Title of Invention

"A COMPOUND-1(2,5,6-TRISUBSTITUTEDPYRIDINE)-3-YI]AMINOCARBONYL]-4-(SUBSTITUTED PHENYL) PIPERAZINE"

Abstract

The present invention relates to novel compound of the general formula (I) and acid addition salt thereof. (I) wherein R1 and R2 are independently hydrogen, V1-C8 alkyl or optionally substituted C3-C6 membered cycloalkyl containing C3-C8; R3, R4, R5, Re and R7 are independently hydrogen , halogen, hydroxy, nitro, C1-C4 lower ester, C1-C4 lower alkyl, C1-C4 lower alkoxy, aryl, arylalkoxy or unsaturated amine; 1 is an integer of 0-7; m and n are independently an integer of 0-1; W is carbon or nitrogen; X is oxygen, sulfur, optionally substituted imine; Y is nitrogen or oxygen; and Z is hydrogen, C1-C8 alkoxy, aryloxy, CrC4 alkylamine, cycloamine containing Ni N5 or oxo group. The present compounds of the above formula (I) has not only strong antimumor activities but lower toxicities, and accordingly are expected as novel antitumor agents.

Full Text

The present invention relates to a compound -l[(2,5,6-trisubstitutedpyridine)-3-yl]aminocarbonyl]-4-(substituted phenyl) piperazine of the general formula (I) (Formula Removed) wherein R2 and R2 are independently hydrogen, C1-C8 alkyl or optionally substituted C3-C6 membered cycloalkyl containing C3-C8; R3, R4, R5, R6 and R7 are independently hydrogen , halogen, hydroxy, nitro, C1-C4 lower ester, C1-C4 lower alkyl, C1-C4 lower alkoxy, aryl, arylalkoxy or unsaturated amine; 1 is an integer of 0-7; m and n are independently an integer of 0-1; W is carbon or nitrogen; X is oxygen, sulfur, optionally substituted irnine; Y is nitrogen or oxygen; and Z is hydrogen, C1-C8 alkoxy, aryloxy, C1-C4 alkylamine, cycloamine containing N1 N5 or oxo group. C1-C8 alkyl means straight or branch alkyl group such as methyl, ethyl, propyl, butyl, isobutyl, tert butyl, pentyl, iso-pentyl, hexyl, heptyl, octyl, 2-methyl pentyl or the like. C1-C4 lower alkyl means methyl, propyl, iso-propyl, n-butyl, iso butyl tert-butyl or the like. Optionally substituted 3-6 membered cycloalkyl containing C3-C8 means substituted or unsubstituted cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, substituted cyclopropyl, substituted cyclopentyl, substituted cyclohexyl or the like. C1-C4lower ester means a carboxyl group esterified by lower alkyl group. C1-C4 lower alkoxy means methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, tert-butyloxy group or the like. Aryloxy means phenoxy, substituted phenoxy, naphthyloxy or substituted naphthyloxy or the like. Cycloamine group containing N1-N5 means pyrrolidinyl, pyrrolinyl, imidazolyl Vehicles which can be used in the preparation of pharmaceutical compositions containing the compounds of the general formulaCI) as active ingredient are sweetening agent, binding agent, dissolving agent, aids for dissolution, wetting agent, emulsifying agent, isotonic agent, adsorbent, degrading agent, antioxident, antiseptics, lubricating agent, filler and perfume or the. like such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, sodium carboxy methyl cellulose, agar, talc, stearic acid, magnesium stearate, calcium stearate, magnesium aluminum silicate, starch, gelatine, tragacanth gum, methyl cellulose, glycine, silica, alginic acid, sodium alginate, water, ethanol, polyethylenglycol, polyvinyl pyrrolidone, sodium chloride, potassium chloride, orange essence, vanila aroma or the like. Daily dosage of the compound of the general formula(I) may be varied depending on age, sex of patient and the degree of desease. Daily dosage is l.0mg to 5.000mg and may be administered one to several times. The compounds of the general formula(l) may be prepared by the following scheme 1. Scheme I (Scheme Removed) wherein R1 R2. R3, R4. R5, R6 R7, W, X, Y, Z, 1 and n are the same above and Liei is a leaving group like hydrogen. The compounds of the general formula(I) may be prepared by reacting a compound of the general formula(a) in the presense of -CX- group-providing agent with a compound of the general formula(b). -CX-group-providing agent comprises 1,1-carbonyldiimidazole, 1,1-carbonylthiodiimidazole, phosgene, thiophosgene. carbonyldiphenoxide, chlorophenoxyformate or the like. The reaction may be carried out in conventional organic solvent such as tetrahydrofuran, dichloromethane, acetonitrile or the like. And also the reaction is preferably carried out in the presence of scavenger such as conventional inorganic or organic base. The reaction may be carried out between 3OC and boiling point of Lhe solvent used, preferably at 50OC 100OC for 5 - 48 hours, preferably for 10 24 hours. Quantity of -CX group -providing agent may be 1 - 1.5 equivalent, preferably 1 1.1 equivalent to the starting compound. The compounds of the general fnrmubil) may be prepared by Scht-me II. Scheme-II (Scheme Removed) wherein R1, R1,2,R3 R4, Rr„ R,-,. R7. W, X. Y. Z . I. n. and Lie, are the same 'above and Lite., is halogen. The compound of the general formula(c) may be prepared by reacting a compound of the general formula(a) in the presence of -CX-providing agent with piperazine in a solvent such as tetrahydrofuran, acetonitrile or the like under the same reaction condition of Scheme I. And then the compound of the general formula(I) may be prepared by reacting the compound of the general formula(c) in a solvent such as tetrahydrofuran or the like with a compound of the general formula (d) at 25 - 80OC for 30 min - 20 hours. The compounds of the general formulat'I) may be prepared by Scheme III. Scheme III (Scheme Removed) wherein, R1, R2, R3, R4, R5, R6, R7, I, m. n. W, X, Y, Z and Liei are the same above and Hal is halogen. The compound of the general fonmula(f) may be prepared by reacting a compound of the general formula(a) with a compound of the general formula(e) and halogenating agent. And then the compound of the general formula(I) may be prepared by reacting the compound of the general formula(f) with a compound of the general formula(b). The compound of the general formula(I') may be prepared by Scheme IV. Scheme IV (Scheme Removed) wherein R1, R2, R3, R4, R5, R6, R7, 1, m, n, VV, X, Y, Z, and Liei are the same above. The comound of the general formula(I') may be prepared" by reacting a compound of the general formula (a') in the presence of CX providing agent in a solvent like leirahydrofuran or the like with a compound, of the general formula (b) at ambient temperature for 30 min 5 hours. The compounds of the general formula(l) may be prepared by Scheme V. Scheme V (Scheme Removed) wherein, R1, R2, R3, R4. R4. R5. R6. R7, I, m, n, W, X, Y, Z are the same above and R8 is C1-C5 aJkyl or aryl group, Lie3 is a leaving group like hydrogen. The compound of general formula(g) and the compound of general formula(h) may be prepared by condensing agent. In the above reactions, if any acid material is formed, any basic material is preferably added as scavenger in order to eleminating the acid material from the reaction phase. Such basic material may be alkali metal hydroxide, alkali earth metal hydroxide, alkali metal oxide, alkali earth metal oxide, alkali metal carbonate, alkali earth metal carbonate, alkali metal hydrogen carbonate, alkali earth metal hydrogen carbonate such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, calcium oxide, magnesium oxide, potassium carbonate, sodium carbonate, calcium carbonate, magnesium carbonate, magnesium bicarbonate, sodium bicarbonate, calcium bicabonaie or the like and organic amines. The compound of the general formula(a) is described in prior an EXAMPLES: The compounds of the general formula(I) and (I') are prepared by the following examples. (Scheme Removed) wherein R1, R2, R3, R4. R4. R5. R6. R7, I, m. n. W, X. Y. '/. are the same above. (Table Removed) Example 1 1 -[(5-ethyl-2-methoxy-6 methylpyridin 3 yl)aminocarbonyl]-4-(2-methoxyph-enyl)piperazine: Phen\l N (5 ethyl 2 methoxy 6-methylpyridin 3 yl)carbamate(0.29g, l.Ommol) and 1 -(2-methoxyphenyl)piperazine(0.l9g, l.Ommol) were dissolved in tetrahydrofurandOml) and DBU(0.15g, l.Omol) was added thereto and the mixture was stirred at nx)m temperature for 2 hours. Then, the reaction mixture was concentrated and chromatographed to obtain 0.33g of the titled compound, yield: 89 % 1H -NMR(500MHZ, CDCl3): δ 1.17 3.11(4H,L,J=4.6Hz)f 3.69(4H,L,J=5.0Hz), 3.88(lH,s), 3.98(3H,s), 6.89(lH,s), 6.94(3H,m), 7.05(lH,m), 8.21 (lH.s). Elemental Analysis: C20H28N4O3: Calc, C.65.60, H.7.34, N.14.57. Found, C.66.l0. H.7.25, N.l 1.57. Example 2 1 [(5 ethyl 2 melhoxy-6-method pyridin 3 yl)aminocarbonyl) 4 phenylpiperazi no: • Phenyl N -(5-elhyl 2 melhoxy-6-methylpyridin 3 yl)carbamate and 1 phenylpiperazine were reacted by the same way with the example 1 to obtain the titled compound. yield: 86 % Example 3 1 -[(5-elhyl 2 methoxy-6-methylpyridin 3 yI)arninocarbonyl]-4 (4 methoxyph enyl)piperazine: Phenyl N-(5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1 (4methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield: 78 % Example 4 1 [(5 ethyl-2-methoxy-6-methylpyridin 3 yl)aminocarbonyl]-4-(3,4-dirnethox ypheny 1) piperazine: Phenyl N (5-ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and l-(3,4-dimethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:69 % Example 5 ] -[(5-ethyl-2-methoxy--6-methylpyridin-3-yl)aminocarbonyl] 4(2,4-dimethox yphenyl)piperazine: Phenyl- N-(5-ethyl-2-methoxy-6-methylpyridin-3-yl)carbarnate and l-(2,4-dimethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield: 77 % Example 6 1 [(5-ethyl 2 methoxy-6-methylpyridin 3 yl)aminocarbonyI]-4 (3,5 dimethox yphenyl)piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1 (3,5 dinutluoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield : 82OC., Example 7 1 [(5 ethyl 2 methoxy (5 methylpyridin-3-yl)aminocarbonyl] 4 (3,4.5 trimetho xyphenyl)piperazine: Phenyl N (5 ethyl-2-methoxy-6-methylpyridin -3 yl)carbamate and 1 (3,4.5 trimethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield : 52 % Example 8 1 [(5-ethyl 2 methoxy-6-methylpyridin-3 yl)aminocarbonyl] 4-(2-ethoxyphen yl)piperazine: Phenyl N (5ethyl-2-methoxy-6-methylpyridin-3 yl)carbamate and l-(2-ethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the tided compound. yield : 78 % Example 9 l-[(5-ethyl-2-methoxy-6-methylpyridin 3 yl)aminocarbonyl]-4-(2 phenoxyphe- nyl)piperazirie: Phenyl-N-(5-ethyl-2-methoxy-6-methylpyridin-3-yl)carbamate and 1-(2-phenoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield : 69 % Example 10 l-[(5-ethyl-2-methoxy-6-methylpyridin- 3-yl)aminocarbonyl]-4-(3-phenoxyphe- nyl)piperazine: Phenyl-N-(5-ethyl- 2 methoxy-6-methylpyridin 3 yl)carbamate and i (3phenoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield : 72 % Example 11 1 [(5 ethyl 2 methoxyl (i mriliylpvridin 3 yl)aminocarbonyl) 1 (2 fluorophenyl) piperazine: > Phenyl N (5 ethyl 2 met box v-6-inetln lpyridin 3 yl)carbamate and 1 (2-fluorophenyl)piperazinc were reacted by the same way with the example 1 to obtain the titled compound. yield : 67 % Example 12 l-[(5-ethyl 2 methoxy-6-methylpyridin 3 yl)aminocarbonyl] 1 (4-fluorophenyl) piperazine: Phenyl -N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and l-(4 fluorophenyl )piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield : 81 % Example 13 l-[(5-ethyl 2 methoxy 6-methylpyridine 3-yl)aminocarbonyl] 4 (3.5 difluorop henyl)piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin-3 yl)carbamate and 1 (3,5 difluorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield : 69 % Example 14 1 [(5 ethyl 2 methoxy-6-methylpyridin -3 -yl)aminocarbonyl] 4- ( a .a .a -triflu oro -m tolyl)pipercudne: Phenyl- N (5 ethyl 2-methoxy -6- methylpyridin-3-yl)carbamate and 1 -( a,a ,a -triflouro m tolyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield: 67 % Example 15 1 [(5-ethyl 2 methoxy-6-methylpyridin -3-yl)aminocarbonyl] 4 (2 chlorophen yl)piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1 (2 chlorophenyl)pipera/ine were reacted by the same way with the example 1 to obtain the titled compound. yield :82 % Example 16 1 [(5 ethyl 2 methoxy-6-meihylpyrainn 3 yl)aminocarbonyl] 1 (3 chlorophen yl)piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1 (3chlorophenyl)piperazine were reacted by the same way with the example ] to obtain the titled compound. yield :84 % Example 17 1 [(5 ethyl 2-methoxy-6-methylpyridin-3 yl)aminocarbonyl] 4 (2,6 dichloroph enyl)piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1 (2,6 dichlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the tilled compound. yield :80 % Example 18 I [(5 ethyl 2 methoxy-6-methylpyridin 3 yl)aminocarbonyl] 4 (3,5 dichloroph enyl)piperazine: Phenyl-N-(5-ethyl-2-methoxy-6 methylpyridin 3-yl)carbamate and l-(3,5-dichlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound, yield :69 °o Example 19 1 [(5-ethyl- 2-methoxy-6- methylpyridin 3-yl)aminocarbonyl]-4 (2,4-dichloroph enyl)piperazine: Phenyl-N-(5-ethyl-2-methoxy-6-methylpyridin 3-yl)carbamate and 1 (2,4 dichlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield 72 % Example 20 1 [(5 ethyl 2 methoxy-6-methylpyridin -3-yl)aminocarbonyl] 4 (2,4,6 trichloro phenyl)pipe rapine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)c'arbamate and 1 (2,4,6 trirh)oroplienyl)pipera/ine were reacted by the same way with the example 1 to obtain the tilled compound. yield :51 % Example 21 1 [(5 ethyl 2 methoxy-6-methylpj ridin 3 yl)aminocarbonyi] 4 (2 bromophen yl)piperazine: Phenyl-N (5ethyl 2 methoxy-6-methylpyridin-3 yl)carbamate and 1 (2bromophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :58 % Example 22 1 [(5-ethyl-2 methoxy-6-methylpyridin-3 yl)aminocarbonyl]-4 (3-bromophen yl)piperazine: PhenyI-N-(5-ethyl 2methoxy-6methylpyridin-3-yl)carbamate and 1 (3 bromophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :66 % Example 23 ] [(5-ethyl-2-methoxy-6-methylpyridin-3 yl)aminccabonyl]-4(4-bromophen- yl)piperazine- Phenyl N -(5-ethyl- 2 methoxy 6- methylpyridin -3 -yl)carbamate and 1-(4-bromophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :64 % Example 24 1 -[(5-ethyl-2-metho\y -6 methylpyridin 3-yl)aminocarbonyl]-4- (2,4-dibromop henyl)piperazine- Phenyl-N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1-(2,4-dibromophenyi)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :68 % Example 26 1 ((5 ethyl 2 mcthox\ nicih-. lp> lidin 3 yl)ainiixxvirbonyl] 1 (2.5 dibromop henyl)pi|X'razine: Phenyl N (5 ethyl 2 methoxy f> methylpyridin 3 yl)carbamate and 1 (2,5 dibromophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled comjxnind. yield :66 % Example 26 1 [(5ethyl-2 methoxy-6-methylpyridin 3 yl)aminocarbonyl]-4-(2-toJyl)pipera zine: Phenyl-N (5 ethyl-2 methoxy (5 methylpyridin 3 yl)carbamate and 1 (2 tolyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :89 % Example 27 1 -[(5-ethyl-2-methoxy-6 methylpyridin 3 yl)aminocarbonyl] 4-(4methylphen yl)piperazine-' Phenyl-N-(5-ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1(4 methylphenyl)pipenizine were reacted by the same way 1 to obtain the titled compound, yield :87 % Example 28 1 [(5-ethyl 2 -methoxy-6-methylpyridin-3-yl)aminocarbonyi]-4-(2.3-dimethylp- henyl)piperazine: Phenyl N (5 -ethyl-2-methoxy-6-methylpyridin-3-yl)carbamate and ] (2.3dirneihylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :82 % Example 29 1[(5- ethyl 2 methoxy-6-methylpyridin 3 yl)aminocarbonyl]-4 (3,5 dimethylp henyl)piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1 (3.3 dimcthylphenyl)pipera/.ine were reacted by the same way with the example 1 to obtain the titled compound. yield :(68 % Example 30 1 [(5 ethyl 2-methoxy-6-methylpyridin 3 yl)aminocarbonyl] 1 (2.6 dimethylp henyl)piperazine-' Phenyl N (5 ethyl 2 methoxy-6-methylpyridin-3- yl)carbamate and 1 (2.6 dimethylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound yield :80 % Example 31 1 [(5 ethyl 2 methoxy-6-methylpyridin 3 yl)aminocarbonyl] 4 (4 isopropylph enyl)piperazine: Phenyl-N (5 ethyl-2-methoxy-6-methylpyridin -3-yl)carbamate and 1 (4-isopropylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :68 % Example 32 1 ((5 ethyl 2-methoxy-6 methylpyridin 3 yl) enyl)piperazine: Phenyl-N- (5-ethyl-2-methoxy-6-methylpyridin -3-y])carbamate and l-(2-isopropylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :65 % Example 33 l-[(5-ethyl -2-methoxy-6-methy]pyridin-3yl)aminocarbonyl] -1 -(4-normalbutyl- phenyl)piperazine: Phenyl-N-(5-ethyl -2-methoxy-6-methylpyridin-3 -yl)carbamate and 1 (4 normalbutylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :57 % Example 34 1 [(5 ethyl 2 methoxy-6-methylpyridin 3 yl)amincx-arbonyl] 4 (1 acetylphen yl)piperazine: Phenyl N (5 ethyl 2 methoxy (5-methylpyridin 3 yl)rarbamate and 1 (4 acetylphenyl)piperazinte were reacted by the same way with the example 1 lo obtain the titled compound. yield :67 % Example 35 1 [(5 ethyl 2 methoxy 6-methylpyridin 3 yl)aminocarbonyl] 1 (2 biphenyl)pi perazine: Phenyl N (5 ethyl 2-methoxy 6-methylpyridin 3yl)carbamate and 1 (2biphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :82 % Example 36 1 [(5-ethyl-2-methoxy-6-methylpyridin 3 yl)aminocarbonyl] 4 (4biphenyl)pi- perazine: Phenyl N-(5-ethyl -2 methoxy-6-methylpyridin 3 yl)carbamate and 1 - (4 - biphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :81 % Example 37 1 [(5 ethyl 2 methoxy-6-melhylpyridin 3-yl)aminocarbonyl] 4-(2hydroxyphe- nyl)piperazine- Phenyl N (5-ethyl -2-methoxy--6-methylpyridin 3 yl)carbamate and l-(2-hydroxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :59 % Example 38 1 - [(5-ethyl 2-methoxy-6-methylpyridin-3 yl)aminocarbony 1]-4-(3-hydroxyphe- nyl)piperazine: Phenyl N (5 ethyl 2 methoxy-6-meUiylpyridin-3 yl)carbamate and 1 (3 hydroxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :6\3 % Example 3!) 1 1(5 cihyl 2 methoxy (5 methylpyridin 3 yl)aminocarbonyl] 4 (4 hydroxyphe nyl)piprazine: Phenyl N (5 ethyl 2 methoxy 1 (4 hydroxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled comixmnd. yield -58 % Example 40 1 [(5 ethyl 2 methoxy 6-methylpyridin 3 yl)aminocarbonyl] 4 (4 acetoxyphe nyl)piperazine-' Phenyl N (5 ethyl 2 methoxy (i methylpyridin 3 yl)carbamate and 1 (3 hydroxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled comixmnd. yield ^9 % Example 41 1 ((5 ethyl -2-methoxy-6-melhylpyridin 3 yl)aminocarbonyl]-4-(3-aceioxyphe nyl)piperazine^ Phenyl N (5 ethyl 2 methoxy-6-melhylpyridin -3 yl)carbamate and 1 (3-acetoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound, yield :87 % Example 42 1 -[(5-ethyl-2"methoxy-6-methylpyridin-3yl)aminocarbonyl]-4-(-4^nitrophenyl) piperazine: Phenyl N (5-ethyl 2 methoxy 6- methylpyridin-3 yl)carbamate and 1 (-1-nitrophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield 70 % Example 43 1 [(5-ethyl 2 methoxy -6 methylpyridin 3 yl)aminocarbonyl] 4 [(2-methylami no)phenyl]piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3-yl)carbamate and 1 12 (methylamino)phenyl]piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :59 % Example 44 1 [(5 ethyl 2 methoxy-6-methylpyridin 3 yl)aminocarbonyl] 4(1 naphthyl)pi perazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1 (1-naphthyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield -63 % Example 45 1 [(5 ethyl 2 methoxy-6 methylpyridin 3 yl)aminocarbonyl] 4(1 anthryl)pipe razine: Phenyl -N-(5ethyl-2-methoxy-6-methylpyridin 3 yl)carbamate and l-(l-anthryl)piperazine were reacted by the same way with the example 1 to obtain the tided compound. yield 57 % Example 46 1 -[(5-ethyl-2-methoxy-6-methylpyridin-3-yl)aminocarbonyl]-4-(2-methoxy-6- methylphenyl)piperazine: Phenyl-N-(5-ethyl-2--methoxy-6-methylpyridin-3-yl)carbamate and 1 (2-methoxy-6-methylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound, yield :67 % Example 47 l-[(5-ethyl-2-methoxy-6^methylpyridin-3-yl)aminocarbonyl]-4--(2-methoxy-5-methylphenyl)piperazine: Phenyl-N-(5-ethyl-2-rnethoxy-6-methylpyridin-3-yl)carbamate and l-(2-methoxy-5-phenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound, yield :62 % Example 48 1 [(5 ethyl -2-methoxy-6-methylpyridin 3 yl)aminocarbonyl] 4 -(5-methoxy 2 methylphenyl)piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1 (5 methoxy 2 melhylphenyl)piperazine were reacted by the same way with the example 1 to obtain the tilled compound. yield -66 % Example 19 1 [(5-ethyh2-methoxy-6-methylpyridin-3yl)aminocarbonyl]-4 (5 chloro 2 methoxyphenyl)piperazine: Phenyl N (5 ethyl 2 methoxy 6-methylpyridin 3 yl)carbamate and 1 (5-chloro-2-methoxyphenyl)pipenizine were reacted by the same way with the example 1 to obtain the titled compound. yield :69 % Example 50 1 ((5-ethyl 2 methoxy-6-methylpyridin-3-yl)aminocarbonyl]-4-(2-chloro-5 methoxyphenyl)piperazine: Phenyl N-(5-ethyl 2methoxy-6-methylpyridin 3 yl)carbamate and 1 (2chloro-5-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :70 % Example 51 1-[(5-ethyl-2-methoxy-6 -methylpyridin 3y])aminocarbor.yI]-4-(3-chloro-4 methoxyphenyl)piperazine: Phenyl -N-(5-ethyl 2 methoxy-6-methylpyridin-3-yl)carbamate and l-(3-chloro-4-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :62 % Example 52 1 [(5 ethyl-2-methoxy-6 methylpyridin 3-yl)aminocarbonyl] 4-(3-hydroxy 4 methoxyphenyl)pipenizine: Phenyl N (5-ethyl 2 methoxy-6-methylpyridin 3 yl)carbamate and 1 (3 hydroxy-4 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the tilled compound. yield :59 % Example 53 I ((5 ethyl 2 methoxy (5 inrttn Ipyriclin 3 yl)aminocarbonyl] 1 (3 acetoxy 4 methoxyphenyl)piperazine'- Phenyl N (5 ethyl 2 methoxy 6" methylpyridin 3 yl)carbamate and 1 (3 acetoxy 4 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the tilled compound. yield :62 % Example 54 1 -[(5-ethyl 2-methoxy-6--methylpyridin- 3-yl)aminocarbonyl] 4-[(2methoxy 5 phenyl )phenyl]piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin -3-yl)carbamate and 1 -[(2-methoxy-5phenyl)phenyl]piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :67 % Example 55 l-[(5 ethyl 2 methoxy-6-methylpyridin-3-yl)aminocarbonyl] 4-(3-hydroxy 2 meihylphenyl)piperazine: Phenyl-N-(5-ethyl -2-melhoxy--6-methylpyridin-3 yl)carbamate and ]-(3-hydroxy-2-methylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound, yield :54 % Example 56 1-[(5-ethyl- 2 methoxy-6 methylpyridin- 3- yl)aminocarbonyl] A (2-hydroxy-6- methylphenyl)piperazine: Phenyl-N-(5-ethyl-2-methoxy-6-meLhylp\Tidin-3-yl)carbamate and 1 (2-hydroxy-6methylphenyl)pipeiazine were reacted by the same way with the example 1 to obtain the titled compound. yield :57 % Example 57 1 [(5 ethyl 2 methoxv-6-methylpyridin 3 yl)aminocarbonyl] 4 (2-by droxy 4 melhylphenyl)piperazine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yl)carbanuite and I (2 hydroxy l melhylphenyl)piperazine were reacted by the same way with-- example l to obtain the titled comixmnd. yield :52 % Example 5.S l -[(5 ethyl 2 methoxv-6-melhylpyridin 3 yl)aminocarbonyl] \ (5 chloro 2 melhylphenyl)piperazine: Phenyl-N-(5-ethyl 2 methoxv-6-methylpyridin 3yl)carbamate and 1 (5 chloro 2 methylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :63 % Example 59 1 -[(5 ethyl 2 methoxy-6-methylpyridin 3-yl)aminocarbonyl] 4 (3-chloro-4- fluorophenyl)piperazine: Pheny|-N-(5ethyl-2methoxy-6-methylpyTidin 3 yl)carbamate and 1 (3 fluorophenyl)piperazine were reacted by the same way with the example 1 to obtain the tilled compound. yield :65 % Example 60 1 -[(5-ethyl-2-methoxy--6-methylpyridin-3-yl)arninocarbonyl]-4-(2-methoxyph- enyl)piperazine: Phenyl-N- (5 ethyl -2 methoxy 6-methylpyridin-3-yl)carbamate and 1 -(2 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield £9 % Example 61 1 -[(5-ethyl-2-methoxy-6-methylpyridin 3 yl)aminocarbonyl]-4- (2chlorophen yl)piperazine: Phenyl-N (5 ethyl 2 methoxy-6-methylpyridin-3 yl)carbamate and 1 (2 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield 72 % Example 62 1 [(5 ethyl 2 methoxy-6-methylpyridin 3 yI)mefhylamin rophenyl)piperazine: Phenyl -N (5 elhyl 2 methoxy-6-methylpyridin 3 ylkarbamate and 1 (4-fluorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :&3 % Example 63 1 [(5-ethyl 2 methoxy-6-methylpyridin-3-yl)methylaminocarbonyl] -1 (3 chlo rophenyl)piperazine: Phenyl N (5 ethyl 2 methoxy 6-methylpyridin-3 yl)carbamate and 1 (3 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :68 % Example 64 1 - {[(5 ethyl 2 methoxy -6 methylpyridin-3 yl]ethylaminocarbonyl} 4 (4 fluor ophenyl)piperazine: Phenyl N (2-(5 ethyl 2 methoxy-6 -methylpyridin -3 yl)elhyl]carbamate and 1 (4 fluorophenyl)pipeni/ine were reacted by the same way with the example 1 to obtain the titled compound, yield :65 % Example 65 1 -{[2- (5 ethyl 2 methoxy-6-methylpyridin 3 \i)ethyl]aminocarbonyH 4 (2 methoxyphenyl)piperazine: Phenyl-N- (5-ethyl-2-methoxy-6-methylpyridin 3-yl)carbamate and l-(2-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :63 % Example 66 1 {[3 (5 ethyl 2 methoxy-6-methylpyridin-3 yl)propyl]aminocarbonyl} 4 (2 methoxyphenyl)piperazine: Phenyl-N [3 (5 ethyl 2 methoxy-6-methylpyridin 3 yl)propyl]carbamate and 1 (2 methoxyphenyl)piperazine were reacted by the same way with the example 1 lo obtain the titled compound. yield :67 % Example 67 1 {f5 (5 ethyl 2 methoxy-6-methylpyridin 3 yl)penlyl]aminocarbonyl} -1 (2 methoxyphenyl)piperazine: Phenyl N [5 (5 ethyl 2 methoxy (j methylpyridin 3 yl)pentyl)carbamate and 1 (2 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :52 % Example 68 1 {[6 (5 ethyl-2 methoxy-6-methylpyridin -3 yl)heptyl]arninocarbony|} 4 (2 methoxyphenyl)piperazine: Phenyl N [6 (5 ethyl 2 methoxy 6-methylpyridin 3-yl)heptyl]carbamate and 1-(2-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :49 % Example 69 I [(5 ethyl 2 methoxy-6-nielhylpyridin 3 yl)aminocarbonyl]methyl 4 (2 met hoxyphenyl)piperazine: a) N-(5-ethy)-2methoxy-6methylpyridin-3-yl)chloroaceiamide: After chloroacetic acid (1.35 g. 14.3 mmol) were dissolved into 20 ml of Letrahydrofuran, added 1.1 carbonyldiimidazole(2.32g, M.3mmol), stirred at room temperature for 1 hour, 3-amino-5--ethyl-2-methoxy-6-methylpyridine (2.0g, 13.0mmol) were added. After the reaction mixture were stirred for 2 hours, the mixture of reaction were concentrated, purified by column chromatography to obtain 2.20g of the titled compound. yield:73.3% 1H-NMR(500MHz,.CDCl3);δ1.17(3H,t)1 2.39(5H,m), 3.99(3H.s), 4.17(2H,s), 8.62(1 H,s) b) 1[(5 ethyl 2 methoxy-6-meihylpyridine-3 -yl)amin(x:arbonyl]methyl 4 (2 methoxyphenyl)pipenizine: After N (5 ethyl 2-methoxy-6-metylpyridine 3 yl chloroacetamide(0.10g, 0.13mmol) and 1 (2 -meihoxyphenyl)piix?razine(0.009)g. 0.17mmol) were dissolved into tetrahydrofuran(oml) and was added I)BH0.060g, 0.43mmol), the reaction mixtures were stirred at nx>m temjxTatuie for 2 hours. After the product of reaction were concent rated. M-iaratcd by column chromatography to obtain 0.12g of the titled eomixnind. yield:70"». Example 70. 1 [(5-ethyl 2 methoxy-6-methylpyridine 3 yl)aminocarbonyl]methyl 4 (3 chl orophenyl)piperazine: N-(5-ethyl 2-methoxy-6-methylpyridine -3-yl)chloroacetamide and 1 (3 chlorophenyl)piperazine were reacted by the same way with the example 69 to obtain the titled compound. yield:68% Example 71. 1 [(5-ethyl-2-methoxy-6 methylpyridine-3-yl)aminocarrxxiyl]methyl-4 (2 flu orophenyl)piperazine: N-(5-ethyl-2-methoxy-6-methylpyridin 3 yl)chloroacetamide and 1 (3-fluorophenyl)piperazine were reacted by the same way with the example 69 to obtain the titled comixwnd. yield: 68 % Example 72. 1 [(5-ethyl -2-methoxy-6 -methylpyridin 3 yl)aminocarbonyl]-4-benzylpiperazi- ne: a) 1 [(5 ethyl-2- methoxy-6-methylpyridin-3 yl)aminocarbonyl]-4-(4-methoxy benzyl )piperazine. After 3-amino-5-ethyl-2-methoxy-6-mediylpyridine(1.06g, 6.35mmol) was dissolved in 20ml of tetrahydrofuran, 1,1 carbonyldiimidazole(1.08g, 6.67mmol) was added thereto. The mixture of reaction was stirred at room temperature for half hour and then benzylpiperazine(1.12g, 6.35mmol) was added. After the reaction mixture was stirred for 2 hours, the reaction mixture was concentrated and chromatographed to obtain 1.78g of the oil phase of the tilled compound. yield:76 % 'H NMR(500MHz,CDClj): 3.5I(2H,l), 3.95 b) 1 (f> ethyl 2 methoxy (i methylpyridin 3 yl)aminocarbonyl piperazine; After 1 |(5 ethyl 2 methoxy (> met In l;n ridiu 3 yl)amiiux'arbonyl] 4 ben/vl piix-razine (1.71};, 1.(51 mwioD was ;iflded the solution of 3()rnl of ethanol and I Oml of glacial acetic acid tn the presence of 5"o 1WC. the reaction mixture were stirred under hydrogen gasMO psD for 4 hours and extracted with dichloromethane. The mixture was dried with anhydrous magnesium sulfate, filtrated, concentrated and chromatographed to obtain 1.2 g of white solid of the titled compound. yield :93% 1H NMR(500MHz. CDCl3) δ l.l6.3H.s). 2.35(3H,s). 2.48(2H,q), 2.94(4H.t), 3.52(4H,t), 8.02(1 H.s) c) 1 [(5 ethyl 2 methoxy (3 methylpyridin 3 yl)aminocarbonyl] 4 benzylpiper azine: After 1 (5 ethyl 2-methoxy-6-methylpyridin 3 yl)aminocarbonyl piperazine (0.16g. 0.57mmol) and benzylchloride(0.076g, 0.60mmol) were added in DMF 5ml in the presence of NaHCO30.l Mg, 136mmol), the reaction mixtures were stirred in 90OC for 4 hours. The reaction solution was cooled at nx)m temperature and the reaction mixture was extracted with dichloromethane and chromatographed to obtain 0.082gm of the titled compound. yield:39% 1H NMR(500MHz. CDCl3): δ 1.16(3H.I). 236(3H,s), 2.48(4H,t), 3.42(4H.t). 3.51(2H,s). 3.9r>(5H,s), 731(5H.s). 8.19(lH,s) Example 73. 1 [(5-ethyl-2-methoxy-6-methylpyridin -3-yl)aminocarboiyl]-4-(4-methoxybe- nzyl)piperazine: 1 - (5-ethyl 2-methoxy-6-metliylpyridin-3-yl)aminocarbonylpiperazine and A methoxybenzylchloride were reacted by the same way with the example 72 to obtain the titled compound. yield:42% Example 74. 1 [(5-ethyl-2-methoxy-6-methylpyridin-3yl)aminocarbonyl]-4-(2-methoxybe- nzyl)piperazine: 1 -(5-ethyl-2-methoxy-6-methylpyridin 3 yl)aminocarbonylpipeazine and 2 methoxybenzylchloride were reacted by the same way with the example 72 to obtain the titled compound. yield:47% Example 75. 1 |(5 ethyl 2 melhoxy (i meihylpvridin 3 yl)aminocarbonyl] 4 (4 fluorobenz yl)piperazine: 1 (5 -ethyl-2-melhoxy-6-methylpyridin 3 yl)aminocarbonylpipeazine and A fluorobenzylchloride were reacted by the same way with the example 72 to obtain the titled compound. yield :52% Example 76. 1 [(2-ethoxy-5-ethyl-6-methylpyridin 3-yl)aminocarbony|]-4-(2-methoxyphe nyl)piperazine: Phenyl-N (2 ethoxy 5 ethyl 6-methylpyridin 3 yl)carbamate and 1 (2-methoxyphenyl)pipera/ine were reacted by the same way with the example 1 to obtain the titled compound. yield :82% Example 77. 1 -[(2-ethoxy-5-ethyl-6-methylpyridin-3 yl)aminocarbonyl]-4-(2-fluorophenyl) piperazine: Phenyl N (2 ethoxy 5 ethyl (5 methylpyridin 3 yl)carbamate and l-(2-fluorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:87% Example 78. 1 -[(2-ethoxy-5-ethyl-6 methylpyridin-3 yl)aminocarbonvi]-4(3-chlorophenyl) piperazine: Phenyl N (2 ethoxy -5 ethyl 6-methylpyridin-3- yl)carbamate and l-(3-chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:83% Example 79. 1 [(2 ethoxy Sethyl ■6-methylpyridin 3 yl)aminocarbonyl] 4(2 ethoxyphenyl) piperazin: Phenyl N (2 ethoxy 5 ethyl (5 methylpyridin 3 yl)carbamate and 1 (2 ethoxyphenyl)piperazine wen- reacted by the same way with the example 1 to obtain the titled coni|X)tind. yield:79?i» Example 80. l-[(5-ethyl-6-methyl 2 phenoxypyridin-3 yl)aminocarbonyl] A (2 methoxyph enyl)piperazine: PhenylN (5 ethyl-6-methyl 2 phenoxypyridin 3 yl)carbamate and l-(2methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:88% Example 81. 1-[(5 ethyl 6-methy 1-2 phenoxypyridin-3 yl)aminocarbonyl] -4-(3 chlorophen yl)piperazine: Phenyl-N-(5 ethyl-6-methyl 2 phenoxypyridin-3-yl)carbamate and l-(3-chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titJed compound. yield :85% Example 82. l-[(5-ethyl-6-methyl-2-phenoxypyridin 3-yl)aminocarbonyl]-4-(3-acetoxyphe nyl)piperazine: Phenyl N (5-ethyl-6-methyl -2-phenoxypyridin 3-yl)carbamate and 1- (3-acetoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the tided compound. yield:83% Example 83. l-[(5-ethyl-6-methyl-2--phenoxypyridin-3-yl)aminocarbon\i]-4-(2-fluorophen- yl)piperazine: Phenyl-N (5 ethyl -6-methyl -2 phenoxypyridin-3-yl)carbamate and 1 (2 fluorophenyl)pipera^ine were reacted by the same way with the example 1 to obtain the titled compound. yield:72% Example 8-1. 1 ((5 ethyl 6 methyl 2 phenoxypvridir. 3 yl)amiuocarbonyl] 4- (3,5 xylyl)pip erazine: Phenyl N (5 ethyl-6-methyl 2 phenoxvpyriclin 3 yl)carbamate and 1 (3,5 xylyl)piperazine were reacted by the same way with the example I to obtain the tilled compound. yieki:78?-o Example 85. 1 [(5-ethyl-6-methyl 2-phenoxypyridin 3yl)aminocarbonyl]-4 (3.5 dimethox yphenyl)piperazine: Phenyl-N (5 ethyl-6-methyl 2 phenoxypyridin-3-yl)carbamate and 1 (3,5 dimethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield 75% Example 86. 1-[(5-ethyl-6-methyl 2-phenoxypyridin-3-yl)aminocarbonyl]-4-(3.5-dichlorop- henyl)piperazine: Phenyl-N (5 ethyl-6-methyl 2 phenoxypyridin-3yl)carbamate - and 1- (3,5 dichlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the tilled compound yield :82% Example 87. 1 [(5-ethyl-6-methyl 2 phenoxypyridin-3yl)aminocarbonyl]--4-(3-hydroxy-4- methoxyphenyl)piperazine: Phenyl N (5ethy 16 methyl 2phenoxypyridin-3-yl)carbamate and 1 -(3-hydroxy-4 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :69% Example 88. 1 [(5 ethyl-6-methyl 2 phenoxypyridin-3yl)aminocarbonyl]-4 (3 hydroxyph enyl)piperaziner Phenyl-N-(5-ethyl-6-methyl 2-phenoxypyridin-3-yl)carbamate and 1 (3 hydroxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the tit let! compound. yiold.72% - Example 89. 1 [(5-ethyl 6methyl 2 meihylaminopyridin 3 yl)aminocarbonyl] 1 (2 metho xyphenyl)piperazine: Phenyl N (5 ethyl-6-methyl 2 methylaminopyridin 3 yl)carbamate and 1 (2 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:73% Example 90. 1 [(5 ethyl-6-methyl 2 methylaminopyridin-3-yl)aminocarbonyl] 4 (3,5 dime thoxyphenyl)piperazine: Phenyl N (5 ethyl-6-methyl 2 methylaminopyridin 3 yl)carbamate and 1 (3,5-dimetoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:82% Example 91. I [(5 ethyl-6-methyl 2 phenoxypyridin 3 yl)aminocarbonyl] 4 (3 chlorophen yl)piperazine: Phenyl N-(5-ethyl 6-methyl 2-methylaminopyridin-3-yl)carbarnate and l-(3 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:79% Example 92. 1 [(5 ethyl-6-methylpyridin 3yl)aminocarbonyl]-4-(2 -methoxyphenyl)piperaz- ine: Phenyl N (5-ethyl-6-meLhylpyridin-3-yl)carbamate and 1 (2 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :80% Example 93. 1 [(5 ethyl-6-methylpyridin 3 yl)aminocarbonyl] -1 (3,5 dimethoxyphenyl)pip erazine: Phenyl N (5 ethyl-6-methylpyridin 3 yl)carbamate and 1 (3,3 flimelhoxypheiiyl)|)i|x,ia/ine were reacted by the same way with the example 1 to obtain the titled coni|X)und. yield :85%. Example 94. 1 ([5 ethyl-6-methyl-2 (1 piperazmyl)pyridin 3 yl]aminocarbonyll 4 (3 chlorophenyl)piperazine: Phenyl N {[5-ethyl 6-meth\12-(l piperazinyl)pyridin 3 yljcarbamate and 1 (3 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:87% Example 95. 1 {[5 ethyl-6-methyl-2-(4 bocpiperazinyl)pyridin 3-yl]aminocarbonyl}-4(3 chlorophenyl)piperazine: Phenyl N-{[5-ethyl -6-methyl 2-(4 boc-piperazinyl)p.\Tidin-3-y!]carbamate and 1 (3 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:92% Example 96. 1 {[5-ethy] 6-methyl-2 (4 -boc-piperazinyl)pyridin-3-yl]aminocarbonyl}-4-{2- methoxyphenyl)piperazine: Phenyl-N-{[5-ethyl-6-methyl-2- (1-boc-piperazinyl)pyridin-3 ylkarbamate and 1 (2 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:94% Example 97. 1 [(5ethyl-2-methoxy-6-methylpyridin-3-yl)aminothiocarbonyl]-4^(2-methox yphenyl)piperazine: Phenyl N (5ethyl-2-methoxy-6-methylpyridin 3 yl)thiocarbamate and 1 (2 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :93% Example 98. 1 ((5 ethyl 2 methoxy b' methylpyridin 3 yl)aminolhi<:b>nyl] 4 (3 rhlorop henyl)|)i|X'razine: Phenyl N (5 ethyl 2 methoxy-6-methylpyridin 3 yI)thi 1 (3 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:88°-o Example 99: 1 -[(5-ethyl-2-methoxy-6-methylpyridin 3 yl)aminothiocarbony]]-4 (2 fluorop henyl)piperazine: Phenyl-N (5-ethyl 2 methoxy-6-methylpyridin-3 yl)thiocarbamate and 1 (2 fluorophenyl)pipenizine were reacted by the same way with the example 1 to obtain the titled compound. yield:82% Example 100. 1 -[(5-ethyl 2-methoxy-6 methylpyridin 3 yl)aminothiocarbonyl]-4(3.5 dimet hoxyphenyl)piperazine: Phenyl N (5 ethyl2 methoxy-6-methylpyridine 3 yl)thiocarbamate and 1 (3,5 dimelhoxyphenyl)piperazine wea reacted by the same way with the example 1 to obtain the titled compound. yield:85% Example 101 1 [(5 ethyl 2 methoxy 6-rnethylpyridin 3 yl)aminothiocarbonyl] A '3,5dichl orophenyl)piperazine: Phenyl N-(5-ethyl 2-methoxy-6-methylpyridin 3 yl)thiocarbamate and 1 (3,5 dichlorophenyl)piperarxe were reacted by the same way with the example 1 to obtain the titled compound. yield :84% Example 102. 1 [(5 ethyl 2-methoxy--6-rnethylpyridin 3 yPoxycarbonyl] 4 (2-methoxyphe nyl)piperazine: Phenyl (5 ethyl 2 methoxy 6 methylpyridin 3 yl)carbonate and 1 (2 methoxyphenyl)piperazir.e were reacted by the same way with the example 1 to-obtain the titled comixmnd. yield:72°o ... ->j-Example 103. 1 [(5-ethyl 2 methoxy-6-methylpyridin 3 yl)oxycarbonyl] 4 (3 chlorophenyl) piperzine: Phenyl (5-ethyl-2-methoxy-6-methylpyridin 3 yl)carbonate and 1 (3 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:74% Example 104. 1 [(Sethyl 2 methoxy-6-methylpyridin 3 yl)oxycarbonyl] 4-(3,5 dimethoxyp henyl)piperazine: Phenyl (5-ethyl 2 methoxy-6-methylpyridin-3-yl)carbonate and 1 (3,5 dimethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:77% Example 105. 1 [(5 ethyl 2 -methoxy-6-methylpyridin 3 yPmethyloxycarbonyl] 4 (2 metho xypheny ! )piperazine- Phenyl-(5-ethyl-2-!nethoxy-6--methylpyridin-3-y!)methy!carbonate and 1 (2-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield -82% Example 106 1 [(5-ethyl-2-methoxy-6-methylpyridin-3-methyloxycarbonyl]-4-(3-chlorop heny-1)piperazine: Phenyl(5-ethyl-2-methoxy -6- methylpyridin 3-y!)methy!carbonate and 1-(3-chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:79% Example 107. 1 [(5,6 dimethyl 2 methoxypyridiii 3 yl)aminocarbonyl] 1 phenylpiperarine Phenyl N '.5,6 dimethyl 2 methoxypvridin 3 yl)rarbamate and I phenylpiperazine were rrncled by the same way with the evunplc 1 to obtain the titled compound. yield :«S4"o Example 108. 3 [(5,6 -dimethyl 2 methoxypyridin-3 -yl)aminoxarbonyl]-4-(2- methoxyphenyl) piperazin Phenyl-N-(5,6-dimethyl 2 methoxypvridin 3 yl)carbamate and 1 (2 methoxyphenyPpipera/ine were reacted by the same way with the example 1 to obtain the tilled compound. yield:88% Example 109. l-[(5,6-dimethyl-2 methoxypyndin-3-yl)aminocarbonyl]-4-(3 chlorophenyl)pi perazinc'- Phenyl-K-(5.6-dimethyl 2-methoxypyridin-3-y!)carbamate and l-(3-chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled commund. yield:92% Example 110. 1-[(5,6-dimethyl-2-methoxypyridin 3-yl)aminocarbonyl]-4-(2-fluorophenyl)pip- erazine: Phenyl N -(5,6 dimethyl -2-methoxypyridin -3-yl)carbamate and l-(2-fiuorophenyi)piperazine were reacted by the same way with the example 1 to obtain the titled compound. ylciu- / a/o Example 111. 1-[(5,6-dimethyl-2-methoxypyridin 3 yl)aminocarbonyl] 4-(3,5-difluorophenyl) piperazine: Phenyl N (5,6 dimethyl- 2 methoxypyridin 3yl)carbamate and 1 (3,5difluorophenyl)pipenizine were reacted by the same way with the example 1 to obtain the titled compound. yield :87"b Example 112. 1 [(5,6 dimethyl 2 methoxypyridin 3 yl)aminothixocatrbonyl) 1 (2 hydroxyphe nyl)piprazine: Phenyl IN (5,6 dimethyl-2 melhoxypyndipeR3 yl)carbamate and 1 (2-hydroxyphenyi)piperazine were reacted by the same way with the example i to obtain the tilled compound. yield :85% Example 113. ] -[(5.6 dimethyl-2-methnxypyridin 3 yl)aminocarbonyl]-4 piperazine: Phenyl N-(5,6 dimethyl 2 methoxypyridin 3 yl)carbamate and 1-(3-hydroxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield 78% Example 114. 1-[(5,6 dimethyl 2 methoxypyridin 3 yl)aminocarbonyl] 4 (4 hydroxyphenyl) piperazine: Phenyl N (5.6 dimethyl 2 methoxypyridin -3 yl)carbamate and 1 (4 hydroxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound, yield :72% Example 115. 1 -[(5,6-dimethyl-2-methoxypyridin-3 yi)arninocarbonyl]-4-(3-aceioxyphenyi) piperazine' Phenyl N (5,6 dimethyl 2 methoxyprrodom 3 yl) carbamata and 1 - (3) -acetoxyphenyl)piperazine were reacted by the sane way with teh exsmple 1 to obtain the titled compound. yie!d:92% Example 116. 1 [(5,6 dimethyl 2 meihoxypyridin 3 yl)aminocarbonyi]-4(4 aceioxyphenyl) piperazine: Phenyl N (5,6 dimethyl 2 meihoxypyridin 3 yl)carbamate and ] (1 acetoxypher.yl)piperazint-* were reacted by the sane way with the example 1 to obtain the tilled compound. yield:89% Example 11V. 1 [(5,6 dimethyl 2 methoxypyridin 3 yl)aminocarbonyl] 4 (3 acetoxy 4 met hoxypheiiyl)piperazine: Phenyl N (5,6 dimethyl 2 melhoxyp> ridine 3 yl)carbamate and 1 (3 acetoxv 1 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:69% Example 118. 1 [(5,6 dimethyl 2 methoxypyridin 3 yl)aminocarbonyl]-4-(3,5 dimethoxyphe nyl)piperazine: Phenyl N (5,6 dimethyl 2 methoxypyridin 3 yl)carbamate and 1(3,5 dimethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield : 88% Example 119. 1 -[(5,6 dimethyl 2 methoxypyridin 3 yl)aminocarbonyl] 4 (2,3 xylyl)piperazine Phenyl-N-(5,6-dimethyl 2 methoxypyridin -3-yl)carbamate and 1-(2,3-xylyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound, yield 72% Example 120. 1 [(5,6 dimethyl 2 methox\ pyridin -3 yl)aminocarbonyl] 4- (3,5 xylyl)piperazine Phenyl N (5,6 dimethyl 2 methoxypyridin-3-yl)carbamate and 1 (3,5 xylyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:68% Example 121. 1 [(5,6 dimethyl 2 methoxvpvridin 3 yl)amitux'arbonyl] A (2,5 xyIyl)piix.Tazine Plienyl N (5.6 dimethyl 2 mcihoxypyridin 3 yl)carbajnate and 1 (2,5 xylyl)piperazine wen- reacted by the same way with (he example 1 u> obtain the titled compound. yieki:72°-o Example 122. 1 [(5.6 dimethyl 2 methoxvpvridin 3 yl)aminocarbonyl] A (2-hydroxy A met hylphenyl)piperazine-' Phenyl N (5.6 dimethyl 2 methoxypyridin 3 yl)carbamate and 1 (2 hydroxy 1 methylphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :77% Example 123. 1 [(5,6 dimethyl 2 methoxypyridin 3 yl)aminocarbonyl]-4-(3 hydroxy A met hoxyphenyl)piperazine Phenyl N-(5.6 dimethyl 2 methoxypyridin 3 yl)carbamate and 1(3 hydroxy -1 metiioxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yieki:69% Example 124. l-[(5,6dimethyl 2-meth()xypyridin-3-yl)aminocarbonyl]-4-(l-naphthyl)pjpera zine: Phenyl -N-(5,6-dimethyl 2 methoxypyridin -3- yl)carbamate and 1 (l+naphthyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield-74% Example 125. 1 [(5,6-dimethyl' 2 methoxypyridirv-3-yl)aminocarbonyl] 4 (1 anthryl)piperazi ne: Phenyl N (5,6 dimethyl 2 methoxypyridin3-yl)earbamale and 1 (1 anthryl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield -62% Example 126. 1 ((5,6 dimethyl 2 methoxypyridin 3 yl)aminothiocarbonyl) 1 (3 chlorophenyl) piperazine: Phenyl N (5,6 dimethyl 2 methoxypyridin 3 yl)thiocarbamate and 1 (3 chlorophenyl)piperazitie were reacted by the same way with the example 1 to obtain the titled compound. yield-69% Example 127. 1 [(5,6 dimethyl 2 methoxypyridin 3 yl)aminocarbonyl] 4- (3.5 dichlorophenyl) piperazine: Phenyl N (5.6dimethyl 2 methoxypyridin 3 yl)thiocarbamate and 1 (3,5 dichlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:82% Example 128. 1-[(5,6 dimethyl 2 methoxypyridin 3-yl)aminocarbonyl] 4 (2-methoxypheyl) piperazine: Phenyl N (5.6 dimethyl 2 nxuhoxypyridin 3 yl)thiocarbamate and l-(2-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound, yield 70% Example 129. 1[(5,6 dimethyl 2-methoxypyridin 3 yl)aminothiocarbonyl]-4 (3,5dirnethoxy - phenyl)piperazine^ Phenyl-N (5,6 dimethyl 2 methoxypyridin 3-yl)thiocarbamate and 1 (3,5 dimethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :69% Example 130. 1 [(2 methoxy 5,6,7 trihydro-1-pyrinden 3 yl}aminocarbonyl] 4 (2 methoxyp henyl)piperazine: Phenyl N (2 methoxy 5,(5,7 irihydro 1 pyrinden 3 yl)carbamate and 1 (2 melhoxyphenyl)pipera/ine were reacted by the same way with the example 1 to obtain the titled compound. yield 64% Example 131. 1 [(2-methoxy 5.(5,7 trihydro 1 pyrinden 3 yl)aminocarbonyl] 'I (3 chlorophe nyl)piperazine: Phenyl N (2 methoxy 5,6,7 trihydro 1 pyrinden 3 yl)carbamate and 1 (3 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:63% Example 132. 1 - [(2 methoxy 5.6,7 trihydro -1 -pyrinden -3 yl)aminocarbonyl] A (2 fluorophe nyl)piperazine: Phenyl N (2 methoxy 5,6,7 trihydro 1-pyrinden 3 yl)carbamate and 1 (2-fluorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:59% Example 133. 1 [(2-methoxy-5,6,7,8 tetrahydroisoquinolin-3 -yl)aminocarbonyl] -•!- i2-methox- yphenyl)piperazine: Phenyl- N(2 methoxy -5,6,7,8-tetrahydroisoquinolin-3-yl)carbamate and l-(2-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. y\e\d-6A% Example 13-1. l-[(2-methoxy-5,6,7,8-tetrahydroisoquinolin-3-yl)aminocarbonyl] -l(3chlorop- henyl)piperazine: Phenyl N (2-methoxy-5,6,7,8 tetrahydroisoquinolin-3 yl)carbamate and 1 (3 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield ffl% Example 135. 1 |(2 melhoxy 5,6,7,8 letrahvdroisoquinolin .3 yl)amiiKxarbonvl] 1 (2 fluorop hrnyl)pipeniz-ine' Phenyl N (2 methoxy 5,6,7,8 teltahydroisoquinolin 3 yl)carbamate and 1 (2 fluorophenyl)pipernzine were reacted by the same way with the example 1 to obtain the titled compound. yield:70% Example 136. 1 [(5 •isopropyl-2-methox> -6-methylpyridin 3-yl)aminocarbonyl] 1 (2 metho xy phenyl )pipera?ine'- Phenyl N (5 isopropyl 2-methoxy-6-methylpyridin 3 yl)carbamate and 1 (2 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the tilled compound. yield :6 Example 137. 1 1(5 isopropyl -2-methoxy 6- methylpyridin -3 yl)aminocarbonyl]-4 (3 chloro- phenyl)piixerazine: Phenyl N (5 isopropyl 2 methoxy 6- methylpyridine 3 yl)carbamate and 1 (3-chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :639% Example 138. l--[(5--isopropyl-2-methoxy--6-methylpyridin--3-yl)aminocarbonyl]-4-(2-fluorop- henyl)piperazine: Phenyl - N (5 - isopropvl - 2 methoxy-6 methylpyridin-3-y1)carbamate and l-(2-fluorophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:59% Example 139. 1 - [(2 -methoxypyridin 3yl)aminocarbonyl]-4-phenylpipera;nne: Phenyl N(2-methoxypyridin 3 )'l)carbamate and 1 phenylpiperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :88% Example WO. 1 [(2 methoxypyridin 3 yl)aminocarbonyl) 4 (2 methoxyphenyl)piperazine Phenyl N (2 methoxypyridin 3 yl)carbamale and 1 (2 rnethoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:86% Example 111. 1 [(2-methoxypyridin 3 yl)aminocarbonyl]-4 (4 rnethoxyphenyl)piperazine: Phenyl N (2 methoxypyridin 3 yl)carbamale and 1 (4 methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :85% Example 142. 1 [(2-methoxypyridin-3 yl)aminocarbonyl] 4 (3 chlorophenyl)piperazine: Phenyl - N (2 rnethoxypridin-3-yl)carbamate and 1 -(3 chlorophenyl)piperazine were reacted by the same way with the example 1 to obtain the tilled compound. yield:72% Example 143. l-[(5-ethyl 2 methoxy-6-methylpyridin 3 yl)aminocarbonyl]-4- [(3 propargyl amino)pyridin-2-yl]piperazine: Phenyl N-(5 ethyl 2 methoxy-6 methylpyridin 3-yl)carbarnate and 1 [(3 propargylamir.O'pyridine 2 yl)piperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:61% Example 141. l[(5-ethyl -2 methoxy-6-methylpyridin-3 yl)methylaminocarbonyl] 4 [(3 pro pargylamino)pyridin 2 yljpiix^razine: Phenyl N (5 ethyl 2 methoxy ft methylpyridin 3 yl)meiln Icarbamate and 1 [(3 propargylaminu;pyridin 2 yllpiperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:74°o Example 115. 1 {[5 ethyl-6-methyl 2(1 II) pyridinon 3 yljmethylamincxarbonyl! 1 [(3 propa rgylamino)pyridin 2 yl)piperazine: Phenyl N [5 ethyl 6 melhyl 2(111) pyridinon 3 yl]methylcarbamate and 1 [(3 propargylamino)pyridin 2 yl]pi|xjrazine were reacted by the same way with the example 1 to obtain the titled compound. yield:77% Example 146: 1-{[5-ethyl-6-methyl 2(1H) pyridinon 3 yl]methylarninocarbony|} 4 [(3 dibe nzylamino)pyridin 2 yljpipenizine: Phenyl N [5 ethyl-6-methyl 2(1H) pyridinon 3 yl]methylcarbamale and 1 [(3 dibenzylamino)pyridine 2 yllpiperazine were reacted by the same way with the example 1 to obtain the titled compound. yield :65% Example 147. 1 {[5-isopropyl-6-methyl 2(1 H) pyridinon 3 yl]melhylaminocarbonyl) 4 [(3 ethylamino)pyridin 2 yllpiperazine PhenylN [5 ethyl-6-methyl 2(1H) pyridinon 3 yllmethylcarbarnaie and 1 [(3 ethylamino)pyridin 2 yllpiperazine were reacted by the same way with the example 1 to obtain the titled compound. yield:62% Example 148. 1 [(5-ethyl-2-methoxy-6-methylpyridin 3- yl)aminocarbonyl]-4 [(2 methoxyp henyl)piperazine-2-yl]piperazine salt of hydrochloride: After l-[(5-ethyl -2-methoxy 6-methylpyridin-3-yl)aminocarbonyl]-4-(2 met hoxyphenyl)pipera.zine(5.0g, 13mmol) was dissolved in 100m] of diethylether, the mixture was saturated by hydrogen chloride gas at 0OC and stirred for 30 minutes and purified to obtain the titled compound. yield:98% Example 149. l[(5ethyl-? methoxy-6-methylpyridin-3 yl)aminocarbonyl] 4 (3 ehlorophen yl)piperazine salt of hydrochloride: 1 [(5 -ethyl-2 methoxy-6-methylpyridin 3 yl)aminocarbonyl] 4 (3 ehlorophen yl)pipera/.ine was reacted by the same way with the example 1 IS lo obtain the titled eomixmiul. yiekl:9H% (Table Removed) Antitumor activities of the compounds of present invention were tested. Antitumor activities of compounds of the present invention were tested in vitro against 5 kinds of human tumor cell lines and 2 kinds of leukemia tumor cell lines. The method of in vitro test is as follows. Example 1) In vitro antitumor effect against human tumor cell lines A. Tumor cell line : A5 19 (human non small lung cell) SKOV 3 (human ovarian) HCT 15 (human colon) XT 498 (human CNS) SKMEL 2 (human melanoma) H. Method of tesuSRB Assay Method) a. Human solid tumor cell lines. A59l(non small lung cell), SKMH1. 2(melanoma). HCT 15( were cultured at .T7"C, in 5"n ('()• incubaler using [tie HPM1 1»>10 media containing 10".> KBS. while they were transfer cu+tured • ueccssiveh once or twice per week Cell culliires were dissolved into (lie solution of 0.25'Vi trvpsin and A mM CDTA l'BS( ) and then cells were M-paraled from media which the cells were slicked on. b. 5 • 10 2 • 10' cells were added into each well of iMi weii plate and cultured in 5°o CO- incubater, at 371', for 21 hours. c. Hach sample drugs was dissolved in a small quantity of DM SO, and diluted to concentrations prescribed in experiment with media, and then the final concentration of DMSO was controlled below 0.5V d. A medium of each well cultured for 21 hours as above b.. was removed by aspiration. 200//I of drug samples prepared in c. was added into each well and the wells were cultured for 18 hours. T/.dime zero) plates were collected at the point of lime drugs were added. e. After Tz plates and plates were treated with cell fixing by TCA of SRI3 assay method, staining of 0.-1% SRB solution, washing with 1% acetic acid, OD values were measured at 520 nm, following elution of dye with 10 mM Tris solution. C. Calculation of result a. Time zero(Tz) value was determined by oblainmenl of SRB protein value at ihe point of lime drugs were added. b. Control value(C) was determined with OD value of well that was not added with drug. c. Drug treated test value(T) was determined with OD value of well treated with dug. d. Drug effects of growth stimulation, net growth inhibition, net killing etc. were determined with Tz, C and T. e. If T > Tz, cellular respor.se function was calculated with lOOxiT Tz). (C Tz), and if T The results are shown in the next table. * REFERENCE ]• P. Skehan, R. Strong, D Scudiero, A. Monks, J. B.Mcmahan, D.T. Vistica, J. Warren, H. Bokesh, S. Kenny and M. R. Boyd : Proc Am. Assoc. Cancer Res.. 30, 612(1989) 21 I.A'. Rubinstein, H.I 1. Shoemarker, K. D. Paull, R.M. simon, S. Tosini, P. Skchan, D. Scudiero, A. Monks and M. R. boyd. ; J. Natl. Cancer Inst.. 82 1113(1990) 3) P Skchan. r. strong, I). Scudien). A monks. J. B Memahan. D t. Vislica, I Warren. H. Bokesh, S. Kenny and M. R. Boxd J. Natl. Cancer ins., 82. 1107(1990) D. Results. It was found that the compounds of present invention have the suijerior antitumor activities to those of the control, cisplatin against 5 kinds of human solid cancer cell lines. Esixnially. compounds of example 1), 6). 13). 1(5). 28), 291. 38). -11). 47). AS), 49). 50), fw). fir. 91), 97). 98). 100), 108). 109). 111). 1131. 115). 118), 119). 120), 121). 12o). 128). 129), 141). 148). 119) have superior antitumor activities to those of cisplatin. (Table Removed) Example 2) * In vitro antitumor effects against animal leukemia cells. A. Material of experiment Tumor cell lines : L1210(mouse leukemia cell) P388 (mouse lymphoid neoplasma cell) B. Method of experiment(Dye Exclusion Assay) 1) L1210 and P388 cells that were cultured in RPMI 1610 media containing 10 °>> FBS were regulated as the cell concentration of 1 v 10° cells ml. 2) Sample drugs diluted with log dose were added into the cells, and it were cultured at 371C, for 48 hours, in 50 % CO2 incubater, and then viable cell number was measured. Viable cell number was measured with dye exclusion test using trypan blue. 3) The concentration of sample compounds of 50% cell growth inhibition compared wilh standard group was determined as IC50,. The results are shown at the next table. * REFERENCE H P.Skehan. R. Strong. I). Seudiero. A. Monks. J. B Mcmahan. I). T. Vistira, J. Warren. H. Bokesh. s. Kenney and M. R. Boyd. : Proc Am. Assnc Cancer Res.. 30. 612(1989). 2) L.V.Rubinstein. R.H. Shoemaker. K.I) Paull. R.M. Simon. s. Tosini,P.Skehan, D. Scudiero. A. Monks. J. Natl. Cancer Inst.. 82, 1113(1990) 3) P.Skehan, R. Strong. D.Scudiero. J. B. Mcmanhan. D.T. \ istica. J. Warren. H. Bokesch. S.Kenney and M.R. Boyd. '• J. Natl. Cancer Inst.. 82. 1107(1990) C. Result As the results of measurement of antitumor activities of comixuinds of the present invention against 1.1210 and P388 mouse cancer cells, it was found that compouds of example 1). 6). 13). 16), 29). 38), 41). 17). 18). 19). 108). 118). 120). 128). MS), 149) had same or more excellent antitumor activities than those of the control drug, mylomicin C. (Table Removed) In vivo antitumor activity test was carried out in mice with samples having significance in in vitro test. Example 3' * In vivo antitumor effects against mouse leukemia P388 cells. A. Material of experiment BDE1 mice were used. B. Method of experiment 1) Leukemia P388 cells being transfer cultured succesively in DBA/2 mouse, were grafted i.p. into each mouse of a group comprising 8 mice of-6-week old BDFI mouse as the dose of 1 * 10'cells/ 0.1 ml. 2) Sample drugs were dissolved in PBS or suspended in 0.5% Tween 80, and then injected into abdominal cavity of mouse at each prescribed concentration on days 1, 5, 9, respectively. 3) With observation every day, survival times of tested mice were measured. Antitumor activities was determined in such a manner that the increasing tato(T C%) of average survival clays of drug treated groups compared with the control group was calculated using the mean survival limes of each tested groups. The results are shown at the next table. * REFERENCE A. Goldin. J. M. Venditti, J. S. Macdonald, F.M.Muggia. J.E.Henney and V. T. DeVita. :Euro. J. S. Macdonald. F. M. Muggia, J. E. Henney and V. T. DeVita: Euro. J. Cancer, 17, 129 (1981). * Experimental Conditions for mouse P38H Animal Tumor Inoculum size Inoculum site Treatment site Treatment lime Parameter Criteria BDFI mouse ( 8 mice/ group ) '■ mouse P388 : 10 cells/mouse : i. p. : i. p. : days I, 5, 9 : median survival lime : T/C % C. Result Through in vivo experimenL using P388 mouse cancer cells, significant aiuiiumor effect of the compounds of example 1), 6), 16), 29) were observed. (Table Removed) Example 1) In vivo antitumor activities against mouse solid tumor. B16 melanoma. A. Material of experiment. BDF1 mouse was used in experiment while being successively transfer cultured in C57BL/6 mice by s.c. B. Methods 1) After Ig of tumor was added into cold balanced salt solution up to be 10ml. it was homogenized (K):l,brei). 2) 0.5 ml Brei of the above 1) were grafted into each BDFI mouse by i. P- 3) Median survival time was measured, and the activity was determined in such a manner thai if T/C was over 125 %, it presented moderate activity, while if it is over 150 %, it had significant activity. The results are shown at the next table. •REFERENCE A. (ioldin, J. M. Venditli. J. S. Macdonald. F. M. Muggia, J.HI.Henney and V. T. IX'Vita. FZuro.J.Cancer. 17, 129(1981). (Table Removed) C. Results With in vivo experiment using B16 mouse melanoma solid tumor, it was observed that the compounds of examples (5), lb) etc. have the significant antimumor activities. (Table Removed) Example 5) * Acute toxicity test ( I.D50 ) Litchfield Wilcoxon method.-6-week old ICR mice(male 30 + 2.0g) was fed freely with solid feed and water at room temperature, 23 +UV and at humidity 60 5%. Sample drugs were injected into the abdominal cavities of mice, while each goup comprises-6-mice. Oserved during H days, external appearances and life or dead were recorded, and then, visible pathogenies were observed from dead animals by dissection. LD50 value was calculated by Lite hfiled wileoxon met hod. The results are shown at the next table. (Table Removed) As deseribed above. it was found that the compouds of the present invention are more safer and have superior antitumor activities to cisplaiin, and accordingly have solved the problems of drugs by the prior art such as restriction of dosage, toxicity, etc. Examples of pharmaceutical preparations Tablets: (examples 1 A) Tablet(250mg) was prepared with the ingredients of the following table by conventional tablet manufacturing metruxl. (Table Removed) Injectable preparations (examples I) 10) Injectable preparations( 5ml of ampoule and vial) were prepared with tin-ingredients of the following tables by the conventional injection manufacturing method. (Table Removed) Suppositomexamples 21 24) Suppository(lg) was prepared with the ingredients of the following table by conventional suppository manufacturing method. (Table Removed) Oral solution (example 25 28) Oral solution( 100ml) was prepared with the ingredients of the following tables by the conventional oral solution manufacturing method. (Table Removed) Troche(examples 29-32) Troche(500mg) was prepared with the ingredients of the following table by conventional troche manufacturing method. (Table Removed) We Claim:- A compound -1 [(2,5,6-trisubstitutedpyridine)-3-yl]aminocarbonyl]-4-(substituted phenyl) piperazine of the general formula (I): (Formula Removed) wherein R1 and R2 are independently selected from the group consisting of hydrogen and C1-C8 alkyl; R3, R4, R5, R6 and R7 are independently selected from the group consisting of hydrogen, halogen, hydroxy, nitro, -OCOC1-C4 lower alkyl, C1-C4 lower alkyl, C1-C4 lower alkoxy, and phenyl; 1 is an integer of 0, 1, 2, 3, 4, 5, 6 or 7; m and n are independently an integer of 0 or 1; W is carbon or nitrogen; X is selected from the group consisting of oxygen and sulfur; Y is NH or oxygen; and Z is selected from the group consisting of C1-C8 alkoxy, phenoxy, C1-C4 alkylamine and oxo group; or a pharmaceutically acceptable acid addition salt thereof. 2. The compound as claimed in claim 1, which is a compound of the formula(I'): (Formula Removed) wherein Rh R;, R3, R4, R5, R6, R7, 1, m, n, VV, X and Y are as defined above. 3. The compound as claimed in claim 1, wherein W is carbon. 4. The compound as claimed in claim 1, wherein W is nitrogen. 5. The compound as claimed is claim 1 as and when used for making pharmaceutical composition for preventing or treating various kinds of tumours. 6. A compound of the general formula (I), substantially as hereinbefore described with reference to the forgoing examples.

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