JP5600754B2 - ピラジン誘導体および神経障害の処置におけるそれらの使用 - Google Patents
ピラジン誘導体および神経障害の処置におけるそれらの使用 Download PDFInfo
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- JP5600754B2 JP5600754B2 JP2012546418A JP2012546418A JP5600754B2 JP 5600754 B2 JP5600754 B2 JP 5600754B2 JP 2012546418 A JP2012546418 A JP 2012546418A JP 2012546418 A JP2012546418 A JP 2012546418A JP 5600754 B2 JP5600754 B2 JP 5600754B2
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- alkyl
- alkoxy
- alkylthio
- halogen
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- 150000003216 pyrazines Chemical class 0.000 title description 2
- 208000012902 Nervous system disease Diseases 0.000 title 1
- 208000025966 Neurological disease Diseases 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 597
- 125000004414 alkyl thio group Chemical group 0.000 claims description 309
- 125000003545 alkoxy group Chemical group 0.000 claims description 238
- 150000001875 compounds Chemical class 0.000 claims description 219
- 229910052736 halogen Inorganic materials 0.000 claims description 161
- 150000002367 halogens Chemical class 0.000 claims description 161
- 229910052739 hydrogen Inorganic materials 0.000 claims description 119
- 239000001257 hydrogen Substances 0.000 claims description 118
- 150000003839 salts Chemical class 0.000 claims description 86
- -1 cyano, amino, aminocarbonyl Chemical group 0.000 claims description 76
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 72
- 125000001424 substituent group Chemical group 0.000 claims description 70
- 125000003118 aryl group Chemical group 0.000 claims description 69
- 125000004043 oxo group Chemical group O=* 0.000 claims description 63
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 60
- 150000002431 hydrogen Chemical class 0.000 claims description 58
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 56
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 55
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 48
- 239000003814 drug Substances 0.000 claims description 44
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 22
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 19
- 125000000304 alkynyl group Chemical group 0.000 claims description 19
- 230000002265 prevention Effects 0.000 claims description 19
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 208000024827 Alzheimer disease Diseases 0.000 claims description 15
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 239000004480 active ingredient Substances 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 208000010877 cognitive disease Diseases 0.000 claims description 12
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 9
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 6
- 150000004702 methyl esters Chemical class 0.000 claims description 6
- FGPUURAPBZPKJF-UHFFFAOYSA-N n-[3-(3-amino-1,5-dimethyl-6-oxo-2h-pyrazin-5-yl)-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound O=C1N(C)CC(N)=NC1(C)C1=CC(NC(=O)C=2N=CC(Br)=CC=2)=CC=C1F FGPUURAPBZPKJF-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 5
- FOLNCKZOMNIALC-UHFFFAOYSA-N n-[3-(5-amino-1,3-dimethyl-2,6-dihydropyrazin-3-yl)-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound C1N(C)CC(N)=NC1(C)C1=CC(NC(=O)C=2N=CC(Br)=CC=2)=CC=C1F FOLNCKZOMNIALC-UHFFFAOYSA-N 0.000 claims description 5
- JHDMJWNJCPZFBW-UHFFFAOYSA-N n-[3-[1-acetyl-5-amino-3-(difluoromethyl)-2,6-dihydropyrazin-3-yl]-4-fluorophenyl]-5-bromo-3-methylpyridine-2-carboxamide Chemical compound C1N(C(=O)C)CC(N)=NC1(C(F)F)C1=CC(NC(=O)C=2C(=CC(Br)=CN=2)C)=CC=C1F JHDMJWNJCPZFBW-UHFFFAOYSA-N 0.000 claims description 5
- YIVQZDWEYRMEFX-UHFFFAOYSA-N n-[3-[5-amino-3-(difluoromethyl)-2,6-dihydro-1h-pyrazin-3-yl]-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound C1NCC(N)=NC1(C(F)F)C1=CC(NC(=O)C=2N=CC(Br)=CC=2)=CC=C1F YIVQZDWEYRMEFX-UHFFFAOYSA-N 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- GBXWORVXRWWDTA-UHFFFAOYSA-N 2,2-dichloroethyl 5-amino-3-[5-[(5-bromo-3-methylpyridine-2-carbonyl)amino]-2-fluorophenyl]-3-(difluoromethyl)-2,6-dihydropyrazine-1-carboxylate Chemical compound CC1=CC(Br)=CN=C1C(=O)NC1=CC=C(F)C(C2(N=C(N)CN(C2)C(=O)OCC(Cl)Cl)C(F)F)=C1 GBXWORVXRWWDTA-UHFFFAOYSA-N 0.000 claims description 4
- GSOCTKHBFREQCV-UHFFFAOYSA-N 5-bromo-3-methylpyridine-2-carboxylic acid Chemical compound CC1=CC(Br)=CN=C1C(O)=O GSOCTKHBFREQCV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- HJOOOXDRGOESCS-UHFFFAOYSA-N n-[3-(3-amino-1,5-dimethyl-6-oxo-2h-pyrazin-5-yl)phenyl]-5-bromopyridine-2-carboxamide Chemical compound O=C1N(C)CC(N)=NC1(C)C1=CC=CC(NC(=O)C=2N=CC(Br)=CC=2)=C1 HJOOOXDRGOESCS-UHFFFAOYSA-N 0.000 claims description 4
- KDEOLGIEXQPNFC-UHFFFAOYSA-N n-[3-(3-amino-2-ethyl-1,5-dimethyl-6-oxo-2h-pyrazin-5-yl)phenyl]-5-bromopyridine-2-carboxamide Chemical compound N1=C(N)C(CC)N(C)C(=O)C1(C)C1=CC=CC(NC(=O)C=2N=CC(Br)=CC=2)=C1 KDEOLGIEXQPNFC-UHFFFAOYSA-N 0.000 claims description 4
- VYTHRSNJIFMUBH-UHFFFAOYSA-N n-[3-(5-amino-1,3-dimethyl-6-oxo-2h-pyrazin-3-yl)-4-fluorophenyl]-3,5-dichloropyridine-2-carboxamide Chemical compound N1=C(N)C(=O)N(C)CC1(C)C1=CC(NC(=O)C=2C(=CC(Cl)=CN=2)Cl)=CC=C1F VYTHRSNJIFMUBH-UHFFFAOYSA-N 0.000 claims description 4
- SGPKXKUDYCPOBE-UHFFFAOYSA-N n-[3-(5-amino-3-methyl-6-oxo-1-pyridin-3-yl-2h-pyrazin-3-yl)-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound O=C1C(N)=NC(C)(C=2C(=CC=C(NC(=O)C=3N=CC(Br)=CC=3)C=2)F)CN1C1=CC=CN=C1 SGPKXKUDYCPOBE-UHFFFAOYSA-N 0.000 claims description 4
- YUOPBZQOSQHOJB-UHFFFAOYSA-N n-[3-[1-acetyl-5-amino-3-(difluoromethyl)-2,6-dihydropyrazin-3-yl]-4-fluorophenyl]-5-(difluoromethoxy)-3-methylpyridine-2-carboxamide Chemical compound C1N(C(=O)C)CC(N)=NC1(C(F)F)C1=CC(NC(=O)C=2C(=CC(OC(F)F)=CN=2)C)=CC=C1F YUOPBZQOSQHOJB-UHFFFAOYSA-N 0.000 claims description 4
- GFKHOTKTQLRBEC-UHFFFAOYSA-N n-[3-[5-amino-3-(difluoromethyl)-1-(2-methoxyacetyl)-2,6-dihydropyrazin-3-yl]-4-fluorophenyl]-5-bromo-3-methylpyridine-2-carboxamide Chemical compound C1N(C(=O)COC)CC(N)=NC1(C(F)F)C1=CC(NC(=O)C=2C(=CC(Br)=CN=2)C)=CC=C1F GFKHOTKTQLRBEC-UHFFFAOYSA-N 0.000 claims description 4
- UUBHPJXFLIBPAK-UHFFFAOYSA-N n-[3-[5-amino-3-(difluoromethyl)-2,6-dihydro-1h-pyrazin-3-yl]-4-fluorophenyl]-5-cyanopyridine-2-carboxamide Chemical compound C1NCC(N)=NC1(C(F)F)C1=CC(NC(=O)C=2N=CC(=CC=2)C#N)=CC=C1F UUBHPJXFLIBPAK-UHFFFAOYSA-N 0.000 claims description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 4
- NWYKTGFANHHXBN-UHFFFAOYSA-N 2-amino-n-[3-[5-amino-3-(difluoromethyl)-2,6-dihydro-1h-pyrazin-3-yl]-4-fluorophenyl]-6-oxo-1h-pyrazine-3-carboxamide Chemical compound C1NCC(N)=NC1(C(F)F)C1=CC(NC(=O)C2=C(NC(=O)C=N2)N)=CC=C1F NWYKTGFANHHXBN-UHFFFAOYSA-N 0.000 claims description 3
- ZKNMXFGYYJETSC-UHFFFAOYSA-N 3-amino-n-[3-[5-amino-3-(difluoromethyl)-2,6-dihydro-1h-pyrazin-3-yl]-4-fluorophenyl]-5-methoxypyrazine-2-carboxamide Chemical compound NC1=NC(OC)=CN=C1C(=O)NC1=CC=C(F)C(C2(N=C(N)CNC2)C(F)F)=C1 ZKNMXFGYYJETSC-UHFFFAOYSA-N 0.000 claims description 3
- HRLVPHGCEGTVLK-UHFFFAOYSA-N 5-cyanopyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(C#N)C=N1 HRLVPHGCEGTVLK-UHFFFAOYSA-N 0.000 claims description 3
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 3
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 3
- VGTILVOMEOFBMU-UHFFFAOYSA-N n-[3-(5-amino-1,3-dimethyl-6-oxo-2h-pyrazin-3-yl)-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound N1=C(N)C(=O)N(C)CC1(C)C1=CC(NC(=O)C=2N=CC(Br)=CC=2)=CC=C1F VGTILVOMEOFBMU-UHFFFAOYSA-N 0.000 claims description 3
- IBPGEEKFYIPLRV-UHFFFAOYSA-N n-[3-(5-amino-1,3-dimethyl-6-oxo-2h-pyrazin-3-yl)-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound N1=C(N)C(=O)N(C)CC1(C)C1=CC(NC(=O)C=2N=CC(Cl)=CC=2)=CC=C1F IBPGEEKFYIPLRV-UHFFFAOYSA-N 0.000 claims description 3
- GMUSGOAHDMSZNC-UHFFFAOYSA-N n-[3-(5-amino-1-ethyl-3-methyl-6-oxo-2h-pyrazin-3-yl)-4-fluorophenyl]-3,5-dichloropyridine-2-carboxamide Chemical compound N1=C(N)C(=O)N(CC)CC1(C)C1=CC(NC(=O)C=2C(=CC(Cl)=CN=2)Cl)=CC=C1F GMUSGOAHDMSZNC-UHFFFAOYSA-N 0.000 claims description 3
- NNONTILIEPOHQT-UHFFFAOYSA-N n-[3-(5-amino-1-ethyl-3-methyl-6-oxo-2h-pyrazin-3-yl)-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound N1=C(N)C(=O)N(CC)CC1(C)C1=CC(NC(=O)C=2N=CC(Br)=CC=2)=CC=C1F NNONTILIEPOHQT-UHFFFAOYSA-N 0.000 claims description 3
- WFPDPMQFKZCRFF-UHFFFAOYSA-N n-[3-(5-amino-1-ethyl-3-methyl-6-oxo-2h-pyrazin-3-yl)-4-fluorophenyl]-5-cyanopyridine-2-carboxamide Chemical compound N1=C(N)C(=O)N(CC)CC1(C)C1=CC(NC(=O)C=2N=CC(=CC=2)C#N)=CC=C1F WFPDPMQFKZCRFF-UHFFFAOYSA-N 0.000 claims description 3
- IPEYSDUMVODEGM-UHFFFAOYSA-N n-[3-(5-amino-3-methyl-6-oxo-1-propan-2-yl-2h-pyrazin-3-yl)-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound N1=C(N)C(=O)N(C(C)C)CC1(C)C1=CC(NC(=O)C=2N=CC(Br)=CC=2)=CC=C1F IPEYSDUMVODEGM-UHFFFAOYSA-N 0.000 claims description 3
- FOLBFWMABGBJIK-UHFFFAOYSA-N n-[3-[5-amino-1-(2-methoxyethyl)-3-methyl-6-oxo-2h-pyrazin-3-yl]-4-fluorophenyl]-3,5-dichloropyridine-2-carboxamide Chemical compound N1=C(N)C(=O)N(CCOC)CC1(C)C1=CC(NC(=O)C=2C(=CC(Cl)=CN=2)Cl)=CC=C1F FOLBFWMABGBJIK-UHFFFAOYSA-N 0.000 claims description 3
- PZMNGGWMBNDIDP-UHFFFAOYSA-N n-[3-[5-amino-1-(2-methoxyethyl)-3-methyl-6-oxo-2h-pyrazin-3-yl]-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound N1=C(N)C(=O)N(CCOC)CC1(C)C1=CC(NC(=O)C=2N=CC(Br)=CC=2)=CC=C1F PZMNGGWMBNDIDP-UHFFFAOYSA-N 0.000 claims description 3
- ZKECAQPFRZAODT-UHFFFAOYSA-N n-[3-[5-amino-3-(difluoromethyl)-2,6-dihydro-1h-pyrazin-3-yl]-4-fluorophenyl]-5-(difluoromethoxy)-3-methylpyridine-2-carboxamide Chemical compound CC1=CC(OC(F)F)=CN=C1C(=O)NC1=CC=C(F)C(C2(N=C(N)CNC2)C(F)F)=C1 ZKECAQPFRZAODT-UHFFFAOYSA-N 0.000 claims description 3
- QQJJZOBMLMQJSH-UHFFFAOYSA-N n-[3-[5-amino-3-methyl-1-(1-methylpyrazol-4-yl)-6-oxo-2h-pyrazin-3-yl]-4-fluorophenyl]-5-bromopyridine-2-carboxamide Chemical compound C1=NN(C)C=C1N1C(=O)C(N)=NC(C)(C=2C(=CC=C(NC(=O)C=3N=CC(Br)=CC=3)C=2)F)C1 QQJJZOBMLMQJSH-UHFFFAOYSA-N 0.000 claims description 3
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 2
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 113
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- 239000000203 mixture Substances 0.000 description 100
- 238000004128 high performance liquid chromatography Methods 0.000 description 73
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 72
- 238000000034 method Methods 0.000 description 62
- 235000019439 ethyl acetate Nutrition 0.000 description 56
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 53
- 238000005160 1H NMR spectroscopy Methods 0.000 description 51
- 239000003795 chemical substances by application Substances 0.000 description 41
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 201000010099 disease Diseases 0.000 description 33
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- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 description 32
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 27
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- 230000000694 effects Effects 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 23
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 20
- 239000013078 crystal Substances 0.000 description 20
- 208000035475 disorder Diseases 0.000 description 20
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000012267 brine Substances 0.000 description 16
- 125000004076 pyridyl group Chemical group 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 125000003373 pyrazinyl group Chemical group 0.000 description 15
- 229940124597 therapeutic agent Drugs 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 7
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29172409P | 2009-12-31 | 2009-12-31 | |
| US61/291,724 | 2009-12-31 | ||
| PCT/EP2010/070502 WO2011080176A1 (en) | 2009-12-31 | 2010-12-22 | Pyrazine derivatives and their use in the treatment of neurological disorders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013516395A JP2013516395A (ja) | 2013-05-13 |
| JP2013516395A5 JP2013516395A5 (https=) | 2014-08-21 |
| JP5600754B2 true JP5600754B2 (ja) | 2014-10-01 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2012546418A Expired - Fee Related JP5600754B2 (ja) | 2009-12-31 | 2010-12-22 | ピラジン誘導体および神経障害の処置におけるそれらの使用 |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US20120277244A1 (https=) |
| EP (1) | EP2519515B1 (https=) |
| JP (1) | JP5600754B2 (https=) |
| KR (1) | KR101419157B1 (https=) |
| CN (1) | CN102712621B (https=) |
| AU (1) | AU2010338365B2 (https=) |
| BR (1) | BR112012015916A2 (https=) |
| CA (1) | CA2785341A1 (https=) |
| CL (1) | CL2012001762A1 (https=) |
| CR (1) | CR20120332A (https=) |
| CU (1) | CU20120099A7 (https=) |
| EA (1) | EA201200952A1 (https=) |
| EC (1) | ECSP12012065A (https=) |
| ES (1) | ES2445536T3 (https=) |
| GT (1) | GT201200219A (https=) |
| HN (1) | HN2012001413A (https=) |
| IL (1) | IL220268A0 (https=) |
| MX (1) | MX2012007754A (https=) |
| NZ (1) | NZ600136A (https=) |
| PE (1) | PE20121640A1 (https=) |
| PH (1) | PH12012501007A1 (https=) |
| PL (1) | PL2519515T3 (https=) |
| PT (1) | PT2519515E (https=) |
| SG (1) | SG181431A1 (https=) |
| TN (1) | TN2012000249A1 (https=) |
| WO (1) | WO2011080176A1 (https=) |
| ZA (1) | ZA201203614B (https=) |
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| CA2628074C (en) | 2005-10-25 | 2014-01-14 | Shionogi & Co., Ltd. | Aminodihydrothiazine derivative |
| US8653067B2 (en) | 2007-04-24 | 2014-02-18 | Shionogi & Co., Ltd. | Pharmaceutical composition for treating Alzheimer's disease |
| JP5383484B2 (ja) | 2007-04-24 | 2014-01-08 | 塩野義製薬株式会社 | 環式基で置換されたアミノジヒドロチアジン誘導体 |
| KR101324426B1 (ko) | 2008-06-13 | 2013-10-31 | 시오노기세야쿠 가부시키가이샤 | β 세크레타제 저해 작용을 갖는 황 함유 복소환 유도체 |
| CN102186841A (zh) | 2008-10-22 | 2011-09-14 | 盐野义制药株式会社 | 具有bace1抑制活性的2-氨基嘧啶-4-酮及2-氨基吡啶衍生物 |
| UA108363C2 (uk) | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
| MX2012006491A (es) | 2009-12-11 | 2012-07-03 | Shionogi & Co | Derivados de oxazina. |
| MX2012014382A (es) * | 2010-06-09 | 2013-01-29 | Janssen Pharmaceutica Nv | Derivados de 5-amino-3, 6-dihidro-1h-pirazin-2-ona utiles como inhibidores de beta-secretasa (bace). |
| MX339640B (es) | 2010-06-09 | 2016-06-01 | Janssen Pharmaceutica Nv * | Derivados de 5, 6-dihidro-2h-[1, 4] oxazin-3-il-amina utiles como inhibidores de la beta-secretasa (bace). |
| US20130102618A1 (en) * | 2010-06-28 | 2013-04-25 | Janssen Pharmaceutica Nv | 3-amino-5,6-dihydro-1h-pyrazin-2-one derivatives useful for the treatment of alzheimer's disease and other forms of dementia |
| JP5816630B2 (ja) | 2010-10-29 | 2015-11-18 | 塩野義製薬株式会社 | ナフチリジン誘導体 |
| EP2634188A4 (en) | 2010-10-29 | 2014-05-07 | Shionogi & Co | FUSIONED AMINODIHYDROPYRIMIDINE DERIVATIVE |
| EP2655376B1 (en) | 2010-12-22 | 2017-08-23 | Janssen Pharmaceutica NV | 5,6-DIHYDRO-IMIDAZO[1,2-a]PYRAZIN-8-YLAMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) |
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