Patent 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.

Full Description:
BACKGROUND OF THE INVENTION  
       [0001]     1. Field of the Invention  
         [0002]     The present invention relates to piperazinylalkylpyrazole derivatives, the preparation method thereof and the selective T-type calcium channel blocking activity thereof.  
         [0003]     2. Background of the Related Art  
         [0004]     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.  
         [0005]     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.  
         [0006]     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)  
         [0007]     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  
       [0008]     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. 
 
         [0009]     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.  
                         
 
         [0010]     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 .  
         [0011]     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.  
                         
 
         [0012]     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).  
         [0013]     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.  
         [0014]     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  
       [0015]     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.  
         [0000]     Reference 1  
       Preparation of 2-[2-(4-phenylpiperazin-1-yl)ethyl]isoindole-1,3-dione  
       [0016]     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.  
         [0017]     Yield: 55.6%  
         [0018]      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)  
         [0000]     Reference 2  
       Preparation of 2-{2-[4-(2,3-dimethylphenyl)piperazin-1-yl]propyl}isoindole-1,3-dione  
       [0019]     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.  
         [0020]     Yield: 93.7%  
         [0021]      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)  
         [0000]     Reference 3  
       Preparation of 2-[4-(2,3-dimethylphenyl)piperazin-1-yl]propylamine  
       [0022]     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.  
         [0023]     Yield: 44.7%  
         [0024]      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)  
         [0000]     Reference 4  
       Preparation of 3-formyl-5-methylpyrazole  
       [0025]     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.  
         [0026]     Yield: 82.4%  
         [0027]      1 H NMR (300 MHz, CDCl 3 ) δ 9.92 (s, 1H), 6.68 (s, 1H), 2.82 (s, 3H)  
         [0000]     Reference 5  
       Preparation of 1-tert-butyl-5-iso-butyl-3-formylpyrazole  
       [0028]     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.  
         [0029]     Yield: 88.8%  
         [0030]      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] 
       [0031]     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.  
         [0032]     Yield: 52.2%.  
         [0033]      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).  
         [0034]     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] 
       [0035]     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.  
         [0036]     Yield: 46.9%  
         [0037]      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] 
       [0038]     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.  
         [0039]     Yield: 64.2%  
         [0040]      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] 
       [0041]     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.  
         [0042]     Yield: 55.6%  
         [0043]      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] 
       [0044]     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.  
         [0045]     Yield: 25.8%  
         [0046]      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] 
       [0047]     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.  
         [0048]     Yield: 50.1%  
         [0049]      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-phenyl piperazin-1-yl)ethyl]aminomethylpyrazole [Compound 7] 
       [0050]     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.  
         [0051]     Yield: 56.2%  
         [0052]      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] 
       [0053]     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.  
         [0054]     Yield: 69.2%  
         [0055]      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] 
       [0056]     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.  
         [0057]     Yield: 78.8%  
         [0058]      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] 
       [0059]     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.  
         [0060]     Yield: 80.0%  
         [0061]      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] 
       [0062]     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.  
         [0063]     Yield: 69.1%  
         [0064]      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] 
       [0065]     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.  
         [0066]     Yield: 71.2%  
         [0067]      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] 
       [0068]     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.  
         [0069]     Yield: 58.4%  
         [0070]      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] 
       [0071]     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.  
         [0072]     Yield: 85.6%  
         [0073]      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] 
       [0074]     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.  
         [0075]     Yield: 90.7%  
         [0076]      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] 
       [0077]     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.  
         [0078]     Yield: 69.2%  
         [0079]      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] 
       [0080]     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.  
         [0081]     Yield: 90.8%  
         [0082]      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] 
       [0083]     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.  
         [0084]     Yield: 96.5%  
         [0085]      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] 
       [0086]     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.  
         [0087]     Yield: 77.9%  
         [0088]      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] 
       [0089]     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.  
         [0090]     Yield: 72.9%  
         [0091]      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] 
       [0092]     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.  
         [0093]     Yield: 71.1%  
         [0094]      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] 
       [0095]     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.  
         [0096]     Yield: 77.8%  
         [0097]      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] 
       [0098]     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.  
         [0099]     Yield: 92.1%  
         [0100]      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] 
       [0101]     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.  
         [0102]     Yield: 65.2%  
         [0103]      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] 
       [0104]     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.  
         [0105]     Yield: 39.3%  
         [0106]      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] 
       [0107]     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.  
         [0108]     Yield: 79.4%  
         [0109]      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] 
       [0110]     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.  
         [0111]     Yield: 73.6%  
         [0112]      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] 
       [0113]     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.  
         [0114]     Yield: 98.7%  
         [0115]      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] 
       [0116]     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.  
         [0117]     Yield: 69.2%  
         [0118]      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] 
       [0119]     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.  
         [0120]     Yield: 92.2%  
         [0121]      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] 
       [0122]     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.  
         [0123]     Yield: 89.1%  
         [0124]      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] 
       [0125]     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.  
         [0126]     Yield: 67.0%  
         [0127]      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] 
       [0128]     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.  
         [0129]     Yield: 60.3%  
         [0130]      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] 
       [0131]     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.  
         [0132]     Yield: 52.8%  
         [0133]      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] 
       [0134]     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.  
         [0135]     Yield: 56.2%  
         [0136]      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] 
       [0137]     Compound 36 was prepared using the same method as that of Example 1 except that 4-(4-methoxyphenyl)piperazin-1-ylethylamine and 5-15 methylpyrazole-3-carbaldehyde were used.  
         [0138]     Yield: 30.1%  
         [0139]      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] 
       [0140]     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.  
         [0141]     Yield: 22.1%  
         [0142]      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] 
       [0143]     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.  
         [0144]     Yield: 34.2%  
         [0145]      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] 
       [0146]     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.  
         [0147]     Yield: 41.3%  
         [0148]      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] 
       [0149]     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.  
         [0150]     Yield: 35.2%  
         [0151]      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] 
       [0152]     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.  
         [0153]     Yield: 29.7%  
         [0154]      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] 
       [0155]     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.  
         [0156]     Yield: 24.2%  
         [0157]      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] 
       [0158]     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.  
         [0159]     Yield: 74.1%  
         [0160]      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] 
       [0161]     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.  
         [0162]     Yield: 47.1%  
         [0163]      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] 
       [0164]     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.  
         [0165]     Yield: 95.9%  
         [0166]      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] 
       [0167]     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.  
         [0168]     Yield: 86.0%  
         [0169]      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] 
       [0170]     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.  
         [0171]     Yield: 89.1%  
         [0172]      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] 
       [0173]     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.  
         [0174]     Yield: 88.9%  
         [0175]      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] 
       [0176]     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.  
         [0177]     Yield: 59.6%  
         [0178]      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] 
       [0179]     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.  
         [0180]     Yield: 95.6%  
         [0181]      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] 
       [0182]     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.  
         [0183]     Yield: 78.6%  
         [0184]      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] 
       [0185]     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.  
         [0186]     Yield: 74.5%  
         [0187]      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] 
       [0188]     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.  
         [0189]     Yield: 79.3%  
         [0190]      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] 
       [0191]     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.  
         [0192]     Yield: 93.3%  
         [0193]      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] 
       [0194]     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.  
         [0195]     Yield: 68.5%  
         [0196]      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] 
       [0197]     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.  
         [0198]     Yield: 69.4%  
         [0199]      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] 
       [0200]     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.  
         [0201]     Yield: 50.4%  
         [0202]      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] 
       [0203]     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.  
         [0204]     Yield: 78.1%  
         [0205]      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] 
       [0206]     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.  
         [0207]     Yield: 81.5%  
         [0208]      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] 
       [0209]     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.  
         [0210]     Yield: 39.4%  
         [0211]      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] 
       [0212]     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.  
         [0213]     Yield: 87.4%  
         [0214]      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] 
       [0215]     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.  
         [0216]     Yield: 76.7%  
         [0217]      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] 
       [0218]     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.  
         [0219]     Yield: 59.3%  
         [0220]      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] 
       [0221]     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.  
         [0222]     Yield: 76.7%  
         [0223]      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] 
       [0224]     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.  
         [0225]     Yield: 60.2%  
         [0226]      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] 
       [0227]     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.  
         [0228]     Yield: 71.8%  
         [0229]      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] 
       [0230]     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.  
         [0231]     Yield: 86.3%  
         [0232]      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] 
       [0233]     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.  
         [0234]     Yield: 74.5%  
         [0235]      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] 
       [0236]     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.  
         [0237]     Yield: 89.4%  
         [0238]      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] 
       [0239]     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.  
         [0240]     Yield: 74.2%  
         [0241]      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] 
       [0242]     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.  
         [0243]     Yield: 64.8%  
         [0244]      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] 
       [0245]     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.  
         [0246]     Yield: 74.3%  
         [0247]      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] 
       [0248]     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.  
         [0249]     Yield: 60.4%  
         [0250]      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] 
       [0251]     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.  
         [0252]     Yield: 65.4%  
         [0253]      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] 
       [0254]     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.  
         [0255]     Yield: 76.5%  
         [0256]      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] 
       [0257]     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.  
         [0258]     Yield: 48.5%  
         [0259]      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] 
       [0260]     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.  
         [0261]     Yield: 77.7%  
         [0262]      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] 
       [0263]     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.  
         [0264]     Yield: 54.8%  
         [0265]      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] 
       [0266]     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.  
         [0267]     Yield: 47.7%  
         [0268]      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] 
       [0269]     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.  
         [0270]     Yield: 68.6%  
         [0271]      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] 
       [0272]     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.  
         [0273]     Yield: 71%  
         [0274]      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)  
         [0275]      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  
         [0276]     IR (KBr, cm −1 ) 3356 (—NH), 2924, 2810, 1502, 1452, 1008  
         [0277]     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] 
       [0278]     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.  
         [0279]     Yield: 70%  
         [0280]      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)  
         [0281]      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] 
       [0282]     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.  
         [0283]     Yield: 69%  
         [0284]      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)  
         [0285]      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  
         [0286]     IR (KBr, cm −1 ) 3356 (—NH), 2958, 2810, 1500, 1452, 1010  
         [0287]     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] 
       [0288]     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.  
         [0289]     Yield: 82%  
         [0290]      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)  
         [0291]      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  
         [0292]     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] 
       [0293]     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.  
         [0294]     Yield: 86%  
         [0295]      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)  
         [0296]      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  
         [0297]     IR (KBr, cm −1 ) 3386 (—NH), 2956, 2810, 1502, 1452, 1008  
         [0298]     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] 
       [0299]     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.  
         [0300]     Yield: 48%  
         [0301]      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] 
       [0302]     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.  
         [0303]     Yield: 74%  
         [0304]      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] 
       [0305]     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.  
         [0306]     Yield: 27%  
         [0307]      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] 
       [0308]     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.  
         [0309]     Yield: 74%  
         [0310]      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)  
         [0311]      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  
         [0312]     IR (KBr, cm −1 ) 3315 (—NH), 2932, 2812, 1450, 1092, 1008, 910  
         [0313]     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] 
       [0314]     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.  
         [0315]     Yield: 72%  
         [0316]      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] 
       [0317]     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.  
         [0318]     Yield: 83%  
         [0319]      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] 
       [0320]     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.  
         [0321]     Yield: 58%  
         [0322]      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),  
         [0323]      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] 
       [0324]     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.  
         [0325]     Yield: 86%  
         [0326]      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)  
         [0327]      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] 
       [0328]     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.  
         [0329]     Yield: 95%  
         [0330]      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)  
         [0331]      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  
         [0332]     IR (KBr, cm −1 ) 3376 (—NH), 2958, 2928, 2812, 1502, 1010  
         [0333]     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] 
       [0334]     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.  
         [0335]     Yield: 68%  
         [0336]      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)  
         [0337]      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] 
       [0338]     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.  
         [0339]     Yield: 95%  
         [0340]      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)  
         [0341]      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] 
       [0342]     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.  
         [0343]     Yield: 62%  
         [0344]      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)  
         [0345]      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  
         [0346]     IR (KBr, cm −1 ) 3276 (—NH), 2926, 2814, 1504, 1010, 910  
         [0347]     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] 
       [0348]     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.  
         [0349]     Yield: 61%  
         [0350]      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] 
       [0351]     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.  
         [0352]     Yield: 41%  
         [0353]      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)  
         [0354]      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  
         [0355]     IR (KBr, cm −1 ) 3356 (—NH), 2924, 2814, 1450, 1010, 912, 806  
         [0356]     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] 
       [0357]     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.  
         [0358]     Yield: 57%  
         [0359]      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)  
         [0360]      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  
         [0361]     IR (KBr, cm −1 ) 3386 (—NH), 2928, 2816, 1488, 1092, 912  
         [0362]     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] 
       [0363]     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.  
         [0364]     Yield: 31%  
         [0365]      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] 
       [0366]     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.  
         [0367]     Yield: 86.2%  
         [0368]      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)  
         [0369]      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] 
       [0370]     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.  
         [0371]     Yield: 49.0%  
         [0372]      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] 
       [0373]     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.  
         [0374]     Yield: 43.6%  
         [0375]      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] 
       [0376]     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.  
         [0377]     Yield: 55.9%  
         [0378]      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] 
       [0379]     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.  
         [0380]     Yield: 53.2%  
         [0381]      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] 
       [0382]     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.  
         [0383]     Yield: 77.4%  
         [0384]      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] 
       [0385]     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.  
         [0386]     Yield: 87.2%  
         [0387]      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] 
       [0388]     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.  
         [0389]     Yield: 87.3%  
         [0390]      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] 
       [0391]     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.  
         [0392]     Yield: 84.5%  
         [0393]      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] 
       [0394]     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.  
         [0395]     Yield: 60.9%  
         [0396]      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)  
         [0397]     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                  
 
         [0398]                                                                                                                                                                                                            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 
 
         [0399]     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 .  
         [0000]     Measurement of T-Type Ca 2+  Channel Blocking Activity of HEK293 Cells by Using Electrophysiological Method  
         [0400]     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 MD 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                  
 
         [0401]     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.  
         [0402]     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.

Technology Classification (CPC): 2