RU2715413C2 - Трициклическое производное соединение, способ его получения и фармацевтическая композиция, содержащая такое соединение - Google Patents

Info

Publication number

RU2715413C2

RU2715413C2 RU2017146130A RU2017146130A RU2715413C2 RU 2715413 C2 RU2715413 C2 RU 2715413C2 RU 2017146130 A RU2017146130 A RU 2017146130A RU 2017146130 A RU2017146130 A RU 2017146130A RU 2715413 C2 RU2715413 C2 RU 2715413C2

Authority

RU

Russia

Prior art keywords

methyl

piperazin

naphthyridin

hexahydrobenzo

oxo

Prior art date

2015-06-09

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 221
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 24
• 238000004519 manufacturing process Methods 0.000 title claims description 9
• 230000000694 effects Effects 0.000 claims abstract description 24
• 201000010099 disease Diseases 0.000 claims abstract description 21
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
• 102100037477 Poly [ADP-ribose] polymerase tankyrase-2 Human genes 0.000 claims abstract description 18
• 101710129674 Poly [ADP-ribose] polymerase tankyrase-2 Proteins 0.000 claims abstract description 18
• 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 claims abstract 4
• 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims abstract 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 270
• -1 {4- [3-chloro-5- (trifluoromethyl) pyridin-2-yl] piperazin-1-yl} methyl Chemical group 0.000 claims description 247
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 140
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 134
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 129
• 238000006243 chemical reaction Methods 0.000 claims description 104
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 54
• 239000000203 mixture Substances 0.000 claims description 46
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 41
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 39
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
• 239000010802 sludge Substances 0.000 claims description 35
• 238000000034 method Methods 0.000 claims description 34
• 150000003839 salts Chemical class 0.000 claims description 34
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 30
• 239000002904 solvent Substances 0.000 claims description 30
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 28
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 28
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 25
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 24
• 238000011282 treatment Methods 0.000 claims description 23
• 125000005843 halogen group Chemical group 0.000 claims description 20
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 19
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 19
• 102100037664 Poly [ADP-ribose] polymerase tankyrase-1 Human genes 0.000 claims description 18
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 18
• 101710129670 Poly [ADP-ribose] polymerase tankyrase-1 Proteins 0.000 claims description 17
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 16
• 230000003287 optical effect Effects 0.000 claims description 15
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 14
• 239000002585 base Substances 0.000 claims description 14
• 125000006239 protecting group Chemical group 0.000 claims description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
• 125000001424 substituent group Chemical group 0.000 claims description 13
• ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 claims description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 11
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 10
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 10
• 206010028980 Neoplasm Diseases 0.000 claims description 10
• 125000003118 aryl group Chemical group 0.000 claims description 10
• 201000011510 cancer Diseases 0.000 claims description 10
• 239000003054 catalyst Substances 0.000 claims description 10
• 239000003153 chemical reaction reagent Substances 0.000 claims description 10
• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• 239000003960 organic solvent Substances 0.000 claims description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 9
• 238000001816 cooling Methods 0.000 claims description 9
• 238000005859 coupling reaction Methods 0.000 claims description 9
• 238000010511 deprotection reaction Methods 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 238000010438 heat treatment Methods 0.000 claims description 9
• 239000012280 lithium aluminium hydride Substances 0.000 claims description 9
• 235000005152 nicotinamide Nutrition 0.000 claims description 9
• 239000011570 nicotinamide Substances 0.000 claims description 9
• 229960003966 nicotinamide Drugs 0.000 claims description 9
• DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 9
• 229910000027 potassium carbonate Inorganic materials 0.000 claims description 9
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 8
• WTYLPQUOPMMOQW-UHFFFAOYSA-N 6h-1,6-naphthyridin-5-one Chemical compound C1=CC=C2C(O)=NC=CC2=N1 WTYLPQUOPMMOQW-UHFFFAOYSA-N 0.000 claims description 8
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 8
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 8
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 8
• 239000004480 active ingredient Substances 0.000 claims description 8
• 238000007112 amidation reaction Methods 0.000 claims description 8
• 238000005576 amination reaction Methods 0.000 claims description 8
• 239000007864 aqueous solution Substances 0.000 claims description 8
• 229910052739 hydrogen Inorganic materials 0.000 claims description 8
• 229910052751 metal Inorganic materials 0.000 claims description 8
• 239000002184 metal Substances 0.000 claims description 8
• PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 8
• 230000002265 prevention Effects 0.000 claims description 8
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 claims description 8
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 7
• 208000002193 Pain Diseases 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 230000004770 neurodegeneration Effects 0.000 claims description 7
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
• 229910052763 palladium Inorganic materials 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 238000011321 prophylaxis Methods 0.000 claims description 7
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 208000001132 Osteoporosis Diseases 0.000 claims description 6
• 150000001412 amines Chemical class 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
• 230000000302 ischemic effect Effects 0.000 claims description 6
• 208000004296 neuralgia Diseases 0.000 claims description 6
• 208000021722 neuropathic pain Diseases 0.000 claims description 6
• 239000011664 nicotinic acid Substances 0.000 claims description 6
• 229960003512 nicotinic acid Drugs 0.000 claims description 6
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 6
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 6
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
• ITAWEZOLJMRDPN-UHFFFAOYSA-N 8-[[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]-2,3,4,4a,6,6a,7,8,9,10,10a,10b-dodecahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C1CC2C(C3CCC(CC3NC2=O)CN4CCN(CC4)C5=CC=C(C=C5)C(F)(F)F)NC1 ITAWEZOLJMRDPN-UHFFFAOYSA-N 0.000 claims description 5
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
• 230000006931 brain damage Effects 0.000 claims description 5
• 231100000874 brain damage Toxicity 0.000 claims description 5
• 208000029028 brain injury Diseases 0.000 claims description 5
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
• 230000008878 coupling Effects 0.000 claims description 5
• 238000010168 coupling process Methods 0.000 claims description 5
• 235000001968 nicotinic acid Nutrition 0.000 claims description 5
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims description 4
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 4
• XWXPRCDFFCVMNT-UHFFFAOYSA-N 1,3-thiazole-5-carbonitrile Chemical compound N#CC1=CN=CS1 XWXPRCDFFCVMNT-UHFFFAOYSA-N 0.000 claims description 4
• XSNYVOJACDGFLR-UHFFFAOYSA-N 1-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-6,7-dihydro-5H-cyclopenta[c]pyridine-4-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=NC=C(C2=C1CCC2)C#N XSNYVOJACDGFLR-UHFFFAOYSA-N 0.000 claims description 4
• YUJOEMXQQWMFHW-UHFFFAOYSA-N 10-fluoro-8-[[4-(2-fluoro-4-nitrophenyl)piperazin-1-yl]methyl]-2,3,4,4a,6,6a,7,8,9,10,10a,10b-dodecahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound C1CC2C(C3C(CC(CC3F)CN4CCN(CC4)C5=C(C=C(C=C5)[N+](=O)[O-])F)NC2=O)NC1 YUJOEMXQQWMFHW-UHFFFAOYSA-N 0.000 claims description 4
• XFINVNDWTKKVHT-UHFFFAOYSA-N 10-fluoro-8-[[4-(3-methylpyridin-2-yl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=NC=CC=C1C XFINVNDWTKKVHT-UHFFFAOYSA-N 0.000 claims description 4
• XMTDEEBBKFYDOX-UHFFFAOYSA-N 10-fluoro-8-[[4-(4-fluoro-2-methylphenyl)piperazin-1-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1CCN(CC1)C1=C(C=C(C=C1)F)C XMTDEEBBKFYDOX-UHFFFAOYSA-N 0.000 claims description 4
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical group C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 4
• LZPDYLRFIGMNHY-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-1,3-oxazole-4-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1OC=C(N=1)C#N LZPDYLRFIGMNHY-UHFFFAOYSA-N 0.000 claims description 4
• VOQLJAINULFPEC-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-1,3-thiazole-4-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1SC=C(N=1)C#N VOQLJAINULFPEC-UHFFFAOYSA-N 0.000 claims description 4
• ONEIDYKHPRMDQO-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]-1,3-thiazole-5-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1SC(=CN=1)C#N ONEIDYKHPRMDQO-UHFFFAOYSA-N 0.000 claims description 4
• PITKHMJQSBHPED-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=C(C#N)C=CC=N1 PITKHMJQSBHPED-UHFFFAOYSA-N 0.000 claims description 4
• CCWTWPIDXUGAKX-UHFFFAOYSA-N 2-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-4-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1C=C(C#N)C=CN=1 CCWTWPIDXUGAKX-UHFFFAOYSA-N 0.000 claims description 4
• GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 4
• OOWRFWSYHOPDLB-UHFFFAOYSA-N 5-[4-(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridine-8-carbonyl)piperazin-1-yl]thiophene-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)C(=O)N1CCN(CC1)C1=CC=C(S1)C#N OOWRFWSYHOPDLB-UHFFFAOYSA-N 0.000 claims description 4
• DBLBOZLZPCJKAH-UHFFFAOYSA-N 5-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyrazine-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1N=CC(=NC=1)C#N DBLBOZLZPCJKAH-UHFFFAOYSA-N 0.000 claims description 4
• RLKUZCOFKFUEHH-UHFFFAOYSA-N 5-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C=1C=CC(=NC=1)C#N RLKUZCOFKFUEHH-UHFFFAOYSA-N 0.000 claims description 4
• QBLCDAXXROYNNC-UHFFFAOYSA-N 5-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]thiophene-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=CC=C(S1)C#N QBLCDAXXROYNNC-UHFFFAOYSA-N 0.000 claims description 4
• AURCLDMUVVKGCY-IRXDYDNUSA-N 6-[(1S,4S)-5-[(10-fluoro-5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]pyridine-3-carbonitrile Chemical compound FC1=CC(=CC=2NC(C=3CCCNC=3C=21)=O)CN1[C@@H]2CN([C@H](C1)C2)C1=NC=C(C#N)C=C1 AURCLDMUVVKGCY-IRXDYDNUSA-N 0.000 claims description 4
• ZUXIOPFYSMZLKD-UHFFFAOYSA-N 6-[3-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]-3,8-diazabicyclo[3.2.1]octan-8-yl]pyridine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CC2CCC(C1)N2C1=NC=C(C#N)C=C1 ZUXIOPFYSMZLKD-UHFFFAOYSA-N 0.000 claims description 4
• XUFWBGKENCGHSD-UHFFFAOYSA-N 6-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridazine-3-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=CC=C(N=N1)C#N XUFWBGKENCGHSD-UHFFFAOYSA-N 0.000 claims description 4
• SLFOPCGYYAWVOV-UHFFFAOYSA-N 6-[4-[(5-oxo-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-8-yl)methyl]piperazin-1-yl]pyridine-2-carbonitrile Chemical compound O=C1C=2CCCNC=2C2=C(N1)C=C(C=C2)CN1CCN(CC1)C1=CC=CC(=N1)C#N SLFOPCGYYAWVOV-UHFFFAOYSA-N 0.000 claims description 4
• FSFKDNPHPFINJD-UHFFFAOYSA-N 8-[(3-pyrazin-2-yl-3,8-diazabicyclo[3.2.1]octan-8-yl)methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound N1=C(C=NC=C1)N1CC2CCC(C1)N2CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 FSFKDNPHPFINJD-UHFFFAOYSA-N 0.000 claims description 4
• BYVRMNFKQPRJNP-IRXDYDNUSA-N 8-[[(1S,4S)-5-(2-fluoro-4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound FC1=C(C=CC(=C1)[N+](=O)[O-])N1[C@@H]2CN([C@H](C1)C2)CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 BYVRMNFKQPRJNP-IRXDYDNUSA-N 0.000 claims description 4
• WPSFTNDXYZENJA-UHFFFAOYSA-N 8-[[3-(6-chloropyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl]methyl]-2,3,4,6-tetrahydro-1H-benzo[h][1,6]naphthyridin-5-one Chemical compound ClC1=CC=C(N=N1)N1CC2CCC(C1)N2CC=1C=CC2=C(NC(C=3CCCNC2=3)=O)C=1 WPSFTNDXYZENJA-UHFFFAOYSA-N 0.000 claims description 4
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• 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
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