Abstract:
The present invention provides for novel piperazinylalkylpyrazole derivatives, the preparation method thereof and the selective T-type calcium channel blocking activity thereof. Particularly, it provides a piperazinylalkylpyrazole derivative as represented by the formula set forth below or its pharmaceutically acceptable salts, and its preparation method thereof. 
                                 
The compound of Formula 1 is a novel piperazinylalkylpyrazole derivative, which particulary has T-type Ca 2+  channel blocking effect and thus can be useful as a therapeutic agent for nerve and muscle pain.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to piperazinylalkylpyrazole derivatives, the preparation method thereof and the selective T-type calcium channel blocking activity thereof. 
     2. Background of the Related Art 
     Depending on the response to membrane depolarization, calcium channels are classified into two main classes, high voltage activated (HVA) Ca 2+  channel and low voltage activated channel (LVA), and particularly, LVA Ca 2+  channel is also called as T-type Ca 2+  channel. Ca 2+  channels exist in neurons, heart, vascular smooth muscle and endocrine cells. The rise of concentration of Ca 2+  causes cell death or damage. Therefore, Ca 2+  channels are known to be involved in the contractions of atrium and smooth muscle, secretion of cortisol and dI-aldosterone in adrenal cortex, nerve stimulation and tissue development, etc. Inhibition of T-type Ca 2+  channel has been reported to have a treatment effect on neuropathic pain, high blood pressure and epilepsy. 
     Some well-known T-type Ca 2+  channel blockers are mibefradil (Ro 40-5967, WO 98/49149), flunarizine (Poauwels, P. J. et al.  J. Life. Sci.  1991, 48, 18981), nicardipine (Richard, S. et al.  J. Neurosci. Lett.  1991, 132 (2), 229) and a number of derivatives thereof. However, these drugs showed some undesirable side effects due to its pharmacokinetic interactions with other drugs metabolized by cytochromes P-450 3A4 and 2D6. Therefore, they are no longer in use. So it is very likely that the selective T-type channel blockers will be developed as an effective therapeutic agent for illnesses of neuropathic nerve and heart-related diseases, such as pain, epilepsy and high blood pressure. 
     T-type Ca 2+  channel antagonists such as piperazinylalkylisoxazole group (A. N. Pae et al.  Bioorganic. Med. Chem. Lett.  2004, 12, 3965-3970) and 3,4-dihydroquinazoline derivatives have been recently reported. (Lee et al.  Bioorganic. Med. Chem. Lett.  2004, 14, 3379-3384) 
     Therefore, an object of the present invention is to provide novel piperazinylalkylpyrazole derivatives or pharmaceutically acceptable salts thereof which have the possibility of being developed into a therapeutic agent for pain, high blood pressure, and epilepsy as a selective T-type Ca 2+  channel inhibitor, and the preparation methods thereof. 
     BRIEF DESCRIPTION OF THE INVENTION 
     An object of the present invention is to provide a piperazinylalkylpyrazole derivative or its pharmaceutically acceptable salt, and the preparation method thereof. Particularly, it is to provide the piperazinylalkylpyrazole derivative as represented by Formula 1 as set forth below or its pharmaceutically acceptable salt, and its preparation method thereof. 
                                
wherein, R 1  represents phenyl, X-substituted phenyl (X include nitro, methyl, chloro, methoxy, etc.; the substitution positions are ortho, meta, and para positions; and can be mono-, di-, tri-, tetra- or entirely-substituted), 1,1-diphenylmethyl, X-substituted diphenylmethyl (X represents chloro, methyl; the substitution position can be ortho, meta, and para positions; and mono, di, tri, tetra or all thereof can be substituted);
     R 2  represents hydrogen, methyl or ethyl groups;   R 3  represents methyl, propyl, isobutyl, phenyl, cyclohexyl, substituted phenyl (wherein, the substituents are methyl, chloro, methoxy, etc.), naphthyl, piperidinyl groups;   R 4  represents hydrogen or C 1-6  lower alkyl, preferably methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, 2-furyl, phenyl, X-substituted phenyl(X represents chloro, methyl, cyclohexyl, piperidinyl, chloro groups, the substitution positions can be ortho, meta, and para positions and mono, di, tri, tetra or all thereof can be substituted); and   n represents an integer from 0 to 3.   
     The compound of Formula 1 is a novel piperazinylalkylpyrazole derivative, which particularly has T-type Ca 2+  channel blocking effect and thus can be useful as a therapeutic agent for nerve and muscle pain. As the compound is believed have a treatment effect for epilepsy and high blood pressure, it is expected to replace the addictive pain killers such as morphine. The compound of Formula (I) (R 2 ═H), as represented in Reaction Scheme 1 below, can be produced by reaction between aldehyde compound as represented by Formula 3 and amine compound as represented by Formula 2 with presence of a suitable reducing agent. 
     
       
                 
         
             
             
         
      
     
     The reducing agents that can be used in the reaction represented by Reaction Scheme 1 are metal hydrides such as NaBH 4 , NaBH(OAc) 3 , NaBH 2 (OAc) 2 , NaBH 3 OAc, KBH 4 , KBH(OAc) 3 , or NaBH 3 CN, and it is preferable to use NaBH(OAc) 3 . 
     As reaction solvents, various types of alcohol such as methanol, ethanol or propanol, tetrahydrofuran, chloroform, or alkyl halides such as methylene chloride can be used. 
     
       
                 
         
             
             
         
      
     
     The amine represented in Formula 2 is 1-R 1  substituted-4-(2-aminoethyl)piperazine, and R 1  is the same as defined in Formula 1. These compounds were prepared from 1-R 1  substituted piperazine and N-1-bromoalkylimide, using a standard amine synthetic method called the Gabriel Synthesis (Gibson, M. S.; Bradshaw, R. W.  Angew. Chem. Int. Ed. Engl.  1968, 7, 919). 
     The aldehyde as represented by Formula 3 was prepared by reducing the corresponding esters or oxidizing the corresponding alcohols. In Formula 3, R 3  and R 4  are defined the same as those in Formula 1. 
     In addition, the compound (R 2 =methyl, ethyl) of Formula 1, as shown below in Reaction Scheme 2, can be prepared by using the aldehydes corresponding to the compound of Formula 1 (R 2 ═H) and reducing agents thereof, wherein NaBH(OAc) 3  is the most preferable metal hydride to be used as the reducing agent. 
     
       
                 
         
             
             
         
      
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The preparation method and effects of the compound of the present invention is explained more in detail using the following examples. However, these examples only exemplifies the present invention, and therefore, the scope of the present invention is not limited to the following examples. In addition, the preparation methods of each corresponding piperazinylalkylamine and pyrazole-5-aldehyde are specifically described in the following References of the representative compounds. 
     Reference 1 
     Preparation of 2-[2-(4-phenylpiperazin-1-yl)ethyl]isoindole-1,3-dione 
     4-phenylpiperazine (4.50 g, 27.74 mmol) was dissolved in 30 ml DMF, then K 2 CO 3  (11.50 g, 83.21 mmol) and N-(2-bromoethyl)phthalimide (8.46 g, 33.28 mmol) were added thereto and stirred at about 80° C. The reaction progress and completion were confirmed using TLC (hexane:EtOAc=1:1). Upon completion of the reaction, water was added to the reaction mixture and then was extracted with CH 2 Cl 2 . The organic layer was dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The concentrate was separated by column chromatography (hexane:EtOAc:CH 2 Cl 2 =3:1:2) to obtain the titled compound. 
     Yield: 55.6% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.81 (m, 2H), 7.68 (m, 2H), 7.22 (m, 2H), 6.89 (d, J=7.41 Hz, 2H), 6.81 (t, J=7.23 Hz, 1H), 3.84 (t, J=6.84 Hz, 2H), 3.11 (t, J=4.71 Hz, 4H), 2.67 (m, 6H) 
     Reference 2 
     Preparation of 2-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]propyl}isoindole-1,3-dione 
     Using the same method as in Reference 1, the above-mentioned compound was prepared by reacting 2-{2-[4-(2,3-dimethylphenyl)piperazine and N-(2-bromopropyl)phthalimide. 
     Yield: 93.7% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.86 (m, 2H), 7.72 (m, 2H), 7.06 (m, 1H), 6.88 (d, J=6.4 Hz, 1H), 6.76 (d, J=7.9 Hz, 1H), 3.81 (t, J=6.9 Hz, 2H), 2.73 (m, 4H), 2.51 (t, J=6.9 Hz, 4H), 2.29 (m, 2H), 2.25 (s, 3H), 2.18 (s, 3H), 1.92 (m, 2H) 
     Reference 3 
     Preparation of 2-[4-(2,3-dimethylphenyl)piperazin-1-yl]propylamine 
     2-{2-[4-(2,3-dimethylpropyl)piperazin-1-yl]propyl}isoindole-1,3-dione (3.0 g, 7.95 mmol) prepared in Reference 2 was dissolved in 50 ml EtOH, then H 2 NNH 2 .H 2 O (1.54 ml, 31.80 mmol) was added and stirred at about 70° C. The reaction progress and completion were confirmed using TLC (hexane: EtOAc=1:1). Upon completion of the reaction, while the temperature was kept at room temperature, the resulting solution was filtered to remove insolubles. The solvent was removed by distilling it under reduced pressure, followed by adding water and extracting the aqueous layer with CH 2 Cl 2 . The organic layer was dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure to obtain the title compound. 
     Yield: 44.7% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.05 (t, J=7.8 Hz, 1H), 6.91 (m, 2H), 3.61 (brs, 2H), 2.89 (m, 6H), 2.52 (m, 4H), 2.28 (m, 2H), 2.25 (s, 3H), 2.19 (s, 3H), 1.84 (m, 2H) 
     Reference 4 
     Preparation of 3-formyl-5-methylpyrazole 
     Under nitrogen environment, 3-ethoxycarbonyl-5-methylpyrazole (1.0 g, 4.34 mmol) was dissolved in 15 ml of purified toluene, and DIBAL (8.68 ml, 8.62 mmol) was slowly added and stirred at −78° C. The reaction progress and completion were confirmed using TLC (hexane:EtOAc=6:1). Upon completion of the reaction, MeOH and water were slowly added to the reaction mixture and the resulting mixture was filtered through a celite bed, and the aqueous layer was extracted with EtOAc. The organic layer was dried over anhydrous MgSO 4  , filtered and concentrated under reduced pressure. The concentrate was separated by column chromatography (hexane:EtOAc:CH 2 Cl 2 =3:1:1) to obtain the title compound. 
     Yield: 82.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 9.92 (s, 1H), 6.68 (s, 1H), 2.82 (s, 3H) 
     Reference 5 
     Preparation of 1-tert-butyl-5-iso-butyl-3-formylpyrazole 
     PCC (0.67 g, 3.12 mmol) and silica gel (0.50 g) were grinded together and dispersed in 10 ml of purified CH 2 Cl 2  followed by treatment with ultrasound at 20° C. for 30 minutes. 1-tert-butyl-5-iso-butyl-3-hydroxymethylpyrazole (0.50 g, 2.08 mmol) was dissolved in 10 ml of purified CH 2 Cl 2  and the solution was added thereto and treated with ultrasound for 15 minutes. The reaction progress and completion were confirmed using TLC (hexane:EtOAc=6:1). Upon completion of the reaction, ether was added to the reaction mixture and then the resulting mixture was filtered through a celite bed, and concentrated under reduced pressure. The concentrate was separated by column chromatography (hexane:EtOAc:CH 2 Cl 2 =3:1:1) to obtain the compound of the present invention. 
     Yield: 88.8% 
       1 H NMR (300 MHz, CDCl 3 ) δ 9.86 (s, 1H), 6.79 (s, 1H), 2.51 (d, J=6.6 Hz, 2H), 1.94 (m, 1H), 1.68 (s, 9H), 0.95 (d, J=6.6 Hz, 6H) 
     EXAMPLE 1 
     Preparation of 5-methyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole[Compound 1] 
     4-phenylpiperazin-1-ylethylamine (50 mg, 0.208 mmol) and 5-methylpyrazole-3-carbaldehyde (25.24 mg, 0.104 mmol) were dissolved in 5 ml of purified CH 2 Cl 2 , and then 4 Å Molecular sieve (5 beads) was added thereto and was stirred for 12 hours at room temperature. Then, NaBH(OAc) 3  (66.28 mg, 0.313 mmol) was added thereto and was stirred for 1 hour at room temperature. The reaction progress and completion were confirmed using TLC (CH 2 Cl 2 :MeOH=5:1). Upon completion of the reaction, water was added to the reaction mixture and the aqueous layer was extracted with CH 2 Cl 2 . The organic layer was dried over anhydrous MgSO 4 , filtered and concentrated under reduced pressure. The concentrate was separated by column chromatography (CH 2 Cl 2 :MeOH=10:1) to obtain the titled compound. 
     Yield: 52.2%. 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.27 (m, 2H), 6.82-6.95 (m, 3H), 6.17 (s, 1H), 4.56 (brs, 1H), 4.01 (s, 2H), 3.17 (t, J=4.8 Hz, 4H), 3.03 (t, J=5.8 Hz, 2H), 2.53-2.57 (m, 5H), 2.61 (t, J=4.8 Hz, 4H). 
     The compounds of the following examples were prepared using the same method as in Example 1 from the corresponding piperazinylamines and pyrazolealdehydes. The following Table 1 illustrates the corresponding piperazinylamines and pyrazolealdehydes used in Examples 2 to 106. 
     
       
         
               
               
               
             
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                 Example 
                 piperazinylamine 
                 pyrazole carbaldehyde 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 4-phenylpiperazin-1- 
                 5-methylpyrazole-3-carbaldehyde 
               
               
                   
                 ylethylamine 
               
               
                 2 
                 same as above 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 3 
                 same as above 
                 5-propyl-1-t-butylpyrazole-3-carbaldehyde 
               
               
                 4 
                 same as above 
                 5-propyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 5 
                 same as above 
                 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 6 
                 same as above 
                 2-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 7 
                 same as above 
                 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 8 
                 same as above 
                 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde 
               
               
                 9 
                 same as above 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                 10 
                 same as above 
                 1-t-butyl-5-(4-methylphenyl)pyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 11 
                 same as above 
                 5-(4-chlorophenyl)-1-t-butylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 12 
                 same as above 
                 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 13 
                 same as above 
                 1-phenyl-5-(4-(piperidin-1- 
               
               
                   
                   
                 yl)phenyl)pyrazole-3-carbaldehyde 
               
               
                 14 
                 4-(2,3- 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                   
                 dimethylphenyl)piperazin- 
               
               
                   
                 1-ylethylamine 
               
               
                 15 
                 same as above 
                 5-propyl-1-t-butylpyrazole-3-carbaldehyde 
               
               
                 16 
                 same as above 
                 5-propyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 17 
                 same as above 
                 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 18 
                 same as above 
                 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 19 
                 same as above 
                 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde 
               
               
                 20 
                 same as above 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                 21 
                 same as above 
                 1-t-butyl-5-(4-methylphenyl)pyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 22 
                 same as above 
                 5-(4-chlorophenyl)-1-t-butylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 23 
                 same as above 
                 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 24 
                 same as above 
                 1-phenyl-5-(4-(piperidin-1- 
               
               
                   
                   
                 yl)phenyl)pyrazole-3-carbaldehyde 
               
               
                 25 
                 4-(2,4- 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                   
                 dimethylphenyl)piperazin- 
               
               
                   
                 1-ylethylamine 
               
               
                 26 
                 same as above 
                 5-propyl-1-t-butylpyrazole-3-carbaldehyde 
               
               
                 27 
                 same as above 
                 5-propyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 28 
                 same as above 
                 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 29 
                 same as above 
                 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 30 
                 same as above 
                 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde 
               
               
                 31 
                 same as above 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                 32 
                 same as above 
                 1-t-butyl-5-(4-methylphenyl)pyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 33 
                 same as above 
                 5-(4-chlorophenyl)-1-t-butylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 34 
                 same as above 
                 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 35 
                 same as above 
                 1-phenyl-5-(4-(piperidin-1- 
               
               
                   
                   
                 yl)phenyl)pyrazole-3-carbaldehyde 
               
               
                 36 
                 4-(4- 
                 5-methylpyrazole-3-carbaldehyde 
               
               
                   
                 methoxyphenyl)piperazin- 
               
               
                   
                 1-ylethylamine 
               
               
                 37 
                 same as above 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 38 
                 same as above 
                 5-propyl-1-t-butylpyrazole-3-carbaldehyde 
               
               
                 39 
                 same as above 
                 5-propyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 40 
                 same as above 
                 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 41 
                 same as above 
                 2-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 42 
                 same as above 
                 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 43 
                 same as above 
                 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde 
               
               
                 44 
                 same as above 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                 45 
                 same as above 
                 1-t-butyl-5-(4-methylphenyl)pyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 46 
                 same as above 
                 5-(4-chlorophenyl)-1-t-butylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 47 
                 same as above 
                 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 48 
                 same as above 
                 1-phenyl-5-(4-(piperidin-1- 
               
               
                   
                   
                 yl)phenyl)pyrazole-3-carbaldehyde 
               
               
                 49 
                 4-(4-nitrophenyl)piperazin- 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                   
                 1-yl ethylamine 
               
               
                 50 
                 same as above 
                 5-propyl-1-t-butylpyrazole-3-carbaldehyde 
               
               
                 51 
                 same as above 
                 5-propyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 52 
                 same as above 
                 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 53 
                 same as above 
                 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 54 
                 same as above 
                 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde 
               
               
                 55 
                 same as above 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                 56 
                 same as above 
                 1-t-butyl-5-(4-methylphenyl)pyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 57 
                 same as above 
                 5-(4-chlorophenyl)-1-t-butylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 58 
                 same as above 
                 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 59 
                 same as above 
                 1-phenyl-5-(4-(piperidin-1- 
               
               
                   
                   
                 yl)phenyl)pyrazole-3-carbaldehyde 
               
               
                 60 
                 4-(2- 
                 5-methylpyrazole-3-carbaldehyde 
               
               
                   
                 fluorophenyl)piperazin-1- 
               
               
                   
                 ylethylamine 
               
               
                 61 
                 same as above 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 62 
                 same as above 
                 5-propyl-1-t-butylpyrazole-3-carbaldehyde 
               
               
                 63 
                 same as above 
                 5-propyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 64 
                 same as above 
                 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 65 
                 same as above 
                 2-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 66 
                 same as above 
                 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 67 
                 same as above 
                 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde 
               
               
                 68 
                 same as above 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                 69 
                 same as above 
                 1-t-butyl-5-(4-methylphenyl)pyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 70 
                 same as above 
                 5-(4-chlorophenyl)-1-t-butylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 71 
                 same as above 
                 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 72 
                 same as above 
                 1-phenyl-5-(4-(piperidin-1- 
               
               
                   
                   
                 yl)phenyl)pyrazole-3-carbaldehyde 
               
               
                 73 
                 4-(3- 
                 5-methylpyrazole-3-carbaldehyde 
               
               
                   
                 chlorophenyl)piperazin-1- 
               
               
                   
                 ylethylamine 
               
               
                 74 
                 same as above 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 75 
                 same as above 
                 5-propyl-1-t-butylpyrazole-3-carbaldehyde 
               
               
                 76 
                 same as above 
                 5-propyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 77 
                 same as above 
                 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 78 
                 same as above 
                 2-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 79 
                 same as above 
                 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 80 
                 same as above 
                 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde 
               
               
                 81 
                 4- 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                   
                 diphenylmethylpiperazin- 
               
               
                   
                 1-ylethylamine 
               
               
                 82 
                 same as above 
                 5-propyl-1-t-butylpyrazole-3-carbaldehyde 
               
               
                 83 
                 same as above 
                 5-propyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 84 
                 same as above 
                 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 85 
                 same as above 
                 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 86 
                 same as above 
                 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde 
               
               
                 87 
                 same as above 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                 88 
                 same as above 
                 1-t-butyl-5-(4-methylphenyl)pyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 89 
                 same as above 
                 5-(4-chlorophenyl)-1-t-butylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 90 
                 same as above 
                 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 91 
                 same as above 
                 1-phenyl-5-(4-(piperidin-1- 
               
               
                   
                   
                 yl)phenyl)pyrazole-3-carbaldehyde 
               
               
                 92 
                 4-(4- 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                   
                 chlorobenzhydril)piperazin- 
               
               
                   
                 1-ylethylamine 
               
               
                 93 
                 same as above 
                 5-propyl-1-t-butylpyrazole-3-carbaldehyde 
               
               
                 94 
                 same as above 
                 5-propyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 95 
                 same as above 
                 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde 
               
               
                 96 
                 same as above 
                 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                 97 
                 same as above 
                 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde 
               
               
                 98 
                 same as above 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                 99 
                 same as above 
                 1-t-butyl-5-(4-methylphenyl)pyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 100 
                 same as above 
                 5-(4-chlorophenyl)-1-t-butylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 101 
                 same as above 
                 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3- 
               
               
                   
                   
                 carbaldehyde 
               
               
                 102 
                 same as above 
                 1-phenyl-5-(4-(piperidin-1- 
               
               
                   
                   
                 yl)phenyl)pyrazole-3-carbaldehyde 
               
               
                 103 
                 4-(2,3- 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                   
                 dimethylphenyl)piperazin- 
               
               
                   
                 1-ylpropylamine 
               
               
                 104 
                 ? 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                 105 
                 4- 
                 5-methyl-1-phenylpyrazole-3-carbaldehyde 
               
               
                   
                 diphenylmethylpiperazin- 
               
               
                   
                 1-ylpropylamine 
               
               
                 106 
                 same as above 
                 1,5-diphenylpyrazole-3-carbaldehyde 
               
               
                   
               
             
          
         
       
     
     EXAMPLE 2 
     Synthesis of 5-methyl-1-phenyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 2] 
     Compound 2 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 46.9% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.36-7.56 (m, 5H), 7.25 (m, 2H), 6.78-6.89 (m, 3H), 6.30 (s, 1H), 4.30 (brs, 1H), 4.10 (s, 2H), 2.91-3.23 (m, 12H), 2.74 (m, 3H) 
     EXAMPLE 3 
     Synthesis of 1-t-butyl-5-propyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 3] 
     Compound 3 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 5-propyl-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 64.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.27 (t, J=7.7 Hz, 2H), 6.93 (d, J=8.1 Hz, 2H), 6.86 (t, J=7.2 Hz, 1H), 6.04 (s, 1H), 3.98 (s, 2H), 3.20 (m, 4H), 2.84 (t, J=5.7 Hz, 2H), 2.58-2.70 (m, 6H), 2.54 (t, J=7.7 Hz, 2H), 1.56-1.77 (m, 11H), 0.96 (t, J=7.2 Hz, 3H) 
     EXAMPLE 4 
     Synthesis of 5-propyl-1-phenyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 4] 
     Compound 4 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 5-propyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 55.6% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.33-7.52 (m, 6H), 7.26 (m, 2H), 6.88 (m, 2H), 6.35 (s, 1H), 3.91 (s, 2H), 3.20 (m, 4H), 2.87 (m, 2H), 2.71 (m, 4H), 2.54-2.67 (m, 4H), 1.62 (m, 2H), 0.93 (t, J=7.3 Hz, 3H) 
     EXAMPLE 5 
     Synthesis of 1-t-butyl-5-iso-butyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 5] 
     Compound 5 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 25.8% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.27 (t, J=8.0 Hz, 2H), 6.93 (m, 2H), 6.86 (t, J=7.2 Hz, 1H), 6.00 (s, 1H), 3.95 (s, 2H), 3.19 (m, 4H), 2.81 (t, J=5.7 Hz, 2H), 2.54-2.69 (m, 6H), 2.42 (m, 2H), 1.88 (m, 1H), 1.62 (s, 9H), 0.92 (d, J=6.6 Hz, 6H) 
     EXAMPLE 6 
     Synthesis of 2-t-butyl-5-isobutyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 6] 
     Compound 6 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 2-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 50.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.28 (t, J=7.6 Hz, 2H), 6.93 (m, 2H), 6.87 (t, J=7.1 Hz, 1H), 6.01 (s, 1H), 3.96 (s, 2H), 3.20 (m, 4H), 2.81 (t, J=5.6 Hz, 2H), 2.55-2.69 (m, 6H), 2.44 (d, J=7.1 Hz, 2H), 1.90 (m, 1H), 1.63 (s, 9H), 0.94 (d, J=6.5 Hz, 6H) 
     EXAMPLE 7 
     Synthesis of 5-iso-butyl-1-phenyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 7] 
     Compound 7 was prepared using the same method as used in Example 1 except that 4-phenylpiperazin-1-ylethylamine and 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 56.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.24-7.44 (m, 5H), 7.16 (m, 2H), 6.79 (m, 3H), 6.10 (s, 1H), 3.81 (s, 2H), 3.09 (m, 4H), 2.77 (t, J=5.6 Hz, 2H), 2.46-2.64 (m, 6H), 2.43 (d, J=7.0 Hz, 2H), 1.75 (m, 1H), 0.79 (d, J=6.3 Hz, 6H) 
     EXAMPLE 8 
     Synthesis of 5-(furan-2-yl)-1-phenyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 8] 
     Compound 8 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde were used. 
     Yield: 69.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.34-7.59 (m, 6H), 7.23 (m, 2H), 6.78-6.97 (m, 3H), 6.75 (m, 1H), 6.32 (s, 1H), 6.98 (s, 1H), 3.96 (s, 2H), 3.27 (m, 4H), 3.06 (m, 2H), 2.91 (m, 4H), 2.82 (m, 2H) 
     EXAMPLE 9 
     Synthesis of 1,5-diphenyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 9] 
     Compound 9 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 78.8% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.28-7.38 (m, 9H), 7.18-7.26 (m, 3H), 6.81-6.91 (m, 3H), 6.60 (s, 1H), 4.23 (brs, 1H), 4.08 (s, 2H), 3.15 (t, J=4.6 Hz, 4H), 3.01 (t, J=5.9 Hz, 2H), 2.70 (t, J=5.9 Hz, 2H), 2.63 (t, J=4.6 Hz, 4H) 
     EXAMPLE 10 
     Synthesis of 1-t-butyl-5-(4-methylphenyl)-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 10] 
     Compound 10 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 1-t-butyl-5-(4-methylphenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 80.0% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.13-7.33 (m, 6H), 6.87 (m, 3H), 6.30 and 6.15 (s, 1H), 4.98 (brs, 1H), 4.24 and 3.95 (s, 2H), 3.27 (m, 2H), 3.17 (m, 4H), 2.91 (m, 4H), 2.66 (m, 2H), 2.39 (s, 3H), 1.41 (s, 9H) 
     EXAMPLE 11 
     Synthesis of 1-t-butyl-5-(4-chlorophenyl)-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 11] 
     Compound 11 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 5-(4-chlorophenyl)-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 69.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.15-7.47 (m, 6H), 6.85 (m, 3H), 6.40 and 6.17 (s, 1H), 4.90 (brs, 1H), 4.24 and 3.99 (s, 2H), 2.51-3.38 (m, 12H), 1.41 (s, 9H) 
     EXAMPLE 12 
     Synthesis of 5-(4-cyclohexylphenyl)-1-phenyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethylpyrazole [Compound 12] 
     Compound 12 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 71.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.19-7.40 (m, 7H), 7.06-7.19 (m, 4H), 6.81-7.13 (m, 3H), 6.63 and 6.52 (s, 1H), 4.60 (brs, 1H), 4.17 and 3.91 (s, 2H), 3.04-3.24 (m, 6H), 2.54-2.87 (m, 6H), 2.48 (m, 1H), 1.78 (m, 4H), 1.14-1.49(m, 6H) 
     EXAMPLE 13 
     Synthesis of 1-phenyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]aminomethyl-5-(4-piperidin-1-yl)phenylpyrazole [Compound 13] 
     Compound 13 was prepared using the same method as that of Example 1 except that 4-phenylpiperazin-1-ylethylamine and 1-phenyl-5-(4-(piperidine-1-yl)phenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 58.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.16-7.39 (m, 7H), 7.07 (t, J=7.3 Hz, 2H), 6.74-6.91 (m, 5H), 6.53 and 6.42 (s, 1H), 3.69 and 3.57 (s, 2H), 3.04-3.33 (m, 10H), 2.85 (m, 4H), 2.65 (m, 2H), 1.68 (m, 4H), 1.60 (m, 2H) 
     EXAMPLE 14 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}aminomethyl-5-methyl-1-phenylpyrazole [Compound 14] 
     Compound 14 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 85.6% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.32-7.53 (m, 5H), 7.06 (t, J=7.6 Hz, 1H), 6.90 (d, J=7.2 Hz, 1H), 6.84 (d, J=7.9 Hz, 1H), 6.35 and 6.32 (s, 1H), 4.06 (s, 1H), 3.00 (t, J=5.9 Hz, 2H), 2.89-2.95 (m, 6H), 2.73 (t, J=6.0 Hz, 4H), 2.64 (m, 3H), 2.41 (s, 3H), 2.20 (s, 3H) 
     EXAMPLE 15 
     Synthesis of 1-t-butyl-3-{2-[4-(2,3-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-5-propylpyrazole [Compound 15] 
     Compound 15 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 5-propyl-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 90.7% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.10 (t, J=7.7 Hz, 1H), 6.93 (m, 2H), 6.07 (s, 1H), 3.97 (s, 1H), 2.91 (m, 4H), 2.84 (t, J=5.8 Hz, 2H), 2.58-2.71 (m, 6H), 2.56 (t, J=7.8 Hz, 2H), 2.29 (s, 3H), 2.24 (s, 3H), 1.56-1.72 (m, 11H), 0.99 (t, J=7.3 Hz, 3H) 
     EXAMPLE 16 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-propylpyrazole [Compound 16] 
     Compound 16 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 5-propyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 69.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.32-7.54 (m, 5H), 7.05 (t, J=7.6 Hz, 1H), 6.89 (d, J=7.2 Hz, 1H), 6.81 (d, J=7.9 Hz, 1H), 6.36 (s, 1H), 4.46 (brs, 1H), 4.08 (s, 2H), 3.02 (t, J=5.9 Hz, 2H), 2.83 (m, 4H), 2.74 (t, J=5.9 Hz, 4H), 2.48-2.69 (m, 6H), 2.26 (s, 3H), 2.22 (s, 3H), 1.62 (m, 2H), 0.92 (t, J=7.3 Hz, 3H) 
     EXAMPLE 17 
     Synthesis of 1-t-butyl-5-iso-butyl-3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 17] 
     Compound 17 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 90.8% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.10 (t, J=7.7 Hz, 1H), 6.92 (m, 2H), 6.03 (s, 1H), 3.97 (s, 2H), 2.92 (t, J=4.6 Hz, 4H), 2.83 (t, J=5.9 Hz, 2H), 2.56-2.72 (m, 6H), 2.45 (d, J=7.1 Hz, 2H), 2.29 (s, 3H), 2.24 (s, 3H), 1.89 (m, 1H), 1.65 (s, 9H), 0.95 (d, J=6.6 Hz, 6H) 
     EXAMPLE 18 
     Synthesis of 5-iso-butyl-3-{2-[4-(2,3-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 18] 
     Compound 18 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 96.5% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.33-7.52 (m, 5H), 7.06 (t, J=7.7 Hz, 1H), 6.90 (d, J=7.3 Hz, 1H), 6.85 (d, J=7.9 Hz, 1H), 6.28 (s, 1H), 4.01 (s, 2H), 2.95 (t, J=6.0 Hz, 2H), 2.86 (t, J=4.5 Hz, 4H), 2.69 (t, J=6.0 Hz, 2H), 2.62 (m, 4H), 2.51 (d, J=7.1 Hz, 2H), 2.27 (s, 3H), 2.22 (s, 3H), 1.83 (m, 1H), 0.87 (d, J=6.6 Hz, 6H) 
     EXAMPLE 19 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}aminomethyl-5-(furan-2-yl)-1-phenylpyrazole [Compound 19] 
     Compound 19 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde were used. 
     Yield: 77.9% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.36-7.52 (m, 6H), 7.07 (t, J=7.7 Hz, 1H), 6.88 (m, 2H), 6.72 and 6.65 (s, 1H), 6.33 (m, 1H), 5.97 (d, J=3.2 Hz, 1H), 3.94 and 3.82 (s, 2H) 3.38 (brs, 1H), 2.95 (t, J=6.1 Hz, 2H), 2.87 (t, J=4.3 Hz, 4H), 2.53-2.75 (m, 6H), 2.27 (s, 3H), 2.21 (s, 3H) 
     EXAMPLE 20 
     Synthesis of 3-{2-[4-(2,3-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-1,5-diphenylpyrazole [Compound 20] 
     Compound 20 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 72.9% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.19-7.37 (m, 10H), 7.05 (t, J=7.7 Hz, 1H), 6.90 (d, J=7.3 Hz, 1H), 6.80 (d, J=7.9 Hz, 1H), 6.68 (s, 1H), 4.16 (s, 2H), 3.08 (t, J=5.9 Hz, 2H), 2.85 (t, J=4.3 Hz, 4H), 2.77 (t, J=5.9 Hz, 2H), 2.66 (m, 4H) 
     EXAMPLE 21 
     Synthesis of 1-t-butyl-3-{2-[4-(2,3-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-5-(4-methyl)phenylpyrazole [Compound 21] 
     Compound 21 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 1-t-butyl-5-(4-methylphenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 71.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.14-7.25 (m, 5H), 7.07 (t, J=7.8 Hz, 1H), 6.90 (m, 2H), 6.18 and 6.06 (s, 1H), 4.59 (brs, 1H), 4.06 and 3.76 (s, 2H), 3.07 (t, J=5.8 Hz, 2H), 2.89 (m, 4H), 2.77 (t, J=5.8 Hz, 2H), 2.66 (m, 4H), 2.41 (s, 3H), 2.27 (s, 3H), 2.22 (s, 3H), 1.44 (s, 9H) 
     EXAMPLE 22 
     Synthesis of 1-t-butyl-3-{2-[4-(2,3-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-5-(4-chlorophenyl)pyrazole [Compound 22] 
     Compound 22 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 5-(4-chlorophenyl)-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 77.8% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.35 (m, 2H), 7.27 (m, 2H), 7.08 (t, J=7.7 Hz, 1H), 6.89 (m, 2H), 6.36 (brs, 1H), 6.23 (s, 1H), 4.12 (s, 2H), 3.11 (m, 2H), 2.89 (m, 4H), 2.81 (m, 2H), 2.67 (m, 4H), 2.27(s, 3H), 2.21 (s, 3H), 1.43 (s, 9H) 
     EXAMPLE 23 
     Synthesis of 5-(4-cyclohexyl)phenyl-3-{2-[4-(2,3-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 23] 
     Compound 23 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 5-(4-cyclohexyl phenyl)-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 92.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.26-7.38 (m, 5H), 7.02-7.17 (m, 4H), 6.91 (m, 2H), 6.83 (d, J=7.9 Hz, 1H), 6.55 and 6.34 (s, 1H), 5.04 (brs, 2H), 4.07 and 3.97 (s, 2H), 2.94 (t, J=4.6 Hz, 2H), 2.85 (t, J=4.3 Hz, 2H), 2.55-2.82 (m, 8H), 2.49 (m, 1H), 2.27 (m, 3H), 2.20 (m, 3H), 1.68-1.95 (m, 6H), 1.40 (m, 4H) 
     EXAMPLE 24 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-(4-piperidin-1-yl)phenylpyrazole [Compound 24] 
     Compound 24 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylethylamine and 1-phenyl-5-(4-(piperidin-1-yl)phenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 65.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.29-7.38 (m, 5H), 7.01-7.13 (m, 4H), 6.91 (t, J=8.1 Hz, 1H), 6.81 (m, 2H), 6.51 (s, 1H), 4.08 (s, 2H), 3.19 (t, J=5.2 Hz, 4H), 3.03 (t, J=5.9 Hz, 2H), 2.83 (m, 4H), 2.73 (t, J=5.9 Hz, 2H), 2.64 (m, 4H), 2.26 (s, 3H), 2.19 (s, 3H), 1.65-1.77 (m, 6H) 
     EXAMPLE 25 
     Synthesis of 3-{2-[4-(2,4-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-5-methyl-1-phenylpyrazole [Compound 25] 
     Compound 25 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 39.3% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.32-7.58 (m, 5H), 6.91-7.04 (m, 3H), 6.21 (s, 1H), 3.85 (s, 2H), 2.89 (m, 4H), 2.74 (t, J=5.6 Hz, 2H), 2.48-2.66 (m, 6H), 2.34 (s, 3H), 2.27 (s, 6H) 
     EXAMPLE 26 
     Synthesis of 1-t-butyl-3-{2-[4-(2,4-dimethylphenyl)piperazin-1-yl]ethyl}aminomethyl-5-propylpyrazole [Compound 26] 
     Compound 26 was obtained using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 5-propyl-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 79.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 6.89-7.05 (m, 3H), 6.06 (s, 1H), 3.97 (s, 2H), 2.91 (t, J=4.2 Hz, 4H), 2.83 (t, J=5.9 Hz, 2H), 2.48-2.67 (m, 6H), 2.28 (s, 6H), 1.64 (s, 9H), 0.98 (t, J=7.3 Hz, 3H) 
     EXAMPLE 27 
     Synthesis of 3-{2-[4-(2,4-dimethylphenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-propylpyrazole [Compound 27] 
     Compound 27 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 5-propyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 73.6% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.33-7.52 (m, 5H), 6.82-7.02 (m, 3H), 6.40 and 6.29 (s, 1H), 4.27 (brs, 1H), 4.18 and 3.89 (s, 2H), 2.64-3.15 (m, 12H), 2.59 (m, 2H), 2.26 (s, 3H), 2.22 (s, 3H), 1.61 (m, 1H), 0.91 (m, 3H) 
     EXAMPLE 28 
     Synthesis of 1-t-butyl-5-iso-butyl-3-{2-[4-(2,4-dimethylphenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 28] 
     Compound 28 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 98.7% 
       1 H NMR (300 MHz, CDCl 3 ) δ 6.91-7.04 (m, 3H), 6.03 (s, 1H), 3.97 (s, 2H), 2.91 (m, 4H), 2.83 (t, J=5.8 Hz, 2H), 2.55-2.71 (m, 6H), 2.45 (d, J=7.1 Hz, 2H), 2.29 (s, 6H), 1.91 (m, 1H), 1.64 (s, 9H), 0.94 (d, J=9.5 Hz, 6H) 
     EXAMPLE 29 
     Synthesis of 5-iso-butyl-3-{2-[4-(2,4-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 29] 
     Compound 29 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 69.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.31-7.52 (m, 5H), 6.86-7.02 (m, 3H), 6.39 and 6.27 (s, 1H), 4.39 (brs, 1H), 4.19 and 3.90 (s, 2H), 3.09 (m, 2H), 2.66-3.02 (m, 8H), 2.62 (m, 2H), 2.50 (m, 2H), 2.26 (s, 3H), 2.21 (s, 3H), 1.80 (m, 1H), 0.85 (m, 6H) 
     EXAMPLE 30 
     Synthesis of 3-{2-[4-(2,4-dimethylphenyl)piperazin-1-yl]ethyl}aminomethyl-5-(furan-2-yl)-1-phenylpyrazole [Compound 30] 
     Compound 30 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde were used. 
     Yield: 92.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.28-7.51 (m, 6H), 6.90 (m, 3H), 6.76 (s, 1H), 6.30 (m, 1H), 5.97 (d, J=2.9 Hz, 1H), 4.99 (brs, 1H), 3.93 (s, 2H), 2.55-3.42 (m, 12H), 2.25 (s, 3H), 2.18 (s, 3H) 
     EXAMPLE 31 
     Synthesis of 3-{2-[4-(2,4-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-1,5-diphenylpyrazole [Compound 31] 
     Compound 31 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 89.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.27-7.38 (m, 8H), 7.23 (m, 2H), 6.97 (t, J=8.3 Hz, 2H), 6.86 (d, J=8.0 Hz, 1H), 6.60 (s, 1H), 4.30 (brs, 1H), 4.07 (s, 2H), 3.00 (t, J=5.9 Hz, 2H), 2.87 (m, 4H), 2.71 (t, J=5.9 Hz, 2H), 2.64 9m, 4H), 2.28 (s, 3H), 2.26 (s, 3H) 
     EXAMPLE 32 
     Synthesis of 1-t-butyl-3-{2-[4-(2,4-dimethyl phenyl)piperazin-1-yl]ethyl}aminomethyl-5-(4-methyl)phenylpyrazole [Compound 32] 
     Compound 32 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 1-t-butyl-5-(4-methylphenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 67.0% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.12-7.24 (m, 4H), 6.86-7.03 (m, 3H), 6.25 and 6.10 (s, 1H), 4.75 (brs, 1H), 4.15 and 3.86 (s, 2H), 3.13 (t, J=5.8 Hz, 2H), 2.89 (m, 4H), 2.82 (t, J=5.8 Hz, 2H), 2.65 (m, 4H), 2.42 (s, 3H), 2.27 (s, 3H), 2.25 (s, 3H), 1.43 (s, 9H) 
     EXAMPLE 33 
     Synthesis of 1-t-butyl-5-(4-chlorophenyl)-3-{2-[4-(2,4-dimethylphenyl)piperazin-1-yl]-ethyl}aminomethylpyrazole [Compound 33] 
     Compound 33 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 5-(4-chlorophenyl)-1-t-butyl pyrazole-3-carbaldehyde were used. 
     Yield: 60.3% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.19-7.43 (m, 4H), 6.85-7.05 (m, 3H), 6.30 and 6.12 (s, 1H), 5.42 (brs, 1H), 4.13 and 3.84 (s, 2H), 2.54-3.18 (m, 12H), 2.26 (m, 6H), 1.42 (s, 9H) 
     EXAMPLE 34 
     Synthesis of 5-(4-cyclohexyl phenyl)-3-{2-[4-(2,4-dimethylphenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 34] 
     Compound 34 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 5-(4-cyclohexyl phenyl)-1-phenyl pyrazole-3-carbaldehyde were used. 
     Yield: 52.8% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.19-7.37 (m, 5H), 7.03-7.17 (m, 4H), 6.84-7.01 (m, 3H), 6.61 (s, 1H), 5.4 (brs, 1H), 3.93 (s, 2H), 2.68-3.26 (m, 12H), 2.46 (m, 1H), 2.21 (m, 6H), 1.66-1.95 (m, 6H), 1.37 (m, 4H) 
     EXAMPLE 35 
     Synthesis of 3-{2-[4-(2,4-dimethylphenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-(4-piperidin-1-yl)phenylpyrazole [Compound 35] 
     Compound 35 was prepared using the same method as that of Example 1 except that 4-(2,4-dimethylphenyl)piperazin-1-ylethylamine and 1-phenyl-5-(4-(piperidin-1-yl)phenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 56.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.24-7.38 (m, 3H), 7.02-7.13 (m, 3H), 6.87-7.01 (m, 3H), 6.74-6.86 (m, 3H), 6.55 and 6.47 (s, 1H), 4.63 (brs, 1H), 4.13 and 3.91 (s, 2H), 3.18 (m, 4H), 3.05 (m, 2H), 2.83 (m, 4H), 2.76 (m, 2H), 2.63 (m, 4H), 2.27 (s, 3H), 2.24 (s, 3H), 1.54-1.75 (m, 6H) 
     EXAMPLE 36 
     Synthesis of 3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethyl-5-methylpyrazole [Compound 36] 
     Compound 36 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 5-methylpyrazole-3-carbaldehyde were used. 
     Yield: 30.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 6.76-6.97 (m, 4H), 6.17 (s, 1H), 4.86 (brs, 1H), 3.97 (s, 2H), 3.75 (s, 3H), 2.91-3.15 (m, 6H), 2.55-2.81 (m, 9H) 
     EXAMPLE 37 
     Synthesis of 3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethyl-5-methyl-1-phenylpyrazole [Compound 37] 
     Compound 37 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 22.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.53 (d, J=7.2 Hz, 2H), 7.45 (t, J=7.5 Hz, 2H), 7.37 (d, J=7.3 Hz, 1H), 6.83-6.92 (m, 4H), 6.20 (s, 1H), 3.85 (s, 2H), 3.78 (s, 3H), 3.07 (t, J=4.7 Hz, 4H), 2.73 (t, J=5.9 Hz, 2H), 2.52-2.60 (m, 6H), 2.33 (s, 3H) 
     EXAMPLE 38 
     Synthesis of 1-t-butyl-3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethyl-5-propylpyrazole [Compound 38] 
     Compound 38 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 5-propyl-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 34.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 6.83-6.92 (m, 4H), 6.04 (s, 1H), 3.96 (s, 2H), 3.77 (s, 3H), 3.09 (m, 4H), 2.82 (t, J=5.6 Hz, 2H), 2.52-2.62 (m, 6H), 2.45 (m, 2H), 1.41-1.68 (m, 11H), 0.95 (t, J=7.3 Hz, 3H) 
     EXAMPLE 39 
     Synthesis of 3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethyl-5-propyl-1-phenylpyrazole [Compound 39] 
     Compound 39 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 5-propyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 41.3% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.39-7.46 (m, 5H), 6.82-6.85 (m, 4H), 6.24 (s, 1H), 3.04 (m, 4H), 2.91 (t, J=5.6 Hz, 2H), 2.57-2.77 (m, 8H), 1.60 (m, 2H), 0.92 (t, J=7.3 Hz, 3H) 
     EXAMPLE 40 
     Synthesis of 1-t-butyl-5-iso-butyl-3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 40] 
     Compound 40 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 35.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 6.55-6.59 (m, 4H), 6.17 (s, 1H), 3.96 (s, 2H), 3.76 (s, 3H), 2.91-3.16 (m, 6H), 2.52-2.78 (m, 8H), 1.98 (m, 1H), 1.60 (s, 9H), 0.98 (d, J=6.3 Hz, 6H) 
     EXAMPLE 41 
     Synthesis of 2-t-butyl-5-iso-butyl-3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 41] 
     Compound 41 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 2-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 29.7% 
       1 H NMR (300 MHz, CDCl 3 ) δ 6.75-6.92 (m, 4H), 6.01 (s, 1H), 3.96 (s, 2H), 3.77 (s, 3H), 3.09 (t, J=4.6 Hz, 4H), 2.81 (t, J=5.8 Hz, 2H), 2.57-2.68 (m, 6H), 2.43 (d, J=7.1 Hz, 2H), 1.89 (m, 1H), 1.62 (s, 9H), 0.93 (d, J=6.6 Hz, 6H) 
     EXAMPLE 42 
     Synthesis of 5-iso-butyl-3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl pyrazole [Compound 42] 
     Compound 42 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 24.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.30-7.55 (m, 5H), 6.69-6.94 (m, 4H), 6.24 (s, 1H), 3.97 (s, 2H), 3.76 (s, 3H), 3.03 (m, 4H), 2.92 (m, 2H), 2.56-2.77 (m, 6H), 2.50 (d, J=6.9 Hz, 2H), 1.82 (m, 1H), 0.86 (d, J=6.3 Hz, 6H) 
     EXAMPLE 43 
     Synthesis of 5-(furan-2-yl)-3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl pyrazole [Compound 43] 
     Compound 43 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde were used. 
     Yield: 74.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.21-7.53 (m, 6H), 6.74-6.91 (m, 4H), 6.72 (s, 1H), 6.30 (m, 1H), 5.95 (m, 1H), 3.99 (s, 2H), 3.82 (s, 3H), 3.71 (m, 4H), 3.11 (m, 4H), 2.85 (m, 2H), 2.76 (m, 2H) 
     EXAMPLE 44 
     Synthesis of 3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethyl-1,5-phenylpyrazole [Compound 44] 
     Compound 44 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 47.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.25-7.37 (m, 8H), 7.23 (m, 2H), 6.78-6.87 (m, 4H), 6.60 (s, 1H), 4.09 (s, 2H), 3.77 (s, 3H), 3.01 (m, 6H), 2.70 (t, J=5.8 Hz, 2H), 2.63 (m, 4H) 
     EXAMPLE 45 
     Synthesis of 1-t-butyl-5-(4-methylphenyl)-3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 45] 
     Compound 45 was prepared using the same method as that Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 1-t-butyl-5-(4-methylphenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 95.9% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.04-7.25 (m, 4H), 6.72-6.94 (m, 4H), 6.45 (s, 1H), 4.07 (s, 2H), 3.69 (s, 3H), 2.53-3.55 (m, 12H), 2.39 (s, 3H), 1.42 (s, 9H) 
     EXAMPLE 46 
     Synthesis of 1-t-butyl-5-(4-chlorophenyl)-3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 46] 
     Compound 46 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 5-(4-chlorophenyl)-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 86.0% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.14-7.43 (m, 4H), 6.69-6.94 (m, 4H), 6.14 and 6.06 (s, 1H), 4.20 and 4.07 (s, 2H), 3.74 (s, 3H), 2.45-3.42 (m, 12H), 1.40 (s, 9H) 
     EXAMPLE 47 
     Synthesis of 5-(4-cyclohexyl phenyl)-3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl pyrazole [Compound 47] 
     Compound 47 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 5-(4-cyclohexylphenyl)-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 89.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.17-7.41 (m, 5H), 6.96-7.15 (m, 4H), 6.66-6.90 (m, 4H), 6.46 (s, 1H), 4.04 (s, 2H), 3.87 (s, 3H), 2.55-3.40 (m, 12H), 2.46 (m, 1H), 1.64-1.95 (m, 6H), 1.37 (m, 4H) 
     EXAMPLE 48 
     Synthesis of 3-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-(4-piperidin-1-yl)phenylpyrazole [Compound 48] 
     Compound 48 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 1-phenyl-5-(4-(piperidin-1-yl)phenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 88.9% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.17-7.44 (m, 5H), 6.98-7.15 (m, 2H), 6.88-6.69 (m, 6H), 6.59 and 6.46 (s, 1H), 4.89 (brs, 1H), 4.18 and 3.90 (s, 2H), 3.75 (s, 3H), 3.13 (m, 4H), 2.99 (m, 2H), 2.72 (m, 4H), 2.61 (m, 2H), 1.44-1.81 (m, 6H), 1.26 (m, 4H) 
     EXAMPLE 49 
     Synthesis of 5-methyl-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 49] 
     Compound 49 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 59.6% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.11 (d, J=9.3 Hz, 2H), 7.23-7.56 (m, 5H), 6.76 (m, 2H), 6.28 and 6.20 (s, 1H), 4.04 and 3.84 (s, 2H), 3.34 (m, 4H), 2.97 (m, 2H), 2.70 (t, J=5.6 Hz, 2H), 2.60 (m, 4H), 2.33 (s, 3H) 
     EXAMPLE 50 
     Synthesis of 1-t-butyl-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethyl-5-propylpyrazole [Compound 50] 
     Compound 50 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 5-propyl-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 95.6% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.12 (d, J=9.4 Hz, 2H), 6.82 (d, J=9.4 Hz, 2H), 6.02 (s, 1H), 3.95 (s, 2H), 3.42 (t, J=5.0 Hz, 4H), 2.81 (t, J=5.8 Hz, 2H), 2.55-2.66 (m, 6H), 2.53 (m, 2H), 1.54-1.71 (m, 11H), 0.94 (t, J=7.4 Hz, 3H) 
     EXAMPLE 51 
     Synthesis of 3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-propylpyrazole [Compound 51] 
     Compound 51 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 5-propyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 78.6% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.09 (d, J=9.3 Hz, 2H), 7.31-7.55 (m, 5H), 6.76 (d, J=9.4 Hz, 2H), 6.23 (s, 1H), 3.94 (s, 2H), 3.36 (t, J=4.7 Hz, 4H), 2.88 (t, J=5.8 Hz, 4H), 2.47-2.71 (m, 6H), 1.61 (m, 2H), 0.97 (t, J=7.3 Hz, 3H) 
     EXAMPLE 52 
     Synthesis of 1-t-butyl-5-iso-butyl-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 52] 
     Compound 52 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 74.5% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.11 (d, J=9.3 Hz, 2H), 6.81 (d, J=9.3 Hz, 2H), 5.95 (s, 1H), 3.95 (s, 2H), 3.41 (t, J=4.7 Hz, 4H), 2.81 (t, J=5.7 Hz, 2H), 2.54-2.68 (m, 6H), 2.43 (d, J=7.1 Hz, 2H), 1.88 (m, 1H), 1.62 (s, 9H), 0.92 (d, J=6.6 Hz, 6H) 
     EXAMPLE 53 
     Synthesis of 5-iso-butyl-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 53] 
     Compound 53 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 79.3% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.09 (d, J=9.2 Hz, 2H), 7.33-7.54 (m, 5H), 6.75 (d, J=9.2 Hz, 2H), 6.22 and 6.17 (s, 1H), 3.94 and 3.81 (s, 2H), 3.36 (m, 4H), 2.89 (t, J=5.5 Hz, 2H), 2.54-2.75 (m, 6H), 2.50 (d, J=7.0 Hz, 2H), 1.81 (m, 1H), 0.86 (d, J=6.5 Hz, 6H) 
     EXAMPLE 54 
     Synthesis of 5-(furan-2-yl)-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 54] 
     Compound 54 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde were used. 
     Yield: 93.3% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.08 (m, 2H), 7.31-7.52 (m, 6H), 6.79 (s, 1H), 6.70 (m, 2H), 6.33 (m, 1H), 6.95 (m, 1H), 4.14 (s, 2H), 3.89 (m, 2H), 3.35 (m, 4H), 2.70 (m, 2H), 2.58 (m, 4H) 
     EXAMPLE 55 
     Synthesis of 1,5-diphenyl-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 55] 
     Compound 55 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 68.5% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.10 (d, J=9.3 Hz, 2H), 7.25-7.39 (m, 8H), 7.23 (m, 2H), 6.75 (d, J=9.4 Hz, 2H), 6.55 (s, 1H), 4.02 (s, 2H), 3.36 (t, J=4.7 Hz, 4H), 2.95 (t, J=5.8 Hz, 2H), 2.66 (t, J=5.8 Hz, 2H), 2.60 (t, J=4.7 Hz, 4H) 
     EXAMPLE 56 
     Synthesis of 1-t-butyl-5-(4-methylphenyl)-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 56] 
     Compound 56 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 1-t-butyl-5-(4-methylphenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 69.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.09 (d, J=7.6 Hz, 2H), 7.11-7.24 (m, 4H), 6.76 (d, J=8.2 Hz, 2H), 6.30 and 6.11 (s, 1H), 4.20 and 3.94 (s, 2H), 3.40 (m, 4H), 2.83 (m, 2H), 2.54-2.75 (m, 6H), 2.41 (s, 3H), 1.42 (s, 9H) 
     EXAMPLE 57 
     Synthesis of 1-t-butyl-5-(4-chlorophenyl)-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 57] 
     Compound 57 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 5-(4-chlorophenyl)-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 50.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.09 (d, J=8.9 Hz, 2H), 7.37 (m, 2H), 7.26 (m, 2H), 6.78 (d, J=8.9 Hz, 2H), 6.17 and 6.07 (s, 1H), 4.08 and 3.71 (s, 2H), 3.52 (m, 4H), 2.51-3.16 (m, 8H), 1.42 (s, 9H) 
     EXAMPLE 58 
     Synthesis of 5-(4-cyclohexylphenyl)-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 58] 
     Compound 58 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 5-(4-cyclohexyphenyl)-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 78.1% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.05 (d, J=9.0 Hz, 2H), 7.19-7.42 (m, 5H), 6.99-7.16 (m, 4H), 6.69 (d, J=9.2 Hz, 2H), 6.59 (s, 1H), 4.06 (s, 2H), 3.38 (m, 4H), 2.78-3.15 (m, 4H), 2.69 (m, 4H), 2.47 (m, 1H), 1.65-1.94 (m, 6H), 1.34 (m, 4H) 
     EXAMPLE 59 
     Synthesis of 1-phenyl-5-(4-piperidin-1-yl)phenyl-3-{2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 59] 
     Compound 59 was prepared using the same method as that of Example 1 except that 4-(4-nitrophenyl)piperazin-1-ylethylamine and 1-phenyl-5-(4-(piperidin-1-yl)phenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 81.5% 
       1 H NMR (300 MHz, CDCl 3 ) δ 8.05 (d, J=9.0 Hz, 2H), 7.24-7.43 (m, 5H), 7.05 (d, J=8.5 Hz, 2H), 6.78 (d, J=8.6 Hz, 2H), 6.66 (d, J=9.3 Hz, 2H), 6.55 (s, 1H), 4.06 (s, 2H), 3.36 (m, 4H), 3.06-3.39 (m, 6H), 2.98 (m, 2H), 2.57 (m, 4H), 1.45-1.75 (m, 6H) 
     EXAMPLE 60 
     Synthesis of 3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethyl-5-20 methylpyrazole [Compound 60] 
     Compound 60 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 5-methylpyrazole-3-carbaldehyde were used. 
     Yield: 39.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.02-7.10 (m, 2H), 6.86-7.01 (m, 2H), 6.16 (s, 1H), 3.99 (s, 2H), 3.08 (m, 4H), 3.00 (t, J=5.5 Hz, 2H), 2.73 (t, J=6.7 Hz, 4H), 2.58-2.69 (m, 5H) 
     EXAMPLE 61 
     Synthesis of 3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethyl-5-methyl-1-phenylpyrazole [Compound 61] 
     Compound 61 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 87.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.52 (m, 2H), 7.44 (m, 2H), 7.36 (d, J=6.5 Hz, 1H), 7.04 (d, J=6.8 Hz, 1H), 6.83-6.99 (m, 3H), 6.19 (s, 1H), 3.83 (s, 2H), 3.06 (m, 4H), 2.70 (m, 2H), 2.41-2.66 (m, 6H), 2.23 (s, 3H) 
     EXAMPLE 62 
     Synthesis of 1-t-butyl-3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethyl-5-propyl pyrazole [Compound 62] 
     Compound 62 was prepared using the same method as Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 5-propyl-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 76.7% 
       1 H NMR (300 MHz, CDCl 3 ) δ 6.98 (m, 1H), 6.78-6.93 (m, 3H), 5.96 (s, 1H), 3.87 (s, 2H), 3.03 (m, 4H), 2.73 (t, J=5.7 Hz, 2H), 2.48-2.62 (m, 6H), 2.45 (d, J=7.9 Hz, 2H), 1.43-1.65 (m, 11H), 0.88 (t, J=7.3 Hz, 3H) 
     EXAMPLE 63 
     Synthesis of 3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-propylpyrazole [Compound 63] 
     Compound 63 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 5-propyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 59.3% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.25-7.62 (m, 5H), 7.02 (d, J=7.3 Hz, 1H), 6.74-6.99 (m, 3H), 6.28 (s, 1H), 4.15 (brs, 1H), 3.99 (s, 2H), 3.05 (m, 4H), 2.94 (m, 2H), 2.43-2.76 (m, 8H), 1.59 (m, 2H), 0.91 (m, 3H) 
     EXAMPLE 64 
     Synthesis of 1-t-butyl-5-iso-butyl-3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 64] 
     Compound 64 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 76.7% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.01-7.09 (m, 2H), 6.87-7.00 (m, 2H), 6.01 (s, 1H), 3.95 (s, 1H), 3.11 (m, 4H), 2.81 (t, J=5.9 Hz, 2H), 2.55-2.68 (m, 6H), 2.44 (d, J=7.1 Hz, 2H), 1.87 (m, 1H), 1.63 (s, 9H), 0.93 (d, J=6.6 Hz, 6H) 
     EXAMPLE 65 
     Synthesis of 2-t-butyl-5-iso-butyl-3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 65] 
     Compound 65 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 2-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 60.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 6.83-7.17 (m, 4H), 6.18 (s, 1H), 5.93 (brs, 1H), 3.99 (s, 2H), 3.06 (m, 4H), 2.95 (m, 2H), 2.52-2.83 (m, 8H), 1.97 (m, 1H), 1.57 (s, 9H), 0.95 (m, 6H) 
     EXAMPLE 66 
     Synthesis of 5-iso-butyl-3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 66] 
     Compound 66 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 71.8% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.44 (m, 2H), 7.40 (m, 3H), 7.01 (m, 1H), 6.92 (m, 3H), 6.21 (s, 1H), 3.93 (s, 2H), 3.07 (m, 4H), 2.89 (t, J=6.0 Hz, 2H), 2.58-2.74 (m, 6H), 2.51 (d, J=6.1 Hz, 2H), 1.83 (m, 1H), 0.87 (d, J=6.6 Hz, 6H) 
     EXAMPLE 67 
     Synthesis of 3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethyl-5-(furan-2-yl)-1-phenylpyrazole [Compound 67] 
     Compound 67 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde were used. 
     Yield: 86.3% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.41-7.52 (m, 4H), 7.38 (m, 1H), 6.86-7.13 (m, 5H), 6.68 (s, 1H), 6.33 (m, 1H), 5.96 (m, 1H), 3.97 (s, 2H), 3.08 (m, 4H), 2.90 (t, J=5.8 Hz, 2H), 2.51-2.73 (m, 6H) 
     EXAMPLE 68 
     Synthesis of 1,5-diphenyl-3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 68] 
     Compound 68 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 74.5% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.18-7.37 (m, 10H), 6.83-7.08 (m, 4H), 6.59 (s, 1H), 4.49 (brs, 1H), 4.07 (s, 2H), 3.06 (m, 4H), 2.99 (m, 2H), 2.59-2.69 (m, 6H) 
     EXAMPLE 69 
     Synthesis of 1-t-butyl-3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethyl-5-(4-methylphenyl)pyrazole [Compound 69] 
     Compound 69 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 1-t-butyl-5-(4-methylphenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 89.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.12-7.24 (m, 5H), 6.86-7.09 (m, 5H), 6.19 (s, 1H), 4.31 (brs, 1H), 4.05 (s, 2H), 3.10 (m, 4H), 3.03 (t, J=5.8 Hz, 2H), 2.75 (t, J=5.8 Hz, 2H), 2.67 (m, 4H), 2.40 (s, 3H), 1.43 (s, 9H) 
     EXAMPLE 70 
     Synthesis of 1-t-butyl-5-(4-chlorophenyl)-3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 70] 
     Compound 70 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 5-(4-chlorophenyl)-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 74.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.35 (d, J=8.2 Hz, 2H), 7.25 (d, J=8.3 Hz, 2H), 7.01-7.12 (m, 2H), 6.87-6.99 (m, 2H), 6.17 (s, 1H), 3.97 (s, 2H), 3.10 (m, 4H), 2.96 (t, J=5.8 Hz, 2H), 2.56-2.79 (m, 6H), 1.43 (s, 9H) 
     EXAMPLE 71 
     Synthesis of 5-(4-cyclohexylphenyl)-3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 71] 
     Compound 71 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 5-(4-cyclohexylphenyl)-1-phenyl pyrazole-3-carbaldehyde were used. 
     Yield: 64.8% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.24-7.39 (m, 5H), 7.08-7.17 (m, 4H), 7.01-7.07 (m, 2H), 6.83-6.99 (m, 3H), 6.52 and 6.47 (s, 1H), 4.02 and 3.82 (s, 2H), 3.06 (m, 4H), 2.96 (t, J=5.8 Hz, 2H), 2.55-2.80 (m, 6H), 2.48 (m, 1H), 1.68-1.94 (m, 6H), 1.38 (t, J=9.9 Hz, 4H) 
     EXAMPLE 72 
     Synthesis of 3-{2-[4-(2-fluorophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-(4-piperidin-1-yl)phenylpyrazole [Compound 72] 
     Compound 72 was prepared using the same method as that of Example 1 except that 4-(2-fluorophenyl)piperazin-1-ylethylamine and 1-phenyl-5-(4-(piperidin-1-yl)phenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 74.3% tk 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.28-7.37 (m, 5H), 6.77-7.11 (m, 8H), 6.48 (s, 1H), 4.04 (s, 2H), 3.18 (t, J=5.1 Hz, 4H), 3.05 (m, 4H), 2.98 (t, J=5.9 Hz, 2H), 2.69 (m, 2H), 2.64 (m, 4H), 1.54-1.75 (m, 6H) 
     EXAMPLE 73 
     Synthesis of 3-{2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl}aminomethyl-5-methylpyrazole [Compound 73] 
     Compound 73 was prepared using the same method as that of Example 1 except that 4-(3-chlorophenyl)piperazin-1-ylethylamine and 5-methylpyrazole-3-carbaldehyde were used. 
     Yield: 60.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.16 (t, J=8.1 Hz, 1H), 6.73-6.87 (m, 3H), 6.17 (s, 1H), 4.90 (brs, 1H), 3.99 (s, 2H), 3.17 (m, 4H), 3.00 (t, J=5.8 Hz, 2H), 2.73 (m, 4H), 2.60 (m, 2H), 2.04 (2, 3H) 
     EXAMPLE 74 
     Synthesis of 3-{2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl}aminomethyl-5-methyl-1-phenylpyrazole [Compound 74] 
     Compound 74 was prepared using the same method as Example 1 except that 4-(3-chlorophenyl)piperazin-1-ylethylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 65.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.49 (m, 3H), 7.39 (m, 2H), 7.12 (t, J=7.8 Hz, 1H), 6.79 (d, J=7.2 Hz, 1H), 6.67 (m, 2H), 6.51 (s, 1H), 4.32 (s, 2H), 3.19 (m, 2H), 3.03 (m, 4H), 2.84 (m, 2H), 2.59 (m, 4H), 2.31 (s, 3H) 
     EXAMPLE 75 
     Synthesis of 1-t-butyl-3-{2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl}aminomethyl-5-propyl pyrazole [Compound 75] 
     Compound 75 was prepared using the same method as that of Example 1 except that 4-(3-chlorophenyl)piperazin-1-ylethylamine and 5-propyl-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 76.5% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.26 (s, 2H), 7.16 (t, J=8.1 Hz, 1H), 6.74-6.92 (m, 3H), 6.03 (s, 1H), 3.18 (t, J=5.0 Hz, 4H), 2.80 (t, J=5.9 Hz, 2H), 2.54-2.64 (m, 6H), 2.52 (m, 2H) 
     EXAMPLE 76 
     Synthesis of 3-{2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-propylpyrazole [Compound 76] 
     Compound 75 was prepared using the same method as that of Example 1 except that 4-(3-chlorophenyl)piperazin-1-ylethylamine and 5-propyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 48.5% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.32-7.53 (m, 5H), 7.15 (t, J=8.1 Hz, 1H), 6.71-6.90 (m, 3H), 6.32 (s, 1H), 3.89 (s, 2H), 3.18 (m, 4H), 2.83 (m, 2H), 2.51-2.74 (m, 8H), 1.65 (m, 2H), 0.94 (t, J=7.4 Hz, 3H) 
     EXAMPLE 77 
     Synthesis of 1-t-butyl-5-iso-butyl-3-{2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 77] 
     Compound 77 was prepared using the same method as that of Example 1 except that 4-(3-chlorophenyl)piperazin-1-ylethylamine and 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 77.7% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.20 (t, J=7.8 Hz, 1H), 6.90 (s, 1H), 6.82 (m, 2H), 6.0 (s, 1H), 3.99 (s, 2H), 3.22 (m, 4H), 2.84 (m, 2H), 2.52-2.74 (m, 6H), 2.46 (d, J=6.9 Hz, 2H), 1.92 (m, 1 HO, 1.65 (s, 9H), 0.96 (d, J=6.3 Hz, 6H) 
     EXAMPLE 78 
     Synthesis of 2-t-butyl-5-iso-butyl-3-{2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 78] 
     Compound 78 was prepared using the same method as that of Example 1 except that 4-(3-chlorophenyl)piperazin-1-ylethylamine and 2-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 54.8% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.16 (t, J=8.1 Hz, 1H), 6.87 (s, 1H), 6.60 (m, 2H), 6.00 (s, 1H), 3.95(s, 2H), 3.18 (m, 4H), 2.80 (t, J=5.7 Hz, 2H), 2.51-2.67 (m, 6H), 2.44 (d, J=7.1 Hz, 2H), 1.90 (m, 1H), 1.63 (s, 9H), 0.93 (d, J=6.6 Hz, 6H) 
     EXAMPLE 79 
     Synthesis of 5-iso-butyl-3-{2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 79] 
     Compound 79 was prepared using the same method as that of Example 1 except that 4-(3-chlorophenyl)piperazin-1-ylethylamine and 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 47.7% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.31-7.58 (m, 5H), 7.14 (t, J=8.1 Hz, 1H), 6.80 (m, 2H), 6.68-6.78 (m, 2H), 6.21 (s, 1H), 3.94 (s, 2H), 3.12 (m, 4H), 2.89 (t, J=5.7 Hz, 2H), 2.52-2.69 (m, 6H), 2.51 (d, J=7.5 Hz, 2H), 1.82 (m, 1H), 1.26 (s, 9H), 0.87 (d, J=6.6 Hz, 6H) 
     EXAMPLE 80 
     Synthesis of 3-{2-[4-(3-chlorophenyl)piperazin-1-yl]ethyl}aminomethyl-5-(furan-2-yl)-1-phenylpyrazole [Compound 80] 
     Compound 80 was prepared using the same method as that of Example 1 except that 4-(3-chlorophenyl)piperazin-1-ylethylamine and 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde were used. 
     Yield: 68.6% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.32-7.56 (m, 6H), 7.13 (t, J=7.8 Hz, 1H), 6.71-6.90 (m, 3H), 6.67 (s, 1H), 6.33 (m, 1H), 5.97 (m, 1H), 3.99 (s, 2H), 3.13 (m, 4H), 2.90 (m, 2H), 2.48-2.71 (m, 6H) 
     EXAMPLE 81 
     Synthesis of 3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethyl-5-methyl-1-phenylpyrazole [Compound 81] 
     Compound 81 was prepared was obtained using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 5-methyl-1-phenyl pyrazole-3-carbaldehyde were used. 
     Yield: 71% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.33-7.46 (m, 8H), 7.12-7.32 (m, 7H), 6.27 (s, 1H), 4.22 (s, 1H), 3.98 (s, 2H), 2.93 (t, J=6.0 Hz, 2H), 2.64 (t, J=6.0 Hz, 2H), 2.50 (m, 4H), 2.38 (m, 4H), 2.29 (s, 3H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 148.6, 142.7, 140.1, 139.5, 129.0, 128.4, 127.8, 127.7, 126.9, 124.8, 106.4, 76.1, 56.0, 53.2, 51.6, 45.9, 44.6, 12.3 
     IR (KBr, cm −1 ) 3356 (—NH), 2924, 2810, 1502, 1452, 1008 
     FABHRMS m/z C 30 H 36 N 5  (M+H) +  calculated value: 466.2971, measured value: 466.2983 
     EXAMPLE 82 
     Synthesis of 1-t-butyl-3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethyl-5-propyl pyrazole [Compound 82] 
     Compound 82 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 5-propyl-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 70% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.42 (d, J=7.1 Hz, 4H), 7.28 (t, J=7.3 Hz, 4H), 7.18 (t, J=7.3 Hz, 2H), 6.01 (s, 1H), 4.23 (s, 1H), 3.91 (s, 2H), 2.76 (t, J=6.0 Hz, 2H), 2.36-2.59 (m, 12H), 1.52-1.68 (m, 11H), 0.95 (t, J=7.4 Hz, 3H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 149.9, 142.7, 141.6, 128.4, 127.9, 126.9, 105.5, 59.5, 57.7, 53.5, 51.9, 46.7, 46.0, 30.3, 23.0, 14.0 
     MP=81-81° C. 
     EXAMPLE 83 
     Synthesis of 3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-propylpyrazole [Compound 83] 
     Compound 83 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 5-propyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 69% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.30-7.47 (m, 8H), 7.22-7.29 (m, 4H), 7.12-7.21 (m, 3H), 6.29 (s, 1H), 4.15 (s, 1H), 4.02(s, 2H), 2.96 (t, J=5.7 Hz, 2H), 2.66 (t, J=5.7 Hz, 2H), 2.25-2.62 (m, 8H), 2.37 (m, 2H), 1.59 (m, 2H), 0.89 (t, J=7.3 Hz, 3H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 147.9, 145.2, 144.5, 142.6, 139.5, 129.0, 128.9, 128.4, 128.0, 127.8, 126.9, 125.3, 104.9, 76.1, 55.6, 53.1, 51.6, 28.2, 22.0, 13.7 
     IR (KBr, cm −1 ) 3356 (—NH), 2958, 2810, 1500, 1452, 1010 
     FABHRMS m/z C 32 H 40 N 5  (M+H) +  Calculated Value: 494.3284, Measured Value: 494.3305 
     EXAMPLE 84 
     Synthesis of 1-t-butyl-5-iso-butyl-3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 84] 
     Compound 84 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 82% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.43 (d, J=7.3 Hz, 4H), 7.28 (t, J=7.3 Hz, 4H), 7.18 (t, J=7.3 Hz, 2H), 5.99 (s, 1H), 4.23 (s, 1H), 3.92 (s, 2H), 2.76 (t, J=5.8 Hz, 2H), 2.44-2.57 (m, 12H), 1.86 (m, 1H), 1.61 (s, 9H), 0.92 (d, J=6.6 Hz, 6H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 149.0, 142.7, 141.4, 128.4, 127.9, 126.9, 106.2, 76.2, 59.4, 57.7, 53.5, 51.8, 46.6, 46.0, 37.4, 30.3, 28.8, 22.5 
     MP=64-65° C. 
     EXAMPLE 85 
     Synthesis of 5-iso-butyl-3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 85] 
     Compound 85 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 86% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.35-7.47 (m, 8H), 7.23-7.32 (m, 5H), 7.12-7.23 (m, 2H), 6.27 (s, 1H), 4.16 (s, 1H), 4.01 (s, 2H), 2.93 (t, J=5.8 Hz, 2H), 2.64 (t, J=5.9 Hz, 4H), 2.37-2.56 (m, 6H), 2.37 (m, 2H), 1.79 (m, 1H), 0.84 (d, J=6.5 Hz, 6H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 148.4, 144.3, 142.6, 139.6, 129.0, 128.9, 128.4, 128.0, 127.8, 126.8, 125.6, 105.4, 76.1, 55.9, 53.1, 51.6, 45.8, 44.5, 35.0, 29.6, 28.3, 22.3 
     IR (KBr, cm −1 ) 3386 (—NH), 2956, 2810, 1502, 1452, 1008 
     FABHRMS m/z C 33 H 42 N 5  (M+H) +  Calculated value: 508.3440, Measured value: 508.3413 
     EXAMPLE 86 
     Synthesis of 3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethyl-5-(2-furyl)-1-phenylpyrazole [Compound 86] 
     Compound 86 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde were used. 
     Yield: 48% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.32-7.50 (m, 10H), 7.22-7.31 (m, 5H), 7.19 (s, 1H) 6.67 (m, 1H), 6.32 (m, 1H), 5.94 (m, 1H), 4.18 (s, 2H), 3.99 (s, 2H), 2.90 (m, 2H), 2.26-2.70 (m, 10H) 
     EXAMPLE 87 
     Synthesis of 1,5-diphenyl-3-{2-[4-(4-diphenyl methyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 87] 
     Compound 87 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 74% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.36-7.39 (m, 4H), 7.22-7.35 (m, 12H), 7.14-7.21 (m, 4H), 6.53 (s, 1H), 4.19 (s, 1H), 4.00 (s, 2H), 2.91 (t, J=6.0 Hz, 2H), 2.62 (t, J=6.0 Hz, 2H), 2.51 (m, 4H), 2.41 (m, 4H) 
     EXAMPLE 88 
     Synthesis of 1-t-butyl-3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethyl-5-(4-methylphenyl)pyrazole [Compound 88] 
     Compound 88 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 1-t-butyl-5-(4-methylphenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 27% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.35-7.48 (m, 4H), 7.20-7.34 (m, 4H), 7.06-7.20 (m, 6H), 6.10 (s, 1H), 4.20 (s, 1H), 3.96 (s, 2H), 2.98 (m, 2H), 2.66 (m, 4H), 2.45-2.59 (m, 6H), 2.41 (s, 3H), 1.40 (s, 9H) 
     EXAMPLE 89 
     Synthesis of 1-t-butyl-5-(4-chlorophenyl)-3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 89] 
     Compound 89 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 5-(4-chlorophenyl)-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 74% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.36-7.46 (m, 4H), 7.22-7.35 (m, 7H), 7.13-7.21 (m, 3H), 6.17 (s, 1H), 4.19 (s, 1H), 3.97 (s, 2H), 2.96 (t, J=5.8 Hz, 2H), 2.66 (t, J=5.8 Hz, 2H), 2.28-2.57 (m, 8H), 1.40 (s, 9H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 144.4, 142.6, 134.6, 132.2, 131.5, 128.4, 128.0, 127.8, 126.9, 108.8, 61.3, 55.5, 53.1, 51.7, 45.6, 44.2, 31.1 
     IR (KBr, cm −1 ) 3315 (—NH), 2932, 2812, 1450, 1092, 1008, 910 
     FABHRMS m/z C 33 H 41 ClN 5  (M+H) +  calculated value: 542.3047, measured value: 542.3050 
     EXAMPLE 90 
     Synthesis of 5-(4-cyclohexylphenyl)-3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 90] 
     Compound 90 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 5-(4-cyclohexyl phenyl)-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 72% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.40 (t, J=8.0 Hz, 4H), 7.20-7.30 (m, 9H), 7.18 (d, J=7.1 Hz, 2H), 7.04 (d, J=8.7 Hz, 2H), 6.79 (d, J=8.7 Hz, 2H), 6.46 (s, 1H), 4.25 (s, 1H), 4.04 (s, 2H), 2.66 (t, J=5.9 Hz, 2H), 2.33-2.62 (m, 11H), 1.68 (m, 4H), 1.44-1.63 (m, 6H) 
     EXAMPLE 91 
     Synthesis of 3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-(4-piperidin-1-yl)phenylpyrazole [Compound 91] 
     Compound 91 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylethylamine and 1-phenyl-5-(4-(piperidin-1-yl)phenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 83% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.39 (d, J=7.2 Hz, 4H), 7.22-7.35 (m, 8H), 7.19 (d, J=7.1 Hz, 2H), 7.06-7.14 (m, 5H), 6.50 (s, 1H), 4.18 (s, 1H), 4.01 (s, 2H), 2.93 (t, J=5.6 Hz, 2H), 2.63 (t, J=5.6 Hz, 2H), 2.31-2.59 (m, 8H), 1.71-1.93 (m, 6H), 1.39 (t, J=9.7 Hz, 4H) 
     EXAMPLE 92 
     Synthesis of 3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethyl-5-methyl-1-phenylpyrazole [Compound 92] 
     Compound 92 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 58% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.71 (m, 1H), 7.54 (m, 1H), 7.41 (d, J=7.4 Hz, 2H), 7.30-7.49 (m, 6H), 7.26 (d, J=6.7 Hz, 2H), 7.21 (d, J=8.8 Hz, 1H), 6.27 (s, 1H), 4.12 (s, 1H), 4.04 (s, 2H), 2.71-2.93 (m, 6H), 2.67 (t, J=5.6 Hz, 2H), 2.49 (m, 4H), 2.30 (s, 3H), 
       13 C NMR (75 MHz, CDCl 3 ) δ 167.7, 142.1, 141.2, 140.4, 139.4, 132.4, 130.9, 129.1, 129.0, 128.8, 128.7, 128.6, 127.7, 127.2, 124.8, 106.5, 75.4, 55.2, 53.0, 51.5, 45.4, 44.2, 12.3 
     EXAMPLE 93 
     Synthesis of 1-t-butyl-3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethyl-5-propylpyrazole [Compound 93] 
     Compound 93 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 5-propyl-1-t-butylpyrazole-3-carbaldehyde were used. 
     Yield: 86% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.33-7.41 (m, 4H), 7.16-7.32 (m, 5H), 6.01 (s, 1H), 4.21 (s, 1H), 3.91 (s, 2H), 2.75 (t, J=5.9 Hz, 2H), 2.53 (t, J=7.6 Hz, 4H), 7.31-7.46 (m, 8H), 1.54-1.69 (m, 11H), 0.95 (t, J=7.3 Hz, 3H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 149.9, 142.1, 141.6, 141.3, 132.5, 129.2, 128.6, 128.5, 127.8, 127.1, 105.5, 75.4, 59.5, 57.7, 53.5, 51.8, 46.7, 46.0, 30.4, 30.3, 23.0, 14.0 
     EXAMPLE 94 
     Synthesis of 3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-propylpyrazole [Compound 94] 
     Compound 94 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 5-propyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 95% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.30-7.45 (m, 8H), 7.13-7.29 (m, 6H), 6.26 (s, 1H), 4.14 (s, 1H), 3.99 (s, 2H), 2.92 (t, J=5.9 Hz, 2H), 2.63 (t, J=5.9 Hz, 2H), 2.56 (t, J=7.7 Hz, 4H), 2.47 (m, 4H), 2.35 (m, 2H), 1.47-1.66 (m, 2H), 0.90 (t, J=7.3 Hz, 3H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 148.6, 145.1, 142.1, 141.3, 139.6, 132.5, 129.1, 129.0, 128.6, 128.5, 127.9, 127.7, 127.1, 125.3, 104.8, 75.4, 56.0, 53.1, 51.6, 46.0, 44.7, 28.2, 22.0, 13.7 
     IR (KBr, cm −1 ) 3376 (—NH), 2958, 2928, 2812, 1502, 1010 
     FABHRMS m/z C 32 H 39 ClN 5  (M+H) +  calculated value: 528.2894, measured value: 528.2895 
     EXAMPLE 95 
     Synthesis of 1-t-butyl-5-iso-butyl-3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethylpyrazole [Compound 95] 
     Compound 95 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 1-t-butyl-5-iso-butylpyrazole-3-carbaldehyde were used. 
     Yield: 68% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.37 (m, 4H), 7.16-7.34 (m, 5H), 5.98 (s, 1H), 4.21 (s, 1H), 3.91 (s, 2H), 2.75 (t, J=5.6 Hz, 2H), 2.53 (t, J=5.6 Hz, 2H), 2.30-2.49 (m, 10H), 1.85 (m, 1H), 1.61 (s, 9H), 0.91 (d, J=6.5 Hz, 6H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 149.0, 142.1, 141.4, 141.3, 132.5, 129.2, 128.6, 128.5, 127.8, 127.1, 106.2, 75.4, 59.5, 57.7, 53.4, 51.8, 46.6, 46.0, 37.5, 30.3, 28.8, 22.5 
     EXAMPLE 96 
     Synthesis of 5-iso-butyl-3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethyl-1-phenylpyrazole [Compound 96] 
     Compound 96 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 5-iso-butyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 95% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.12-7.51 (m, 14H), 6.28 (s, 1H), 4.19 (s, 1H), 3.86 (s, 2H), 2.90 (m, 4H), 2.77 (m, 4H), 2.35-2.61 (m, 6H), 1.80 (m, 1H), 0.84 (d, J=5.1 Hz, 6H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 149.1, 143.9, 141.6, 140.8, 139.8, 132.6, 128.9, 128.6, 128.6, 127.8, 127.6, 127.2, 125.6, 106.5, 74.9, 54.8, 53.0, 51.5, 50.2, 48.7, 35.1, 28.3, 22.3 
     EXAMPLE 97 
     Synthesis of 3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethyl-5-(2-furyl)-1-phenylpyrazole [Compound 97] 
     Compound 97 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 1-phenyl-5-(2-furyl)pyrazole-3-carbaldehyde were used. 
     Yield: 62% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.29-7.44 (m, 10H), 7.26 (d, J=7.9 Hz, 4H), 7.22 (s, 1H), 6.67 (t, J=7.8 Hz, 1H), 6.32 (m, 1H), 5.93 (m, 1H), 4.14 (s, 1H), 4.03 (s, 2H), 2.94 (t, J=5.7 Hz, 2H), 2.65 (t, J=6.0 Hz, 4H), 2.50 (m, 4H), 2.36 (m, 2H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 144.1, 142.6, 142.4, 142.1, 141.3, 139.9, 135.5, 135.0, 132.5, 129.1, 129.0, 129.0, 128.6, 128.6, 127.7, 127.1, 125.7, 125.6, 111.2, 109.0, 105.4, 56.0, 53.1, 51.5, 45.8, 44.6, 29.7 
     IR (KBr, cm −1 ) 3276 (—NH), 2926, 2814, 1504, 1010, 910 
     FABHRMS m/z C 33 H 35 ClN 5 O (M+H) +  Calculated Value: 552.2507, Measured Value: 552.2530 
     EXAMPLE 98 
     Synthesis of 3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethyl-1,5-diphenylpyrazole [Compound 98] 
     Compound 98 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 61% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.34-7.41 (m, 4H), 7.23-7.33 (m, 10H), 7.14-7.22 (m, 5H), 6.53 (s, 1H), 4.16 (s, 1H), 4.00 (s, 2H), 2.91 (t, J=5.6 Hz, 2H), 2.61 (t, J=5.6 Hz, 2H), 2.49 (m, 4H), 2.38 (m, 4H) 
     EXAMPLE 99 
     Synthesis of 1-t-butyl-3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]-ethyl}aminomethyl-5-(4-methylphenyl)pyrazole [Compound 99] 
     Compound 99 was prepared using the same method as that of Example 1 except for using 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 1-t-butyl-5-(4-methylphenyl)pyrazole-3-carbaldehyde. 
     Yield: 41% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.32-7.40 (m, 4H), 7.18-7.31 (m, 5H), 7.13 (d, J=5.8 Hz, 2H), 7.08 (d, J=6.3 Hz, 2H), 6.15 (s, 1H), 4.18 (s, 1H), 4.06 (s, 2H), 2.72 (t, J=5.6 Hz, 4H), 2.49 (m, 4H), 2.32-2.45 (m, 7H), 1.38 (s, 9H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 141.9, 141.1, 138.5, 132.6, 130.4, 130.1, 129.1, 128.7, 128.6, 128.5, 128.4, 127.7, 127.2, 108.8, 61.5, 52.8, 51.6, 45.0, 43.5, 31.1, 31.1, 29.7, 21.3 
     IR (KBr, cm −1 ) 3356 (—NH), 2924, 2814, 1450, 1010, 912, 806 
     FABHRMS m/z C 34 H 44 ClN 5 (M+H) +  Calculated Value: 556.3207, Measured Value: 556.3207 
     EXAMPLE 100 
     Synthesis of 1-t-butyl-3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethyl-5-(4-chlorophenyl)pyrazole [Compound 100] 
     Compound 100 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 5-(4-chlorophenyl)-1-t-butyl pyrazole-3-carbaldehyde were used. 
     Yield: 57% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.30-7.41 (m, 6H), 7.08-7.29 (m, 8H), 6.22 (s, 1H), 4.18 (s, 1H), 4.05 (s, 2H), 3.03 (t, J=5.6 Hz, 2H), 2.72 (m, 4H), 2.30-2.59 (m, 6H), 1.39 (s, 9H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 142.8, 141.9, 141.1, 134.8, 132.6, 131.9, 131.5, 131.5, 129.1, 128.7, 128.6, 128.1, 128.0, 127.7, 127.2, 109.1, 61.5, 61.0, 54.5, 52.9, 51.6, 45.0, 43.5, 31.1, 29.7 
     IR (KBr, cm −1 ) 3386 (—NH), 2928, 2816, 1488, 1092, 912 
     FABHRMS m/z C 33 H 40 ClN 5  (M+H) +  Calculated Value: 576.2657, Measured Value: 576.2661 
     EXAMPLE 101 
     Synthesis of 3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethyl-5-(4-cyclohexylphenyl)-1-phenylpyrazole [Compound 101] 
     Compound 101 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 5-(4-cyclohexyl phenyl)-1-phenyl pyrazole-3-carbaldehyde were used. 
     Yield: 31% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.31-7.39 (m, 6H), 7.11-7.30 (m, 8H), 7.06-7.16 (m, 3H), 7.04 (m, 1H), 6.50 (s, 1H), 4.13 (s, 1H), 4.05 (s, 2H), 2.99 (t, J=5.5 Hz, 2H), 2.66 (t, J=5.4 Hz, 4H), 2.41-2.69 (m, 6H), 2.36 (m, 1H), 1.70-1.94 (m, 6H), 1.39 (t, J=9.7 Hz, 4H) 
     EXAMPLE 102 
     Synthesis of 3-{2-[4-(4-chlorobenzhydryl)piperazin-1-yl]ethyl}aminomethyl-1-phenyl-5-(4-piperidine-1-ylphenyl)pyrazole [Compound 102] 
     Compound 102 was prepared using the same method as that of Example 1 except that 4-(4-chlorobenzhydryl)piperazin-1-ylethylamine and 1-phenyl-5-(4-piperidine-1-yl)phenyl)pyrazole-3-carbaldehyde were used. 
     Yield: 86.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.15-7.40 (m, 14H), 7.00 (m, 2H), 6.76 (m, 2H), 6.47 (s, 1H), 6.01 (brs, 1H), 4.24 (s, 1H), 4.11 (s, 2H), 2.56-2.77 (m, 6H), 2.49 (m, 6H), 2.32 (m, 2H), 1.51-1.74 (m, 6H) 
       13 C NMR (75 MHz, CDCl 3 ) δ 176.2, 170.4, 151.6, 147.4, 144.8, 141.6, 139.9, 129.9, 129.3, 129.0, 129.0, 128.8, 128.7, 128.6, 128.6, 128.5, 127.7, 125.1, 115.2, 106.2, 74.9, 56.4, 54.7, 52.8, 51.5, 50.6, 49.5, 25.6, 24.2 
     EXAMPLE 103 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]propyl}aminomethyl-5-methyl-1-phenylpyrazole [Compound 103] 
     Compound 103 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylpropylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 49.0% 
       1 H NMR (300 MHz, CDCl 3 ) δ7.36 (m, 5H), 6.97 (m, 1H), 6.88 (m, 2H), 6.55 (s, 1H), 4.14 (m, 2H), 3.24 (m, 2H), 2.70 (m, 10H), 2.27 (s, 3H), 2.23 (s, 3H), 2.11 (s, 3H), 2.02 (m, 2H) 
     EXAMPLE 104 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]propyl}aminomethyl-1,5-diphenylpyrazole [Compound 104] 
     Compound 104 was prepared using the same method as that of Example 1 except that 4-(2,3-dimethylphenyl)piperazin-1-ylpropylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 43.6% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.56 (d, J=7.7 Hz, 2H), 7.45 (t, J=7.5 Hz, 2H), 7.35 (t, J=7.0 Hz, 1H), 7.08 (t, J=7.6 Hz, 1H), 6.92 (m, 2H), 6.22 (s, 1H), 3.81 (m, 2H), 2.91 (m, 4H), 2.66 (m, 8H), 2.46 (t, J=6.9 Hz, 2H), 2.27 (s, 3H), 2.22 (s, 3H), 1.69 (m, 4H), 0.96 (t, J=8.3 Hz, 3H) 
     EXAMPLE 105 
     Synthesis of 3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]propyl}aminomethyl-5-methyl-1-phenylpyrazole [Compound 105] 
     Compound 105 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylpropylamine and 5-methyl-1-phenylpyrazole-3-carbaldehyde were used. 
     Yield: 55.9% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.36 (m, 6H), 7.28 (m, 2H), 7.21 (m, 4H), 7.15 (m, 3H), 6.44 (s, 1H), 4.06 (s, 2H), 3.95 (s, 2H), 3.13 (m, 2H), 2.54 (m, 4H), 2.31 (m, 4H), 2.02 (m, 2H), 1.93 (m, 2H), 1.24 (s, 3H) 
     EXAMPLE 106 
     Synthesis of 3-{2-[4-(4-diphenylmethyl)piperazin-1-yl]propyl}aminomethyl-1,5-diphenylpyrazole [compound 106] 
     Compound 106 was prepared using the same method as that of Example 1 except that 4-diphenylmethylpiperazin-1-ylpropylamine and 1,5-diphenylpyrazole-3-carbaldehyde were used. 
     Yield: 53.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.51 (m, 2H), 7.41 (m, 6H), 7.26 (m, 4H), 7.18 (m, 3H), 6.19 (s, 1H), 4.20 (s, 1H), 3.78 (s, 2H), 2.65 (m, 4H), 2.39 (m, 8H), 2.05 (m, 2H), 1.71 (m, 4H), 1.01 (m, 3H) 
     EXAMPLE 107 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}methylaminomethyl-5-methyl-1-phenylpyrazole [Compound 107] 
     3-2-[4-(2,3-dimethyl phenyl)piperazin-1-yl]ethylaminomethyl-5-methyl-1-phenylpyrazole (30 mg, 0.074 mmol) and formaldehyde (0.06 ml, 0.743 mmol) were dissolved in 5 ml of purified CH 2 Cl 2  and stirred at room temperature for 1 hour. NaBH(OAc) 3  (47.24 mg, 0.223 mmol) was added thereto and stirred for 6 hours at room temperature. The reaction progress and the completion were confirmed using TLC (CH 2 Cl 2 :MeOH=5:1). Upon completion of the reaction, water was added to the reaction mixture and the aqueous layer was extracted with CH 2 Cl 2 . The organic layer was dried over anhydrous MgSO 4 , filtered and then concentrated under reduced pressure. The concentrate was separated by column chromatography (CH 2 Cl 2 :MeOH=10:1) to obtain the titled compound. 
     Yield: 77.4% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.44 (m, 5H), 7.06 (m, 1H), 6.91 (m, 2H), 6.27 (s, 1H), 3.75 (m, 2H), 2.93 (m, 6H), 2.75 (m, 6H), 2.45 (s, 3H), 2.33 (s, 3H), 2.26 (s, 3H), 2.21 (s, 3H) 
     EXAMPLE 108 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}methylaminomethyl-1-phenyl-5-propylpyrazole [Compound 108] 
     Compound 108 was prepared from 3-2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethylaminomethyl-1-phenyl-5-propylpyrazole using the same method as that of Example 107. 
     Yield: 87.2% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.65 (d, J=7.4 Hz, 2H), 7.45 (t, J=7.2 Hz, 2H), 7.35 (m, 1H), 7.08 (t, J=7.5 Hz, 1H), 6.91 (d, J=7.9 Hz, 2H), 6.20 (s, 1H), 3.53 (s, 2H), 2.91 (m, 4H), 2.59 (m, 10H), 2.28 (s, 6H), 2.19 (s, 3H), 1.73 (m, 2H), 1.00 (m, 3H) 
     EXAMPLE 109 
     Synthesis of 3-{2-[4-(2,3-dimethyl phenyl)piperazin-1-yl]ethyl}ethylaminoethyl-5-methyl-1-phenylpyrazole [Compound 109] 
     3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}aminoethyl-5-methyl-1-phenylpyrazole (30 mg, 0.074 mmol) and acetaldehyde (0.04 ml, 0.743 mmol) were dissolved in 5 ml of purified CH 2 Cl 2  and stirred for 1 hour at room temperature. NaBH(OAc) 3  (47.24 mg, 0.223 mmol) was added thereto and stirred for 10 hours at room temperature. The reaction progress and completion was confirmed using TLC (CH 2 Cl 2 :MeOH=5:1). Upon completion of the reaction, water was added to the reaction mixture and the aqueous layer was extracted with CH 2 Cl 2 . The organic layer was dried over anhydrous MgSO 4 , filtered and then was concentrated under reduced pressure. The concentrated solution was separated using column chromatography (CH 2 Cl 2 :MeOH=10:1) to obtain the titled compound. 
     Yield: 87.3% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.44 (m, 5H), 7.07 (m, 1H), 6.91 (m, 2H), 6.33 (s, 1H), 3.92 (s, 2H), 2.93 (m, 6H), 2.82 (m, 4H), 2.73 (m, 4H), 2.34 (s, 3H), 2.27 (s, 3H), 2.21 (s, 3H), 1.23 (t, J=8.5 Hz, 3H) 
     EXAMPLE 110 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}ethylaminoethyl-1-phenyl-5-propylpyrazole [Compound 110] 
     Compound 110 was prepared from 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]ethyl}aminoethyl-1-phenyl-5-propylpyrazole using the same method as that of Example 109. 
     Yield: 84.5% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.63 (d, J=7.2 Hz, 2H), 7.44 (t, J=7.8 Hz, 2H), 7.35 (m, 1H), 7.07 (t, J=7.3 Hz, 1H), 6.90 (d, J=7.6 Hz, 2H), 6.21 (s, 1H), 3.62 (s, 2H), 2.89 (m, 4H), 2.66 (m, 4H), 2.59 (m, 4H), 2.45 (m, 2H), 2.27 (s, 3H), 2.21 (s, 3H), 1.72 (m, 4H), 0.89 (m, 6H) 
     EXAMPLE 111 
     Synthesis of 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]propyl}ethylaminoethyl-1-phenyl-5-propylpyrazole [Compound 111] 
     Compound 111 was prepared from 3-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]propyl}aminoethyl-1-phenyl-5-propylpyrazole using the same method as that of Example 109. 
     Yield: 60.9% 
       1 H NMR (300 MHz, CDCl 3 ) δ 7.45 (m, 5H), 7.07 (t, J=7.7 Hz, 1H), 6.89 (m, 2H), 6.46 (s, 1H), 4.08 (s, 2H), 2.98 (m, 4H), 2.87 (m, 4H), 2.68 (m, 4H), 2.58 (m, 2H), 2.34 (s, 3H), 2.27 (s, 3H), 2.19 (s, 3H), 1.37 (m, 2H), 0.89 (m, 3H) 
     The following Table 2 summarizes the substituents according to Example 1 to Example 111 and the corresponding reaction scheme. 
     
       
         
               
             
               
             
               
             
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
             
          
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
             
          
           
               
                   
               
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Example 
                 n 
                 R1 
                 R2 
                 R3 
                 R4 
               
               
                   
               
             
          
           
               
                 1 
                 1 
                 phenyl 
                 hydrogen 
                 hydrogen 
                 methyl 
               
               
                 2 
                 1 
                 phenyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 3 
                 1 
                 phenyl 
                 hydrogen 
                 1-t-butyl 
                 propyl 
               
               
                 4 
                 1 
                 phenyl 
                 hydrogen 
                 1-phenyl 
                 propyl 
               
               
                 5 
                 1 
                 phenyl 
                 hydrogen 
                 1-t-butyl 
                 iso-butyl 
               
               
                 6 
                 1 
                 phenyl 
                 hydrogen 
                 2-t-butyl 
                 iso-butyl 
               
               
                 7 
                 1 
                 phenyl 
                 hydrogen 
                 2-t-butyl 
                 iso-butyl 
               
               
                 8 
                 1 
                 phenyl 
                 hydrogen 
                 1-phenyl 
                 2-furyl 
               
               
                 9 
                 1 
                 phenyl 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                 10 
                 1 
                 phenyl 
                 hydrogen 
                 1-t-butyl 
                 4-methylphenyl 
               
               
                 11 
                 1 
                 phenyl 
                 hydrogen 
                 1-t-butyl 
                 4-chlorophenyl 
               
               
                 12 
                 1 
                 phenyl 
                 hydrogen 
                 1-phenyl 
                 4-cyclohexylphenyl 
               
               
                 13 
                 1 
                 phenyl 
                 hydrogen 
                 1-phenyl 
                 4-(piperidine-1- 
               
               
                   
                   
                   
                   
                   
                 yl)phenyl 
               
               
                 14 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 15 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-t-butyl 
                 propyl 
               
               
                 16 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 propyl 
               
               
                 17 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-t-butyl 
                 iso-butyl 
               
               
                 18 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 iso-butyl 
               
               
                 19 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 2-furyl 
               
               
                 20 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                 21 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-t-butyl 
                 4-methylphenyl 
               
               
                 22 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-t-butyl 
                 4-chlorophenyl 
               
               
                 23 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 4-cyclohexylphenyl 
               
               
                 24 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 4-(piperidine-1- 
               
               
                   
                   
                   
                   
                   
                 yl)phenyl 
               
               
                 25 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 26 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-t-butyl 
                 propyl 
               
               
                 27 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 propyl 
               
               
                 28 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-t-butyl 
                 iso-butyl 
               
               
                 29 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 iso-butyl 
               
               
                 30 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 2-furyl 
               
               
                 31 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                 32 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-t-butyl 
                 4-methylphenyl 
               
               
                 33 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-t-butyl 
                 4-chlorophenyl 
               
               
                 34 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 4-cyclohexylphenyl 
               
               
                 35 
                 1 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 4-(piperidine-1- 
               
               
                   
                   
                   
                   
                   
                 yl)phenyl 
               
               
                 36 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 hydrogen 
                 methyl 
               
               
                 37 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 38 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-t-butyl 
                 propyl 
               
               
                 39 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-phenyl 
                 propyl 
               
               
                 40 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-t-butyl 
                 iso-butyl 
               
               
                 41 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 2-t-butyl 
                 iso-butyl 
               
               
                 42 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-phenyl 
                 iso-butyl 
               
               
                 43 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-phenyl 
                 2-furyl 
               
               
                 44 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                 45 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-t-butyl 
                 4-methylphenyl 
               
               
                 46 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-t-butyl 
                 4-chlorophenyl 
               
               
                 47 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-phenyl 
                 4-cyclohexylphenyl 
               
               
                 48 
                 1 
                 4-methoxyphenyl 
                 hydrogen 
                 1-phenyl 
                 4-(piperidine-1- 
               
               
                   
                   
                   
                   
                   
                 yl)phenyl 
               
               
                 49 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 50 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-t-butyl 
                 propyl 
               
               
                 51 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1˜phenyl 
                 propyl 
               
               
                 52 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-t-butyl 
                 iso-butyl 
               
               
                 53 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-phenyl 
                 iso-butyl 
               
               
                 54 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-phenyl 
                 2-furyl 
               
               
                 55 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                 56 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-t-butyl 
                 4-methylphenyl 
               
               
                 57 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-t-butyl 
                 4-chlorophenyl 
               
               
                 58 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-phenyl 
                 4-cyclohexylphenyl 
               
               
                 59 
                 1 
                 4-nitrophenyl 
                 hydrogen 
                 1-phenyl 
                 4-(piperidine-1- 
               
               
                   
                   
                   
                   
                   
                 yl)phenyl 
               
               
                 60 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 hydrogen 
                 methyl 
               
               
                 61 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 62 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-t-butyl 
                 propyl 
               
               
                 63 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-phenyl 
                 propyl 
               
               
                 64 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-t-butyl 
                 iso-butyl 
               
               
                 65 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 2-t-butyl 
                 iso-butyl 
               
               
                 66 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-phenyl 
                 iso-butyl 
               
               
                 67 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-phenyl 
                 2-furyl 
               
               
                 68 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                 69 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-t-butyl 
                 4-methylphenyl 
               
               
                 70 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-t-butyl 
                 4-chlorophenyl 
               
               
                 71 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-phenyl 
                 4-cyclohexylphenyl 
               
               
                 72 
                 1 
                 2-flurophenyl 
                 hydrogen 
                 1-phenyl 
                 4-(piperidine-1- 
               
               
                   
                   
                   
                   
                   
                 yl)phenyl 
               
               
                 73 
                 1 
                 3-chlorophenyl 
                 hydrogen 
                 hydrogen 
                 methyl 
               
               
                 74 
                 1 
                 3-chlorophenyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 75 
                 1 
                 3-chlorophenyl 
                 hydrogen 
                 1-t-butyl 
                 propyl 
               
               
                 76 
                 1 
                 3-chlorophenyl 
                 hydrogen 
                 1-phenyl 
                 propyl 
               
               
                 77 
                 1 
                 3-chlorophenyl 
                 hydrogen 
                 1-t-butyl 
                 iso-butyl 
               
               
                 78 
                 1 
                 3-chlorophenyl 
                 hydrogen 
                 2-t-butyl 
                 iso-butyl 
               
               
                 79 
                 1 
                 3-chlorophenyl 
                 hydrogen 
                 1-phenyl 
                 iso-butyl 
               
               
                 80 
                 1 
                 3-chlorophenyl 
                 hydrogen 
                 1-phenyl 
                 2-furyl 
               
               
                 81 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 82 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-t-butyl 
                 propyl 
               
               
                 83 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-phenyl 
                 propyl 
               
               
                 84 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-t-butyl 
                 iso-butyl 
               
               
                 85 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-phenyl 
                 iso-butyl 
               
               
                 86 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-phenyl 
                 2-furyl 
               
               
                 87 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                 88 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-t-butyl 
                 4-methylphenyl 
               
               
                 89 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-t-butyl 
                 4-chlorophenyl 
               
               
                 90 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-phenyl 
                 4-cyclohexylphenyl 
               
               
                 91 
                 1 
                 diphenylmethyl 
                 hydrogen 
                 1-phenyl 
                 4-(piperidine-1- 
               
               
                   
                   
                   
                   
                   
                 yl)phenyl 
               
               
                 92 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 93 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-t-butyl 
                 propyl 
               
               
                 94 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-phenyl 
                 propyl 
               
               
                 95 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-t-butyl 
                 iso-butyl 
               
               
                 96 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-phenyl 
                 iso-butyl 
               
               
                 97 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-phenyl 
                 2-furyl 
               
               
                 98 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                 99 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-t-butyl 
                 4-methylphenyl 
               
               
                 100 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-t-butyl 
                 4-chlorophenyl 
               
               
                 101 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-phenyl 
                 4-cyclohexylphenyl 
               
               
                 102 
                 1 
                 4-chlorobenzhydril 
                 hydrogen 
                 1-phenyl 
                 4-(piperidine-1- 
               
               
                   
                   
                   
                   
                   
                 yl)phenyl 
               
               
                 103 
                 2 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 104 
                 2 
                 2,3-dimethylphenyl 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                 105 
                 2 
                 diphenylmethyl 
                 hydrogen 
                 1-phenyl 
                 methyl 
               
               
                 106 
                 2 
                 diphenylmethyl 
                 hydrogen 
                 1-phenyl 
                 phenyl 
               
               
                   
               
             
          
         
       
     
                                                                                                                                                                                     Example   n   R1   R2   R3   R4                    107   1   2,3-dimethylphenyl   methyl   1-phenyl   methyl       108   1   2,3-dimethylphenyl   methyl   1-phenyl   propyl       109   1   2,3-dimethylphenyl   ethyl   1-phenyl   methyl       110   1   2,3-dimethylphenyl   ethyl   1-phenyl   propyl       111   2   2,3-dimethylphenyl   ethyl   1-phenyl   propyl                    
Evaluation of Pharmacological Effects
 
     In order to evaluate the pharmaceutical effects induced by the compounds of the present invention, the inhibitory effects were examined according to the following procedure. As the first step, those that show more than 50% of inhibition to the calcium channel (α 1H ) expressed in  Xenopus oocytes  were screened. For the second step, α 1G  Ca 2+  channel activities expressed in HEK 293 cells were measured to determine the effective inhibition concentration IC 50 . 
     Measurement of T-type Ca 2+  Channel Blocking Activity of HEK293 Cells by Using Electrophysiological Method 
     The culture medium was prepared by adding 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (v/v) to Dulbecco&#39;s modified Eagle&#39;s medium (DMEM). The cells were cultured in an incubator having a wet condition of 95% air/5% CO 2  at 37° C. The medium was replaced every 3 to 4 days and the cells were sub-cultured every week such that only the cells that expressed α 1G  T-type Ca 2+  channels could be grown using G-418 (0.5 mg/ml) solution. The cells that were used to measure T-type Ca 2+  channel activity were incubated on a cover slip coated by poly-L-lysine (0.5 mg/ml) every time they were sub-cultured and then recorded after 2 to 3 days. T-type Ca 2+  channel currents at the single-cell level were determined by the electrophysiological whole-cells patch clamp technique using EPC-9 amplifier (HEKA, German). Extracellular solution of NaCl 140 mM, CaCl 2  2 mM, HEPES 10 mM (pH 7.4), and intracellular solution of KCl 130 mM, HEPES 10 mM, EGTA 11 mM, MgATP 5 mM (pH 7.4) were used for T-type Ca 2+  channel blocking activity. As the low voltage-activated T-type Ca 2+  channel activity protocol, a fine glass electrode of 3-4 MΩ resistance containing the above-prepared intracellular solution was inserted into a single cell to become the whole-cell recording mode, followed by fixing the potential of the cell membrane at −100 mV and measuring the inward current of the T-type Ca 2+  channel activity when hypopolarized at −30 mV (50 ms duration) every 15 seconds. Each compound was dissolved in 100% dimethylsulfoxide (DMSO) to prepare 10 mM stock solution, and then the effect of T-type Ca 2+  channel current at 1,000 fold diluted concentration of 10 μM (including 0.1% DMSO) was initially measured before IC 50  values were determined by testing the effects at the concentration range for the IC 50  measurement (in general, 0.1-100 μM). Specifically, cells were treated with each compound along with the extracellular solution until T-type Ca 2+  channel currents were stabilized under whole-cell voltage-clamp conditions and the inhibition level of the peak current due to the compound was calculated and expressed in percentage. From these results the effective inhibition concentration was determined, and the results thereof are shown in the following Table 3. 
     
       
         
               
               
               
               
             
           
               
                 TABLE 3 
               
               
                   
               
               
                   
                 % Inhibition in 
                 % Inhibition in 
                   
               
               
                 compound 
                 oocyte (100 μM) 
                 HEK293 (10 μM) 
                 IC 50  (μM) 
               
               
                   
               
             
             
               
                 compound 4 
                 80.14 
                 94.5 ± 2.8 
                 0.30 ± 0.03 
               
               
                 compound 7 
                 77.08 
                 87.9 ± 2.7 
                 0.82 ± 0.04 
               
               
                 compound 15 
                 27.50 
                 79.4 ± 1.6 
                 1.43 ± 0.15 
               
               
                 compound 16 
                 74.60 
                 95.9 ± 0.7 
                 0.58 ± 0.05 
               
               
                 compound 18 
                 92.04 
                 92.7 ± 5.7 
                 1.02 ± 0.10 
               
               
                 compound 37 
                 — 
                 53.0 ± 1.6 
                 9.41 ± 0.55 
               
               
                 compound 39 
                 67.83 
                 91.6 ± 0.5 
                 0.90 ± 0.07 
               
               
                 compound 42 
                 73.34 
                 95.6 ± 1.8 
                 1.04 ± 0.15 
               
               
                 compound 51 
                 51.27 
                 95.3 ± 1.4 
                 0.66 ± 0.07 
               
               
                 compound 52 
                 56.43 
                 94/1 ± 0.5 
                 1.77 ± 0.20 
               
               
                 compound 53 
                 74.44 
                 94.8 ± 1.3 
                 1.06 ± 0.02 
               
               
                 compound 63 
                 54.94 
                 93.8 ± 1.4 
                 0.66 ± 0.04 
               
               
                 compound 76 
                 44.68 
                 75.8 ± 1.0 
                 0.90 ± 0.09 
               
               
                 compound 81 
                 95.42 
                 97.4 ± 1.3 
                 0.57 ± 0.06 
               
               
                 compound 82 
                 24.76 
                 60.5 ± 0.6 
                 4.42 ± 0.89 
               
               
                 compound 83 
                 97.81 
                 92.4 ± 1.8 
                 0.30 ± 0.04 
               
               
                 compound 84 
                 40.35 
                 89.9 ± 0.3 
                 2.19 ± 0.03 
               
               
                 compound 92 
                 34.52 
                 79.2 ± 3.3 
                 0.33 ± 0.66 
               
               
                 compound 94 
                 92.93 
                 100 
                 0.65 ± 0.03 
               
               
                 Mibefradil 
                 86.0  
                 — 
                 0.84 
               
               
                   
               
             
          
         
       
     
     As shown in the above results of the experiments, the compounds of present invention as represented by Formula 1 has an inhibitory effect of T-type Ca 2+  channel, and particularly Compounds 4, 7, 16, 51, 63, 81, 83, 92, 94 were shown to have inhibitory effect of T-type Ca 2+  channel similar to or stronger than that of mibefradil. 
     The present invention provides novel compounds and the preparation method thereof. Since the compounds of the present invention can selectively block T-type Ca 2+  ion channels, they are much more effective in treating pain, high blood pressure and epilepsy than any other conventional drugs.