiphenyl-4-yl] Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 2H), 7.38-7.18 (m, 7H), 7.12 (t, 2H), 6.97 (t, 1H), 6.38 (s, 1H), 5.93 (dd 2H), 2.30 (m, 1H), 1.08 (d, 6H)

Example 163. 3- (3-Cyclopropanesulfonyl-aminobiphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.44-7.31 (m, 6H), 7.27-7.12 (m, 4H), 7.10 (t, 1H), 6.97 (t, 1H), 6.30 (s, 1H), 5.93 (d, 2H), 0.96 (d, 2H), 4.96 (d, 2H)

Example 164. Preparation of 5- (3'-methanesulfonyl-aminobiphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole &lt; / RTI &gt;

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 2H), 7.38-7.14 (m, 8H), 7.10 (t, 1H), 6.97 (t, 1H), 6.38 (s, 1H), 5.93 (dd (D, 1H), 4.92 (s, 1H), 3.66 (dd,

Example 165. Preparation of 5- (4'-acetaminobiphenyl-4-yl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) -3- Pyridine (2.2 uL, 0.02 mmol) and acetyl chloride (1.4 uL, 0.02 mmol) were added to 0.3 mL of dichloromethane at 0 &lt; 0 &Lt; / RTI &gt; for 2 h. Distilled water was added to the reaction mixture and extracted twice with dichloromethane. The extract was washed with 1N hydrochloric acid, saturated sodium carbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 2.2 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.53 (d, 2H), 7.46-7.38 (m, 4H), 7.25-7.17 (m, 4H), 7.07 (t, 1H), 6.96 (t, 1H), 5.90 (dd, 1 H), 4.96 (s, 1 H), 3.65 (dd,

Examples 166 to 173

(Trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) -3- Dihydro-1H-pyrazole was used in place of acetyl chloride and acyl chloride or sulfonyl chloride corresponding to Example 166-173 was used in place of acetyl chloride. 173 were prepared.

Example 166. 5- (4'-Butyrylaminobiphenyl-4-yl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.55 (d, 2H), 7.43 (d, 2H), 7.41 (d, 2H), 7.21-7.17 (m, 3H), 7.12-7.07 (m, 2H), 6.96 2H), 1.87 (m, 2H), 1.01 (d, 1H), 5.90 (d, t, 3H)

Example 167. 5- (4'-Isobutyrylaminobiphenyl-4-yl) -l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) 4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.56 (d, 2H) 7.47-7.41 (m, 4H), 7.21-7.07 (m, 5H), 6.96 (t, 1H), 5.90 (dd, 1H), 4.93 ( (d, 1H), 3.65 (dd, 1H), 3.22 (dd,

Example 168. Preparation of 5- [4 '- (2,2-dimethyl-propionyl) -aminobiphenyl-4-yl] Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.56 (d, 2H), 7.47-7.41 (m, 4H), 7.33 (s, 1H), 7.20-7.17 (m, 3H), 7.09 (t, 1H), 6.96 (d, 1H), 5.90 (dd, 1H), 4.94 (s, 1H), 3.65

Example 169. 5- [4 '- (Ethanesulfonyl) -aminobiphenyl-4-yl] -1- (2- chloro-phenyl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.47 (d, 2H), 7.40 (d, 2H), 7.26-7.17 (m, 6H), 7.09 (t, 1H), 6.96 (t, 1H), 6.40 (s 2H), 1.38 (t, 3H), 3.32 (d, 2H)

Example 170. Preparation of 5- [4 '- (propane-l-sulfonyl) -aminobiphenyl-4-yl] Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.47 (d, 2H), 7.40 (d, 2H), 7.26-7.17 (m, 6H), 7.09 (t, 1H), 6.96 (t, 1H), 6.38 (s (T, 2H), 1.86 (m, 2H), 1.02 (t, 2H) 3H)

Example 171. 5- [4 '- (2-Methyl-propane-l-sulfonyl) -aminobiphenyl-4-yl] Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.47 (d, 2H), 7.40 (d, 2H), 7.26-7.17 (m, 6H), 7.09 (t, 1H), 6.96 (t, 1H), 6.34 (s 2H), 2.30 (m, 1H), 1.28 (d, 1H), 5.92 (dd, 6H)

Example 172. l- (4-cyclopropanesulfonyl-aminobiphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.47 (d, 2H), 7.41 (d, 2H), 7.27-7.17 (m, 6H), 7.09 (t, 1H), 6.96 (t, 1H), 6.33 (s (M, 2H), 0.99 (m, 2H), 5.92 (d, 1H), 4.93 (s, 2H)

Example 173. 3- (4-Methanesulfonyl-aminobiphenyl-4-yl) -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole &lt; / RTI &gt;

^{1 H NMR (400 MHz, CDCl} 3) 7.49 (d, 2H), 7.41 (d, 2H), 7.27-7.17 (m, 6H), 7.09 (t, 1H), 6.96 (t, 1H), 6.38 (s (S, 3H), 3.63 (dd, IH), 3.93 (s,

Example 174. l- (2-Chloro-phenyl) -5- [4- (4-BOC-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; (95.0 mg, 2.99 mmol), Pd ₂ (dba) ₃ (91.0 mg, cat.), BINAP (124.0 mg, cat.) and sodium t-butoxide (287.0 mg, 2.99 mmol) were added to 20.0 mL of toluene, and the mixture was stirred at 100 DEG C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/4) to obtain 480.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.23 (dd, 1H), 7.10 (d, 1H), 7.06-7.01 (m, 3H), 6.94 (dd, 1H), 6.71 (d, 2H), 5.80 (dd 1H), 5.01 (s, 1H), 3.62-3.48 (m, 5H), 3.17 (dd,

Example 175. l- (2-Chloro-phenyl) -5- [4- (4- methanesulfonyl-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Step 1. Preparation of l- (2-chloro-phenyl) -5- [4- (piperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) 5-dihydro-lH-pyrazole hydrochloride

(4-BOC-piperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) -hydro Methyl] -4,5-dihydro-1H-pyrazole (480.0 mg, 0.8 mmol) was added to 5.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 450.0 mg of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.31 (d, 1H), 7.21 (d, 1H), 7.11-7.09 (m, 3H), 6.94 (t, 1H), 6.84 (d, 2H), 5.83 ( dd, 1 H), 3.62 (dd, 1 H), 3.30 (m, 8 H), 3.14

Step 2. Synthesis of l- (2-chloro-phenyl) -5- [4- (4- methanesulfonyl-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

(2-chloro-phenyl) -5- [4- (piperazin-1-yl) -phenyl] -3- [di- (trifluoromethyl) (30.3 mg, 0.06 mmol), triethylamine (42.3 uL, 0.30 mmol) and methanesulfonyl chloride (10.4 mg, 0.09 mmol) were dissolved in dichloromethane And the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 15.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.20 (s, 1H), 7.97 (s, 1H), 7.38-7.32 (m, 1H), 6.91 (s, 1H), 6.77 (t, 1H), 6.69 (t (D, 1H), 5.58 (dd, IH), 3.68 (dd, IH), 3.37 (t, 4H), 3.23

Examples 176 to 182

(2-chloro-phenyl) -5- [4- (piperazin-1-yl) -phenyl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-1H-pyrazole hydrochloride and replacing the methanesulfonyl chloride with the corresponding sulfonyl chloride or acyl chloride in Example 176-182, The compounds of Examples 176 to 182 were each prepared in the same manner as in Step 2.

Example 176. l- (2-Chloro-phenyl) -5- [4- (4-ethanesulfonyl-piperazin- 1 -yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.23 (d, 1H), 7.13 (d, 1H), 7.09-7.03 (m, 3H), 6.95 (dd, 1H), 6.73 (d, 2H), 5.82 (dd 2H), 1.38 (t, 3H), 2.40 (s, 3H)

Example 177. l- (2-Chloro-phenyl) -5- [4- (4-isopropylsulfonyl-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.13 (d, 1H), 7.09-7.03 (m, 3H), 6.95 (dd, 1H), 6.72 (d, 2H), 5.81 (dd (M, 4H), 3.25-3.12 (m, 6H), 1.35 (d, 6H)

Example 178. l- (2-Chloro-phenyl) -5- [4- (4- cyclopropanesulfonyl-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.14 (d, 1H), 7.09-7.03 (m, 3H), 6.95 (dd, 1H), 6.73 (d, 2H), 5.82 (dd 1H), 4.95 (s, 1H), 3.59 (dd, 1H), 3.42-3.37 (m, 4H), 3.22-3.13 (m, 5H), 2.30-2.23 , &Lt; / RTI &gt; 2H), 1.02-0.96 (m, 2H)

Example 179. l- (2-Chloro-phenyl) -5- [4- (4-dimethylsulfamoyl-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.13 (d, 1H), 7.09-7.02 (m, 3H), 6.95 (dd, 1H), 6.72 (d, 2H), 5.81 (dd 2H), 3.93 (s, 1H), 3.59 (dd, 1H), 3.35-3.30 (m, 4H), 3.21-3.13

Example 180. l- (2-Chloro-phenyl) -5- [4- (4-isobutyryl-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.13 (d, 1H), 7.09-7.03 (m, 3H), 6.95 (dd, 1H), 6.72 (d, 2H), 5.81 (dd 1H), 1.13 (d, 6H), 1.94 (m, 2H)

Example 181. l- (2-Chloro-phenyl) -5- [4- (4-dimethylcarbamoyl-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.23 (d, 1H), 7.13 (d, 1H), 7.09-7.01 (m, 3H), 6.94 (dd, 1H), 6.72 (d, 2H), 5.80 (dd 2H), 4.84 (s, IH), 3.58 (dd, IH), 3.35-3.29 (m, 4H), 3.21-3.08

Example 182. l- (2-chloro-phenyl) -5- {4- [4- (pyrrolidine- 1 -sulfonyl) -piperazin- 1- yl] -phenyl} -3- [ Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (dd, 1H), 7.13 (d, 1H), 7.10-7.02 (m, 3H), 6.95 (dd, 1H), 6.72 (d, 2H), 5.81 (dd (M, 4H), 4.95 (s, IH), 3.58 (dd, IH), 3.39-3.31

L-yl] -phenyl} -3- (2-chloro-phenyl) -5- {4- [ (Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(2-chloro-phenyl) -5- [4- (piperazin-1-yl) -phenyl] -3- [di- (trifluoromethyl) 2-hydroxyisobutyric acid (7.0 mg, 0.07 mmol) and dichloromethane (1.0 mL) were added to HOBT (30.0 mg, 0.06 mmol) (15.0 mg, 0.11 mmol), EDAC (21.0 mg, 0.11 mmol) and triethylamine (23.0 uL, 0.17 mmol) were added thereto, followed by stirring at room temperature for 12 hours. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to give the title compound (10.0 mg) as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.14 (d, 1H), 7.10-7.03 (m, 3H), 6.95 (dd, 1H), 6.73 (d, 2H), 5.82 (dd (S, 6H), 4.94 (brs, IH), 4.09 (br s, IH), 3.82-3.77 (m, 4H)

Example 184. l- (2-Chloro-phenyl) -5- [4- (4-BOC-homopiperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; Boc-homopiperazine (589.0 uL, 2.99 mmol), Pd ₂ (dba) ₃ (91.0 mg, cat.), BINAP (124.0 mg, , cat.) and sodium t-butoxide (287.0 mg, 2.99 mmol) were added to 20.0 mL of toluene, and the mixture was stirred at 100 DEG C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/4) to obtain 350.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (dd, 1H), 7.13-7.03 (m, 2H), 6.97-6.90 (m, 3H), 6.47 (d, 2H), 5.76 (dd, 1H), 5.04 (m, 2H), 1.36 (d, 9H), 1.32 (m, 2H)

Example 185. l- (2-Chloro-phenyl) -5- [4- (4-methanesulfonyl-homopiperazin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Step 1. Preparation of l- (2-chloro-phenyl) -5- [4- (homopiperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole hydrochloride

(4-BOC-homopiperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) - Hydroxy-methyl] -4,5-dihydro-1H-pyrazole (350.0 mg, 0.8 mmol) was added to 5.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 330.0 mg of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.21 (d, 1H), 7.10 (d, 1H), 7.01-6.93 (m, 3H), 6.84 (t, 1H), 6.53 (d, 2H), 5.71 ( 2H), 3.91 (s, 2H), 3.10 (br, 2H), 3.03 (dd, , 2H)

Step 2. Synthesis of l- (2-chloro-phenyl) -5- [4- (4-methanesulfonyl-homopiperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Yl) -phenyl) -3- [di- (trifluoromethyl) -hydro (pyridin-2-yl) (30.3 mg, 0.06 mmol), triethylamine (42.3 uL, 0.30 mmol) and methanesulfonyl chloride (10.4 mg, 0.09 mmol) were dissolved in dichloromethane Methane (1.0 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 10.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.12 (d, 1H), 7.09-6.92 (m, 4H), 6.48 (d, 2H), 5.78 (dd, 1H), 4.94 (s 3H), 1.98-1.93 (m, 2H), 3.67-3.40 (m, 7H)

Examples 186-191

5- (4- (Homopiperazin-l-yl) -phenyl) -3- [di- (trifluoromethyl) -hydro Hydroxy-methyl] -4,5-dihydro-1H-pyrazole hydrochloride and replacing methanesulfonyl chloride with the corresponding sulfonyl chloride or acyl chloride in Example 186-191, , The compounds of Examples 186 to 191 were prepared respectively.

Example 186. l- (2-Chloro-phenyl) -5- [4- (4-ethanesulfonyl-homopiperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.13-7.04 (m, 2H), 7.00-6.92 (m, 3H), 6.49 (d, 2H), 5.77 (dd, 1H), 4.95 (s, 1H), 3.62-3.52 (m, 5H), 3.46-3.41 (m, 2H), 3.22-3.14 (m, 3H), 2.90 (t, 3 H)

Example 187. l- (2-Chloro-phenyl) -5- [4- (4-isopropylsulfonyl-homopiperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.13-7.04 (m, 2H), 6.99-6.92 (m, 3H), 6.47 (d, 2H), 5.77 (dd, 1H), 4.95 (s, 1H), 3.63-3.52 (m, 5H), 3.45-3.42 (m, 2H), 3.22-3.11 (m, 4H), 2.04-1.97

Example 188. l- (2-Chloro-phenyl) -5- [4- (4- cyclopropanesulfonyl-homopiperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.14-7.04 (m, 2H), 6.99-6.92 (m, 3H), 6.48 (d, 2H), 5.78 (dd, 1H), 4.95 (m, 2H), 1.09-1.05 (m, IH), 3.62-3.46 (m, 7H), 3.25 (m, 2 H), 0.80 - 0.74 (m, 2 H)

Example 189. l- (2-Chloro-phenyl) -5- [4- (4-dimethylsulfamoyl-homopiperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.14-7.04 (m, 2H), 6.98-6.92 (m, 3H), 6.47 (d, 2H), 5.78 (dd, 1H), 4.95 (s, 1H), 3.59-3.52 (m, 5H), 3.44-3.40 (m, 2H), 3.22-3.14

Example 190. l- (2-Chloro-phenyl) -5- [4- (4-isobutyryl-homopiperazin-l-yl) -phenyl] Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.13 (d, 1H), 7.09-7.03 (m, 3H), 6.95 (dd, 1H), 6.72 (d, 2H), 5.81 (dd 1H), 1.13 (d, 6H), 1.94 (m, 2H)

Example 191. l- (2-Chloro-phenyl) -5- [4- (4-dimethylcarbamoyl-homopiperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.24 (d, 1H), 7.13-7.03 (m, 2H), 6.98-6.91 (m, 3H), 6.49 (d, 2H), 5.76 (dd, 1H), 5.00 (s, 1H), 3.59-3.41 (m, 7H), 3.22-3.16 (m, 3H)

Example 192. l- (2-Chloro-phenyl) -5- [4- (l, l-dioxo-thiomorpholin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; (100.0 mg, 0.20 mmol), thiomorpholine-1,1-dioxide (32.0 mg, 0.24 mmol), Pd ₂ (dba) ₃ (9.0 mg, cat.), BINAP 12.0 mg, cat.) And sodium t-butoxide (29.0 mg, 0.30 mmol) were added to 20.0 mL of toluene, and the mixture was stirred at 100 ° C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 40.0 mg of the title compound as a white liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.25 (d, 1H), 7.19-7.00 (m, 4H), 6.98 (d, 1H), 6.71 (d, 2H), 5.83 (dd, 1H), 4.93 (s (D, 1H), 3.83-3.74 (m, 4H), 3.60 (dd,

Example 193. l- (2-chloro-phenyl) -5- {4- [4- (N-BOC- amino) -piperidin- l-yl] -phenyl} -3- [ Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; (300.0 mg, 0.60 mmol), 4- (N-BOC-amino) -piperidine (180.0 mg, 0.90 mmol) and Pd ₂ (dba) ₃ (27.0 mg, cat. ), BINAP (37.0 mg, cat.) And sodium t-butoxide (115.0 mg, 1.20 mmol) were added to 5.0 mL of toluene and the mixture was stirred at 100 ° C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 210.0 mg of the title compound as a white liquid.

¹ H NMR (400 MHz, CDCl ₃ ) 7.26-7.22 (m, 1 H), 7.14-6.92 (m, 5H), 6.72 (d, 2H), 5.79 (m, 2H), 1.46-1.12 (m, 11H), 2.76 (t, 2H)

Example 194. l- (2-Chloro-phenyl) -5- {4- [4-amino-piperidin- l-yl] -phenyl} -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole hydrochloride

Yl) -phenyl} -3- [di (l- (2-chloro-phenyl) Methyl] -4,5-dihydro-1H-pyrazole (210.0 mg, 0.34 mmol) was added to 5.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 200.0 mg of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.49 (d, 2H), 7.33 (t, 3H), 7.17 (d, 1H), 7.11 (t, 1H), 6.94 (t, 1H), 5.93 (dd, 2H), 2.23-2.09 (m, 2H), 3.72-3.63 (m, 3H), 3.61-3.48 (m, 3H), 3.10 (dd,

Example 195. l- (2-Chloro-phenyl) -5- [4- (4-cyclopropanesulfonylamino-piperidin- l-yl) -phenyl] -3- [di- (trifluoromethyl ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) - (2-chloro-phenyl) -5- {4- [4-amino-piperidin- (30.0 mg, 0.06 mmol), triethylamine (37.3 uL, 0.27 mmol) and cyclopropanesulfonyl chloride (10.4 mg, 0.08 mmol) were added to a solution of Was added to 1.0 mL of dichloromethane, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to give the title compound (10.0 mg) as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.23 (d, 1H), 7.13 (d, 1H), 7.08 (t, 1H), 7.03 (d, 2H), 6.94 (t, 1H), 6.71 (d, 2H ), 5.80 (dd, IH), 4.94 (s, IH), 4.16 (d, IH), 3.69-3.42 (m, 4H), 3.18 2H), 1.02-0.99 (m, 2H), 1.62-1.55 (m, 2H), 1.25-1.17

Example 196. l- (2-Chloro-phenyl) -5- [4- (5-carboxypyridin-3- yl) -phenyl] -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole &lt; / RTI &gt;

(4- (5-methoxycarbonyl-pyridin-3-yl) -phenyl) -3- [di- (trifluoromethyl) (6.0 mg, 0.01 mmol) was added to methanol (0.5 mL), and then potassium hydroxide (2.0 mg, 0.03 mmol) was dissolved in 0.5 mL of distilled water And the mixture was stirred at 70 ° C for 2 hours. The reaction mixture was washed with diethyl ether, and 1N hydrochloric acid salt was added thereto, followed by extraction with ethyl acetate. The extract was washed with saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 5.0 mg of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 9.18 (s, 1H), 9.12 (s, 1H), 8.94 (s, 1H), 7.66 (d, 2H), 7.39 (m, 3H), 7.21 (d, 1H ), 7.11 (t, IH), 6.93 (t, IH), 5.99 (dd,

Example 197. l- (2-Chloro-phenyl) -5- {3 '- [3- (methyl- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Yl) -1- (2-chloro- N-methyl-amino) -propane-l-sulfonyl] Dihydro-1H-pyrazole (9.0 mg, 0.012 mmol) was added dichloromethane (0.5 mL) and trifluo (trifluoromethyl) (9.0 uL, 0.12 mmol) was added, and the mixture was stirred at room temperature for 48 hours. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 5.0 mg of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.02 (s, 1H), 7.85 (d, 1H), 7.76 (d, 1H), 7.59 (dd, 1H), 7.47 (d, 2H), 7.27-7.25 (m (Dd, 1H), 7.20 (d, 1H), 7.20 (d, t, 2 H), 2.36 (s, 3 H), 1.95 - 1.86 (m, 2 H)

Example 198. l- (2-Chloro-phenyl) -5- {4 '- [3- (methyl- amino) -propane- 1 -sulfonyl] (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(2-Chloro-pyridin-2-yl) -methanone was prepared in a similar manner as described in example 121 except that 5- {4 '- [3- Trifluoromethyl) -4,5-dihydro-lH-pyrazole (7.0 mg, 0.010 mmol) was added to a solution of 0.5 mL of dichloromethane and trifluoroacetic acid (9.0 uL, 0.12 mmol) were added thereto, and the mixture was stirred at room temperature for 48 hours. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 3.0 mg of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.92 (d, 2H), 7.66 (d, 2H), 7.46 (d, 2H), 7.28-7.25 (m, 3H), 7.20 (d, 1H), 7.10 (dd 3H), 2.66 (t, 2H), 2.37 (s, 3H), 1.93 (dd, 1.86 (m, 2 H)

Example 199. l- (2-Chloro-phenyl) -5- [3 '-( methanesulfonyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) -hydroxy- ] -4,5-dihydro-lH-pyrazole

Yl) -3- [di- (trifluoromethyl) -hydroxy-benzoic acid methyl ester prepared in Example 43, l- (2-chloro- -Methyl] -4,5-dihydro-1H-pyrazole (25.0 mg, 0.05 mmol) was added to 2.0 mL of dichloromethane and then methachloro and benzoic acid (77%, 31.0 mg, 0.13 mmol) And the mixture was stirred at room temperature for 30 minutes. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/3) to obtain the title compound (10.0 mg) as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.06 (s, 1H), 7.89 (d, 1H), 7.77 (d, 1H), 7.61 (t, 1H), 7.47 (d, 2H), 7.28-7.18 (m 1H), 3.97 (s, 3H), 2.45 (d, 2H) 3H)

Example 200. l- (2-Chloro-phenyl) -5- [4- (6-methanesulfonyl-pyridin- 3- yl) -phenyl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

(4- (6-methylsulfanyl-pyridin-3-yl) -phenyl) -3- [di- (trifluoromethyl) - (77%, 8.1 mg, 0.04 mmol) at 0 &lt; 0 &gt; C was added to dichloromethane (2.0 mL) Was slowly added thereto, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 2.5 mg of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.84 (s, 1H), 8.12 (d, 1H), 8.03 (d, 1H), 7.48 (d, 2H), 7.32 (d, 2H), 7.26 (m, 1H ), 7.21 (d, IH), 7.14 (t, IH), 7.00 (t, IH), 5.98 (dd, IH), 3.70 (dd, 3.22 (dd, 1 H)

Example 201. Preparation of 5- (3'-ethoxy-biphenyl-4-yl) -1- (2- fluoro- phenyl) -3- [di- (trifluoromethyl) 4,5-dihydro-lH-pyrazole

Step 1. Preparation of 5- (3'-ethoxy-biphenyl-4-yl) -l- (2- fluoro-phenyl) -4,5-dihydro- lH- pyrazole-

3-butenoic acid methyl ester (190.0 mg, 0.61 mmol) prepared in Step 3 of Reference Example 3, 2-fluorophenylhydrazine Hydrochloride (110.0 mg, 0.67 mmol) was added to 3.0 mL of acetic acid, and the mixture was stirred at 125 占 폚 for 1 hour. The reaction mixture was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with a saturated aqueous solution of sodium hydrogencarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 250.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.57 (t, 1H), 7.44 (d, 2H), 7.31-7.19 (m, 3H), 7.09-7.02 (m, 3H), 6.92-6.84 (m, 3H) (T, 3H), 5.77 (d, IH), 4.06 (q, 2H), 3.90

Step 2. Preparation of 5- (3'-ethoxy-biphenyl-4-yl) -l- (2- fluoro- phenyl) -4,5-dihydro- lH- pyrazole-

(2-fluoro-phenyl) -4,5-dihydro-1H-pyrazole-3 -Carboxylic acid methyl ester (250.0 mg, 0.60 mmol) and 4.0 mL of an aqueous solution of potassium hydroxide (67.0 mg, 1.19 mmol) dissolved in 4.0 mL of distilled water were added to 4.0 mL of methanol, followed by stirring at 70 ° C for 2 hours. The reaction mixture was concentrated under reduced pressure to remove methanol. The resulting residue was washed with diethyl ether, acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 200.0 mg of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.53 (t, 1H), 7.46 (d, 2H), 7.30 (t, 1H), 7.21 (d, 2H), 7.09-7.01 (m, 3H), 6.95-6.91 (m, 2H), 6.86 (d, IH), 5.84 (dd, IH), 4.06 (q, 2H), 3.73 (dd,

Step 3. Preparation of 5- (3'-ethoxy-biphenyl-4-yl) -1- (2- fluoro-phenyl) -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole

(3-ethoxy-biphenyl-4-yl) -1- (2-fluoro-phenyl) -4,5-dihydro-1H-pyrazole- -Carboxylic acid (200.0 mg, 0.49 mmol) was added to 2.0 mL of thionyl chloride, and the mixture was stirred at 100 占 폚 for 2 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was concentrated with toluene under reduced pressure for 3 times to obtain a dark brown liquid 5- (3'-ethoxy-biphenyl-4-yl) -4,5-dihydro-lH-pyrazole-3-carbonyl chloride.

This dark brown liquid of 5- (3'-ethoxy-biphenyl-4-yl) -1- (2-fluoro-phenyl) -4,5-dihydro-lH- pyrazole-3-carbonyl chloride , TMAF (101.0 mg, 1.09 mmol) was added to 2.0 mL of 1,2-dimethoxyethane, and CF ₃ TMS (160.0 uL, 1.09 mmol) was slowly added to the reaction mixture at -78 ° C under nitrogen. Lt; 0 &gt; C for 2 hours. The reaction mixture was quenched with a 1N aqueous hydrochloric acid solution and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 175.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.46 (d, 2H), 7.33-7.27 (m, 2H), 7.19 (d, 2H), 7.08 (d, 1H), 7.04-7.00 (m, 2H), 6.98 2H), 3.65 (dd, 1H), 3.15 (dd, 1H), 1.42 (t, 3H)

Examples 202 to 205

(3'-ethoxy-biphenyl-4-yl) -2-oxo-3-butenoic acid methyl ester prepared in Reference Example 3, Step 3 was used instead of 2-fluorophenylhydrazine hydrochloride instead of 2- The compounds of Examples 202 to 205 were prepared in the same manner as in Example 201, except that hydrazine hydrochloride corresponding to 202 to 205 was used.

Example 202. Preparation of 5- (3'-ethoxy-biphenyl-4-yl) -1- (2,4- difluoro-phenyl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.47 (d, 2H), 7.31 (t, 1H), 7.24-7.18 (m, 3H), 7.08 (d, 1H), 7.04 (s, 1H), 6.86 (d 2H), 3.63 (dd, 1H), 3.17 (dd, 1H), 1.42 (d, t, 3H)

Example 203. l- (2,4-Dichloro-phenyl) -5- (3'-ethoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.45 (d, 2H), 7.32-7.26 (m, 2H), 7.17 (d, 2H), 7.13-7.02 (m, 4H), 6.86 (d, 1H), 5.87 (t, 3H), 4.65 (d, 2H), 3.65 (dd,

Example 204. l- (2-Chloro-4-fluoro-phenyl) -5- (3 ' -ethoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.44 (d, 2H), 7.30 (t, 1H), 7.20 (d, 2H), 7.13-7.00 (m, 4H), 6.85 (d, 1H), 6.79 (t 2H), 3.63 (dd, 1H), 3.24 (dd, 1H), 1.42 (t, 3H)

Example 205. l- (4-Chloro-2-fluoro-phenyl) -5- (3 ' -ethoxy- biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.46 (d, 2H), 7.34-7.21 (m, 2H), 7.16 (d, 2H), 7.10-6.92 (m, 4H), 6.86 (d, 1H), 5.71 (d, 1H), 4.42 (s, 1H), 4.07 (q, 2H), 3.65 (dd,

Example 206. l- (2-Chloro-phenyl) -5- (3-fluoro-3'-methylsulfanyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy-benzoic acid methyl ester prepared in step 5 of reference example 4, (50.0 mg, 0.10 mmol), 3-methylthiophenylboronic acid (17.8 mg, 0.11 mmol), potassium carbonate (40.0 mg, 0.29 mmol), Pd dppf) Cl ₂ (7.0 mg, cat.) was added to a mixed solvent of 750.0 μL of 1,4-dioxane and 150.0 μL of distilled water, and the mixture was stirred for 15 minutes and then at 90 ° C. for 2 hours. Ethyl acetate was added to the reaction mixture, which was then washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/4) to obtain 20.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.32 (d, 2H), 7.29-7.21 (m, 6H), 7.14-7.10 (m, 2H), 6.98 (t, 1H), 6.14 (dd, 1H), 4.94 (d, IH), 3.65 (dd, IH), 3.21 (dd,

Examples 207 to 214

Chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy-benzoic acid methyl ester prepared in step 5 of reference example 4, Methyl] -4,5-dihydro-1H-pyrazole was used in place of 3-methylthiophenylboronic acid and the boronic acid corresponding to Examples 207 to 214 was used in place of 3-methylthiophenylboronic acid, To prepare the compounds of Examples 207 to 214, respectively.

Example 207. l- (2-Chloro-phenyl) -5- (3-fluoro-4'-methylsulfanyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.32 (d, 2H), 7.27-7.19 (m, 6H), 7.15-7.10 (m, 2H), 6.97 (t, 1H), 6.13 (dd, 1H), 4.94 (d, IH), 3.64 (dd, IH), 3.21 (dd,

Example 208. l- (2-Chloro-phenyl) -5- (3-fluoro-4'-methanesulfonyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.98 (d, 2H), 7.66 (d, 2H), 7.35 (t, 1H), 7.29-7.25 (m, 3H), 7.20 (d, 1H), 7.14 (t (D, 1H), 6.99 (d, 1H), 6.17 (sd, 1H)

Example 209. l- (2-Chloro-phenyl) -5- (3'-ethoxy-3-fluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.32-7.10 (m, 7H), 7.04 (d, 1H), 6.99-6.95 (m, 2H), 6.87 (d, 1H), 6.13 (dd, 1H), 4.93 (s, 1H), 4.05 (q, 2H), 3.65 (dd,

Example 210. l- (2-Chloro-phenyl) -5- (3-fluoro-2'-methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.28-7.17 (m, 6H), 7.14-7.07 (m, 2H), 7.00-6.87 (m, 3H), 6.11 , 3.65 (dd, 1 H), 3.27 (dd, 1 H), 2.12 (s, 3 H)

Example 211. l- (2-Chloro-phenyl) -5- (4'-acetyl-3-fluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.99 (d, 2H), 7.57 (d, 2H), 7.34-7.20 (m, 5H), 7.13 (t, 1H), 6.99 (t, 1H), 6.16 (dd (D, 1H), 4.93 (s, 1H), 3.67 (dd,

Example 212. l- (2-Chloro-phenyl) -5- [2-fluoro-4- (1-BOC-1,2,3,6-tetrahydropyridin- - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.22 (d, 2H), 7.17 (t, 1H), 7.11 (t, 1H)., 7.01-6.92 (m, 3H), 6.09 (dd, 1H), 6.00 ( (m, 3H), 3.16 (dd, IH), 2.39 (s, 2H), 1.47 (s, 9H)

Example 213. l- (2-Chloro-phenyl) -5- [2-fluoro-4- (6-methoxy-pyridin- ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.29 (s, 1H), 7.67 (d, 1H), 7.31-7.26 (m, 3H), 7.17-7.09 (m, 3H), 6.98 (t, 1H), 6.77 (s, 3H), 3.65 (dd, IH), 3.20 (dd, IH)

Example 214. l- (2-Chloro-phenyl) -5- (3,4'-difluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.43 (t, 2H), 7.29-7.24 (m, 3H), 7.19-7.06 (m, 5H), 6.97 (t, 1H), 6.14 (dd, 1H), 4.93 (s, 1 H), 3.65 (dd, 1 H), 3.21 (dd, 1 H)

Example 215. l- (2-Chloro-phenyl) -5- (3-fluoro-3'-methanesulfinyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(3-fluoro-3'-methylsulfanyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) (31.0 mg, 0.06 mmol) was added to 2.0 mL of dichloromethane, and then metachloro and benzoic acid (77%, 22.8 mg, 0.12 mmol, ) Was added slowly, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1, 1/1) to obtain 5.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.79 (s, 1H), 7.60-7.56 (m, 3H), 7.33-7.19 (m, 5H), 7.13 (t, 1H), 6.97 (t, 1H), 5.16 (d, IH), 3.67 (dd, IH), 3.22 (dd,

Example 216. l- (2-Chloro-phenyl) -5- [3-fluoro-4 '-( 1 -hydroxy- 1 -methyl- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(4-acetyl-3-fluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) -hydro (10.0 mg, 0.02 mmol) was added to 1.0 mL of tetrahydrofuran, and then methylmagnesium chloride (3.0 M in tetrahydrofuran, 30.0 uL, 0.09 mmol) was slowly added thereto, and the mixture was stirred at -78 ° C for 5 hours. The reaction mixture was quenched with a saturated aqueous ammonium chloride solution at O &lt; 0 &gt; C and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/3) to obtain 5.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.52 (d, 2H), 7.46 (d, 2H), 7.30-7.21 (m, 4H), 7.19-7.09 (m, 2H), 6.97 (t, 1H), 6.13 (s, 3H), 1.60 (s, 3H), 1.65 (s, 3H)

Example 217. l- (2-Chloro-phenyl) -5- (3-fluoro-3'-methanesulfonyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(3-fluoro-3'-methylsulfanyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) (31.0 mg, 0.06 mmol) was added to 2.0 mL of dichloromethane, and then metachloro and benzoic acid (77%, 22.8 mg, 0.12 mmol, ) Was added slowly, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/3, 1/1) to obtain 15.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.04 (s, 1H), 7.93 (d, 1H), 7.76 (d, 1H), 7.62 (t, 1H), 7.34 (t, 1H), 7.28-7.24 (m (Dd, 1H), 7.21 (d, 1H), 7.14 (t, 1H), 6.99 1H), 3.07 (s, 3H)

Example 218. 5- [6- (2-acetyl-phenyl) -pyridin-3-yl] -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl &lt; / RTI &gt; prepared in Step 4 of Reference Example 5 and 5- (6-bromo-pyridin- (20 mg, 0.04 mmol), 2-acetylphenylboronic acid (8.0 mg, 0.05 mmol), Pd (dppf) Cl ₂ (3.0 mg, cat.), 2N 0.4 mL of an aqueous solution of sodium carbonate was added to 0.4 mL of N, N-dimethylformamide, and the mixture was stirred at 100 DEG C for 16 hours. Ethyl acetate was added to the reaction mixture, which was then washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 5.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.42 (s, 1H), 7.58-7.44 (m, 6H), 7.25 (m, 1H), 7.16 (d, 1H), 7.09 (t, 1H), 6.97 (t (D, 1H), 5.96 (dd, 1H), 4.86 (s,

Examples 219 to 232

(Trifluoromethyl) -hydroxy-methyl &lt; / RTI &gt; prepared in Step 4 of Reference Example 5 and 5- (6-bromo-pyridin- ] -4,5-dihydro-1H-pyrazole was used in place of 2-acetylphenylboronic acid and the boronic acid corresponding to Example 219-232 was used in place of 2-acetylphenylboronic acid, 219 to 232 were respectively prepared.

Example 219. 5- [6- (3-acetyl-phenyl) -pyridin-3-yl] -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.51 (d, 2H), 8.13 (d, 1H), 7.98 (d, 1H), 7.67 (d, 1H), 7.59-7.52 (m, 2H), 7.27 (m (Dd, 1H), 7.21 (d, 1H), 7.12 (t, 1H), 6.99 1H), 2.66 (s, 3H)

Example 220. 5- [6- (4-Acetyl-phenyl) -pyridin-3- yl] -l- (2- chloro-phenyl) -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.55 (s, 1H), 8.08 (s, 4H), 7.69 (d, 1H), 7.60 (d, 1H), 7.27 (d, 1H), 7.21 (d, 1H 1H), 6.99 (t, 1H), 6.99 (t, 1H), 5.99 (dd,

Example 221. l- (2-Chloro-phenyl) -5- [6- (2-methoxy-phenyl) -pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.51 (s, 1H), 7.78-7.70 (m, 2H), 7.50 (d, 1H), 7.47 (t, 1H), 7.28 (d, 1H), 7.20 (d (D, IH), 3.96 (s, 3H), 3.69 (s, 3H) dd, 1 H)

Example 222. l- (2-Chloro-phenyl) -5- [6- (3-methoxy-phenyl) -pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.47 (s, 1H), 7.60 (d, 1H), 7.54-7.50 (m, 2H), 7.46 (d, 1H), 7.34 (t, 1H), 7.27 (d , 7.50 (d, 1H), 7.12 (t, 1H), 7.05-6.93 (m, 2H), 5.97 dd, 1 H), 3.25 (dd, 1 H)

Example 223. [0354] 1- (2-Chloro-phenyl) -5- [6- (4- methoxy- phenyl) -pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.43 (s, 1H), 7.87 (d, 2H), 7.54-7.47 (m, 2H), 7.27 (d, 1H), 7.19 (d, 1H), 7.10 (t 3H), 3.69 (dd, IH), 3.24 (dd, IH)

Example 224. l- (2-Chloro-phenyl) -5- [6- (3-methylsulfanyl-phenyl) -pyridin-3- yl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.50 (s, 1H), 7.84 (s, 1H), 7.66-7.58 (m, 2H), 7.36 (t, 1H), 7.30-7.02 (m, 5H), 7.00 (d, IH), 5.98 (dd, IH), 4.89 (s, IH), 3.72

Example 225. l- (2-Chloro-phenyl) -5- [6- (4-methylsulfanyl-phenyl) -pyridin-3-yl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.48 (s, 1H), 7.87 (d, 2H), 7.65-7.57 (m, 2H), 7.31-7.15 (m, 4H), 7.12 (t, 1H), 7.00 (d, 1H), 5.97 (dd, IH), 4.89 (s, IH), 3.71 (dd,

Example 226. l- (2-Chloro-phenyl) -5- [6- (4-methanesulfonyl-phenyl) -pyridin-3- yl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.53 (s, 1H), 8.12 (d, 2H), 8.01 (d, 2H), 7.68 (d, 1H), 7.61 (d, 1H), 7.27 (d, 1H 1H), 7.22 (d, 1H), 7.13 (t, IH), 7.00 (t, IH), 6.01 (dd, , 3.07 (s, 3H)

Example 227. l- (2-Chloro-phenyl) -5- [6- (6-methoxy-pyridin- 3- yl) -pyridin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.69 (s, 1H), 8.48 (s, 1H), 8.16 (d, 1H), 7.53 (s, 2H), 7.27 (d, 1H), 7.20 (d, 1H 1H), 3.97 (s, 3H), 3.70 (dd, IH), 6.99 (d, , 3.23 (dd, 1 H)

Example 228. l- (2-Chloro-phenyl) -5- [6- (2-ethoxy- phenyl) -pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.50 (s, 1H), 7.87 (d, 1H), 7.77 (d, 1H), 7.55-7.25 (m, 3H), 7.22 (d, 1H), 7.14 (t 2H), 3.69 (dd, 1H), 3.28 (dd, 1H), 1.33 (d, t, 3H)

Example 229. l- (2-Chloro-phenyl) -5- [6- (3-ethoxy- phenyl) -pyridin- 3- yl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.48 (s, 1H), 8.22 (s, 1H), 7.60-7.10 (m, 7H), 7.05-6.92 (m, 2H), 5.95 (dd, 1H), 4.87 (s, 1 H), 4.09 (q, 2H), 3.71 (dd,

Example 230. l- (2-Chloro-phenyl) -5- [6- (4-ethoxy-phenyl) -pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.44 (s, 1H), 7.88 (d, 2H), 7.58-7.48 (m, 2H), 7.26 (d, 1H), 7.19 (d, 1H), 7.10 (t 2H), 3.69 (dd, 1H), 3.24 (dd, 1H), 1.43 (d, t, 3H)

Example 231. l- (2-Chloro-phenyl) -5- [6- (2-isopropoxy-phenyl) -pyridin-3- yl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.46 (s, 1H), 7.78 (d, 1H), 7.72 (d, 1H), 7.45 (d, 1H), 7.33-7.25 (m, 2H), 7.20 (d (D, 1H), 7.19 (t, 1H), 7.01-6.98 (m, 3H), 5.95 3.32 (dd, 1 H), 1.27 (d, 3 H), 1.20 (d, 3 H)

Example 232. l- (2-chloro-phenyl) -5- [6- (4-fluoro-phenyl) -pyridin- Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.46 (s, 1H), 7.90 (t, 2H), 7.57-7.51 (m, 2H), 7.27 (d, 1H), 7.21 (d, 1H), 7.11 (t , 3.99 (dd, 1 H), 3.24 (dd, 1 H), 4.99

Example 233. l- (2-Chloro-phenyl) -5- [6- (1-BOC-1,2,3,6-tetrahydropyridin-4- yl) -pyridin- [Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

(Trifluoromethyl) -hydroxy-methyl &lt; / RTI &gt; prepared in Step 4 of Reference Example 5 and 5- (6-bromo-pyridin- ] -4,5-dihydro-1H-pyrazole (400.0 mg, 0.80 mmol) and tert-butyl 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan- -yl) -5,6-dihydropyridin--1 (2H) - carboxylic acid (295.3 mg, 0.96 mmol), Pd (PPh 3) 4 (92.5 mg, 0.08 mmol), 2N aqueous sodium carbonate solution to 4.0 mL 1,2- Was added to a mixed solvent of 10.0 mL of dimethoxyethane and 4.0 mL of ethanol, and the mixture was stirred at 90 DEG C for 3 hours. Ethyl acetate was added to the reaction mixture, which was then washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 400.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.35 (s, 1H), 7.42 (d, 1H), 7.26-7.21 (m, 2H), 7.17 (d, 1H), 7.08 (t, 1H), 6.97 (t 2H), 3.64 (d, 1H), 3.57 (t, 2H), 3.20 (dd, 1H), 2.53 (d, 2H), 1.48 (s, 9H)

Example 234. l- (2-Chloro-phenyl) -5- [6- (4-BOC-piperazin- l-yl) -pyridin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl &lt; / RTI &gt; prepared in Step 4 of Reference Example 5 and 5- (6-bromo-pyridin- (400 mg, 0.80 mmol), 1-BOC-piperazine (222.4 mg, 1.19 mmol), Pd ₂ (dba) ₃ (36.7 mg, 0.04 mmol), BINAP (49.8 mg, 0.08 mmol) and sodium t-butoxide (137.8 mg, 1.43 mmol) were added to 20.0 mL of toluene, and the mixture was stirred at 100 ° C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 65.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.95 (s, 1H), 7.27-7.23 (m, 3H), 7.17 (d, 1H), 7.10 (t, 1H), 6.98 (t, 1H), 6.47 (d (Dd, 1H), 5.83 (dd, 1H), 4.91 (s, 1H), 3.60

Example 235. l- (2-chloro-phenyl) -5- [6- (1,2,3,6-tetrahydropyridin-4- yl) -pyridin- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole hydrochloride

(2-chloro-phenyl) -5- [6- (1-BOC-1,2,3,6-tetrahydropyridin-4-yl) -pyridin- Methyl-4, 5-dihydro-1H-pyrazole (400.0 mg, 0.66 mmol) was added to 2.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, And stirred for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain 350.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CD} 3 OD) 8.61 (s, 1H), 8.29 (d, 1H), 8.05 (d, 1H), 7.42 (d, 1H), 7.30 (d, 1H), 7.22 (t, 1H), 7.05 (t, IH), 6.81 (s, IH), 6.05 (dd, IH), 4.00 (s, 2H), 3.81 ), 2.88 (d, 2H)

Example 236. l- (2-Chloro-phenyl) -5- [6- (piperazin-l-yl) -pyridin- Methyl] -4,5-dihydro-1H-pyrazole hydrochloride

(2-chloro-phenyl) -5- [6- (4-BOC-piperazin-l-yl) -pyridin-3-yl] -3- [di- (trifluoromethyl) Methyl) -4,5-dihydro-1H-pyrazole (65.0 mg, 0.11 mmol) was added to 2.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain 60.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.95 (s, 1H), 7.27-7.23 (m, 3H), 7.17 (d, 1H), 7.10 (t, 1H), 6.98 (t, 1H), 6.47 (d (Br, 4H), 3.16 (dd, IH), 3.01 (br, 4H)

Example 237. l- (2-chloro-phenyl) -5- [6- (l-methanesulfonyl-l, 2,3,6-tetrahydropyridin-4- yl) -pyridin- 3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Yl) -3- [di (2-chloro-phenyl) -5- [6- (1,2,3,6- tetrahydropyridin-4-yl) -pyridin- (30.0 mg, 0.06 mmol), methanesulfonyl chloride (6.0 uL, 0.08 mmol), and triethylamine (0.015 mmol) in THF 38.0 uL, 0.28 mmol) was added to 1.0 mL of dichloromethane, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 5.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.37 (s, 1H), 7.51-7.31 (m, 2H), 7.27-7.17 (m, 2H), 7.11 (t, 1H), 6.99 (t, 1H), 6.60 (d, 1H), 5.93 (dd, IH), 4.85 (s, IH), 3.98 (brs, 2H), 3.68 (dd, s, 3H), 2.69 (brs, 2H)

Example 238. l- (2-chloro-phenyl) -5- [6- (1-cyclopropanesulfonyl-l, 2,3,6-tetrahydropyridin-4- yl) -pyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Yl) -3- [di (2-chloro-phenyl) -5- [6- (1,2,3,6- tetrahydropyridin-4-yl) -pyridin- -LH-pyrazole hydrochloride (30.0 mg, 0.06 mmol), cyclopropanesulfonyl chloride (8.0 uL, 0.08 mmol), triethylamine (38.0 uL, 0.28 mmol) were added to 1.0 mL of dichloromethane, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 10.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.36 (s, 1H), 7.45 (d, 1H), 7.26 (m, 2H), 7.18 (d, 1H), 7.11 (t, 1H), 6.99 (t, 1H 2H), 3.19 (brs, 2H), 3.68 (dd, IH), 3.52 (brs, 2H), 3.19 (dd, , 2.68 (brs, 2H), 2.29 (m, 1H), 1.22-1.18 (m, 2H), 1.02-0.96

Example 239. l- (2-Chloro-phenyl) -5- [6- (4- methanesulfonyl-piperazin- l-yl) -pyridin- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Yl) -3- [di- (trifluoromethyl) -hydro (pyridin-3-yl) -pyridin- (30.0 mg, 0.06 mmol), methanesulfonyl chloride (7.0 uL, 0.09 mmol) and triethylamine (41.0 uL, 0.30 mmol) were dissolved in dichloromethane Methane (1.0 mL), and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 5.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.96 (s, 1H), 7.32-7.21 (m, 3H), 7.10 (t, 1H), 6.94 (t, 1H), 6.48 (d, 1H), 5.83 (dd (M, 1H), 3.65-3.53 (m, 5H), 3.31-3.18 (m, 5H)

Example 240. l- (2-Chloro-phenyl) -5- [6- (4-cyclopropanesulfonyl-piperazin- l-yl) -pyridin- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

Yl) -3- [di- (trifluoromethyl) -hydro (pyridin-3-yl) -pyridin- (30.0 mg, 0.06 mmol), cyclopropanesulfonyl chloride (9.0 uL, 0.09 mmol) and triethylamine (41.0 uL, 0.30 mmol) were added to a solution of di Was added to 1.0 mL of chloromethane, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 10.0 mg of the title compound as a yellow liquid.

¹ H NMR (400 MHz, CDCl ₃ ) 7.96 (s, 1H), 7.27-7.25 (m, 2H), 7.17 (d, (D, 1H), 5.83 (dd, IH), 4.89 (s, IH), 3.65-3.56 (m, 5H), 3.34 (brs, 1.17 (m, 2H), 1.00-0.96 (m, 2H)

Example 241. l- (3-Acetyl-2-fluoro-biphenyl-4-yl) Methyl] -4,5-dihydro-1H-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -methanone in step 5 of reference Example 6, (2-chloro-phenyl) 4,5-dihydro -1H- pyrazole (30.0 mg, 0.056 mmol), 3- acetyl-phenyl boronic acid (10.4 mg, 0.064 mmol), Pd (PPh 3) 4 (6.7 mg, 0.006 mmol), 2N sodium carbonate 145.0 [mu] L of the aqueous solution was added to a mixed solvent of 2.0 mL of 1,2-dimethoxyethane and 0.5 mL of ethanol, followed by stirring at 90 DEG C for 3 hours. Ethyl acetate was added to the reaction mixture, which was then washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 5.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.04 (s, 1H), 7.94 (d, 1H), 7.67 (d, 1H), 7.52 (t, 1H), 7.37-7.26 (m, 3H), 7.16 (t 1H), 3.64 (dd, IH), 3.64 (d, IH)

Examples 242 to 254

(Trifluoromethyl) -hydroxy-methyl] -methanone in step 5 of reference Example 6, (2-chloro-phenyl) -4,5-dihydro-1H-pyrazole was used in place of 3-acetylphenylboronic acid, and boronic acid corresponding to Example 242-254 was used in place of 3-acetylphenylboronic acid, Example 242 To 254 were prepared, respectively.

Example 242. 5- (4'-Acetyl-2-fluoro-biphenyl-4-yl) Methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.00 (d, 2H), 7.56 (d, 2H), 7.36-7.24 (m, 3H), 7.16 (t, 1H), 7.04-6.98 (m, 3H), 5.94 (dd, 1 H), 2.64 (s, 3H), 3.70 (dd,

Example 243. l- (2-Chloro-phenyl) -5- (2-fluoro-2'-methoxy- biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.40-7.12 (m, 6H), 7.05-6.94 (m, 5H), 5.88 (dd, 1H), 4.96 (s, 1H), 3.90 (s, 3H), 3.66 (dd, 1 H), 3.25 (dd, 1 H)

Example 244. l- (2-Chloro-phenyl) -5- (2-fluoro-3'-methoxy- biphenyl- 4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.33-7.26 (m, 3H), 7.20 (d, 1H), 7.13 (t, 1H), 7.04-6.95 (m, 5H), 6.89 (d, 1H), 5.89 (s, 3H), 3.66 (dd, IH), 3.23 (dd, IH)

Example 245. l- (2-Chloro-phenyl) -5- (2-fluoro-4'-methoxy- biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.40 (d, 2H), 7.31-7.25 (m, 3H), 7.21 (d, 1H), 7.14 (t, 1H), 7.03-6.92 (m, 5H), 5.91 (dd, 1 H), 3.96 (s, 3 H), 3.66 (dd,

Example 246. l- (2-Chloro-phenyl) -5- (2'-ethoxy-2-fluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.33-7.10 (m, 6H), 7.03-6.90 (m, 5H), 5.87 (dd, 1H), 4.92 (s, 1H), 3.97 (q, 2H), 3.66 (dd, 1 H), 3.27 (dd, 1 H), 1.21 (t, 3 H)

Example 247. l- (2-Chloro-phenyl) -5- (3'-ethoxy-2-fluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.30-7.26 (m, 4H), 7.20 (d, 1H), 7.13 (t, 1H), 7.04-6.94 (m, 4H), 6.88 (d, 1H), 5.87 (t, 3H), 3.40 (d, 2H), 3.90 (s, 2H)

Example 248. l- (2-Chloro-phenyl) -5- (4'-ethoxy-2-fluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.38 (d, 2H), 7.30-7.25 (m, 4H), 7.20 (d, 1H), 7.13 (t, 1H), 7.02-6.91 (m, 5H), 5.88 (t, 3H), 3.45 (d, 2H), 3.65 (dd,

Example 249. l- (2-chloro-phenyl) -5- (2-fluoro-3'-methylsulfanyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.32-7.20 (m, 7H), 7.14 (t, 1H), 7.04-6.95 (m, 3H), 5.89 (dd, 1H), 4.90 (s, 1H), 3.67 (dd, 1 H), 3.22 (dd, 1 H), 2.49 (s, 3 H)

Example 250. l- (2-Chloro-phenyl) -5- (2-fluoro-4'-methylsulfanyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.31 (d, 2H), 7.29-7.26 (m, 4H), 7.20 (d, 1H), 7.14 (t, 1H), 7.03-6.94 (m, 3H), 5.89 (dd, 1 H), 4.90 (s, 1 H), 3.66 (dd,

Example 251. l- (2-Chloro-phenyl) -5- (2-fluoro-4 ' -methylsulfonyl- biphenyl-4-yl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.98 (d, 2H), 7.65 (d, 2H), 7.34-7.22 (m, 3H), 7.15 (t, 1H), 7.07-7.00 (m, 3H), 5.93 (dd, 1H), 4.90 (s, 1H), 3.69 (dd,

Example 252. l- (2-chloro-phenyl) -5- (2,4'-difluoro-biphenyl-4-yl) -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.42 (m, 2H), 7.30-7.21 (m, 3H), 7.16-7.10 (m, 3H), 7.07-6.95 ), 4.95 (s, IH), 3.68 (dd, IH), 3.23

Example 253. l- (2-Chloro-phenyl) -5- (2-fluoro-2 ' -isopropoxy-biphenyl-4-yl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.31 (d, 2H), 7.27-7.10 (m, 4H), 7.01-6.88 (m, 5H), 5.90 (dd, 1H), 4.98 (s, 1H), 4.35 (m, 1H), 3.68 (dd, 1H), 3.29 (dd,

Example 254. l- (2-Chloro-phenyl) -5- [3-fluoro-4- (6- methoxy-pyridin- ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.25 (s, 1H), 7.68 (d, 1H), 7.31-7.25 (m, 3H), 7.21 (d, 1H), 7.14 (t, 1H), 7.02-6.99 (m, 3H), 6.78 (d, IH), 5.89 (dd, IH), 4.90 (s,

Example 255. l- (2,4-difluoro-phenyl) -5- (3'-methylsulfanyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl ester prepared in Step 2 of Reference Example 7, 5- (4-bromo-phenyl) ] -4,5-dihydro -1H- pyrazole (50.0 mg, 0.10 mmol), 3- ( methylthio) phenylboronic acid (25.0 mg, 0.15 mmol), Pd (PPh 3) 4 (11.5 mg, cat.), 0.5 mL of ethanol and 0.5 mL of 2N sodium carbonate were added to 2.0 mL of 1,2-dimethoxyethane, and the mixture was stirred at 88 DEG C for 2 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/10) to give 6.1 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.46 (d, 2H), 7.40 (s, 1H), 7.34-7.20 (m, 6H), 6.76-6.69 (m, 2H), 5.62 (dd, 1H), 4.87 (s, 1 H), 3.63 (dd, 1 H), 3.17 (dd,

Examples 256 to 263

(Trifluoromethyl) -hydroxy-methyl ester prepared in Step 2 of Reference Example 7, 5- (4-bromo-phenyl) ] -4,5-dihydro-1H-pyrazole was used in place of 3- (methylthio) -phenylboronic acid and the boronic acid corresponding to Example 256 to 263 was used in place of 3- The compounds of Examples 256 to 263 were each prepared in the same manner.

Example 256. l- (2,4-Difluoro-phenyl) -5- (4'-methylsulfanyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.51-7.43 (m, 4H), 7.32-7.18 (m, 5H), 6.75-6.69 (m, 2H), 5.62 (dd, 1H), 4.87 (s, 1H) , 3.64 (dd, 1 H), 3.17 (dd, 1 H), 2.51 (s, 3 H)

Example 257. l- (2,4-Difluoro-phenyl) -5- (4'-methylsulfonyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.98 (d, 2H), 7.70 (d, 2H), 7.51 (d, 2H), 7.25 (s, 3H), 6.75-6.69 (m, 2H), 5.63 (dd , 3.08 (s, 3H), 2.28 (d, IH)

Example 258. l- (2,4-Difluoro-phenyl) -5- (4- (6-methoxy-pyridin- 3- yl) -phenyl) -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.32 (s, 1H), 7.72 (d, 1H), 7.41 (d, 2H), 7.24-7.20 (m, 4H), 6.80-6.69 (m, 3H), 5.60 (s, 3H), 3.64 (dd, IH), 3.16 (dd, IH)

Example 259. l- (2,4-Difluoro-phenyl) -5- (2'-methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.27-7.12 (m, 9H), 6.75-6.70 (m, 2H), 5.60 (dd, 1H), 4.89 (s, 1H), 3.63 (dd, 1H), 3.21 (dd, 1 H), 2.17 (s, 3 H)

Example 260. l- (2,4-Difluoro-phenyl) -5- (4-pyrimidin-5-yl-phenyl) -3- [di- (trifluoromethyl) Dihydro-lH-pyrazole &lt; / RTI &gt;

^{1 H NMR (400 MHz, CDCl} 3) 9.19 (s, 1H), 8.89 (s, 2H), 7.49 (d, 2H), 7.31-7.24 (m, 4H), 6.78-6.69 (m, 2H), 5.66 (dd, 1 H), 5.02 (s, 1 H), 3.67 (dd,

Example 261. l- (2,4-Difluoro-phenyl) -5- (4'-tetrazol-l-yl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 9.01 (s, 1H), 7.79-7.72 (m, 4H), 7.52 (d, 2H), 7.29-7.20 (m, 3H), 6.78-6.70 (m, 2H) , 5.65 (dd, IH), 4.89 (s, IH), 3.66

Yl) -phenyl] -3- [di- (trifluoromethyl) pyridin-2-yl] ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.60 (d, 1 H), 7.41 (d, 2H), 7.34 (d, 1H), 7.26-7.23 (m, 2H), 6.52 (s, IH), 5.63 (dd, IH), 4.85 (s, IH), 3.69

Example 263. [0858] 5- [4- (l-Benzenesulfonyl-lH-indol-2-yl) -phenyl] -l- (2,4- difluoro-phenyl) -3- [ Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.29 (d, 1H), 7.43-7.33 (m, 4H), 7.28-7.16 (m, 9H), 6.80-6.76 (m, 2H), 6.49 (s, 1H) , 5.64 (dd, IH), 4.85 (s, IH), 3.67 (dd, IH), 3.25

Example 264. l- (2,4-Difluoro-phenyl) -5- (4- (2- methyl-pyridin-3- yl) -phenyl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Step 1. l- (2,4-Difluoro-phenyl) -5- [4- (4,4,5,5-tetramethyl- l, 3,2-dioxaborolan- Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl ester prepared in Step 2 of Reference Example 7, 5- (4-bromo-phenyl) (2.9 g, 5.66 mmol), bis (pinacolato) diboron (3.45 g, 13.59 mmol) and Pd (dppf) Cl ₂ (0.28 g, 0.34 mmol) , dppf (0.19 g, 0.34 mmol) and potassium acetate (3.34 g, 33.98 mmol) were added to 30 mL of 1,4-dioxane and stirred at 80 ° C for 2 hours. The reaction mixture was filtered through a pad of celite, distilled water was added to the obtained filtrate, and the mixture was extracted three times with diethyl ether. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/100) to obtain 2.5 g of the title compound as a white liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.42 (d, 2H), 7.22 (q, 1H), 7.01 (d, 2H), 6.77-6.68 (m, 2H), 5.52 (dd, 1H), 4.81 (s , 3.61 (dd, 1 H), 3.10 (dd, 1 H), 1.33 (s, 12 H)

Step 2. Preparation of l- (2,4-difluoro-phenyl) -5- (4- (2-methyl-pyridin-3- yl) -phenyl) -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

3-bromo-2-methylpyridine was added to a to a 1.5 mL 1,2- dimethoxyethane _{Pd (PPh 3) 4 (8.5} mg, cat.) In (25.0 mg, 0.14 mmol). To the reaction mixture was added 1- (2,4-difluoro-phenyl) -5- [4- (4,4,5,5-tetramethyl-1,3,2-dioxane (Trifluoromethyl) -4,5-dihydro-1H-pyrazole (40.0 mg, 0.07 mmol), ethanol 364.0 uL, 364.0 uL 2N sodium carbonate was added thereto, followed by stirring at 88 deg. C for 2 hours. Distilled water was added to the reaction mixture and extracted twice with diethyl ether. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 3.3 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.48 (d, 1H), 7.44 (d, 1H), 7.24-7.14 (m, 6H), 6.77-6.70 (m, 2H), 5.61 (t, 1H), 5.08 (br, IH), 3.65 (dd, IH), 3.20 (dd,

Examples 265 to 300

The title compound was prepared from 1- (2,4-difluoro-phenyl) -5- [4- (4,4,5,5-tetramethyl-l, 3,2-dioxaborolane Yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole was used, and 3-bromo- The compounds of Examples 265 to 300 were prepared in the same manner as in the step 2 of Example 264 except that the substituted aryl bromide corresponding to Example 265 to 300 was used instead of the pyridine.

Example 265. l- (2,4-Difluoro-phenyl) -5- [4- (6-trifluoromethyl-pyridin- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.88 (s, 1H), 7.97 (d, 1H), 7.73 (d, 1H), 7.51 (d, 2H), 7.29 (d, 2H), 7.25 (m, 1H 1H), 3.66 (dd, IH), 3.16 (dd, IH)

Example 266. l- (2,4-Difluoro-phenyl) -5- [4- (5-methoxycarbonyl-pyridin- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 9.17 (s, 1H), 8.92 (s, 1H), 8.41 (s, 1H), 7.53 (d, 2H), 7.29-7.26 (m, 6.75-6.70 (m, 2H), 5.64 (dd, IH), 4.89 (s, IH), 3.66 (dd,

Example 267. l- (2,4-Difluoro-phenyl) -5- [4- (5-formyl-6-methoxy- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.54 (s, 1H), 8.24 (s, 1H), 7.45 (d, 2H), 7.26-7.23 (m, 3H), 6.77-6.69 (m, 2H), 5.62 (s, 3H), 3.64 (dd, IH), 3.16 (dd, IH)

Example 268. 5- [4- (2-Cyano-pyridin-3-yl) -phenyl) -l- (2,4- difluoro-phenyl) -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.69 (d, 1H), 7.80 (d, 1H), 7.56 (t, 1H), 7.49 (d, 2H), 7.32 (d, 2H), 7.23 (m, 1H ), 6.78-6.72 (m, 2H), 5.63 (dd, IH), 4.86 (s, IH)

Example 269. l- (2,4-Difluoro-phenyl) -5- [4- (5-fluoro-pyridin- 3- yl) -phenyl) -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.60 (s, 1H), 8.44 (s, 1H), 7.52 (d, 1H), 7.47 (d, 2H), 7.27-7.23 (m, 3H), 6.77-6.69 (m, 2H), 5.64 (dd, IH), 4.98 (s, IH), 3.66

Example 270. l- (2,4-Difluoro-phenyl) -5- [4- (2-methoxy-pyridin- 3- yl) -phenyl) -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.14 (d, 1H), 7.55 (d, 1H), 7.47 (d, 2H), 7.24-7.16 (m, 3H), 6.94 (t, 1H), 6.75-6.71 (s, 3H), 3.62 (dd, IH), 3.17 (dd, IH)

Example 271. l- (2,4-Difluoro-phenyl) -5- [4- (5-methyl-pyridin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.57 (s, 1H), 8.40 (s, 1H), 7.61 (s, 1H), 7.46 (d, 2H), 7.26-7.23 (m, 3H), 6.76-6.69 (m, 2H), 5.61 (dd, IH), 5.25 (br, IH), 3.65 (dd, IH), 3.17

Example 272. 5- [4- (6-Cyano-pyridin-3-yl) -phenyl] -l- (2,4- difluoro- phenyl) -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.93 (s, 1H), 7.94 (d, 1H), 7.74 (d, 1H), 7.51 (d, 2H), 7.31-7.26 (m, 3H), 6.77-6.70 (m, 2H), 5.66 (dd, IH), 4.85 (s, IH), 3.67

Example 273. 3- (5-cyano-pyridin-3-yl) -phenyl) -l- (2,4- difluoro- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.96 (s, 1H), 8.84 (s, 1H), 8.07 (s, 1H), 7.47 (d, 2H), 7.29-7.24 (m, 3H), 6.78-6.69 (m, 2H), 5.66 (dd, IH), 4.92 (s, IH), 3.66

Example 274. l- (2,4-Difluoro-phenyl) -5- [4- (6-methanesulfanyl-pyridin- 3- yl) -phenyl] -3- [di- (trifluoromethyl ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.60 (s, 1H), 7.63 (d, 1H), 7.44 (d, 2H), 7.28-7.22 (m, 4H), 6.77-6.70 (m, 2H), 5.61 (dd, 1 H), 4.86 (s, 1 H), 3.64 (dd,

Example 275. l- (2,4-Difluoro-phenyl) -5- [4- (6-ethoxy-pyridin- 3- yl) -phenyl] -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.30 (s, 1H), 7.71 (d, 1H), 7.41 (d, 2H), 7.26-7.20 (m, 3H), 6.77-6.72 (m, 3H), 5.60 (d, 1H), 4.87 (s, 1H), 4.38 (q, 2H), 3.64 (dd,

Example 276. l- (2,4-Difluoro-phenyl) -5- [4- (6-methoxy-4-methyl- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.91 (s, 1H), 7.22-7.17 (m, 5H), 6.75-6.71 (m, 2H), 6.62 (s, 1H), 5.61 (dd, 1H), 4.87 (s, 3H), 3.65 (d, 2H), 3.40 (d,

Example 277. l- (2,4-Difluoro-phenyl) -5- [4- (6-fluoro-pyridin- 3- yl) -phenyl] -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.36 (s, 1H), 7.90 (t, 1H), 7.43 (d, 2H), 7.26-7.16 (m, 3H), 6.97 (d, 1H), 6.77-6.69 (m, 2H), 5.63 (dd, IH), 4.87 (s, IH), 3.65

Example 278. l- (2,4-Difluoro-phenyl) -5- [4- (6-fluoro-4-methyl- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.96 (s, 1H), 7.26-7.16 (m, 5H), 6.81 (s, 1H), 6.77-6.69 (m, 2H), 5.63 (dd, 1H), 4.88 (s, 1 H), 3.65 (dd, 1 H), 3.19 (dd,

Example 279. l- (2,4-Difluoro-phenyl) -5- [4- (3-methyl-pyridin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.48 (s, 1H), 7.55 (d, 1H), 7.43 (d, 2H), 7.26-7.15 (m, 4H), 6.73-6.69 (m, 2H), 5.63 (dd, 1 H), 5.01 (s, 1 H), 3.64 (dd,

Example 280. l- (2,4-Difluoro-phenyl) -5- [4- (4-methyl-pyridin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.50 (d, 1H), 7.86 (d, 2H), 7.47 (s, 1H), 7.26-7.19 (m, 3H), 7.05 (d, 1H), 6.74-6.66 (m, 2H), 5.63 (dd, IH), 4.94 (s, IH), 3.64 (dd,

Example 281. l- (2,4-Difluoro-phenyl) -5- [4- (5-methyl-pyridin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.47 (s, 1H), 7.84 (d, 2H), 7.55 (d, 2H), 7.26-7.21 (m, 3H), 6.73-6.67 (m, 2H), 5.62 (dd, 1 H), 4.92 (s, 1 H), 3.63 (dd,

[0253] Example 282. l- (2,4-difluoro-phenyl) -5- [4- (6-methyl-pyridin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.87 (d, 2H), 7.60 (t, 1H), 7.44 (d, 1H), 7.26-7.22 (m, 3H), 7.08 (d, 1H), 6.74-6.66 (m, 2H), 5.64 (dd, IH), 4.89 (s, IH), 3.63 (dd,

Example 283. ^ - (2,4-difluoro-phenyl) -5- [4-pyridin-2- 4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.66 (s, 1H), 7.88 (d, 2H), 7.73 (t, 1H), 7.65 (d, 1H), 7.26-7.23 (m, 4H), 6.76-6.67 (m, 2H), 5.63 (dd, IH), 4.93 (s, IH), 3.64

Example 284. l- (2,4-Difluoro-phenyl) -5- {3 '- [(2-hydroxy- ethyl) -methyl- sulfamoyl] [Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.94 (s, 1H), 7.77-7.74 (m, 2H), 7.58 (t, 1H), 7.50 (d, 2H), 7.29-7.25 (m, 3H), 6.77 2H), 3.17 (dd, IH), 3.65 (d, 2H), 3.65 (d, 2.86 (s, 3 H)

Example 285. l- (2,4-Difluoro-phenyl) -5- {4 '- [(2-hydroxy- ethyl) -methyl- sulfamoyl] [Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.51-7), 2.51 (s, 3H) 7.84 (d, 2H), 7.67 (d, 2H), 7.50 (d, 2H), 7.29-7.25 (m, 3H) (Dd, 2H), 3.17 (dd, 1 H), 3.78 (d, 2H) ), 2.86 (s, 3H)

Example 286. l- (2,4-Difluoro-phenyl) -5- (3'-fluoro-4'-methanesulfonyl-biphenyl- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.98 (t, 1H), 7.50-7.47 (m, 3H), 7.39 (d, 1H), 7.29-7.26 (m, 3H), 6.77-6.69 (m, 2H) , 5.64 (dd, 1 H), 4.83 (s, 1 H), 3.66 (dd,

Example 287. l- (2,4-Difluoro-phenyl) -5- (3 ', 5'-difluoro-4'-methanesulfonyl- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.47 (d, 2H), 7.29-7.26 (m, 3H), 7.21 (d, 2H), 6.78-6.69 (m, 2H), 5.65 (dd, 1H), 4.82 (s, 3H), 3.13 (dd, &lt; RTI ID = 0.0 &gt; 1H)

Example 288. l- (2,4-Difluoro-phenyl) -5- (2 ', 5'-difluoro-4'-methanesulfonyl- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.74 (t, 1H), 7.46 (d, 2H), 7.29-7.22 (m, 4H), 6.79-6.70 (m, 2H), 5.65 (dd, 1H), 4.83 (s, 1H), 3.66 (dd, IH), 3.25 (s, 3H), 3.16

Example 289. l- (2,4-difluoro-phenyl) -5- (2 ', 6'-difluoro-4'-methanesulfonyl- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.57 (d, 2H), 7.39 (d, 2H), 7.30-7.23 (m, 3H), 6.79-6.72 (m, 2H), 5.62 (dd, 1H), 4.83 (d, IH), 3.65 (dd, IH), 3.17 (dd,

Example 290. l- (2,4-Difluoro-phenyl) -5- (3'-cyano-4'-methanesulfonyl-biphenyl- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.22 (d, 1H), 8.03 (s, 1H), 7.92 (d, 1H), 7.51 (d, 2H), 7.31-7.26 (m, 3H), 6.79-6.69 (m, 2H), 5.67 (dd, IH), 4.85 (s, IH), 3.66 (dd,

Example 291. l- (2,4-Difluoro-phenyl) -5- [4- (5- methanesulfonyl-pyridin- 2- yl) -phenyl] -3- [di- (trifluoromethyl ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 9.16 (s, 1H), 8.24 (d, 1H), 7.97 (d, 2H), 7.85 (d, 1H), 7.31-7.23 (m, 3H), 6.76-6.67 (m, 2H), 5.66 (dd, IH), 4.87 (s, IH), 3.66 (dd,

Example 292. l- (2,4-Difluoro-phenyl) -5- (4'-methanesulfonyl-3'-trifluoromethyl-biphenyl- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.34 (d, 1H), 8.02 (s, 1H), 7.88 (d, 1H), 7.53 (d, 2H), 7.31-7.26 (m, 3H), 6.79-6.69 (m, 2H), 5.66 (dd, IH), 4.84 (s, IH), 3.67 (dd,

Example 293. l- (2,4-Difluoro-phenyl) -5- (4'-methanesulfonyl-2'-trifluoromethyl-biphenyl- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.30 (s, 1H), 8.11 (d, 1H), 7.50 (d, 1H), 7.21-7.17 (m, 5H), 6.77-6.71 (m, 2H), 5.61 (dd, 1 H), 4.84 (s, 1 H), 3.66 (dd,

Example 294. l- (2,4-Difluoro-phenyl) -5- {[2 ', 6'-fluoro-4' - (tetrazol- } -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.34 (d, 2H), 7.26-7.22 (m, 6H), 6.76-6.66 (m, 4H), 5.60 (dd, (dd, 1 H), 3.16 (dd, 1 H)

Example 295. l- (2,4-Difluoro-phenyl) -5- {4- [4-methyl-6- (tetrazol- l-yl) -pyridin- - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 9.53 (s, 1H), 8.28 (s, 1H), 7.99 (s, 1H), 7.30-7.26 (m, 5H), 6.80-6.72 (m, 2H), 5.65 (dd, 1 H), 2.36 (s, 3 H), 3.86 (s,

Example 296. 5- {3 '- [3- (N-BOC-N-methyl-amino) -propane- 1 -sulfonyl] -biphenyl-4-yl} -1- (2,4- Phenyl) -3- (di- (trifluoromethyl) -hydroxy-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.04 (s, 1H), 7.86 (d, 1H), 7.80 (d, 1H), 7.67-7.57 (m, 1H), 7.51 (d, 2H), 7.26-7.24 (d, IH), 3.66 (dd, IH), 3.32-3.27 (m, 2H), 3.19-3.10 , 3H), 2.80 (s, 3H), 2.01 - 1.93 (m, 2H), 1.39

Example 297. 5- {4 '- [3- (N-BOC-N-methyl-amino) -propane- 1 -sulfonyl] -biphenyl-4-yl} -1- (2,4- Phenyl) -3- (di- (trifluoromethyl) -hydroxy-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.93 (d, 2H), 7.70 (d, 2H), 7.51 (d, 2H), 7.27-7.25 (m, 3H), 6.77-6.68 (m, 2H), 5.65 (d, 1H), 4.92 (brs, 1H), 3.66 (dd, 1H), 3.30 (t, 2H), 3.19-3.08 (m, 3H), 2.80 ), 1.40 (s, 9H)

Example 298. l- (2,4-Difluoro-phenyl) -5- (3'-dimethylsulfamoyl-biphenyl-4-yl) -3- (di- (trifluoromethyl) Hydroxy-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.92 (s, 1H), 7.75-7.72 (m, 2H), 7.59 (t, 1H), 7.50 (d, 2H), 7.29-7.24 (m, 3H), 6.77 (M, 2H), 5.65 (dd, IH), 4.88 (brs, IH), 3.65

Example 299. l- (2,4-Difluoro-phenyl) -5- (4'-dimethylsulfamoyl-biphenyl-4-yl) -3- (di- (trifluoromethyl) Hydroxy-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.81 (d, 2H), 7.67 (d, 2H), 7.51 (d, 2H), 7.30-7.24 (m, 3H), 6.77-6.68 (m, 2H), 5.65 (dd, IH), 4.90 (brs, IH), 3.66 (dd, IH), 3.16

Example 300. l- (2,4-Difluoro-phenyl) -5- {4 '- [(2-hydroxy-ethyl) -methanesulfonyl-amino] biphenyl- (Di- (trifluoromethyl) -hydroxy-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.56 (d, 2H), 7.48-7.41 (m, 5H), 7.22 (d, 2H), 6.77-6.69 (m, 2H), 5.63 (dd, 1H), 4.88 (brs, 1 H), 3.87 (t, 2H), 3.74-3.60 (m, 3H), 3.17 (dd,

Example 301. l- (2,4-Difluoro-phenyl) -5- [4- (l-BOC-l, 2,3,6-tetrahydropyridin- [Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

(Trifluoromethyl) -hydroxy-methyl ester prepared in Step 2 of Reference Example 7, 5- (4-bromo-phenyl) ] -4,5-dihydro-1H-pyrazole (2000.0 g, 3.98 mmol) and tert-butyl 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolane- (1475.0 mg, 4.77 mmol), Pd (dppf) Cl ₂ (291.3 mg, cat.) And potassium carbonate (2746.0 mg, 19.88 mmol) were added to a solution of Was added to a mixed solvent of 57.6 mL of 1,4-dioxane and 14.4 mL of water, and the mixture was stirred at 90 DEG C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/8) to obtain 1.6 g of the title compound as a white solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.09 (d, 2H), 6.74-6.66 (m, 2H), 6.01 (br, 1H), 5.56 (dd, 1H), 4.88 (s, 1H), 4.04 (s, 2H), 3.59 (t, 2H), 3.55 s, 9H)

Example 302. l- (2,4-difluoro-phenyl) -5- [4- (l, 2,3,6-tetrahydropyridin-4- yl) -phenyl] Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole trifluoroacetic acid salt

(2,4-difluoro-phenyl) -5- [4- (1-BOC-l, 2,3,6-tetrahydropyridin-4- yl) -phenyl] - (800.0 mg, 1.32 mmol) trifluoroacetic acid salt (1.0 mL, 13.05 mmol) was added to a 0 &lt; RTI ID = 0.0 &gt; Was added to 6.0 mL of dichloromethane, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure to obtain 800.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.44 (q, 1H), 7.37 (d, 2H), 7.18 (d, 2H), 6.83-6.76 (m, 2H), 6.13 (s, 1H), 5.60 ( 2H), 3.75 (s, 2H), 3.67 (d, 2H)

Example 303. l- (2,4-Difluoro-phenyl) -5- [4- (l-methanesulfonyl-l, 2,3,6-tetrahydropyridin-4- yl) -phenyl] - 3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(2,4-difluoro-phenyl) -5- [4- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- (30.0 mg, 0.05 mmol), triethylamine (20.3 uL, 0.15 mmol) and methanesulfonyl chloride were added to a solution of 2- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- lH- pyrazole trifluoroacetic acid salt Sulfonyl chloride (4.6 uL, 0.06 mmol) was added to 1.0 mL of dichloromethane at 0 &lt; 0 &gt; C and stirred at room temperature for 12 hours. Distilled water was added to the reaction mixture and extracted twice with dichloromethane. The extract was washed with 1N hydrochloric acid, saturated sodium carbonate and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/3) to obtain 2.1 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.11 (d, 2H), 6.75-6.67 (m, 2H), 6.04 (s, 1H), 5.57 (dd, 1H), 2.84 (s, 3H), 2.60 (s, 2H) s, 2H)

Examples 304 to 312

(2,4-difluoro-phenyl) -5- [4- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole trifluoroacetic acid salt and replacing the methanesulfonyl chloride with the corresponding sulfonyl chloride Or acyl chloride was used in place of acyl chloride, the compounds of Examples 304 to 312 were respectively prepared.

Example 304. l- (2,4-Difluoro-phenyl) -5- [4- (l-ethanesulfonyl- l, 2,3,6-tetrahydropyridin-4- yl) -phenyl] - 3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.10 (d, 2H), 6.75-6.67 (m, 2H), 6.04 (s, 1H), 5.57 (dd, 1H), 4.83 (s, 1H), 3.98 (s, 2H), 3.57 (dd, s, 2 H), 1.37 (t, 3 H)

Example 305. l- (2,4-difluoro-phenyl) -5- {4- [l- (propane- l-sulfonyl) - l, 2,3,6-tetrahydropyridin- ] -Phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.10 (d, 2H), 6.75-6.67 (m, 2H), 6.03 (s, 1H), 5.57 (dd, 1H), 4.93 (s, 1H), 3.97 (s, 2H), 3.61 (dd, s, 2H), 1.87 (q, 2H), 1.05 (t, 3H)

Example 306. l- (2,4-Difluoro-phenyl) -5- {4- [l- (propane-2- sulfonyl) -l, 2,3,6-tetrahydropyridin- ] -Phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.10 (d, 2H), 6.75-6.67 (m, 2H), 6.04 (s, 1H), 5.55 (dd, 1H), 4.83 (s, 1H), 4.01 (s, 2H), 3.57 (dd, s, 2H), 1.35 (d, 6H)

Example 307. l- (2,4-Difluoro-phenyl) -5- [4- (1-dimethylsulfamoyl- l, 2,3,6-tetrahydropyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.10 (d, 2H), 6.75-6.67 (m, 2H), 6.03 (s, 1H), 5.57 (dd, 1H), 4.83 (s, 1H), 3.90 (s, 2H), 3.60 (dd, s, 2H)

Example 308. l- (2,4-difluoro-phenyl) -5- [4- (1-cyclopropanesulfonyl-l, 2,3,6- tetrahydropyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.11 (d, 2H), 6.75-6.67 (m, 2H), 6.04 (s, 1H), 5.57 (dd, 1H), 4.83 (s, 1H), 4.00 (s, 2H), 3.61 (dd, (m, IH), 1.20 (d, 2H), 0.98 (d, 2H)

Example 309. l- (2,4-Difluoro-phenyl) -5- [4- (1-cyclopentanesulfonyl- 1,2,3,6-tetrahydropyridin-4- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.10 (d, 2H), 6.75-6.67 (m, 2H), 6.02 (s, 1H), 5.57 (dd, 1H), 4.85 (s, 1H), 4.00 (s, 2H), 3.57 (dd, (s, 2H), 2.00 (m, 4H), 1.80 (s, 2H), 1.60

Example 310. l- (2,4-Difluoro-phenyl) -5- [4- (l-isobutyryl- l, 2,3,6-tetrahydropyridin-4- yl) -phenyl] - 3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.10 (d, 2H), 6.75-6.67 (m, 2H), 6.07-6.01 (d, 1H) , 5.57 (dd, 1 H), 4.85 (s, 1 H), 4.21-4.16 (d, 2H), 3.79-3.68 (m, 1 H), 2.52 - 2.47 (d, 2H), 1.12 (d, 6H)

Example 311. l- (2,4-Difluoro-phenyl) -5- [4- (1-dimethylcarbamoyl- l, 2,3,6-tetrahydropyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.23 (m, 2H), 7.19 (q, 1H), 7.10 (d, 2H), 6.74-6.66 (m, 2H), 6.04 (s, 1H), 5.56 (dd, 1H), 4.87 (s, 1H), 3.89 (s, 2H), 3.59 (dd, s, 2H)

Example 312. l- (2,4-Difluoro-phenyl) -5- [4- (l-isobutylsulfonyl-l, 2,3,6-tetrahydropyridin- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.26-7.18 (m, 3H), 7.11 (d, 2H), 7.74-6.67 (m, 2H), 6.03 (s, 1H), 5.57 (dd, 1H), 4.85 (d, 2H), 3.60 (d, 2H), 3.60 (d, 2H) m, 1 H), 1.11 (d, 6 H)

Example 313. [0351] 1- (2,4-Difluoro-phenyl) -5- [4- (4- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl ester prepared in Step 2 of Reference Example 7, 5- (4-bromo-phenyl) (500.0 mg, 0.99 mmol), 1-BOC-piperazine (222.0 mg, 1.19 mmol), Pd ₂ (dba) ₃ (45.0 mg, cat.), BINAP (62.0 mg, cat.) And sodium tert-butoxide (143.0 mg, 1.49 mmol) were added to 10.0 mL of toluene, and the mixture was stirred at 100 ° C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 340.0 mg of the title compound as a yellow liquid.

¹ H NMR (400 MHz, CDCl ₃ ) 7.17 (dd, 1 H), 7.01 (d, 2H), 6.77-6.65 (m, 4H), 5.49 (m, 5 H), 3.15 - 3.08 (m, 5 H), 1.47 (s, 9 H)

Example 314. l- (2,4-Difluoro-phenyl) -5- [4- (piperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole hydrochloride

(2,4-difluoro-phenyl) -5- [4- (4-BOC-piperazin-1-yl) -phenyl] -3- [di- (trifluoromethyl) Methyl) -4,5-dihydro-1H-pyrazole (340.0 mg, 0.6 mmol) was added to 5.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 300.0 mg of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.31 (d, 1H), 7.21 (d, 1H), 7.11-7.09 (m, 3H), 6.94 (t, 1H), 6.84 (d, 2H), 5.83 ( dd, 1 H), 3.62 (dd, 1 H), 3.30 (m, 8 H), 3.14

Example 315. l- (2,4-Difluoro-phenyl) -5- [4- (4- methanesulfonyl-piperazin- l-yl) -phenyl] -3- [ Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(2,4-difluoro-phenyl) -5- [4- (piperazin-1-yl) -phenyl] -3- [di- (trifluoromethyl) (23.0 uL, 0.17 mmol) and methanesulfonyl chloride (5.0 uL, 0.07 mmol) were dissolved in dichloro &lt; RTI ID = 0.0 & Methane (1.0 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 10.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.16 (dd, 1H), 7.03 (d, 2H), 6.77 (d, 2H), 6.74-6.66 (m, 2H), 5.51 (dd, 1H), 4.84 (s (M, 4H), 3.10 (dd, IH), 2.81 (s, 3H)

Examples 316 to 319

(2,4-difluoro-phenyl) -5- [4- (piperazin-1-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-1H-pyrazole hydrochloride and substituting the sulfonyl chloride corresponding to Examples 316 to 319 in place of methanesulfonyl chloride was carried out in the same manner as in Example 315 To prepare the compounds of Examples 316 to 319, respectively.

Example 316. l- (2,4-Difluoro-phenyl) -5- [4- (4-ethanesulfonyl-piperazin- l-yl) -phenyl] -3- [ Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.17 (dd, 1H), 7.03 (d, 2H), 6.77 (d, 2H), 6.74-6.66 (m, 2H), 5.49 (dd, 1H), 4.84 (s 2H), 1.39 (t, 3H), 2.13 (d, 1H)

L-yl] -phenyl} -3- [di (trifluoromethyl) phenyl] -5- {4- [4- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.17 (dd, 1H), 7.02 (d, 2H), 6.76 (d, 2H), 6.74-6.66 (m, 2H), 5.51 (dd, 1H), 4.85 (s (D, IH), 3.56 (dd, IH), 3.48-3.44 (m, 4H), 3.24-3.08

Example 318. l- (2,4-Difluoro-phenyl) -5- [4- (4- cyclopropanesulfonyl-piperazin- l-yl) -phenyl] -3- [ Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.18 (dd, 1H), 7.03 (d, 2H), 6.77 (d, 2H), 6.74-6.66 (m, 2H), 5.51 (dd, 1H), 4.87 (s (M, 1H), 3.56 (dd, 1H), 3.42-3.40 (m, 4H), 3.23-3.20 (m, 4H), 3.11 , 2H), 1.01-0.98 (m, 2H)

Example 319. l- (2,4-Difluoro-phenyl) -5- [4- (4-dimethylsulfamoyl-piperazin- l-yl) -phenyl] -3- [ Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

¹ H NMR (400 MHz, CDCl ₃ ) 7.18 (dd, 1 H), 7.02 (d, 2H), 6.77-6.66 (m, 4H), 5.51 (M, 4H), 3.11 (dd, IH), 2.85 (s, 6H)

Example 320. l- (2,4-Difluoro-phenyl) -5- [4- (4-BOC-homopiperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl ester prepared in Step 2 of Reference Example 7, 5- (4-bromo-phenyl) (500.0 mg, 0.99 mmol), 1-BOC-homopiperazine (235.0 uL, 1.19 mmol), Pd ₂ (dba) ₃ (45.0 mg, cat.), BINAP (62.0 mg, cat.) And sodium t-butoxide (143.0 mg, 1.49 mmol) were added to 10.0 mL of toluene and the mixture was stirred at 100 ° C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 250.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 6.95 (d, 2H), 6.72-6.66 (m, 2H), 6.52 (d, 2H), 5.46 (dd, 1H), 4.93 (s, 1H), 3.56-3.47 (m, 7H), 3.29-3.08 (m, 3H), 1.91-1.87 (m, 2H), 1.35

Example 321. l- (2,4-Difluoro-phenyl) -5- [4- (homopiperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole hydrochloride

(2,4-difluoro-phenyl) -5- [4- (4-BOC-homopiperazin-l-yl) -phenyl] -3- [ Methyl-4, 5-dihydro-1H-pyrazole (340.0 mg, 0.6 mmol) was added to 5.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 250.0 mg of the title compound as a pale yellow solid.

^{1 H NMR (400 MHz, CDCl} 3) 7.40 (dd, 1H), 7.15 (d, 2H), 7.08 (d, 2H), 6.79-6.70 (m, 2H), 5.52 (dd, 1H), 3.90-3.87 (m, 2H), 3.66-3.54 (m, 5H), 3.37-3.35 (m, 2H), 3.04 (dd,

Example 322. l- (2,4-Difluoro-phenyl) -5- [4- (4-methanesulfonyl-homopiperazin- l-yl) -phenyl] -3- [ Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

(2,4-difluoro-phenyl) -5- [4- (homopiperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) (22.0 uL, 0.16 mmol) and methanesulfonyl chloride (5.0 uL, 0.07 mmol) were added to a solution of di (tert-butoxycarbonylamino-methyl) -4,5-dihydro- lH- pyrazole hydrochloride (30.0 mg, 0.06 mmol) To 1.0 mL of chloromethane, the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 10.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.16 (dd, 1H), 6.96 (d, 2H), 6.73-6.66 (m, 2H), 6.52 (d, 2H), 5.47 (dd, 1H), 4.87 (s 2H), 3.12 (dd, IH), 2.66 (s, 3H), 2.05 - 1.97 (m, 2H), 3.62-3.45 (m, 7H)

Examples 323 to 326

(2,4-difluoro-phenyl) -5- [4- (homopiperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-1H-pyrazole hydrochloride and the sulfonyl chloride corresponding to Examples 323 to 326 was used in place of methanesulfonyl chloride. The compounds of Examples 323 to 326 were respectively prepared.

Example 323. l- (2,4-Difluoro-phenyl) -5- [4- (4-ethanesulfonyl-homopiperazin- l-yl) -phenyl] -3- [ Dimethyl-methyl) -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.16 (dd, 1H), 6.96 (d, 2H), 6.73-6.67 (m, 2H), 6.51 (d, 2H), 5.47 (dd, 1H), 4.87 (s 2H), 2.04-1.99 (m, 2H), 1.26 (t, 3H), 3.63-3.45 (m, 7H) )

Yl)] - phenyl} -3- [3-methyl-lH-pyrrolo [ Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.15 (dd, 1H), 6.96 (d, 2H), 6.73-6.68 (m, 2H), 6.51 (d, 2H), 5.47 (dd, 1H), 4.87 (s (M, 2H), 1.28 (d, 6H), &lt; RTI ID =

Example 325. l- (2,4-Difluoro-phenyl) -5- [4- (4-cyclopropanesulfonyl-homopiperazin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.16 (dd, 1H), 6.96 (d, 2H), 6.73-6.66 (m, 2H), 6.52 (d, 2H), 5.47 (dd, 1H), 4.88 (s 2H), 1.10-1. 07 (m, 1H), 3.61-3.50 (m, 7H), 3.28 (t, 2H), 3.12 (dd, , 2H), 0.81-0.78 (m, 2H)

Example 326. l- (2,4-Difluoro-phenyl) -5- [4- (4-dimethylsulfamoyl-homopiperazin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.16 (dd, 1H), 6.96 (d, 2H), 6.73-6.66 (m, 2H), 6.51 (d, 2H), 5.47 (dd, 1H), 4.89 (s 2H), 3.12 (dd, 1H), 2.64 (s, 6H), 2.00-1.96 (m, 2H)

Example 327. l- (2,4-Difluoro-phenyl) -5- {3 '- [3- (methyl- amino) -propane- 1 -sulfonyl] - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Yl) -1- (2,4-difluoro-phenyl) -propan-1-sulfonyl] Dihydro-1H-pyrazole (23.0 mg, 0.03 mmol) in dichloromethane (0.5 mL) was added dropwise to a solution of 4- (trifluoromethyl) ) And triflu or o acetic acid (24.0 uL, 0.31 mmol) were added thereto, and the mixture was stirred at room temperature for 72 hours. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 15.0 mg of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.04 (s, 1H), 7.90-7.77 (m, 2H), 7.66-7.48 (m, 3H), 7.28-7.23 (m, 3H), 6.75-6.68 (m, 2H), 5.60 (dd, 1 H), 3.63 (dd, 1 H), 3.24-3.11 (m, 3H), 3.01 (brs, -1.91 (m, 2 H)

Example 328. l- (2,4-Difluoro-phenyl) -5- {4 '- [3- (methyl-amino) -propane- 1 -sulfonyl] - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Yl) -1- (2,4-difluoro-phenyl) -propionic acid ethyl ester was prepared in an analogous manner as described in example 297 using 5- {4 '- [3- Dichloro-1H-pyrazole (15.0 mg, 0.02 mmol) in dichloromethane (0.5 mL) was added dropwise to a solution of 4- ) And trifluoroacetic acid (16.0 uL, 0.12 mmol) were added, and the mixture was stirred at room temperature for 72 hours. The reaction mixture was washed with distilled water, 1N hydrochloric acid salt, saturated sodium hydrogencarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain the title compound (10.0 mg) as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.94 (d, 2H), 7.68 (d, 2H), 7.50 (d, 2H), 7.27-7.24 (m, 3H), 6.76-6.68 (m, 2H), 5.61 2H), 2.37 (s, 3H), 1.94-1.89 (m, 2H), 2.64 (d,

Example 329. l- (2,4-Difluoro-phenyl) -5- [3'-methanesulfonyl-biphenyl-4-yl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-lH-pyrazole

(3-methylsulfanyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) - (77%, 45.0 mg, 0.18 mmol) at 0 ° C was added to dichloromethane (1.0 mL), and the mixture was stirred at 0 ° C for 1 h. Was slowly added thereto, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 7.5 mg of the title compound as a pale yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.08 (s, 1H), 7.90 (d, 1H), 7.80 (d, 1H), 7.64 (t, 2H), 7.51 (d, 2H), 7.30-7.26 (m 2H), 6.75-6.69 (m, 2H), 5.65 (dd, IH), 3.66 (dd,

Example 330. l- (2-Chloro-phenyl) -5- {5- [3- (methylsulfanyl) -phenyl] -thiophen-2- yl} -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl) methyl] -4,5-dihydro -1H- pyrazole (100.0 mg, 0.20 mmol), 3- methyl-thiophenyl boronic acid (50.4 mg, 0.30 mmol), Pd (PPh 3) 4 (23.0 mg, 0.02 mmol ), 1.0 mL of a 2N sodium carbonate aqueous solution was added to a mixed solution of 2.0 mL of 1,2-dimethoxyethane and 1.0 mL of ethanol, and the mixture was stirred at 88 DEG C for 4 hours. Ethyl acetate was added to the reaction mixture, which was then washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 9.2 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.30 (d, 2H), 7.25-7.11 (m, 5H), 7.08 (t, 1H), 6.98 (s, 1H), 6.76 (s, 1H), 6.19 (dd (D, 1H), 4.90 (s, 1H), 3.62 (dd,

Examples 331 to 334

Chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl) Methyl] -4,5-dihydro-1H-pyrazole was used in place of 3-methylthiophenylboronic acid, and boronic acid corresponding to Examples 331 to 334 was used in place of 3-methylthiophenylboronic acid. To give the compounds of Examples 331 to 334, respectively.

Example 331. l- (2-Chloro-phenyl) -5- {5- [4- (methylsulfanyl) -phenyl] -thiophen-2- yl} -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.36 (d, 2H), 7.30 (d, 1H), 7.25-7.17 (m, 3H), 7.08 (t, 1H), 7.00 (t, 1H), 6.90 (s (D, 1H), 6.76 (s, 1H), 6.20 (sd, 1H)

Example 332. l- (2-Chloro-phenyl) -5- {5- [4- (methylsulfonyl) -phenyl] -thiophen-2- yl} -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.88 (d, 2H), 7.61 (d, 2H), 7.31 (d, 1H), 7.20 (d, 1H), 7.12-7.08 (m, 2H), 7.01 (t (S, 3H), 3.63 (dd, IH), 3.63 (s,

Thiophen-2-yl} -3- [di (trifluoromethyl) phenyl] -5- {5- [ Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.54 (s, 1H), 7.51 (d, 1H), 7.31 (d, 1H), 7.18 (d, 1H), 7.13-7.07 (m, 2H), 7.01 (t (D, 1H), 6.92 (s, 1H), 6.78 (s, 1H) 3H)

Example 334. l- (2-Chloro-phenyl) -5- [5- (l-BOC-l, 2,3,6-tetrahydropyridin-4- yl) -thiophen- - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.29 (d, 1H), 7.18 (d, 1H), 7.11 (t, 1H), 7.03 (t, 1H), 6.66 (d, 1H), 6.59 (d, 1H ), 6.15 (dd, IH), 5.92 (br, IH), 4.88 (s, IH) 4.01 (s, 2H), 3.62 2.37 (m, 2 H), 1.49 (s, 9 H)

Example 335. l- (2-chloro-phenyl) -5- [5- (l, 2,3,6-tetrahydropyridin-4- yl) -thiophen- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole hydrochloride

-5- [5- (1-BOC-1,2,3,6-tetrahydropyridin-4-yl) -thiophen-2-yl] Hydroxy-methyl] -4,5-dihydro-1H-pyrazole (590.0 mg, 0.97 mmol) was added to 2.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, Lt; / RTI &gt; for 2 h. The reaction mixture was concentrated under reduced pressure to obtain 590.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.28 (d, 2H), 7.06 (t, 1H), 6.97 (t, 1H), 6.79-6.74 (m, 2H), 5.16 (dd, 1H), 5.97 ( 2H), 3.63 (d, 2H), 3.63 (d, 2H)

Example 336. l- (2-chloro-phenyl) -5- [5- (l-methanesulfonyl-l, 2,3,6-tetrahydropyridin-4- yl) -thiophen- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

5- [5- (1,2,3,6-tetrahydropyridin-4-yl) -thiophen-2-yl] -3- [ Dihydro-1H-pyrazole hydrochloride (30.0 mg, 0.06 mmol), methanesulfonyl chloride (6.0 uL, 0.08 mmol), triethylamine (38.0 uL, 0.28 mmol) were added to 1.0 mL of dichloromethane, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 5.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.50 (d, 1H), 7.25 (d, 1H), 7.10 (t, 1H), 7.00 (d, 1H), 6.68 (s, 1H), 6.60 (s, 1H 2H), 3.63 (dd, 1H), 3.45-3.35 (m, 3H), 2.82 (s, 3H), 2.51 (brs, 2H)

Example 337. l- (2-chloro-phenyl) -5- [5- (1-cyclopropanesulfonyl-l, 2,3,6-tetrahydropyridin-4- yl) -thiophen- ] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole

5- [5- (1,2,3,6-tetrahydropyridin-4-yl) -thiophen-2-yl] -3- [ Dihydro-1H-pyrazole hydrochloride (30.0 mg, 0.06 mmol), cyclopropanesulfonyl chloride (8.0 uL, 0.08 mmol), triethyl Amine (38.0 uL, 0.28 mmol) was added to 1.0 mL of dichloromethane, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 15.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.30 (d, 1H), 7.19-7.00 (m, 3H), 6.68 (s, 1H), 6.61 (s, 1H), 6.16 (d, 1H), 5.95 (s (M, 2H), 3.32 (d, 2H), 3.32 (brs, 2H) 1H), 1.20-1.16 (m, 2H), 1.00-0.94 (m, 2H)

Example 338. l- (2-Chloro-phenyl) -5- {5- [3- (methylsulfonyl) -phenyl] -thiophen-2- yl} -3- [di- (trifluoromethyl) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Yl) -3 - [(trifluoromethyl) phenyl] -5- {5- [3- (methylsulfanyl) -phenyl] -thiophen- (77.0%, 6.0 mg, 0.15 mmol) was added to dichloromethane (1.0 mL) at 0 &lt; 0 &gt; C, 0.02 mmol) was slowly added thereto, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 10.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.05 (s, 1H), 7.78 (d, 1H), 7.70 (d, 1H), 7.54 (t, 1H), 7.32 (d, 1H), 7.20 (d, 1H 1H), 3.63 (dd, 1H), 3.39 (dd, 1H), 3.06 (s, 3H)

Example 339. l- (2-Chloro-phenyl) -5- {5- [6- (methylsulfonyl) -pyridin- 3- yl] -thiophen- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

5- [5- (6- (methylsulfanyl) -pyridin-3-yl] -thiophen-2-yl} -3- [di- (49.0 mg, 0.03 mmol) was added to 1.0 mL of dichloromethane, followed by the addition of metachloro and benzoic acid (77%) at 0 &lt; 0 &gt; C, , 15.0 mg, 0.05 mmol) was slowly added thereto, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 17.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.76 (s, 1H), 8.02 (d, 1H), 7.93 (d, 1H), 7.32 (d, 1H), 7.21-7.09 (m, 3H), 7.03 (t (D, 1H), 6.87 (s, 1H), 6.34 (dd,

Example 340. Preparation of 5- (2-chloro-phenyl) -l- [3 '-( methylsulfanyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-2H-pyran-2- dihydro -1H- pyrazole (50.0 mg, 0.10 mmol), 3- methyl-thiophenyl boronic acid (25.1 mg, 0.15 mmol), Pd (PPh 3) 4 (11.5 mg, 0.01 mmol), 2N aqueous sodium carbonate 0.5 mL Was added to a mixed solution of 2.0 mL of 1,2-dimethoxyethane and 0.5 mL of ethanol, followed by stirring at 90 ° C for 2 hours. Ethyl acetate was added to the reaction mixture, which was then washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/10) to obtain 3.7 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.44-7.38 (m, 3H), 7.32 (s, 1H), 7.27-7.22 (m, 4H), 7.16 (t, 2H), 6.96 (d, 2H), 5.89 (dd, 1 H), 4.86 (s, 1 H), 3.80 (dd,

Examples 341 to 343

(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-2H-pyran-2- Dihydro-1H-pyrazole was used in place of 3-methylthiophenylboronic acid and boronic acid corresponding to that of Example 341 to 343 was used in place of 3-methylthiophenylboronic acid, the reaction of Examples 341 to 343 Respectively.

Example 341. 5- (2-Chloro-phenyl) -l- [4 '-( methylsulfanyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) -hydroxy- ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.47-7.42 (m, 5H), 7.30-7.20 (m, 4H), 7.16 (d, 1H), 6.96 (d, 2H), 5.86 (dd, 1H), 4.87 (s, 1 H), 3.80 (dd, 1 H), 2.93 (dd,

Example 342. l- (2-chloro-phenyl) -l- [4 '- (methylsulfonyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.99 (d, 2H), 7.68 (d, 2H), 7.50-7.47 (m, 3H), 7.30-7.20 (m, 2H), 7.13 (d, 1H), 7.01 (d, 2H), 5.90 (dd, IH), 4.86 (s, IH), 3.81 (dd,

Example 343. 3- (2-Chloro-phenyl) -l- {4- [6- (methylsulfanyl) -pyridin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.60 (s, 1H), 7.71 (d, 1H), 7.46 (d, 1H), 7.41 (d, 2H), 7.30-7.20 (m, 3H), 7.14 (d (Dd, 2H), 5.88 (dd, 1H), 4.86 (s,

Example 344. 5- (2-Chloro-phenyl) -1- [4- (l-BOC-l, 2,3,6-tetrahydropyridin- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt; (500.0 mg, 1.00 mmol), tert-butyl 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan- (73.0 mg, 0.10 mmol), potassium carbonate (690.0 mg, 4.98 mmol) and Pd (dppf) Cl ₂ (73.0 mg, 0.10 mmol) were added to a 1,4-dioxane Was added to a mixed solution of 15.0 mL of dioxane and 4.0 mL of distilled water, and the mixture was stirred at 85 DEG C for 16 hours. Distilled water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 435.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.45 (d, 1H), 7.29-7.17 (m, 4H), 7.12 (d, 1H), 6.86 (d, 2H), 5.92 (brs, 1H), 5.84 (dd 2H), 2.48 (s, 2H), 2.48 (s, 2H), 2.48 (s, 9H)

Example 345. 5- (2-chloro-phenyl) -l- [3 '-( methylsulfonyl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl ] -4,5-dihydro-lH-pyrazole

Yl) -3- [di- (trifluoromethyl) -hydroxy-benzooxazol-4-yl) -Methyl] -4,5-dihydro-1H-pyrazole (10.0 mg, 0.005 mmol) was added to 1.0 mL of dichloromethane and then methachloro and benzoic acid (77%, 10.0 mg, 0.01 mmol) And the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 8.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.09 (s, 1H), 7.82 (d, 1H), 7.73 (d, 1H), 7.58 (t, 1H), 7.50-7.46 (m, 3H), 7.30-7.20 (m, 2H), 7.12 (d, IH), 7.00 (d, 2H), 5.91 (dd, IH), 4.90 dd, 1 H)

Example 346. 5- (2-Chloro-phenyl) -l- {4- [6- (methylsulfonyl) -pyridin- 3- yl] -phenyl} -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(2-chloro-phenyl) -l- {4- [6- (methylsulfanyl) -pyridin-3-yl] -phenyl} -3- [di- (trifluoromethyl) (10.0 mg, 0.005 mmol) was added to 1.0 mL of dichloromethane, followed by dropwise addition of metachloro and benzoic acid (77%, 10.0 mg, 0.01 &lt; RTI ID = 0.0 & mmol) was added slowly, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 2.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.86 (s, 1H), 8.09 (d, 1H), 8.02 (d, 1H), 7.50-7.47 (m, 3H), 7.30-7.20 (m, 3H), 7.11 (d, IH), 7.04 (d, 2H), 5.91 (dd, IH), 4.86

Example 347. l- (2-Chloro-phenyl) -l- [4- (4-BOC-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-2H-pyran-2- (500.0 mg, 1.00 mmol), 1-BOC-piperazine (241.0 mg, 1.30 mmol), Pd ₂ (dba) ₃ (45.0 mg, 0.05 mmol), BINAP ) And sodium tert-butoxide (144.0 mg, 1.50 mmol) were added to 10.0 mL of toluene, and the mixture was stirred at 100 ° C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 280.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.44 (d, 1H), 7.28-7.19 (m, 3H), 6.87-6.80 (m, 4H), 5.75 (dd, 1H), 4.88 (s, 1H), 3.74 (d, 1H), 3.54 (t, 4H), 2.99 (t, 4H)

Example 348. 5- (2-Chloro-phenyl) -l- [4- (l, 2,3,6-tetrahydropyridin-4- yl) -phenyl] -3- [di- (trifluoromethyl ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole hydrochloride

The title compound was obtained as white powder starting from 5- (2-chloro-phenyl) -1- [4- (1-BOC-1,2,3,6-tetrahydropyridin-4- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole (435.0 mg, 0.72 mmol) was added to 2.0 mL of a saturated solution of hydrochloric acid in ethyl acetate and stirred at room temperature for 2 hours Respectively. The reaction mixture was concentrated under reduced pressure to obtain 400.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.49 (d, 1H), 7.38-7.27 (m, 3H), 7.19 (t, 1H), 7.05 (d, 1H), 6.93 (d, 2H), 6.01 ( 2H), 2.86 (dd, 1 H), 2.73 (brs, 2 H), 3.42 (m,

Example 349. 5- (2-Chloro-phenyl) -l- [4- (piperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) , 5-dihydro-lH-pyrazole hydrochloride

(4-BOC-piperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) -hydro Methyl] -4,5-dihydro-1H-pyrazole (280.0 mg, 0.46 mmol) was added to 2.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to obtain 270.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CD} 3 OD) 7.49 (d, 1H), 7.29 (t, 1H), 7.24-7.18 (m, 3H), 7.07 (d, 1H), 6.98 (d, 2H), 5.76 ( (dd, 1H), 3.80 (dd, 1H), 3.58-3.48 (m, 8H), 2.86

Example 350. 5- (2-Chloro-phenyl) -l- [4- (1-cyclopropanesulfonyl-l, 2,3,6- tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

The title compound was prepared from 5- (2-chloro-phenyl) -1- [4- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [ (20.0 mg, 0.04 mmol), cyclopropanesulfonyl chloride (6.0 uL, 0.06 mmol) and triethylamine (26.0 uL, 0.06 mmol) in dichloromethane 0.19 mmol) were added to 1.0 mL of dichloromethane, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 15.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.45 (d, 1H), 7.28-7.18 (m, 4H), 7.12 (d, 1H), 6.87 (d, 2H), 5.95 (s, 1H), 5.84 (dd (Dd, IH), 4.85 (s, IH), 4.004 (m, 2H) m, 1 H), 1.22-1.17 (m, 2H), 1.01-0.95 (m, 2H)

Example 351. 5- (2-Chloro-phenyl) -l- [4- (4- cyclopropanesulfonyl-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -thiazol-4-yl] (20.0 mg, 0.04 mmol), cyclopropanesulfonyl chloride (6.0 uL, 0.06 mmol) and triethylamine (25.0 uL, 0.18 mmol) were dissolved in dichloromethane And the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/1) to obtain 15.0 mg of the title compound as a yellow liquid.

¹ H NMR (400 MHz, CDCl ₃ ) 7.44 (d, 1 H), 7.28-7.17 (m, 3H), 6.88-6.81 (m, 4H), 5.75 (d, 1H), 3.44 (t, 4H), 3.13 (t, 4H), 2.87 (dd, 1H), 2.32-2.25 , 2H)

Example 352. 5- (2-chloro-phenyl) -l- [3 '-( methylsulfanyl) -biphenyl-3-yl] -3- [di- (trifluoromethyl) -hydroxy- ] -4,5-dihydro-lH-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-2H-pyran-3- carboxylic acid ethyl ester in step 2 of Reference Example 10 dihydro -1H- pyrazole (50.0 mg, 0.10 mmol), 3- methyl-thiophenyl boronic acid (20.0 mg, 0.15 mmol), Pd (PPh 3) 4 (11.5 mg, 0.01 mmol), 2N aqueous sodium carbonate 0.5 mL Was added to a mixed solution of 2.0 mL of 1,2-dimethoxyethane and 0.5 mL of ethanol, followed by stirring at 90 ° C for 2 hours. Ethyl acetate was added to the reaction mixture, which was then washed with distilled water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/10) to obtain 5.3 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.46 (d, 1H), 7.34-7.17 (m, 8H), 7.09 (d, 2H), 6.87 (d, 1H), 5.90 (dd, 1H), 4.87 (s (Dd, 1H), 2.49 (s, 3H)

Examples 353 to 356

(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-2H-pyran-3- carboxylic acid ethyl ester in step 2 of Reference Example 10 Dihydro-1H-pyrazole was used in place of 3-methylthiophenylboronic acid and boronic acid corresponding to Example 353 to 356 was used in place of 3-methylthiophenylboronic acid. Respectively.

Example 353. 2,3-dimethyl-5- (2-chloro-phenyl) -l- [4 '-( methylsulfanyl) ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.46 (d, 1H), 7.40 (d, 2H), 7.33-7.14 (m, 7H), 7.09 (d, 1H), 6.82 (d, 1H), 5.89 (dd (D, 1H), 4.87 (s, 1H), 3.79 (dd,

Example 354. Preparation of 5- (2-chloro-phenyl) -l- [4 '- (methylsulfonyl) -biphenyl-3-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl ] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.98 (d, 2H), 7.64 (d, 2H), 7.47 (d, 1H), 7.33-7.22 (m, 3H), 7.17 (s, 2H), 7.12 (d (Dd, 1H), 6.90 (d, 1H), 5.92 (dd,

Example 355. 5- (2-Chloro-phenyl) -l- {3- [6- (methylsulfanyl) -pyridin- 3- yl] -phenyl} -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 8.55 (s, 1H), 7.60 (d, 1H), 7.47 (d, 1H), 7.31-7.21 (m, 4H), 7.17 (d, 1H), 7.11 (s , 7.08 (d, 1H), 6.88 (d, 1H), 5.90 (dd, 1H), 4.84 3H)

Example 356. 5- (2-chloro-phenyl) -l- [3- (l-BOC-l, 2,3,6-tetrahydropyridin- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

^{1 H NMR (400 MHz, CDCl} 3) 7.45 (d, 1H), 7.26-7.13 (m, 4H), 6.95 (s, 1H), 6.91 (d, 1H), 6.74 (d, 1H), 5.93 (br (Dd, 1H), 5.84 (dd, IH), 4.88 (s, IH), 4.04 (s, 2H), 3.77 (dd, 2H), 1.47 (s, 9H)

Example 357. l- (2-chloro-phenyl) -l- [3 '-( methylsulfonyl) -biphenyl-3-yl] -3- [di- (trifluoromethyl) -hydroxy- ] -4,5-dihydro-lH-pyrazole

Yl) -3- [di- (trifluoromethyl) -hydroxy-benzoic acid methyl ester, prepared in example 352, -Methyl] -4,5-dihydro-1H-pyrazole (30.0 mg, 0.055 mmol) was added to 1.0 mL of dichloromethane and then methachloro and benzoic acid (77%, 27.0 mg, 0.110 mmol) And the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 15.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.06 (s, 1H), 7.89 (d, 1H), 7.75 (d, 1H), 6.73 (t, 1H), 7.48 (d, 1H), 7.32-7.23 (m (Dd, 1H), 7.18 (d, 1H), 7.18 (d, 1H)

Example 358. 5- (2-Chloro-phenyl) -l- {3- [6- (methylsulfonyl) -pyridin- 3- yl] -phenyl} -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(2-chloro-phenyl) - l- {3- [6- (methylsulfanyl) -pyridin-3- yl] -phenyl} -3- [di- (trifluoromethyl) (10.0 mg, 0.02 mmol) was added to 1.0 mL of dichloromethane, followed by the addition of metachloro and benzoic acid (77%, 9.0 mg, 0.04 mmol) at 0 ° C. mmol) was added slowly, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with saturated sodium bicarbonate and extracted three times with dichloromethane. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 4.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 8.80 (s, 1H), 8.12 (d, 1H), 7.99 (d, 1H), 7.48 (D, 1H), 7.31 (t, 1H), 7.27-7.23 (m 2H), 7.16 (d, 1H), 7.12 (d, 2H), 6.99 (d, 1H), 5.92 (dd, 3H), 2.97 (dd, 1 H)

Example 359. 5- (2-Chloro-phenyl) -l- [3- (4-BOC-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Methyl] -4,5-dihydro-1H-pyrazole

(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-2H-pyran-3- carboxylic acid ethyl ester in step 2 of Reference Example 10 (500.0 mg, 1.00 mmol), 1-BOC-piperazine (275.0 mg, 1.49 mmol), Pd ₂ (dba) ₃ (47.0 mg, 0.05 mmol), BINAP (63.0 mg, 0.10 mmol ) And sodium tert-butoxide (143.0 mg, 1.79 mmol) were added to 12.0 mL of toluene, and the mixture was stirred at 100 ° C for 12 hours. The reaction mixture was filtered through a pad of celite, and a saturated aqueous solution of ammonium chloride was added to the resulting filtrate, which was then extracted three times with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/5) to obtain 95.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.44 (d, 1H), 7.25-7.19 (m, 2H), 7.14 (d, 1H), 7.07 (t, 1H), 6.54 (s, 1H), 6.47 (d (D, 1H), 6.33 (d, 1H), 5.84 (dd, 1H), 3.73 (dd, 9H)

Example 360. l- (2-Chloro-phenyl) -l- [3- (l-methylsulfonyl- l, 2,3,6-tetrahydropyridin- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(2-chloro-phenyl) -1- [3- (1-BOC-1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- (350.0 mg, 0.71 mmol) was added to 3.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 1 hour Respectively. The reaction mixture was concentrated under reduced pressure to give 5- (2-chloro-phenyl) -1- [3- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole hydrochloride (400.0 mg).

The above yellow liquid 5- (2-chloro-phenyl) -1- [3- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (trifluoromethyl (30.0 mg, 0.055 mmol), methanesulfonyl chloride (7.6 mg, 0.066 mmol) and triethylamine (31.0 uL, 0.221 mmol) in tetrahydrofuran Was added to 1.0 mL of dichloromethane, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 2/1) to obtain 14.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.47 (d, 1H), 7.28-7.13 (m, 4H), 6.91-6.89 (m, 2H), 6.78 (d, 1H), 5.97 (s, 1H), 5.96 (t, 2H), 2.96 (s, 3H), 2.55 (d, 2H) m, 2H)

Example 361. 5- (2-Chloro-phenyl) -1- [3- (1-cyclopropanesulfonyl- 1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(2-chloro-phenyl) -1- [3- (1-BOC-1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- (350.0 mg, 0.71 mmol) was added to 3.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 1 hour Respectively. The reaction mixture was concentrated under reduced pressure to give 5- (2-chloro-phenyl) -1- [3- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole hydrochloride (400.0 mg).

The above yellow liquid 5- (2-chloro-phenyl) -1- [3- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (trifluoromethyl (30.0 mg, 0.055 mmol), cyclopropanesulfonyl chloride (9.3 mg, 0.066 mmol) and triethylamine (31.0 uL, 0.221 mmol) in tetrahydrofuran ) Was added to 1.0 mL of dichloromethane, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 14.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.47 (d, 1H), 7.28-7.13 (m, 4H), 6.91-6.89 (m, 2H), 6.80 (d, 1H), 5.96 (s, 1H), 5.88 (dd, 1H), 4.85 (s, 1H), 3.98 (t, 2H), 3.76 (dd, m, 1 H), 1.24 (m, 2 H), 1.02 (m, 2 H)

Example 362. 5- (2-Chloro-phenyl) -l- [3- (4-methylsulfonyl-piperazin- l-yl) -phenyl] -3- [di- (trifluoromethyl) Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(4-BOC-piperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) -hydro Methyl] -4,5-dihydro-1H-pyrazole (100.0 mg, 0.20 mmol) was added to 3.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to give 5- (2-chloro-phenyl) -1- [3- (piperazin- 1 -yl) -phenyl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-1H-pyrazole hydrochloride (400.0 mg).

The title compound was obtained as a yellow liquid from 5- (2-chloro-phenyl) -1- [3- (piperazin-1-yl) -phenyl] -3- [di- (trifluoromethyl) (30.0 mg, 0.055 mmol), methanesulfonyl chloride (7.6 mg, 0.066 mmol) and triethylamine (31.0 uL, 0.221 mmol) were added to 1.0 mL of dichloromethane and the mixture was stirred at room temperature Lt; / RTI &gt; for 16 h. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 15.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.44 (d, 1H), 7.28-7.08 (m, 5H), 6.52 (s, 1H), 6.47 (d, 1H), 6.40 (d, 1H), 5.83 (dd 2H), 2.80 (s, 3H), 3.85 (d, 1H)

Example 363. 3- (5-Chloro-phenyl) -l- [3- (4-cyclopropanesulfonyl-piperazin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole

(4-BOC-piperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) -hydro Methyl] -4,5-dihydro-1H-pyrazole (100.0 mg, 0.20 mmol) was added to 3.0 mL of a saturated solution of hydrochloric acid in ethyl acetate, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to give 5- (2-chloro-phenyl) -1- [3- (piperazin- 1 -yl) -phenyl] -3- [di- (trifluoromethyl) -Methyl] -4,5-dihydro-1H-pyrazole hydrochloride (400.0 mg).

The title compound was obtained as a yellow liquid from 5- (2-chloro-phenyl) -1- [3- (piperazin-1-yl) -phenyl] -3- [di- (trifluoromethyl) (30.0 mg, 0.055 mmol), cyclopropanesulfonyl chloride (9.3 mg, 0.066 mmol) and triethylamine (31.0 uL, 0.221 mmol) were added to 1.0 mL of dichloromethane The mixture was stirred at room temperature for 16 hours. The reaction mixture was washed with distilled water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a yellow liquid residue. The residue was purified by silica gel column chromatography (developing solvent: ethyl acetate / n-hexane = 1/2) to obtain 15.0 mg of the title compound as a yellow liquid.

^{1 H NMR (400 MHz, CDCl} 3) 7.44 (d, 1H), 7.28-7.08 (m, 5H), 6.52 (s, 1H), 6.47 (d, 1H), 6.40 (d, 1H), 5.83 (dd 1H), 1.24 (m, 1H), 4.85 (d, 1H), 3.85 (d, 2H), 1.01 (m, 2H)

Test example. Measurement of transcriptional activity of LXRβ

The expression construct was prepared by inserting the human LXR [beta] cDNA ligand binding domain (LBD) into the expression vector pFA (Stratagene, USA). That is, the expression construct pFA-hLXR? / GAL4 was prepared by inserting LBD adjacent to the yeast GAL4 transcription factor DNA binding domain (DBD) (Willey et al. Genes & Development 9 1033-1045 (1995)). PUAS (Stratagene, USA), a GAL4-responsive luciferase reporter plasmid, contains 5 copies of the GAL4 response element and a luciferase reporter gene located adjacent to the promoter. The transcriptional activity of LXR [beta] was measured by introducing pFA-hLXR [beta] / GAL4 and pUAS through transient transfection into mammalian cells.

HEK293 human kidney cells (sATCC, CRL-1573) were grown in DMEM (Gibco) medium supplemented with 10% FBS (Gibco) until reaching confluency of about 70-80% in a T-75 flask And incubated at 37 ° C in a CO ₂ incubator. The culture containing the cells in each well of a 96-well plate was added to a concentration of about 5 X 10 ⁴ cells and pFA-hLXR? / GAL4 (Lipofectamine ^™ , Invitrogen) was added according to the manufacturer's protocol using a cationic lipid transfection reagent And pUAS were added and incubated at 37 캜 for about 3 hours to perform transient transfection. The test substance was dissolved in dimethyl sulfoxide (DMSO) at a concentration of 50, 30, 10, 3, 1, 0.3, 0.1, 0.03, and 0.01 μM and 100 μl of each well of the 96 well plate Respectively. After incubation at 37 ° C for 24 hours, the medium was removed from the cells and the cell lysis buffer (25 mM Tricine pH 7.8, 2 mM DTT, 2 mM EGTA, 10% glycerol, 1% Triton X-100) 20 [mu] l each. After stirring at room temperature for 15 minutes, luciferase assay reagent prepared by adding 10 ml of luciferase buffer (Promega) to 1 vial of luciferase substrate (Promega) was added in an amount of 100 μl per well, and then diluted with a luminometer ).

The dose-response curve for calculating the EC ₅₀ value of the test substance for an increase in the transcriptional activity of LXR [beta] was determined as the positive control, N- (2,2,2-tri Trifluoromethyl-ethyl) -phenyl] -benzenesulfonamide was used as a negative control, and &lt; RTI ID = 0.0 &gt; Vehicle (DMSO). The volume-response curve was generated from a 9 point curve with different concentrations by 1/2 log unit. The EC ₅₀ value of the test substance is defined as the concentration which initiates the reaction corresponding to half between the top (peak value) and the bottom (baseline) value by the positive control, calculated according to the following equation.

Y = Bottom + (Top-Bottom) / (1 + 10 ^{(( logEC50- X) * Hill Slope )} ).

In the above equation, Y denotes the observed value, X denotes the log (Conc), Hill Slope denotes the slope of the curve, and Top and Bottom denote the maximum value and the baseline value of the positive control group, respectively .

The EC ₅₀ values of the test substances measured as above are shown in Tables 1 and 2 below. In the following Tables 1 and 2, the respective EC ₅₀ values represent the mean values of three independent tests.

* In the above Tables 1 and 2, Emax represents the fold value as compared to the control group (DMSO treated group).

As can be seen from the results of Tables 1 and 2, the compounds according to the present invention have an excellent transcription-increasing activity of LXR [beta] and thus can be used for the prevention and treatment of cholesterol gallstone, hyperlipidemia, or cholesterol metabolism including coronary and atherosclerosis Can be usefully applied.

Claims (12)

Claims 1. A compound of the formula 1: < EMI ID =
&Lt; Formula 1 &gt;

Wherein,
L and L 'are, independently of each other, - (CH ₂ ) _n -, n is 0,
Ring X is benzene,
Ring Y is benzene, pyridine, or thiophene,
R ₁ and R ₃ are independently of each other hydrogen or halogen,
R ₂ is halogen; Phenyl; Pyridinyl; 1,2,3,6-tetrahydropyridinyl; Or piperazinyl,
When R ₂ is phenyl, pyridinyl, 1,2,3,6-tetrahydropyridinyl, or a piperazinyl group, the phenyl, pyridinyl, 1,2,3,6-tetrahydropyridinyl, or piperazine C ₁ -C ₅ alkylthio; C ₁ -C ₅ alkylsulfonyl; C ₃ -C ₆ cycloalkylsulfonyl; And C _{1 to} C ₅ alkoxycarbonyl, each of which may be optionally substituted with one or more groups selected from the group consisting of halogen,
R ₄ is halogen; A phenyl group; A heteroaryl group selected from the group consisting of furanyl, pyridinyl, pyrimidinyl, indolyl, benzofuranyl, benzothiophenyl, and quinolinyl; Or a heterocyclic group selected from the group consisting of 1,2,3,6-tetrahydropyridinyl, piperidinyl, piperazinyl, 1,1-dioxo-thiomorpholinyl and homopiperazinyl,
When R ₄ is a phenyl group, the phenyl group may be substituted with halogen; Hydroxy; Cyano; C ₁ -C ₅ alkyl optionally substituted with one or more substituents selected from the group consisting of halogen and hydroxy; C ₁ -C ₅ alkoxy optionally substituted by one or more halogen; C ₁ -C ₅ alkylthio; C ₁ -C ₅ alkylsulfonyl; C ₁ -C ₅ alkylsulfinyl; C ₁ -C ₅ alkylcarbonyl; Hydroxycarbonyl; Triazolyl; Tetrazolyl; -NR'R ''';-NR''SO ₂ R ''';-NR'C (= O) R ''';

; And

, Wherein R "and R '" are independently of each other hydrogen, C ₁ -C ₅ alkyl optionally substituted by one or more substituents selected from hydroxy, , Or C ₃ -C ₆ cycloalkyl and p is 0, 1, 2, or 3,
When R ₄ is a heteroaryl group or a heterocyclic group, the heteroaryl group or the heterocyclic group may be substituted with halogen; Cyano; C ₁ -C ₅ alkyl optionally one or more optionally substituted with halogen; C ₁ -C ₅ alkoxy; Formyl; C ₁ -C ₅ alkylthio; C ₁ -C ₅ alkylsulfonyl optionally substituted by one or more halogen; C ₃ -C ₆ cycloalkylsulfonyl; Benzenesulfonyl; Pyrrolidin-1-yl-sulfonyl; Mono or di-C ₁ -C ₅ alkylaminosulfonyl; C ₁ -C ₅ alkylcarbonyl optionally substituted with hydroxy; C ₃ -C ₆ cycloalkylcarbonyl; C ₃ -C ₆ cycloalkyl-C ₁ -C ₅ alkylcarbonyl; Benzoyl optionally substituted with halogen; Benzylcarbonyl; Thiophenecarbonyl; C ₁ -C ₅ alkoxycarbonyl; Hydroxycarbonyl; Mono or di-C ₁ -C ₅ alkylaminocarbonyl; Amino; C ₃ -C ₆ cycloalkylsulfonylamino; C ₁ -C ₅ alkoxycarbonylamino; Tetrazolyl, &lt; / RTI &gt; and &lt; RTI ID = 0.0 &gt;
R ₅ is C (CF ₃ ) ₂ OH. delete delete delete delete delete The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein R &lt; ₃ &gt; is hydrogen. 2. The compound of claim 1, wherein R &lt; ₃ &gt; is halogen; Wherein the ring X and the ring Y are benzene, or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein R &lt; ₃ &gt; is hydrogen; R &lt; ₄ &gt; is halogen; Ring X and ring Y are benzene; Wherein R ₂ is selected from the group consisting of phenyl, pyridinyl, 1,2,3,6-tetrahydropyridinyl, or piperazine (said phenyl, pyridinyl, 1,2,3,6-tetrahydropyridinyl, C ₁ -C ₅ alkylthio, C ₁ -C ₅ alkylsulfonyl, C ₃ -C ₆ cycloalkylsulfonyl; And C ₁ -C ₅ alkoxycarbonyl, or a pharmaceutically acceptable salt thereof. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, 2. The compound of claim 1, wherein the compound is selected from the group consisting of:
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3-c] -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3-c] -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3-c] -LH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro- 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &5-dihydro-lH-pyrazole;
3-yl] -3- [di- (trifluoromethyl) -hydro- &lt; / RTI &gt; Methyl-4, &lt; / RTI &gt;5-dihydro-lH-pyrazole;
3-yl] -3- [di- (trifluoromethyl) -hydro- &lt; / RTI &gt; Methyl-4, &lt; / RTI &gt;5-dihydro-lH-pyrazole;
4- [1- (2-Chloro-phenyl) -5- [3- (1-BOC-1,2,3,6-tetrahydropyridin-4- yl) -phenyl] -3- [ ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy- &lt; / RTI &gt; -Methyl] -4,5-dihydro-lH-pyrazole trifluoroacetic acid salt;
Phenyl) - l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -1- (2-chloro-phenyl) -3- [di- (trifluoromethoxy) Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethoxy) phenyl] -5- [3- (1-isobutyryl-l, 2,3,6-tetrahydropyridin- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethoxy) phenyl] -5- [3- (1-pentanoyl-1,2,3,6-tetrahydropyridin-4- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- [1- (3-methyl-butyryl) -1,2,3,6-tetrahydropyridin-4-yl] -phenyl} -3- [ Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -5- {3- [1- (2,2-dimethyl-propionyl) -1,2,3,6-tetrahydropyridin-4- yl] -phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di (trifluoromethyl) phenyl) -5- [3- (1-cyclopentanecarbonyl-1,2,3,6-tetrahydropyridin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (tri (cyclohexanecarbonyl) -1,2,3,6-tetrahydropyridin-4-yl) Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- [1- (2-Chloro-phenyl) -5- {3- [l- (2- cyclopentyl- acetyl) - 1,2,3,6- tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- (2-chloro-phenyl) -5- {3- [1- (3-cyclopentyl-propionyl) -1,2,3,6-tetrahydropyridin-4- yl] -phenyl} -3 - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- (2-chloro-phenyl) -5- {3- [1- (thiophene-2- carbonyl) -1,2,3,6-tetrahydropyridin-4- yl] -phenyl} -3- [Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole;
Phenyl) - l- (2-chloro-phenyl) -3- [di- (trifluoromethyl) ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethoxy) -phenyl] -5- [3- (1-phenylacetyl-1,2,3,6-tetrahydropyridin- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -1- (2-chloro-phenyl) -3- [di [1- (4-chloro-benzoyl) -1,2,3,6-tetrahydropyridin- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethoxy) phenyl] -5- [3- (1 -methanesulfonyl-l, 2,3,6-tetrahydropyridin- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethoxy) phenyl] -5- [3- (1-ethanesulfonyl-l, 2,3,6-tetrahydropyridin- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
4- [1- (2-chloro-phenyl) -5- {3- [1- (propane- 1 -sulfonyl) - 1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- [1- (2-chloro-phenyl) -5- {3- [1- (propane- 2- sulfonyl) -1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
1 - (2-Chloro-phenyl) -5- {3- [1- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
5- [3- (1-Trifluoromethanesulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di (trifluoromethyl) phenyl] -5- [3- (1-cyclopropanesulfonyl-l, 2,3,6-tetrahydropyridin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di (trifluoromethyl) phenyl] -5- [3- (1-cyclopentanesulfonyl-l, 2,3,6-tetrahydropyridin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (tri (cyclohexylmethyl) -1H-pyrazol-3-yl] Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di (trifluoromethyl) phenyl] -5- [3- (1-dimethylsulfamoyl-l, 2,3,6-tetrahydropyridin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-benzoic acid methyl ester was prepared in accordance with the general method of example 1 from 5- (2'-acetyl-biphenyl- -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3-d] -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-benzoic acid was prepared in accordance with the general method of example 1 from 5- (4'-acetyl-biphenyl- -LH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
4-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro-lH-pyrazole;
4-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro-lH-pyrazole;
4-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro-lH-pyrazole;
4-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4- (4-methoxy- , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dimethoxy-biphenyl- , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-methoxy-phenyl) , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-methoxy-phenyl) , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dimethoxy- , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dimethoxy-biphenyl- , 5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-benzoic acid was prepared in accordance with the general method of example 1 from 5- (2'-chloro-biphenyl- -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3-d] -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-benzoic acid was prepared in accordance with the general method of example 1 from 5- (4'-chloro-biphenyl- -LH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4-tert-butoxycarbonylamino- , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro- , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4- (4-fluoro-phenyl) , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4- (4-fluoro-phenyl) , 5-dihydro-lH-pyrazole;
Methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- -LH-pyrazole;
Methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- -LH-pyrazole;
Methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- -LH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- Dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- Dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- Dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-di &lt; RTI ID = 0.0 &gt;Hydro-1H-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3-d] -LH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- Dihydro-lH-pyrazole;
- (2-chloro-phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - 4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] - (3-chloro-phenyl) 4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] - &lt; RTI ID = 0.0 &gt; (5-chloro-2 ' -methoxy- 4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- &lt; / RTI &gt;Dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H (trifluoromethyl) - pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-pyrazol- 1H-pyrazole;
Hydroxy-methyl] -4,5-dihydro-lH-pyrrolo [2,3-c] - pyrazole;
Methyl-4- (2-chloro-phenyl) -5- [4- (6-methoxy-pyridin- , 5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-fluoro-pyridin- , 5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-benzo [ 1H-pyrazole;
Methyl) -4,5-dihydro- benzo [b] thiophen-2-yl-phenyl) - dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-benzoic acid was prepared in accordance with the general method of example 1 from 5- (3'-carboxy-biphenyl- -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3-c] -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3- -LH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - 4,5-dihydro-lH-pyrazole;
Methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) 4,5-dihydro-lH-pyrazole;
Methyl] - (2-chloro-phenyl) -5- [4- (6-methylsulfanyl-pyridin- 4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 &lt; RTI ID = 0.0 &gt; , 5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-fluoro- , 5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-fluoro- , 5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-ylmethyl] Methyl] -4,5-dihydro-lH-pyrazole;
4- [2- (4-Chloro-phenyl) -5- 5-dihydro-lH-pyrazole;
Methyl] -4, &lt; RTI ID = 0.0 &gt; 2- (2- &lt; / RTI &5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] - &lt; / RTI &-4,5-dihydro-lH-pyrazole;
3- [di- (trifluoromethyl) -hydroxy-methyl] -piperazin-1- yl] -piperazin-1- -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-ylmethyl] Methyl] -4,5-dihydro-lH-pyrazole;
Methyl-4- (2-chloro-phenyl) -5- [4- (2- cyano-pyridin- , 5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-fluoro-pyridin- , 5-dihydro-lH-pyrazole;
Methyl-4, &lt; RTI ID = 0.0 &gt; (2, &lt; / RTI &5-dihydro-lH-pyrazole;
Phenyl-3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-ylmethyl] -pyridin- Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole;
Methyl] -4, &lt; RTI ID = 0.0 &gt; (2, &lt; / RTI &5-dihydro-lH-pyrazole;
Methyl] -4, &lt; RTI ID = 0.0 &gt; (2, &lt; / RTI &5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-pyrazolo [3,4-d] -LH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 &lt; RTI ID = 0.0 & , 5-dihydro-lH-pyrazole;
Yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-methoxy-pyridin- 4,5-dihydro-lH-pyrazole;
Yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2- Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-fluoro-phenyl) , 5-dihydro-lH-pyrazole;
4-yl} -3- [di- (trifluoromethoxy) -phenyl] -5- {4 '- [(2- hydroxy- ethyl) -methanesulfonyl-amino] Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -methyl-sulfamoyl] -biphenyl-4-yl} -3- ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -methyl-sulfamoyl] -biphenyl-4-yl} -3- ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- - dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- - dihydro-lH-pyrazole;
(2-Chloro-phenyl) -3- [2- (3-fluoro-phenyl) Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
(2-Chloro-phenyl) -3- [2- (4-fluoro-phenyl) Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl-3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl) Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -phenyl} -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2- Methyl] -4,5-dihydro-lH-pyrazole;
- (lH-1,2,4-triazol-l-yl) -biphenyl-4-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4-yl] -3- [di- (trifluoromethyl) - lH-pyrrolo [2,3-d] ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl) -pyridin-2-yl] ] -4,5-dihydro-lH-pyrazole;
4-yl] -3- [di- (trifluoromethyl) - [l- (2-chloro-phenyl) -5- ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4-yl] -3- [di- (trifluoromethyl) -hydroxy- &lt; / RTI &gt; -Methyl] -4,5-dihydro-lH-pyrazole;
Boc-1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (trifluoromethyl) ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy- &lt; / RTI &gt; -Methyl] -4,5-dihydro-lH-pyrazole trifluoroacetic acid salt;
4- [1- (2-chloro-phenyl) -5- [4- (1-acetyl-1,2,3,6- tetrahydropyridin-4- yl) -phenyl] -3- [ ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- [4- (1-Butyryl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (trifluoro- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- (2-chloro-phenyl) -5- {4- [1- (2-methyl- propionyl) -1,2,3,6-tetrahydropyridin- [Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole;
Phenyl] -3- [di- (trifluoromethoxy) phenyl] -5- [4- (1-pentanoyl-1,2,3,6-tetrahydropyridin-4- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- [1- (3-methyl-butyryl) -1,2,3,6-tetrahydropyridin-4-yl] -phenyl} -3- [ Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -5- {4- [1- (2,2-dimethyl-propionyl) -1,2,3,6-tetrahydropyridin-4- yl] -phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di (trifluoromethyl) phenyl] -5- [4- (1-cyclopentylcarbonyl-1,2,3,6-tetrahydropyridin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (tri (cyclohexylmethyl) -1H-pyrazolo [3,4-d] pyrimidin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- [1- (2-chloro-phenyl) -5- [4- (1- cyclopentyl-acetyl- 1,2,3,6-tetrahydropyridin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- [4- (1-cyclopentyl-propionyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- [1- (2-thiophenecarbonyl) -1,2,3,6-tetrahydropyridin-4-yl] -phenyl} -3- [ Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- [l- (2-Chloro-phenyl) -5- [4- (1-benzoyl- l, 2,3,6- tetrahydropyridin-4- yl) -phenyl] -3- [di- (trifluoromethyl ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethoxy) -phenyl] -5- [4- (1-phenylacetyl-1,2,3,6-tetrahydropyridin- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- [1- (4-chlorobenzoyl) -1,2,3,6-tetrahydropyridin-4-yl] -phenyl} -3- [ (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- [4- (1 -methanesulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (trifluoro- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethoxy) phenyl] -5- [4- (1-ethanesulfonyl-l, 2,3,6-tetrahydropyridin- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
4- [1- (propane-1-sulfonyl) -l, 2,3,6-tetrahydropyridin-4-yl] -phenyl} -3- [ Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -3- [di (2-chloro-phenyl) -5- {4- [ - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -5- {4- [1- (2-methyl-propane-l-sulfonyl) -l, 2,3,6- tetrahydropyridin-4- yl] -phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- [1- (2-Chloro-phenyl) -5- [4- (1- trifluoromethanesulfonyl- 1,2,3,6-tetrahydropyridin- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (tri (2-chloro-phenyl) -5- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- (2-chloro-phenyl) -5- {4- [1- (N, N- dimethylsulfamoyl) -1,2,3,6-tetrahydropyridin-4- yl] -phenyl} -3 - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di (trifluoromethyl) phenyl] -5- [4- (1-cyclopentanesulfonyl-l, 2,3,6-tetrahydropyridin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (tri (methoxymethoxy) -phenyl] -5- [4- (1-cyclohexanesulfonyl-1,2,3,6-tetrahydropyridin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
1 - (2-Chloro-phenyl) -5- {4- [1- (pyrrolidine- 1 -sulfonyl) - 1,2,3,6-tetrahydropyridin-4-yl] -phenyl} -3 - [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3-d] -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-di &lt; RTI ID = 0.0 &gt;Hydro-1H-pyrazole;
Methyl) -4,5-dimethyl-5- (3'-isobutyrylaminobiphenyl-4-yl) Dihydro-lH-pyrazole;
(2-chloro-phenyl) -3- [di- (trifluoromethyl) - (3-methyl- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4, 5-trifluoromethyl-5- (3'-ethanesulfonyl-aminobiphenyl- - dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl) -methyl] -pyridin- ] -4,5-dihydro-lH-pyrazole;
(2-chloro-phenyl) -3- [di- (trifluoromethyl) - (3-methyl- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Methyl] -4, &lt; / RTI &gt;&lt; RTI ID = 0.0 &gt; 5- (3 ' -cyclopropanesulfonyl-aminobiphenyl- 5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5 (trifluoromethyl) -5- (3-methanesulfonyl-aminobiphenyl- - dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-5H-pyrrolo [2,3-d] -LH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-di &lt; RTI ID = 0.0 &gt;Hydro-1H-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- &lt; / RTI &gt;Dihydro-lH-pyrazole;
(2-chloro-phenyl) -3- [di- (trifluoromethyl) - (4-fluoro- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4-tert-butoxycarbonylamino-5- [4 '- (ethanesulfonyl) , 5-dihydro-lH-pyrazole;
(Trifluoromethyl) - &lt; / RTI &gt; hydroxy-methyl &lt; RTI ID = 0.0 &gt; ] -4,5-dihydro-lH-pyrazole;
(2-chloro-phenyl) -3- [di- (trifluoromethyl) - (4-methyl- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt;5-dihydro-lH-pyrazole;
Methyl) -4,5 (trifluoromethyl) -5- (4-methanesulfonyl-aminobiphenyl-4-yl) - dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 &lt; RTI ID = 0.0 & , 5-dihydro-lH-pyrazole;
Yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -piperazin- -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] - &lt; / RTI &-4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl) -piperazin-1- ] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl) -piperazin-1- ] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl) -piperazin-1- ] -4,5-dihydro-lH-pyrazole;
Yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -piperazin-1- -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl) -methanone &lt; / RTI &gt; ] -4,5-dihydro-lH-pyrazole;
L-yl] -phenyl} -3- [di- (trifluoromethyl) -piperazin-l-yl] ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
L-yl] -phenyl} -3- (di- ((2-chloro-phenyl) Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) 4,5-dihydro-lH-pyrazole;
Yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl- [l- ] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl) -pyridin-2-yl] ] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl) Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl] Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-ylmethyl] Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl) -pyridin- ] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl) Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl) Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) - (2-chloro-phenyl) -5- {4- [4- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) 4,5-dihydro-lH-pyrazole hydrochloride;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy- [l- (4-fluoro- -Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5 (trifluoromethyl) - dihydro-lH-pyrazole;
4-yl} -3- [di- (trifluoromethoxy) -phenyl] -5- {3 '- [3- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4-yl} -3- [di- (trifluoromethoxy) -phenyl] -5- {4 '- [3- Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro-lH-pyrazole;
Methyl] - (2-chloro-phenyl) -5- [4- (6-methanesulfonyl-pyridin- 4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro- &lt; / RTI &gt;Dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-fluoro-phenyl) , 5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt;5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (3-ethoxy- 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (3-ethoxy-biphenyl- 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -5- (3-fluoro-3'-methylsulfanyl- -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -5- (3-fluoro-4'-methylsulfanyl- -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -5- (3-fluoro-4'-methanesulfonyl- -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (3-chloro-phenyl) 4,5-dihydro-lH-pyrazole;
Methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-fluoro-phenyl) , 5-dihydro-lH-pyrazole;
4- (l-BOC-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy- &lt; / RTI &gt; -Methyl] -4,5-dihydro-lH-pyrazole;
Methyl] -4, &lt; / RTI &gt;&lt; RTI ID = 0.0 &gt;5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -5- (3-fluoro-3'-methanesulfinyl- -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl-ethyl) -biphenyl-4-yl] Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -5- (3-fluoro-3'-methanesulfonyl- -4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &gt;5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4, &lt; / RTI &gt;5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4, &lt; / RTI &gt;5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4-tert-butoxycarbonylamino- , 5-dihydro-lH-pyrazole;
3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-fluoro-phenyl) , 5-dihydro-lH-pyrazole;
Methyl-4- (2-chloro-phenyl) -5- [6- (4-methoxy- phenyl) -pyridin- , 5-dihydro-lH-pyrazole;
3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) 4,5-dihydro-lH-pyrazole;
3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) 4,5-dihydro-lH-pyrazole;
3- [di- (trifluoromethyl) -hydroxy-methyl] - (4-methoxy-phenyl) -pyridin- 4,5-dihydro-lH-pyrazole;
3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-ylmethyl] -pyridin- Methyl] -4,5-dihydro-lH-pyrazole;
3- [di- (trifluoromethyl) -hydroxy-methyl] -4-tert-butoxycarbonylamino- , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 4-dihydro- , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4- (4-methoxy-phenyl) , 5-dihydro-lH-pyrazole;
3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) 4,5-dihydro-lH-pyrazole;
Methyl-4- (2-chloro-phenyl) -5- [6- (4- fluoro-phenyl) -pyridin- , 5-dihydro-lH-pyrazole;
3-yl] -3- [di- (2-chloro-phenyl) -5- [6- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
3-yl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2- Methyl] -4,5-dihydro-lH-pyrazole;
3-yl] -3- [di- (trifluoromethyl) pyridin-4-yl] ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole hydrochloride;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 (4-fluoro-phenyl) , 5-dihydro-lH-pyrazole hydrochloride;
Yl) -3- [di (2-chloro-phenyl) -5- [6- (1 -methanesulfonyl-l, 2,3,6-tetrahydropyridin- - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
3- (2-chloro-phenyl) -5- [6- (1-cyclopropanesulfonyl-1,2,3,6-tetrahydropyridin- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
3-yl] -3- [di- (trifluoromethyl) -hydro- pyridin-3-yl) Methyl-4, &lt; / RTI &gt;5-dihydro-lH-pyrazole;
3- [di- (trifluoromethyl) - (2-chloro-phenyl) -5- [6- (4- cyclopropanesulfonyl- piperazin- 1 -yl) -pyridin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4-tert-butoxycarbonylamino-5- (3'-acetyl-2-fluoro- , 5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] -4-tert-butoxycarbonylamino-5- (4-acetyl-2-fluoro- , 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-fluoro-phenyl) 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-fluoro-phenyl) 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-fluoro-phenyl) 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-chloro-phenyl) 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (3-ethoxy-2-fluoro-biphenyl- 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (4-ethoxy-2-fluoro-biphenyl- 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -5- (2- fluoro-3'-methylsulfanyl- -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -5- (2- fluoro-4'-methylsulfanyl- -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -5- (2- fluoro-4'-methylsulfonyl- -4,5-dihydro-lH-pyrazole;
Methyl-4, &lt; RTI ID = 0.0 &gt; 2- (2-chloro-phenyl) 5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -5- (2- fluoro-2 ' -isopropoxy- -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy- [l- (3-fluoro- -Methyl] -4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) -hydroxy-methyl] - &lt; / RTI &gt;&lt; RTI ID = 0.0 &4,5-dihydro-lH-pyrazole;
Methyl- [l- (2,4-difluoro-phenyl) -5- (4'-methylsulfanyl- 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (4-methylsulfonyl- 4,5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2- Methyl] -4,5-dihydro-lH-pyrazole;
Methyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 4,5-difluoro-phenyl) - dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2- Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy- &lt; / RTI &gt; -Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -phenyl] -l- (2,4-difluoro-phenyl) -3- [di- (trifluoromethyl) - Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Methyl-pyridin-3-yl) -phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl ] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydro- phenyl) -5- [4- (6-trifluoromethyl-pyridin- Methyl-4, &lt; / RTI &gt;5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydro- phenyl) -5- [4- (5-methoxycarbonyl-pyridin- Methyl-4, &lt; / RTI &gt;5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -5- [4- (5-formyl-6-methoxy-pyridin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
(Trifluoromethyl) - &lt; / RTI &gt; hydroxy- Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2- Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2- Methyl] -4,5-dihydro-lH-pyrazole;
Methyl-pyridin-3-yl) -phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl-lH-pyrrolo [ ] -4,5-dihydro-lH-pyrazole;
Phenyl-3- [di- (trifluoromethyl) -hydroxy-pyridin-3-yl) -pyridin- Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) - 3- [di- (trifluoromethyl) - &lt; / RTI &gt; Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy- &lt; / RTI &gt; -Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl) Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) pyridin-2-ylmethyl] -piperazin-1- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2- Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -phenyl] -3- [di- (trifluoromethyl) pyridin-l-yl] -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Methyl-pyridin-2-yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl-lH-pyrrolo [ ] -4,5-dihydro-lH-pyrazole;
Methyl-pyridin-2-yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl- ] -4,5-dihydro-lH-pyrazole;
Methyl-pyridin-2-yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl ] -4,5-dihydro-lH-pyrazole;
Methyl-pyridin-2-yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl- ] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dimethyl-lH-pyrrolo [ Dihydro-lH-pyrazole;
Yl) -3 - [(2-hydroxy-ethyl) -methyl-sulfamoyl] -biphenyl- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3 - [(2-hydroxy-ethyl) -methyl-sulfamoyl] -biphenyl- Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) - (3-fluoro-4'-methanesulfonyl-biphenyl- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
The title compound was prepared from 1- (2,4-difluoro-phenyl) -5- (3 ', 5'-difluoro-4'-methanesulfonyl- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
The title compound was prepared from 1- (2,4-difluoro-phenyl) -5- (2 ', 5'-difluoro-4'-methanesulfonyl- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
The title compound was prepared from 1- (2,4-difluoro-phenyl) -5- (2 ', 6'-difluoro-4'-methanesulfonyl- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
Methanesulfonyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) - Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-phenyl) -5- [4- (5-methanesulfonyl-pyridin- -Methyl] -4,5-dihydro-lH-pyrazole;
- (2,4-Difluoro-phenyl) -5- (4'-methanesulfonyl-3'-trifluoromethyl-biphenyl-4-yl) -3- [di- (trifluoromethyl ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Methanesulfonyl-2 ' -trifluoromethyl-biphenyl-4-yl) -3- [di- (trifluoromethyl) ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -biphenyl] -4-yl} -3- (4-fluorophenyl) -5- {[2 ', 6'- [Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole;
3-yl] -phenyl} -3- [di- (4-fluoro-phenyl) (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4-yl) - l- (2,4-difluoro-phenyl) -piperidine-l- -3- (di- (trifluoromethyl) -hydroxy-methyl) -4,5-dihydro-lH-pyrazole;
4-yl} - l- (2,4-difluoro-phenyl) - lH-indol-3- -3- (di- (trifluoromethyl) -hydroxy-methyl) -4,5-dihydro-lH-pyrazole;
3- (di- (trifluoromethyl) -hydroxy-methyl) -5- (3'-dimethylsulfamoyl-biphenyl- -4,5-dihydro-lH-pyrazole;
3- (di- (trifluoromethyl) -hydroxy-methyl) -5- (4'-dimethylsulfamoyl-biphenyl- -4,5-dihydro-lH-pyrazole;
Amino] biphenyl-4-yl} -3- (di- (l- (4-fluoro-phenyl) Trifluoromethyl) -hydroxy-methyl) -4,5-dihydro-lH-pyrazole;
- [4- (1-BOC-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [ Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
5- [4- (1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (trifluoromethyl) ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole trifluoroacetic acid salt;
- [4- (1 -methanesulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- [4- (1-Ethanesulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl) -5- {4- [1- (propane-1-sulfonyl) -l, 2,3,6-tetrahydropyridin-4- yl] -phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- (4-fluoro-phenyl) -5- {4- [1- -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
5- [4- (1-Dimethylsulfamoyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
5- [4- (1-cyclopropanesulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
5- [4- (1-cyclopentanesulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- [4- (1-isobutyryl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di - (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
5- [4- (1-Dimethylcarbamoyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4- (1-isobutylsulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [ Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
- [4- (4-BOC-piperazin-l-yl) -phenyl] -3- [di- (trifluoromethyl) -hydroxy- Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 &lt; RTI ID = 0.0 & , 5-dihydro-lH-pyrazole hydrochloride;
Phenyl] -3- [di- (trifluoromethyl) -hydro- phenyl) -5- [4- (4- methanesulfonyl-piperazin- Methyl-4, &lt; / RTI &gt;5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydro- phenyl) -5- [4- (4-ethanesulfonyl-piperazin- Methyl-4, &lt; / RTI &gt;5-dihydro-lH-pyrazole;
1-yl] -phenyl} -3- [di- (trifluoromethoxy) phenyl] -5- {4- [4- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) - (4-methylsulfanyl) -piperazin-1- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) - (4-methylsulfamoyl-piperazin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-phenyl) -5- [4- (4-BOC-homopiperazin- -Methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] - (2-methyl-pyridin- 4,5-dihydro-lH-pyrazole hydrochloride;
Phenyl] -3- [di- (trifluoromethyl) - [4- (4-methanesulfonyl-homopiperazin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) - [4- (4-ethanesulfonyl-homopiperazin- Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl] -phenyl} -3- [di (trifluoromethyl) phenyl] -5- {4- [4- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) pyridin-2-ylmethyl] -1H-pyrazolo [3,4-d] pyrimidin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -5- [4- (4-dimethylsulfamoyl-homopiperazin- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (4-fluoro-phenyl) -5- {3 '- [3- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (4-fluoro-phenyl) -5- {4 '- [3- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] - (3-methanesulfonyl- 4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl] Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl] Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl] Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) pyridin-2-yl] - (4- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Thiophen-2-yl] -3- [di-t-butoxycarbonylamino-l- (Trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Thiophen-2-yl] -3- [di- (trifluoromethoxy) phenyl] -5- [ Methyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole hydrochloride;
5- [5- (1 -methanesulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -thiophen- Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
5- (5- (1-Cyclopropanesulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -thiophen- [Di- (trifluoromethyl) -hydroxy-methyl] -4,5-dihydro-1H-pyrazole;
Yl} -3- [di- (trifluoromethyl) -hydroxy-isoquinolin-2-yl] Methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) pyridin-3-yl] -thiophene- -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dimethoxy- 5-dihydro-lH-pyrazole;
Methyl] -4, &lt; RTI ID = 0.0 &gt; 5- (2-chloro-phenyl) 5-dihydro-lH-pyrazole;
4-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro-lH-pyrazole;
Yl) -phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl) -pyridin- ] -4,5-dihydro-lH-pyrazole;
Boc-1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (trifluoromethyl) ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
4-yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, 5-dihydro-lH-pyrazole;
Yl) -phenyl} -3- [di- (trifluoromethyl) -hydroxy-methyl) -pyridin- ] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 &lt; RTI ID = 0.0 & , 5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy- &lt; / RTI &gt; -Methyl] -4,5-dihydro-lH-pyrazole hydrochloride;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4,5-di (trifluoromethyl) Hydro-1H-pyrazole hydrochloride;
- [4- (1-cyclopropanesulfonyl-l, 2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl) -pyridin-2-yl] ] -4,5-dihydro-lH-pyrazole;
Yl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl) -pyridin-3-yl] ] -4,5-dihydro-lH-pyrazole;
Boc-1,2,3,6-tetrahydropyridin-4-yl) -phenyl] -3- [di- (trifluoromethyl) ) -Hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Yl) -3- [di- (trifluoromethyl) -hydroxy-methyl] -4, &lt; RTI ID = 0.0 &5-dihydro-lH-pyrazole;
Phenyl) -3- [di- (trifluoromethyl) -hydroxy-methyl) -pyridin-3-yl] ] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -4 &lt; RTI ID = 0.0 & , 5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethoxy) phenyl] -1- [3- (1-methylsulfonyl-l, 2,3,6-tetrahydropyridin- Dimethyl-methyl) -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di (trifluoromethyl) phenyl] -1- [3- (1-cyclopropanesulfonyl-l, 2,3,6-tetrahydropyridin- Fluoromethyl) -hydroxy-methyl] -4,5-dihydro-lH-pyrazole;
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl] -piperazin-1- -4,5-dihydro-lH-pyrazole; And
Phenyl] -3- [di- (trifluoromethyl) -hydroxy-methyl) -piperazin-1- ] -4,5-dihydro-lH-pyrazole. delete delete