FI62532C - Analogifoerfarande foer framstaellning av farmakologiskt aktiva 3-fenylsubstituerade-6-hydrazinpyridazin-derivat - Google Patents
Analogifoerfarande foer framstaellning av farmakologiskt aktiva 3-fenylsubstituerade-6-hydrazinpyridazin-derivat Download PDFInfo
- Publication number
- FI62532C FI62532C FI751790A FI751790A FI62532C FI 62532 C FI62532 C FI 62532C FI 751790 A FI751790 A FI 751790A FI 751790 A FI751790 A FI 751790A FI 62532 C FI62532 C FI 62532C
- Authority
- FI
- Finland
- Prior art keywords
- butylamino
- hydroxypropoxy
- formula
- methyl
- solution
- Prior art date
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- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 title claims description 34
- 230000000144 pharmacologic effect Effects 0.000 title 1
- -1 -CONH2> -CH2CONH2 Chemical group 0.000 claims description 106
- 150000001875 compounds Chemical class 0.000 claims description 67
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 32
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 32
- 238000002360 preparation method Methods 0.000 claims description 29
- 239000000460 chlorine Substances 0.000 claims description 24
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000007787 solid Substances 0.000 claims description 19
- 229910052794 bromium Inorganic materials 0.000 claims description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 5
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 3
- 101150065749 Churc1 gene Proteins 0.000 claims description 3
- 102100038239 Protein Churchill Human genes 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- XDLNRRRJZOJTRW-UHFFFAOYSA-N thiohypochlorous acid Chemical compound ClS XDLNRRRJZOJTRW-UHFFFAOYSA-N 0.000 claims description 2
- 239000002893 slag Substances 0.000 claims 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 241001122767 Theaceae Species 0.000 claims 1
- CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 claims 1
- 239000003337 fertilizer Substances 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 150000007965 phenolic acids Chemical group 0.000 claims 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 147
- 239000000243 solution Substances 0.000 description 122
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 105
- 239000000203 mixture Substances 0.000 description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 63
- 238000010992 reflux Methods 0.000 description 52
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 48
- 238000001704 evaporation Methods 0.000 description 48
- 230000008020 evaporation Effects 0.000 description 47
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- 238000006243 chemical reaction Methods 0.000 description 41
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 239000012258 stirred mixture Substances 0.000 description 39
- 239000003921 oil Substances 0.000 description 38
- 235000019198 oils Nutrition 0.000 description 38
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 36
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 31
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 31
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 27
- 229960000583 acetic acid Drugs 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 21
- 239000000377 silicon dioxide Substances 0.000 description 20
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 16
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 16
- 229910000027 potassium carbonate Inorganic materials 0.000 description 16
- 239000000284 extract Substances 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 12
- 238000009835 boiling Methods 0.000 description 11
- 238000001953 recrystallisation Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- RWYZJCNSYIXCBP-UHFFFAOYSA-N 1-(tert-butylamino)-3-[4-(dimethylamino)-2-(6-hydrazinylpyridazin-3-yl)phenoxy]propan-2-ol Chemical compound CN(C)C1=CC=C(OCC(O)CNC(C)(C)C)C(C=2N=NC(NN)=CC=2)=C1 RWYZJCNSYIXCBP-UHFFFAOYSA-N 0.000 description 6
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 6
- QBQVEOIVSWQRDU-UHFFFAOYSA-N 4-(2-hydroxyphenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC=CC=C1O QBQVEOIVSWQRDU-UHFFFAOYSA-N 0.000 description 6
- 239000005711 Benzoic acid Substances 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000018044 dehydration Effects 0.000 description 6
- 238000006297 dehydration reaction Methods 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 6
- KYEACNNYFNZCST-UHFFFAOYSA-N 1-methylpyrrolidine-2,5-dione Chemical compound CN1C(=O)CCC1=O KYEACNNYFNZCST-UHFFFAOYSA-N 0.000 description 5
- UXNQKCOMUCSBSS-UHFFFAOYSA-N 2-phenyl-1,5-dihydropyridazin-6-one Chemical compound N1C(=O)CC=CN1C1=CC=CC=C1 UXNQKCOMUCSBSS-UHFFFAOYSA-N 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 241001061127 Thione Species 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- JTEVRTFFPRBPHQ-UHFFFAOYSA-N 2-(6-chloropyridazin-3-yl)-5-methoxyphenol Chemical compound OC1=CC(OC)=CC=C1C1=CC=C(Cl)N=N1 JTEVRTFFPRBPHQ-UHFFFAOYSA-N 0.000 description 4
- ACTLOQLEUUYVRQ-UHFFFAOYSA-N 3-chloro-4-phenylpyridazine Chemical class ClC1=NN=CC=C1C1=CC=CC=C1 ACTLOQLEUUYVRQ-UHFFFAOYSA-N 0.000 description 4
- DDHVIKQPVLQZHU-UHFFFAOYSA-N 4-(6-chloropyridazin-3-yl)benzene-1,3-diol Chemical compound OC1=CC(O)=CC=C1C1=CC=C(Cl)N=N1 DDHVIKQPVLQZHU-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 230000010933 acylation Effects 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- HNZVSMJLUPKDQF-UHFFFAOYSA-N 1-(tert-butylamino)-3-[2-(6-chloropyridazin-3-yl)-5-methoxyphenoxy]propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC(OC)=CC=C1C1=CC=C(Cl)N=N1 HNZVSMJLUPKDQF-UHFFFAOYSA-N 0.000 description 3
- HKMVJOOZSUOYNM-UHFFFAOYSA-N 1-(tert-butylamino)-3-[5-methoxy-2-(6-methoxypyridazin-3-yl)phenoxy]propan-2-ol Chemical compound CC(C)(C)NCC(O)COC1=CC(OC)=CC=C1C1=CC=C(OC)N=N1 HKMVJOOZSUOYNM-UHFFFAOYSA-N 0.000 description 3
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 3
- GAPVBMQBWAUBHC-UHFFFAOYSA-N 2-oxopropanoyl 2-oxopropanoate Chemical compound CC(=O)C(=O)OC(=O)C(C)=O GAPVBMQBWAUBHC-UHFFFAOYSA-N 0.000 description 3
- KFVDVTYLBHWHHJ-UHFFFAOYSA-N 4-(2-hydroxy-5-nitrophenyl)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)C1=CC([N+]([O-])=O)=CC=C1O KFVDVTYLBHWHHJ-UHFFFAOYSA-N 0.000 description 3
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- 238000004440 column chromatography Methods 0.000 description 3
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229940014800 succinic anhydride Drugs 0.000 description 3
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- 230000024883 vasodilation Effects 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- DPZNOMCNRMUKPS-UHFFFAOYSA-N 1,3-Dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1 DPZNOMCNRMUKPS-UHFFFAOYSA-N 0.000 description 2
- YRILCWMUOZISCD-UHFFFAOYSA-N 1-(tert-butylamino)-3-[5-ethoxy-2-(6-methoxypyridazin-3-yl)phenoxy]propan-2-ol Chemical compound C(C)(C)(C)NCC(COC1=C(C=CC(=C1)OCC)C1=CC=C(N=N1)OC)O YRILCWMUOZISCD-UHFFFAOYSA-N 0.000 description 2
- YQQSRZSUGBETRS-UHFFFAOYSA-N 1h-pyridazine-6-thione Chemical compound SC1=CC=CN=N1 YQQSRZSUGBETRS-UHFFFAOYSA-N 0.000 description 2
- SSDAKJLEKSSAMH-UHFFFAOYSA-N 2,4-dihydro-1h-pyridazin-3-one Chemical group O=C1CC=CNN1 SSDAKJLEKSSAMH-UHFFFAOYSA-N 0.000 description 2
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- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- RVCVDUWHPXZWKO-UHFFFAOYSA-N ethyl 4-[2-[3-(tert-butylamino)-2-hydroxypropoxy]-4-chlorophenyl]-4-oxobutanoate Chemical compound CCOC(=O)CCC(=O)C1=CC=C(Cl)C=C1OCC(O)CNC(C)(C)C RVCVDUWHPXZWKO-UHFFFAOYSA-N 0.000 description 1
- VUADNYMMYVFKRN-UHFFFAOYSA-N ethyl 4-[4-chloro-2-(oxiran-2-ylmethoxy)phenyl]-4-oxobutanoate Chemical compound CCOC(=O)CCC(=O)C1=CC=C(Cl)C=C1OCC1OC1 VUADNYMMYVFKRN-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- UUBJKHVFGWGJKX-UHFFFAOYSA-N hydrate tetrahydrochloride Chemical compound O.Cl.Cl.Cl.Cl UUBJKHVFGWGJKX-UHFFFAOYSA-N 0.000 description 1
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
- WFNVFNILGYZHHK-UHFFFAOYSA-N hydrazine;pyridazine Chemical class NN.C1=CC=NN=C1 WFNVFNILGYZHHK-UHFFFAOYSA-N 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 229910000372 mercury(II) sulfate Inorganic materials 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- DDZBYCVFPQTSNL-UHFFFAOYSA-N methyl 4-(2-hydroxy-5-methoxyphenyl)-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(OC)=CC=C1O DDZBYCVFPQTSNL-UHFFFAOYSA-N 0.000 description 1
- VBWYLHOOTXQVLG-UHFFFAOYSA-N methyl 4-(2-hydroxy-5-methylphenyl)-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(C)=CC=C1O VBWYLHOOTXQVLG-UHFFFAOYSA-N 0.000 description 1
- MEQVMVVOUNBUPM-UHFFFAOYSA-N methyl 4-(3-chloro-2-hydroxyphenyl)-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC=CC(Cl)=C1O MEQVMVVOUNBUPM-UHFFFAOYSA-N 0.000 description 1
- DNBQWGFNJAYACL-UHFFFAOYSA-N methyl 4-(5-chloro-2-hydroxyphenyl)-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(Cl)=CC=C1O DNBQWGFNJAYACL-UHFFFAOYSA-N 0.000 description 1
- LXGIYTCAUIGEPT-UHFFFAOYSA-N methyl 4-[2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-chlorophenyl]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(Cl)=CC=C1OCC(O)CNC(C)(C)C LXGIYTCAUIGEPT-UHFFFAOYSA-N 0.000 description 1
- TXAMJDVCLBHVCH-UHFFFAOYSA-N methyl 4-[2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-methoxyphenyl]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(OC)=CC=C1OCC(O)CNC(C)(C)C TXAMJDVCLBHVCH-UHFFFAOYSA-N 0.000 description 1
- RDWRMRQNWVSMNK-UHFFFAOYSA-N methyl 4-[2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-methylphenyl]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(C)=CC=C1OCC(O)CNC(C)(C)C RDWRMRQNWVSMNK-UHFFFAOYSA-N 0.000 description 1
- KFBNTRCOECZDBA-UHFFFAOYSA-N methyl 4-[3-(tert-butylamino)-2-hydroxypropoxy]-3-(4-methoxy-4-oxobutanoyl)benzoate Chemical compound COC(=O)CCC(=O)C1=CC(C(=O)OC)=CC=C1OCC(O)CNC(C)(C)C KFBNTRCOECZDBA-UHFFFAOYSA-N 0.000 description 1
- FCZHDAXPBAHZMH-UHFFFAOYSA-N methyl 4-[5-methoxy-2-(oxiran-2-ylmethoxy)phenyl]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(OC)=CC=C1OCC1OC1 FCZHDAXPBAHZMH-UHFFFAOYSA-N 0.000 description 1
- MRXAFPLRXZFIKV-UHFFFAOYSA-N methyl 4-[5-methyl-2-(oxiran-2-ylmethoxy)phenyl]-4-oxobutanoate Chemical compound COC(=O)CCC(=O)C1=CC(C)=CC=C1OCC1OC1 MRXAFPLRXZFIKV-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- MAGVJLLHDZWQFM-UHFFFAOYSA-N n-chloro-n-methylmethanamine Chemical compound CN(C)Cl MAGVJLLHDZWQFM-UHFFFAOYSA-N 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- YVUHWORBFNMMTD-UHFFFAOYSA-N pyridazine;sulfuric acid Chemical compound OS(O)(=O)=O.C1=CC=NN=C1 YVUHWORBFNMMTD-UHFFFAOYSA-N 0.000 description 1
- 150000004892 pyridazines Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 238000011935 selective methylation Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/56—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups bound to carbon atoms of six-membered aromatic rings and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
- C07C65/40—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups containing singly bound oxygen-containing groups
-
- 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
- C07D237/12—Halogen atoms or nitro radicals
-
- 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
- C07D237/18—Sulfur atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB26864/74A GB1527712A (en) | 1974-06-18 | 1974-06-18 | Hydrazinopyridazines |
| GB2686474 | 1974-06-18 | ||
| GB2075 | 1975-01-02 | ||
| GB2075 | 1975-01-02 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI751790A7 FI751790A7 (en, 2012) | 1975-12-19 |
| FI62532B FI62532B (fi) | 1982-09-30 |
| FI62532C true FI62532C (fi) | 1983-01-10 |
Family
ID=26235616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI751790A FI62532C (fi) | 1974-06-18 | 1975-06-16 | Analogifoerfarande foer framstaellning av farmakologiskt aktiva 3-fenylsubstituerade-6-hydrazinpyridazin-derivat |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4053601A (en, 2012) |
| JP (1) | JPS5113782A (en, 2012) |
| CA (1) | CA1067078A (en, 2012) |
| CH (1) | CH617429A5 (en, 2012) |
| DE (1) | DE2527066A1 (en, 2012) |
| DK (1) | DK145099C (en, 2012) |
| ES (1) | ES438685A1 (en, 2012) |
| FI (1) | FI62532C (en, 2012) |
| FR (1) | FR2275213A1 (en, 2012) |
| IE (1) | IE42214B1 (en, 2012) |
| IL (1) | IL47351A (en, 2012) |
| LU (1) | LU72739A1 (en, 2012) |
| NL (1) | NL7507267A (en, 2012) |
| SE (1) | SE416650B (en, 2012) |
| SU (1) | SU862824A3 (en, 2012) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4314943A (en) * | 1977-07-13 | 1982-02-09 | Mead Johnson & Company | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols |
| US4272440A (en) * | 1978-02-24 | 1981-06-09 | Smithkline Corporation | Intermediates for preparing hydroxyphenylpyridazinones |
| IN148775B (en, 2012) * | 1978-08-04 | 1981-06-13 | Smithkline & French Lab Ltd Uk | |
| US4495352A (en) * | 1979-02-13 | 1985-01-22 | Mead Johnson & Company | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols |
| DE3028453A1 (de) * | 1980-07-26 | 1982-03-18 | Zinser Textilmaschinen Gmbh, 7333 Ebersbach | Spinnmaschine |
| US4340733A (en) * | 1980-09-02 | 1982-07-20 | Smithkline Corporation | Process for preparing 3-chloro-6-(2-hydroxyphenyl)-pyridazines |
| EP0101156A3 (en) * | 1982-06-24 | 1984-08-22 | Smith Kline & French Laboratories Limited | Process for preparing 6-(2-hydroxyphenyl)-3-pyridazinone |
| DE3302442A1 (de) * | 1983-01-26 | 1984-07-26 | Basf Ag, 6700 Ludwigshafen | Neue pyridazinone, verfahren zu ihrer herstellung, diese verbindungen enthaltende therapeutische mittel und deren verwendung |
| GB8323553D0 (en) * | 1983-09-02 | 1983-10-05 | Smith Kline French Lab | Pharmaceutical compositions |
| JPH0629254B2 (ja) * | 1986-09-08 | 1994-04-20 | 帝国臓器製薬株式会社 | ピリダジノン誘導体 |
| EP1461323B1 (en) | 2001-06-12 | 2013-10-09 | Wellstat Therapeutics Corporation | Compounds for the treatment of metabolic disorders |
| WO2008013838A2 (en) * | 2006-07-25 | 2008-01-31 | Cephalon, Inc. | Pyridizinone derivatives |
| US20150119399A1 (en) | 2012-01-10 | 2015-04-30 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| TW202216671A (zh) * | 2020-06-25 | 2022-05-01 | 瑞士商諾華公司 | １，４—二取代的嗒𠯤化合物之製造方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE758146A (fr) * | 1969-10-29 | 1971-04-28 | Smith Kline French Lab | Derives de l'amidine |
| US3818097A (en) * | 1969-10-29 | 1974-06-18 | Smith Kline French Lab | Method of inhibiting histamine activity with isothioureas |
| IT1054107B (it) * | 1970-12-15 | 1981-11-10 | Isf Spa | Nuove 3,idrazinopiridazine 6,sostituite ad attivita antiiperten siva e loro preparazione |
| US3975530A (en) * | 1972-09-05 | 1976-08-17 | Smith Kline & French Laboratories Limited | N-cyano-N'-heterocyclic-alkyl quanidine inhibitors of H2 histamine receptors |
-
1975
- 1975-05-19 IE IE1124/75A patent/IE42214B1/en unknown
- 1975-05-26 IL IL47351A patent/IL47351A/xx unknown
- 1975-05-30 DK DK245275A patent/DK145099C/da not_active IP Right Cessation
- 1975-06-03 US US05/583,379 patent/US4053601A/en not_active Expired - Lifetime
- 1975-06-12 CA CA229,160A patent/CA1067078A/en not_active Expired
- 1975-06-16 FI FI751790A patent/FI62532C/fi not_active IP Right Cessation
- 1975-06-16 LU LU72739A patent/LU72739A1/xx unknown
- 1975-06-17 CH CH787175A patent/CH617429A5/de not_active IP Right Cessation
- 1975-06-17 SE SE7506947A patent/SE416650B/xx unknown
- 1975-06-17 JP JP50074260A patent/JPS5113782A/ja active Pending
- 1975-06-18 FR FR7519034A patent/FR2275213A1/fr active Granted
- 1975-06-18 ES ES438685A patent/ES438685A1/es not_active Expired
- 1975-06-18 NL NL7507267A patent/NL7507267A/xx not_active Application Discontinuation
- 1975-06-18 DE DE19752527066 patent/DE2527066A1/de not_active Ceased
-
1978
- 1978-12-22 SU SU782145553D patent/SU862824A3/ru active
Also Published As
| Publication number | Publication date |
|---|---|
| CH617429A5 (en, 2012) | 1980-05-30 |
| FR2275213B1 (en, 2012) | 1979-08-10 |
| JPS5113782A (en, 2012) | 1976-02-03 |
| IE42214L (en) | 1975-12-18 |
| DK245275A (da) | 1975-12-19 |
| DK145099B (da) | 1982-08-30 |
| IE42214B1 (en) | 1980-07-02 |
| DE2527066A1 (de) | 1976-01-08 |
| AU8158175A (en) | 1976-12-02 |
| SE416650B (sv) | 1981-01-26 |
| LU72739A1 (en, 2012) | 1975-10-08 |
| SU862824A3 (ru) | 1981-09-07 |
| FI62532B (fi) | 1982-09-30 |
| US4053601A (en) | 1977-10-11 |
| SE7506947L (sv) | 1975-12-19 |
| DK145099C (da) | 1983-01-31 |
| IL47351A0 (en) | 1975-07-28 |
| ES438685A1 (es) | 1977-05-16 |
| NL7507267A (nl) | 1975-12-22 |
| IL47351A (en) | 1980-02-29 |
| FI751790A7 (en, 2012) | 1975-12-19 |
| CA1067078A (en) | 1979-11-27 |
| FR2275213A1 (fr) | 1976-01-16 |
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