Tricyclic derivative compound, method of preparation thereof, and pharmaceutical compositions containing it
Patent Information
- Application Number
- IR139650140003010568
- Authority / Receiving Office
- IR · IR
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2016-06-03
- Filing Date
- 2017-12-05
- Publication Date
- 2025-11-15
- Estimated Expiration
- 2037-12-05
Abstract
Description
...................... :Khairat ...................... :Harashm Yoqqh Tormsha and Tekalo Millibain Daftar Naramke and Yaql Dr. Mahesht Bakt, 011 Kꢐp, Yashpar Namsakht, Yaghrb Fi'at Dishe Hakuch, Saraliyo Nakhiba 11112122 - 11101022 : Nalft 6.44 52.90 17.42 21.22 111.98 179.64 4.82 11.47 53 54 55 56 57 58 59 60 61 62 63 64 114 115 116 117 118 119 120 121 122 123 124 125 126 127 176 177 178 179 180 181 182 183 184 185 186 187 188 189 7.47 7.28 30.09 6.67 7.33 159.00 5.27 5.98 11.57 1.95 4.65 4.81 4.02 4.80 13.97 19.42 3.49 5.04 11.12 27.82 4.46 5.79 11.78 13.28 5.92 7.09 7.55 7.08 77.15 10.38 47.98 7.43 7.85 65 Tankyrase-2 and Tankyrase-1 enzymes Chiasma: 1 Experimental Example For the present study, the presence of tankyrase-2 or tankyrase-1 inhibitors or inhibitors of the BPS Bioscience Chiasma (cat. 80578 or cat. 80573) was used for the purpose of the assay. The 2-well plate was filled with 7.5 mM PBST (96-well) and the BPS Bioscience tube was filled with 7.5 mM PBST (96-well) and the tube was then washed.Dash habanko tasa 06 tamd hab adrgtinssa hadraj hab w dash htssh,)Na. 2 HPO 4 2.5 mM NaH 2 PO 4 , 145 mM NaCl, 0.05% Tween 20, pH 7.4 Bioscience BPS (Bioscience BPS) buffer, 12 mM NaCl, 0.05% Tween 20, pH 7.4, 10 11101022: Tankyrase-2 enzyme (40 ng / well) and tankyrase-1 enzyme or enzyme-binding protein, such as 12-fold and 15-fold, were added to the PBST medium with 0.05% PBST, and the reaction mixture was stirred for 1 h.The streptavidin-linked PARP-binding protein was incubated for 21 days in a 12-well plate with PBST and HRP (Strep-HRP, 1:50 dilution) for 12 h. The reaction was carried out in a 1:100 dilution. The reaction was carried out in a 1:100 dilution with PBST and HRP. The Synergy™ H4 was incubated with HRP for 12 h. (BioTek Instruments, Inc., USA) was used to analyze the radioactivity of the samples, and (Systat Software Inc., USA) SigmaPlot 10 was used to analyze the samples with the IC chip. 50 .) The other part is 8 and 0. 011 ...................... :Khairat ...................... :Harashm Yoqqh Tormsha and Tekalo Millilabin Daftar Naramkeh and Yaaql Dr. Mahesht Bakt, 011 Kp, Yashpr Namsakht, Yaghr Fiyaat Dishe Hakouch, Saraliyo Nakhiba 11112122 - 11101022 : Naft 0 Dolj TNK-1 enzyme (nM) TNK-1 enzyme (nM) TNK-1 enzyme (nM) Example Example Example 59.58 34.03 8.46 4.15 4.04 1 7 84 85 134 135 11.76 012 ...................... :Khairat ...................... :Harashm Yoqqh Tormsha and Tekalo Millilabin Daftar Naramkeh and Yaaql Dr. Mahesht Bakt 011, KꢀP, Yashper Namsakht, Yaghar Fiat, Disheh Hakoch, Sarali and Nakhiyaba 11112122 - 11101022: Naleft 35.18 89.07 34.95 31.35 56.42 20.10 16.75 4.96 5.07 30.98 35.20 12.87 3.59 3.36 10.57 18.53 5.82 39 48 50 51 52 53 54 56 57 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 80 81 89 137 139 140 141 142 143 145 149 150 151 152 158 160 161 166 167 169 170 171 172 174 176 177 178 180 181 182 183 184 185 186 187 189 90 91 92 4.42 93 42.44 11.45 6.77 21.45 6.29 94 95 14.26 18.05 56.67 16.97 17.33 10.65 32.04 36.28 97.20 32.39 9.65 96 26.52 1.37 8.81 97 36.72 5.59 98 12.11 13.68 26.18 15.02 16.17 13.87 13.21 14.03 49.19 5.77 99 18.92 25.16 28.81 12.46 50.71 11.40 25.12 38.47 18.77 12.55 10.66 5.00 100 101 102 103 104 107 108 110 111 112 113 119 120 122 123 124 125 128 129 131 132 133 16.65 162.00 90.32 116.40 14.78 27.33 8.05 12.37 14.19 16.34 15.55 17.26 11.38 11.28 16.28 10.96 39.86 45.93 10.20 7.28 3.92 11.57 3.33 10.43 10.40 25.76 5.56 46.16 37.08 35.79 47.13 22.92 16.05 9.89 2.77 35.07 82 14.19 012 ...................... :Khairat ...................... :Harashm Yoqqh Tormsha and Tekalo Millilabin Office of the Nramake and Yaqel Dr. Mahesht Bakt, 011 Copy, Unauthorized Yashar, Yagharb Fiyat Dishe Hakouch, Saraliy Nakhiba 11112122 - 11101022 : Naft 8 Dolj Ahlouls Za Hdaftsa with PARP-1 Regiming of the Rham Shiazma: 2 Experimental Example of the PAR Devolt Ardqom, Present Ethreot Tabitrk PARP-1 Regiming of the Rham Yahiavant Sirber Vermanz Heb.The cells were cultured in 1% RPMI medium at 2 x 10 HCT-15 cell lines. 4 HCT-15 Head Mattress or Headless Mattress (FBS) 06 TMD CO 2 2 and the other can be 20 times then, the number of cells / well under the example of the tabiter of the number of cells or the number of cells with the population, the number of cells after 012.
Claims
1Claims 1- A tricyclic derivative compound represented by the following formula 1, its optical isomer, its racemate or its pharmaceutically acceptable salt: Formula 1 wherein: L is -CH2- or -C(=O)-; R1 is hydrogen, a halogen atom or C1-C3 alkoxy; each of R2 and R3 is independently hydrogen or C1-C3 alkyl, or R2 and R3 are joined together to form a ring.Ring A, phenyl or heteroaryl is substituted with a substituent selected from the group consisting of pyridine, pyrazine, pyrimidine pyridazine, thiophene, thiazole, thiadiazole, oxazole, oxadiazole, indole, indazole, dihydrocyclopentapyridine, dihydrofuropyridine, oxazolopyridine, benzoxazole and benzoisoxazole, wherein one or more hydrogen atoms of phenyl are substituted with a substituent selected from halogen atom, -CN, -CF3, alkylC1-C3, alkoxyC1-C3, -CH2-OR4, -C(=O)-R4, -C(=O)-OR4, -S(=O)2-R4, -NH-C(=O)-R4, -NO2, -NR4R5 and -C(=O)-NR6R7, and heteroaryl is unsubstituted, one or more hydrogen atoms of Heteroaryl is substituted by a halogen atom, -CN, -CF3, C1-C3 alkyl, C1-C3 alkoxy, -CH2-OR4, -C(=O)-OR4, -S(=O)2-R4 and -C(=O)-NR6R7: R4 is C1-C3 alkyl: R5 is C1-C3 alkyl: R6 is hydrogen or C1-C3 alkyl: and R7 is C1-C3 alkyl or C3-C7 cycloalkyl (wherein the compounds of Examples 95, 118, 146, 179 and 189 are omitted). 2- (modified). The tricyclic derivative compound, its optical isomer, its racemate or pharmaceutically acceptable salt according to claim 1, wherein: L is -CH2- or -C(=O)-; R1 is hydrogen, a halogen atom or C1-C3 alkoxy; each of R2 and R3 is, independently, hydrogen or C1-C3 alkyl, or R2 and R3 are joined together to form a ring. Ring A, phenyl or heteroaryl, is substituted with a substituent selected from the group consisting of pyridine, pyrazine, pyrimidine, pyridazine, thiophene, thiazole, thiadiazole, oxazole, indole, indazole, dihydrocyclopentapyridine, dihydrofuropyridine, oxazolopyridine, benzoxazole and benzoisoxazole, wherein one or more hydrogen atoms of phenyl are substituted with a substituent selected from the group consisting of halogen atom, -CN, alkylC1-C3, alkoxy -C1-C3, -C(=O)-R4, -NH-C(=O)-R4, -NO2, -NR4R5 and -C(=O)-NR6R7 and pyridine is not substituted, or one or more hydrogen atoms of pyridine are substituted with a substituent selected from the group consisting of halogen atom, -CN, alkylC1-C3, alkoxy C1-C3, -CH2-OR4 and -S(=O)2-R4 when pyridine is substituted with C1, 1R and not F) are substituted, and pyrazine, pyrimidine, pyridazine,thiophene, thiazole, thiadiazole, oxazole, indole, indazole, dihydrocyclopentapyridine, dihydrofuropyridine, oxazolopyridine, benzoxazole or benzoisoxazole are not substituted, or one or more hydrogen atoms of pyrazine, pyrimidine, pyridazine, thiophene, thiazole, thiadiazole, oxazole, indole, indazole, dihydrocyclopentapyridine, dihydrofuropyridine, oxazolopyridine, benzoxazole or benzoisoxazole are selected from the group consisting of halogen atom -CN, alkyl C1-C3, alkoxy C1-C3, -C(=O)-R4, -C(=O)-NR6R7 (when thiazole is not substituted with CN-, -C(=O)L -C(=O)); R4 is C1-C3 alkyl; R5 is C1-C3 alkyl; R6 is hydrogen or C1-C3 alkyl; and R7 is C1-C3 alkyl or C3-C7 cycloalkyl. 3- (modified) The tricyclic derivative compound, its optical isomer, its racemate or pharmaceutically acceptable salt according to claim 2, wherein: L is -CH2- or -C(=O)-; R1 is hydrogen, a halogen atom or C1-C3 alkoxy; each of R2 and R3 is, independently, hydrogen or C1-C3 alkyl, or R2 and R3 are joined together to form a ring. Ring A, phenyl or heteroaryl, is substituted with a substituent selected from the group consisting of pyridine, pyrazine, pyrimidine, pyridazine, thiophene, thiazole, thiadiazole, oxazole, indole, indazole, dihydrocyclopentapyridine, dihydrofuropyridine, oxazolopyridine, benzoxazole and benzoisoxazole, wherein one or more hydrogen atoms of phenyl are substituted with a substituent selected from the group consisting of halogen atom, -CN, alkyl -C1-C3, alkoxy -C1-C3, -C(=O)-R4, -C(=O)-OR4, -NH-C(=O)R4, -NO2, --NR4R5 and -C(=O)-NR6R7 and pyridine is not substituted, or one or more hydrogen atoms of pyridine are substituted with a substituent selected from the group consisting of halogen atom (selected from F and Br), -CN, -CF3, -C1-C3 alkyl, -C1-C3 alkoxy, -CH2-OR4 and -S(=O)2R4 are substituted, thiazole is not substituted, or one orSeveral hydrogen atoms of thiazole are substituted with a substituent selected from the group consisting of -C(=O)-OR4 and -C(=O)-NR6R7, and pyrazine, pyrimidine, pyridazine, thiophene, thiadiazole, oxazole, indole, indazole, dihydrocyclopentapyridine, dihydrofuropyridine, oxazolopyridine, benzoxazole or benzoisoxazole are not substituted, or one or more hydrogen atoms of pyrazine, pyrimidine, pyridazine, thiophene, thiadiazole, oxazole, indole, indazole, dihydrocyclopentapyridine, dihydrofuropyridine, oxazolopyridine, benzoxazole or benzoisoxazole are substituted with substituents selected from the group consisting of halogen atom, -CN, C1-C3 alkyl, C1-C3 alkoxy-, R4 is C1-C3 alkyl: R5 is C1-C3 alkyl; R6 is hydrogen or C1-C3 alkyl; and R7 is C1-C3 alkyl or C3-C7 cycloalkyl. 4- Primary The tricyclic derivative compound, its optical isomer, its racemate or pharmaceutically acceptable salt according to claim 1, wherein: each of R2 and R3 is, independently, hydrogen or C1-C3 alkyl. 5- Primary The tricyclic derivative compound, its optical isomer, its racemate or pharmaceutically acceptable salt according to claim 4, wherein: ring A is substituted with one or more substituents. 6- Primary A tricyclic derivative compound, optical isomer thereof, racemate thereof or pharmaceutically acceptable salt thereof according to claim 1, wherein: R2 and R3 are joined together to form a ring. 7-(deleted) 8-(deleted) 9-(deleted) 10-(modified) The tricyclic derivative compound, its optical isomer, its racemate or pharmaceutically acceptable salt according to claim 1, wherein: said compound is in the form of any of the following compounds: 1) 8-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 2) 8-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-10-methoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 3) 10-ethoxy-8-{[4-(4-fluorpphenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 4) 10-ethoxy-8-{[4-(pyrimidin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 5) 10-ethoxy-8-{[4-(pyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 6) 10-ethoxy-8-{[4-(5-fluoropyrimidin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 7) 10-ethoxy-8-{[4-(5-fluoropyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 8) 10-ethoxy-8-{[4-(6-fluoropyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 9) 10-ethoxy-8-{[4-(3-fluoropyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 10) 8-{[4-(5-chloro-3-fluoropyridin-2-yl)piperazin-1-yl]methyl}-10-ethoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 11) 10-ethoxy-8-{[4-(6-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 12) 8-({4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}methyl)-10-ethoxy-1,2,3,4-tretrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 13) 8-{[4-(5-chloropyridin-2-yl)piperazin-1-yl]methyl}-10-ethoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 14) 8-{[4-(6-chloropyridin-2-yl)piperazin-1-yl]methyl}-10-ethoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 15) 8-{[4-(3-chloropyridin-2-yl)piperazin-1-yl]methyl}-10-ethoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 16) 8-{[4-(5-bromopyridin-2-yl)piperazin-1-yl]methyl}-10-ethoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 17) 10-ethoxy-8-{[4-(3-methylpyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 18) 6-{4-{(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperzin-1-yl}-N-methylnicotinamide; 19) 6-{4-{(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-N-ethylnicotinamide; 20) N-cyclopropyl-6-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinamide; 21) 8-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}-10-ethoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 22) 8-{[4-(4-bromophenyl)piperazin-1-yl]methyl}-10-ethoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 23) 4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 24) 3-fluoro-4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 25) 3-chloro-4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 26) 4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-3-methylbenzonitrile; 27) 10-ethoxy-8-{[4-(4-fluoro-2-methylphenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 28) 4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-3,5-difluorobenzonitrile; 29) 4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-2-fluorobenzonitrile; 30) 4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-N-ethylbenzamide; 31) 4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-2-fluoro-N-methylbenzamide; 32) 4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-N-ethyl-2-fluorobenzamide; 33) 3-chloro-4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-N-ethylbenzamide;; 34) 3-chloro-N-cyclopropyl-4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 35) 3-chloro-4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-N-methylbenzamide; 36) 4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-N,3-dimethylbenzamide; 37) 4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-N-ethyl-3-methylbenzamide; 38) N-cyclopropyl-4-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-3-methylbenzamide; 39) 10-methoxy-8-{[4-(pyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 40) 10-methoxy-8-{[4-(3-methylpyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 41) 8-{[4-(5-fluoropyridin-2-yl)piperazin-1-yl]methyl}-10-methoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 42) 4-{4-[(10-methoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 43) 8-{[4-(4-fluoro-2-methylphenyl)piperazin-1-yl]methyl}-10-methoxy-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 44) 4-{4-[(10-methoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-3-methylbenzonitrile; 45) 3-fluoro-4-{4-[(10-methoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 46) 3,5-difluoro-4-{4-[(10-methoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 47) 2-fluoro-4-{4-[(10-methoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 48) 8-{[4-(4-fluorophenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 49) 8-{[4-(4-fluoro-2-methylphenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 50) 3-fluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 51) 3-chloro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 52) 3-bromo-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 53) 3-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 54) 3-methoxy-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 55) 8-({4-[4-(diethylamino)-2-fluorophenyl]piperazin-1-yl}methyl)-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5-(6H)-one; 56) 3-acetyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 57) 4-fluoro-2-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 58) 3,5-difluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 59) 8-{[4-(2-fluoro-4-nitrophenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 60) 2-fluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 61) 2-chloro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 62) 4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-2-(trifluoromethyl)benzonitrile; 63) 2-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 64) N-ethyl-3-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 65) N-cyclopropyl-3-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 66) 3-fluoro-N-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 67) N-ethyl-3-fluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 68) N-(3-fluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}phenyl)propionamide; 69) N-cyclopropyl-3-fluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 70) 3-chloro-N-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 71) 3-chloro-N-ethyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 72) 3-chloro-N-cyclopropyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 73) 3-bromo-N-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 74) 3-bromo-N-ethyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)mehyl]piperazin-1-yl}benzamide; 75) 3-bromo-N-cyclopropyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 76) 2-fluoro-N-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 77) N-ethyl-2-fluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 78) N-cyclopropyl-2-fluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 79) N-ethyl-2-fluoro-N-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 80) 2-chloro-N-methyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 81) 2-chloro-N-ethyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 82) 2-chloro-N-cyclopropyl-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 83) ethyl 2-chloro-5-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzoate; 84) N-ethyl-3,5-difluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 85) N-cyclopropyl-3,5-difluoro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzamide; 86) 8-{[4-(pyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 87) 8-({4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}methyl)-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 88) 8-({4-[3-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}methyl)-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 89) 6-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinonitrile; 90) 8-{[4-(3-methylpyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 91) 8-{[4-(5-fluoro-3-methylpyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 92) 8-{[4-(pyrazin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 93) 8-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 94) 8-{[4-(3,5-dichloropyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 96) N-ethyl-6-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinamide; 97) N-cyclopropyl-6-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinamide; 98) 8-{[4-(thiazol-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 99) ethyl 2-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}thiazole-4-carboxylate; 100) N-ethyl 2-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}thiazole-4-carboxamide; 101) 2-fluoro-4-{8-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]-3,8-diazabicyclo[3,2,1]octan-3-yl}benzonitrile; 102) 6-{8-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]-3,8-diazabicyclo[3,2,1]octan-3-yl}nicotinonitrile; 103) 2-fluoro-4-{(1S,4S)-5-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl}benzonitrile; 104) 6-{(1S,4S)-5-[(oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl}nicotinonitrile; 105) 10-ethoxy-8-{[4-(5-fluoropyrimidin-2-yl)-2-methylpiperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 106) 10-ethoxy-8-{[4-(5-fluoropyridin-2-yl)-2-methylpiperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 107) 3-fluoro-4-{3-methyl-4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 108) (R)-3-fluoro-4-{3-methyl-4-[(5-oxo-1,2,3,4,5,6- hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 109) (S)-3-fluoro-4-{3-methyl-4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 110) (R)-3-fluoro-4-{2-methyl-4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 111) 2-fluoro-4-{3-methyl-4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 112) (R)-2-fluoro-4-{3-methyl-4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 113) (S)-2-fluoro-4-{3-methyl-4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 114) (R)-2-fluoro-4-{2-methyl-4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 115) 8-({4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}methyl)-1,2,3,4-tetrahydrobenzo[h][1,2]naphthyridin-5(6H)-one; 116) 6-{4-[(10-ethoxy-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinonitrile; 117) 8-({4-[2-chloro-4-(trifluoromethyl)phenyl]piperazin-1-yl}methyl)-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 119) 8-{[4-(3-fluoro-4-nitrophenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 120) 8-{[4-(5-chloropyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 121) 8-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}methyl)-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 122) 8-({4-[5-(methylsulfonyl)pyridin-2-yl]piperazin-1-yl}methyl)-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 123) 5-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}picolinonitrile; 124) 2-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}isonicotinonitrile; 125) 2-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinonitrile; 126) 6-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}picolinonitrile; 127) 8-{[4-(4-methoxypyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 128) 8-({4-[5-(methoxymethyl)-pyridin-2-yl]piperazin-1-yl}methyl)-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 129) 5-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}pyrazine-2-carbonitrile; 130) 8-{[4-(6-methylpyridazin-3-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 131) 8-{[4-(6-methoxypyridazin-3-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 132) 6-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}pyridazine-3-carbonitrile; 133) 5-chloro-6-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinonitrile; 134) 6-chloro-4-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinonitrile; 135) 4-chloro-6-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinonitrile; 136) 5-chloro-2-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}isonicotinonitrile; 137) 4-methoxy-6-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}nicotinonitrile; 138) 8-{[4-(5-bromo-4-methoxypyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 139) 2-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}thiazole-4-carbonitrile; 140) 5-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}thiophene-2-carbonitrile; 141) ethyl 2-{4-[((5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}thiazole-5-carboxylate; 142) 2-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}thiazole-5-carbonitrile; 143) 5-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-1,3,4-thiadiazole-2-carbonitrile; 144) 2-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}oxazole-4-carbonitrile; 145) 5-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-1,2,4-thiadiazole-3-carbonitrile; 147) 8-{[4-(5-chlorobenzo[d]oxazol-2-yl)piperazin-1-yl]methy l}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 148) 8-{[4-(2-methylbenzo[d]oxazol-6-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 149) 8-{[4-(3-methylbenzo[d]isoxazol-5-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 150) 8-{[4-(1H-indol-6-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 151) 8-{[4-(1H-indazol-5-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 152) 8-{[4-(1H-indazol-6-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 153) 8-{[4-(benzo[d]isoxazol-5-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 154) 8-{[4-(oxazolo[4,5-b]pyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 155) 8-{[4-(oxazolo[5,4-b]pyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 156) 8-{[4-(2,3-dihydrofuro[2,3-b]pyridin-6-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 157) 1-{4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-6,7-dihydro-5H-cyclopenta[c]pyridine-4-carbonitrile; 158) 8-{[3-(pyrazin-2-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 159) 6-{3-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]-3,8-diazabicyclo[3.2.1]octan-8-yl)nicotinonitrile; 160) 8-{[3-(6-chloropyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 161) 3-fluoro-4-{(1S,4S)-5-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl}benzonitrile; 162) 8-{[(1S,4S)-5-(2-fluoro-4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl}-11,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 163) 8-{[(1S,4S)-5-(6-chloropyridazin-3-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl}-10-fluoro-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 164) 10-fluoro-8-{[(1S,4S)-5-(pyridazin-2-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 165) (S)-2-fluoro-4-{2-methyl-4-[(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}benzonitrile; 166) 10-fluoro-8-{[4-(2-fluoro-4-nitrophenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 167) 10-fluoro-8-{[4-(pyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 168) 10-fluoro-8-{[4-(3-methylpyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 169) 10-fluoro-8-{[4-(5-fluoropyridin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 170) 6-{4-[(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl]methyl}piperazin-1-yl)nicotinonitrile; 171) 2-{4-[(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl]methyl}piperazin-1-yl)thiazole-5-carbonitrile; 172) 10-fluoro-8-{[4-(4-fluorphenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 173) 2-fluoro-4-{[4-(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl]methyl}piperazin-1-yl)benzonitrile; 174) 4-{[4-(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl]methyl}piperazin-1-yl)-2-(trifluoromethyl)benzonitrile; 175) 10-fluoro-8-{[4-(4-fluoro-2-methylphenyl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 176) 3-fluoro-4-{4-[(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl]methyl}piperazin-1-yl)benzonitrile; 177) 6-{(1S,4S)-5-[(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl}nicotinonitrile; 178) 10-fluoro-8-{[4-(pyrazin-2-yl)piperazin-1-yl]methyl}-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 180) 5-{4-[(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}picolinonitrile; 181) 8-{[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl}-10-fluoro-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridin-5(6H)-one; 182) 6-{4-[(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}pyridazine-3-carbonitrile; 183) 5-{4-[(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}thiophene-2-carbonitrile; 184) 6-{8-[(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]-3,8-diazabicyclo[3,2,1]octan-3-yl}nicotinonitrile; 185) 4-{4-[(10-fluoro-5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl}-3-methoxybenzonitrile; 186) 5-[4-(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-16 carbonyl)piperazin-1-yl]thiophene-2-carbonitrile; 187) 6-[4-(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-carbonyl)piperazin-1-yl]nicotinonitrile; and 188) 2-[4-(5-oxo-1,2,3,4,5,6-hexahydrobenzo[h][1,6]naphthyridin-8-carbonyl)piperazin-1-yl]thiazole-4-carbonitrile. 11- (Primary) A method for preparing a tricyclic derivative compound represented by formula 1a, its optical isomer, its racemate or a pharmaceutically acceptable salt thereof, said method comprising the following steps: 1) preparing an acid chloride using a reagent that converts a nicotinic acid compound of formula 2 into an acid chloride, and subjecting said acid chloride to an amidation reaction with an aniline of formula 3, or subjecting the nicotinic acid compound of formula 2 to a coupling reaction with aniline of formula 3, thereby preparing a compound of formula 4; 2) adding a protecting group to the compound of formula 4 prepared in step (1), thereby preparing the N-protected compound of formula 5; 3) cyclizing the compound of formula 5 prepared in step (2), in the presence of a metal catalyst, thereby preparing the compound of formula 6; 4) subjecting the compound of formula 6 prepared in step (3) to a ring reduction reaction with hydrogen in the presence of a palladium (Pd) catalyst, resulting in the preparation of the compound of formula 7; 5) reducing the compound of formula 7 prepared in step (4) with a reducing agent such as lithium aluminum hydride (LAH), thereby preparing the compound of formula 8; 6) subjecting the compound of formula 8 prepared in step (5) to a halogenation reaction and an amination reaction with an amine compound, as a result of which the compound of formula 9 is prepared; 7) Removing the protecting group from the compound of formula 9 prepared in step (6) by a deprotection reaction, thereby preparing the compound of formula 1a; [Reaction Scheme 1] wherein: X is a halogen atom; Y is hydrogen, C1-C3 alkoxy or a halogen atom; Alk is a C1-C10 straight-chain or branched alkyl; Pro is a protecting group selected from the group consisting of an aryl group, a benzyl group, a benzyloxymethyl group, a para-methoxybenzyl group (PMB) and a methoxymethyl group (MOM); and B is as follows: wherein: Ring A, R2 and R3 are as defined in claim 1. 12- (Valieh) A method for preparing a tricyclic derivative compound represented by formula 1a, its optical isomer, its racemate or a pharmaceutically acceptable salt thereof, said method comprising the following steps: 1) removing the protecting group from the compound of formula 8, by a deprotection reaction, resulting in the preparation of the compound of formula 10; and 2) Subjecting the compound of formula 10 prepared in step (1) to a halogenation reaction and an amination reaction with an amine compound, thereby preparing the compound of formula 1a. [Reaction Scheme 2] wherein: Y is hydrogen, C1-C3 alkoxy or a halogen atom; Pro is a protecting group selected from the group consisting of an aryl group, a benzyl group, a benzyloxymethyl group, a para-methoxybenzyl group (PMB) and a methoxymethyl group (MOM); and B is as follows: wherein: Ring A, R2 and R3 are as defined in claim 1. 13- (Initial) A method for preparing a tricyclic derivative compound represented by formula 1b, its optical isomer, its racemate or a pharmaceutically acceptable salt thereof, said method comprising the following steps: 1) Removal of the protecting group from the compound of formula 7 by a deprotection reaction, resulting in the preparation of the compound of formula 11; 2) adding an aqueous solution of potassium hydroxide or sodium hydroxide slowly dropwise to the compound of formula 11 prepared in step (1), thereby preparing the compound of formula 12, which is a hydrolyzed carboxylic acid; 3) Subjecting the compound of formula 12 prepared in step (2) to a coupling reaction with an amine compound, thereby preparing the compound of formula 1b. [Reaction Scheme 3] wherein: Y is hydrogen, C1-C3 alkoxy or a halogen atom; Alk is C1-C10 straight-chain or branched alkyl; Pro is a protecting group selected from the group consisting of an aryl group, a benzyl group, a benzyloxymethyl group, a para-methoxybenzyl (PMB) group and a methoxymethyl (MOM) group; and B is as follows: wherein: Ring A, R2 and R3 are as defined in claim 1. 14- (Modified) A pharmaceutical composition for preventing or treating a disease caused by PARP-1, tankyrase-1 or tankyrase-2 activity, said composition comprising as an active ingredient a tricyclic derivative, an optical isomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6 and 10. 15- (Initial) The pharmaceutical composition according to claim 14, wherein: said disease is one or more selected from the group consisting of neurodegenerative disease, cardiovascular disease, diabetic neuropathy, osteoarthritis, osteoporosis and cancer. 16-(Initial) The pharmaceutical composition according to claim 15, wherein: the neurodegenerative disease is one or more selected from the group consisting of neuropathic pain, epilepsy, stroke, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, schizophrenia, chronic or acute pain, ischemic brain injury, neuronal loss after hypoxia, nerve damage and trauma. 17-(Primary) Pharmaceutical compositions according to claim 15, wherein: the cardiovascular disease is one or more selected from the group consisting of atherosclerosis, hyperlipidemia, cardiovascular tissue damage, coronary artery disease, myocardial infarction, angina pectoris and cardiogenic shock. 18- (Modified) A pharmaceutical composition comprising as an active ingredient a tricyclic derivative, an optical isomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6 and 10. 19- (Modified) Use of a tricyclic derivative, an optical isomer thereof, a racemate thereof or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6 and 10 in the preparation of a medicament for the prevention or treatment of diseases caused by PARP-1, tankyrase-1 or tankyrase-2 activity.