FI113963B - Menetelmä terapeuttisesti käyttökelpoisten 3 (2H) -Pyridatsinonijohdannaisten valmistamiseksi - Google Patents
Menetelmä terapeuttisesti käyttökelpoisten 3 (2H) -Pyridatsinonijohdannaisten valmistamiseksi Download PDFInfo
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- FI113963B FI113963B FI956300A FI956300A FI113963B FI 113963 B FI113963 B FI 113963B FI 956300 A FI956300 A FI 956300A FI 956300 A FI956300 A FI 956300A FI 113963 B FI113963 B FI 113963B
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- 238000000034 method Methods 0.000 title claims abstract description 49
- 230000008569 process Effects 0.000 title claims abstract description 31
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims description 30
- -1 4-substituted piperazine ring Chemical group 0.000 claims abstract description 56
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 31
- 125000005843 halogen group Chemical group 0.000 claims abstract description 29
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000003277 amino group Chemical group 0.000 claims abstract description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 13
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 136
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000000217 alkyl group Chemical class 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000005493 quinolyl group Chemical group 0.000 claims description 7
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 150000004885 piperazines Chemical group 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- QYWHYLNYDQJLNO-UHFFFAOYSA-N 4-[[3-[2-(4-benzylpiperazin-1-yl)-2-oxoethoxy]-4-methoxyphenyl]methylamino]-5-chloro-1h-pyridazin-6-one Chemical compound C1=C(OCC(=O)N2CCN(CC=3C=CC=CC=3)CC2)C(OC)=CC=C1CNC=1C=NNC(=O)C=1Cl QYWHYLNYDQJLNO-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 125000004122 cyclic group Chemical group 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 568
- 239000000460 chlorine Substances 0.000 description 483
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 245
- 238000006243 chemical reaction Methods 0.000 description 86
- 239000000203 mixture Substances 0.000 description 85
- 239000002904 solvent Substances 0.000 description 63
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 61
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 59
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
- 239000000243 solution Substances 0.000 description 49
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 42
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 230000002829 reductive effect Effects 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 37
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 238000004821 distillation Methods 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 230000000052 comparative effect Effects 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000003814 drug Substances 0.000 description 20
- 235000019441 ethanol Nutrition 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- 229940079593 drug Drugs 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 239000013078 crystal Substances 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 16
- 239000011780 sodium chloride Substances 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 13
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 235000011181 potassium carbonates Nutrition 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 150000003939 benzylamines Chemical class 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 8
- 241000251730 Chondrichthyes Species 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 206010006482 Bronchospasm Diseases 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 230000007885 bronchoconstriction Effects 0.000 description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 6
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 229910052987 metal hydride Inorganic materials 0.000 description 6
- 150000004681 metal hydrides Chemical class 0.000 description 6
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- NWGXLZBWFNFBQO-UHFFFAOYSA-N COc1ccc(CNOC=C=O)cc1 Chemical compound COc1ccc(CNOC=C=O)cc1 NWGXLZBWFNFBQO-UHFFFAOYSA-N 0.000 description 5
- 208000007536 Thrombosis Diseases 0.000 description 5
- 238000006482 condensation reaction Methods 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 229960000582 mepyramine Drugs 0.000 description 5
- 239000002674 ointment Substances 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
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- 238000003786 synthesis reaction Methods 0.000 description 5
- 210000003437 trachea Anatomy 0.000 description 5
- 241000700198 Cavia Species 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000003266 anti-allergic effect Effects 0.000 description 4
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- 208000006673 asthma Diseases 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
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- 238000007796 conventional method Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 229910010272 inorganic material Inorganic materials 0.000 description 4
- 239000011147 inorganic material Substances 0.000 description 4
- JVTZFYYHCGSXJV-UHFFFAOYSA-N isovanillin Chemical compound COC1=CC=C(C=O)C=C1O JVTZFYYHCGSXJV-UHFFFAOYSA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
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- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
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- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
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- 241001465754 Metazoa Species 0.000 description 3
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- NXSOFSOGWSOKAQ-UHFFFAOYSA-N benzyl n-[(3-hydroxy-4-methoxyphenyl)methyl]carbamate Chemical compound C1=C(O)C(OC)=CC=C1CNC(=O)OCC1=CC=CC=C1 NXSOFSOGWSOKAQ-UHFFFAOYSA-N 0.000 description 3
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- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 3
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 3
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
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- 125000006247 phenyl propyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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- 229960003712 propranolol Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 238000000159 protein binding assay Methods 0.000 description 1
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
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- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
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- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
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- 229940082004 sodium laurate Drugs 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IPAMPJWEHZJUGO-UHFFFAOYSA-N tert-butyl n-[(3-hydroxy-4-methoxyphenyl)methyl]carbamate Chemical compound COC1=CC=C(CNC(=O)OC(C)(C)C)C=C1O IPAMPJWEHZJUGO-UHFFFAOYSA-N 0.000 description 1
- XLFPTPNGFVRKQV-UHFFFAOYSA-N tert-butyl n-[(4-formylpiperazin-1-yl)-phenylmethyl]carbamate Chemical compound C=1C=CC=CC=1C(NC(=O)OC(C)(C)C)N1CCN(C=O)CC1 XLFPTPNGFVRKQV-UHFFFAOYSA-N 0.000 description 1
- UBSGDLHYSHCAIE-UHFFFAOYSA-N tert-butyl n-[4-(piperazin-1-ylmethyl)phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1CN1CCNCC1 UBSGDLHYSHCAIE-UHFFFAOYSA-N 0.000 description 1
- RXRINVPIPKNMRJ-UHFFFAOYSA-N tert-butyl n-[4-[(4-formylpiperazin-1-yl)methyl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1CN1CCN(C=O)CC1 RXRINVPIPKNMRJ-UHFFFAOYSA-N 0.000 description 1
- NESFGDHBQDLVCB-UHFFFAOYSA-N tert-butyl n-[[4-methoxy-3-[2-oxo-2-[4-(quinolin-2-ylmethyl)piperazin-1-yl]ethoxy]phenyl]methyl]carbamate Chemical compound COC1=CC=C(CNC(=O)OC(C)(C)C)C=C1OCC(=O)N1CCN(CC=2N=C3C=CC=CC3=CC=2)CC1 NESFGDHBQDLVCB-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
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- 229940075420 xanthine Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/22—Nitrogen and oxygen atoms
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/20—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15919493 | 1993-06-29 | ||
| JP15919493 | 1993-06-29 | ||
| JP11272194 | 1994-05-26 | ||
| JP11272194 | 1994-05-26 | ||
| JP9401015 | 1994-06-24 | ||
| PCT/JP1994/001015 WO1995001343A1 (en) | 1993-06-29 | 1994-06-24 | Pyridazinone derivatives with pharmaceutical activity |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI956300A0 FI956300A0 (fi) | 1995-12-28 |
| FI956300A7 FI956300A7 (fi) | 1995-12-28 |
| FI113963B true FI113963B (fi) | 2004-07-15 |
Family
ID=26451823
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI956300A FI113963B (fi) | 1993-06-29 | 1995-12-28 | Menetelmä terapeuttisesti käyttökelpoisten 3 (2H) -Pyridatsinonijohdannaisten valmistamiseksi |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US5728702A (cs) |
| EP (1) | EP0706517B1 (cs) |
| KR (1) | KR100255416B1 (cs) |
| CN (1) | CN1044906C (cs) |
| AT (1) | ATE172454T1 (cs) |
| AU (1) | AU676341B2 (cs) |
| CA (1) | CA2166326C (cs) |
| CZ (1) | CZ289231B6 (cs) |
| DE (1) | DE69414112T2 (cs) |
| DK (1) | DK0706517T3 (cs) |
| ES (1) | ES2124413T3 (cs) |
| FI (1) | FI113963B (cs) |
| HU (1) | HU221009B1 (cs) |
| IL (1) | IL110040A (cs) |
| NO (1) | NO306675B1 (cs) |
| NZ (1) | NZ267510A (cs) |
| RO (1) | RO114791B1 (cs) |
| RU (1) | RU2138486C1 (cs) |
| SK (1) | SK280786B6 (cs) |
| TW (1) | TW408114B (cs) |
| UA (1) | UA34481C2 (cs) |
| WO (1) | WO1995001343A1 (cs) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2147841T3 (es) * | 1994-01-25 | 2000-10-01 | Nissan Chemical Ind Ltd | Derivados de piridazinona. |
| DE4430755A1 (de) * | 1994-08-30 | 1996-03-07 | Boehringer Mannheim Gmbh | Neue Phosphanoxide, Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel |
| DE19533975A1 (de) * | 1995-09-14 | 1997-03-20 | Merck Patent Gmbh | Arylalkyl-diazinone |
| US6207665B1 (en) | 1997-06-12 | 2001-03-27 | Schering Aktiengesellschaft | Piperazine derivatives and their use as anti-inflammatory agents |
| WO1999050248A1 (en) * | 1998-03-31 | 1999-10-07 | Nissan Chemical Industries, Ltd. | Pyridazinone hydrochloride compound and method for producing the same |
| KR100717557B1 (ko) * | 1999-11-11 | 2007-05-15 | 닛산 가가쿠 고교 가부시키 가이샤 | 벤질아민 화합물의 제조 방법 |
| SE9904377D0 (sv) * | 1999-12-01 | 1999-12-01 | Astra Pharma Prod | Pharmaceutical combinations |
| RU2179848C1 (ru) * | 2001-03-30 | 2002-02-27 | Государственное учреждение Тверская государственная медицинская академия | Применение антидепрессанта амитриптилина у больных раком легкого |
| AP2004003008A0 (en) | 2001-10-22 | 2004-06-30 | Pfizer Prod Inc | Piperazine derivatives with CCR1 receptor antagonist activity |
| RU2220738C1 (ru) * | 2002-08-30 | 2004-01-10 | Гапонюк Петр Яковлевич | Средство для лечения ринита |
| US20060080140A1 (en) * | 2004-02-09 | 2006-04-13 | Epic Systems Corporation | System and method for providing a clinical summary of patient information in various health care settings |
| WO2010099388A1 (en) * | 2009-02-27 | 2010-09-02 | Indigo Pharmaceuticals | Combinational use of a pde3 inhibitor and other agents |
| CN116768868B (zh) * | 2023-08-15 | 2023-12-08 | 云南省药物研究所 | 一种哒嗪酮硫代衍生物及其制备方法和应用 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1265798A (en) * | 1984-12-10 | 1990-02-13 | Motoo Mutsukado | 3(2h)pyridazinone, process for its preparation and anti-allergic agent containing it |
| JPH0641454B2 (ja) * | 1985-02-27 | 1994-06-01 | 日産化学工業株式会社 | ピリダジノン誘導体 |
| US4892947A (en) * | 1985-04-27 | 1990-01-09 | Nissan Chemical Industries Ltd. | 3(2H)Pyridazinone, process for its preparation and anti-allergic agent containing it |
| US4978665A (en) * | 1987-01-20 | 1990-12-18 | Nissan Chemical Industries Ltd. | 3(2H)pyridazinone, and antagonistic agent against SRS-A containing it |
| JPH02256668A (ja) * | 1988-12-20 | 1990-10-17 | Nissan Chem Ind Ltd | ピリダジノン誘導体 |
| DE69132329T2 (de) * | 1990-04-25 | 2000-11-30 | Nissan Chemical Industries, Ltd. | Pyridazinonderivat |
| ES2147841T3 (es) * | 1994-01-25 | 2000-10-01 | Nissan Chemical Ind Ltd | Derivados de piridazinona. |
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1994
- 1994-06-17 IL IL11004094A patent/IL110040A/xx not_active IP Right Cessation
- 1994-06-24 EP EP94918564A patent/EP0706517B1/en not_active Expired - Lifetime
- 1994-06-24 CZ CZ19953299A patent/CZ289231B6/cs not_active IP Right Cessation
- 1994-06-24 UA UA95125405A patent/UA34481C2/uk unknown
- 1994-06-24 AU AU69833/94A patent/AU676341B2/en not_active Ceased
- 1994-06-24 KR KR1019950705969A patent/KR100255416B1/ko not_active Expired - Fee Related
- 1994-06-24 RO RO95-02293A patent/RO114791B1/ro unknown
- 1994-06-24 ES ES94918564T patent/ES2124413T3/es not_active Expired - Lifetime
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- 1994-06-24 CA CA002166326A patent/CA2166326C/en not_active Expired - Fee Related
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- 1994-06-24 RU RU96101173A patent/RU2138486C1/ru not_active IP Right Cessation
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- 1994-06-24 DK DK94918564T patent/DK0706517T3/da active
- 1994-06-24 WO PCT/JP1994/001015 patent/WO1995001343A1/en active IP Right Grant
- 1994-06-24 SK SK1624-95A patent/SK280786B6/sk unknown
- 1994-06-24 HU HU9503807A patent/HU221009B1/hu not_active IP Right Cessation
- 1994-06-25 TW TW083105779A patent/TW408114B/zh not_active IP Right Cessation
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1995
- 1995-12-28 NO NO955328A patent/NO306675B1/no unknown
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1997
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