CS241015B2 - Method of 2-benzyl-1,2-dihydro-1-oxophthalazine-4-ylacetic acid's derivatives production - Google Patents
Method of 2-benzyl-1,2-dihydro-1-oxophthalazine-4-ylacetic acid's derivatives production Download PDFInfo
- Publication number
- CS241015B2 CS241015B2 CS789084A CS908478A CS241015B2 CS 241015 B2 CS241015 B2 CS 241015B2 CS 789084 A CS789084 A CS 789084A CS 908478 A CS908478 A CS 908478A CS 241015 B2 CS241015 B2 CS 241015B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- hydrogen
- formula
- atom
- fluoro
- pharmaceutically acceptable
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 22
- RQPPZGICNYEPHM-UHFFFAOYSA-N 2-(3-benzyl-4-oxophthalazin-1-yl)acetic acid Chemical class O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=CC=CC=C1 RQPPZGICNYEPHM-UHFFFAOYSA-N 0.000 title claims 2
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 50
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- -1 alkali metal alkoxide Chemical class 0.000 claims description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 239000002585 base Substances 0.000 claims description 19
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 239000007858 starting material Substances 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- 229910052794 bromium Inorganic materials 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 4
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims 1
- 150000008041 alkali metal carbonates Chemical class 0.000 claims 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 102000016912 Aldehyde Reductase Human genes 0.000 abstract description 15
- 108010053754 Aldehyde reductase Proteins 0.000 abstract description 15
- LKBFFDOJUKLQNY-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-4-oxo-1-phthalazinyl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=CC=C(Br)C=C1F LKBFFDOJUKLQNY-UHFFFAOYSA-N 0.000 abstract description 7
- 238000001727 in vivo Methods 0.000 abstract description 4
- RIIVBOIBIOLLPO-UHFFFAOYSA-N 2-phthalazin-1-ylacetic acid Chemical class C1=CC=C2C(CC(=O)O)=NN=CC2=C1 RIIVBOIBIOLLPO-UHFFFAOYSA-N 0.000 abstract description 3
- 230000001771 impaired effect Effects 0.000 abstract description 3
- 239000003112 inhibitor Substances 0.000 abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 208000002177 Cataract Diseases 0.000 abstract description 2
- 102000004190 Enzymes Human genes 0.000 abstract description 2
- 108090000790 Enzymes Proteins 0.000 abstract description 2
- 206010025415 Macular oedema Diseases 0.000 abstract description 2
- 208000017442 Retinal disease Diseases 0.000 abstract description 2
- 206010038923 Retinopathy Diseases 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 201000010230 macular retinal edema Diseases 0.000 abstract description 2
- 230000002093 peripheral effect Effects 0.000 abstract description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 230000001537 neural effect Effects 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 229910052717 sulfur Chemical group 0.000 abstract 1
- 239000011593 sulfur Chemical group 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 15
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 9
- 239000000600 sorbitol Substances 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 206010012601 diabetes mellitus Diseases 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 150000005846 sugar alcohols Chemical class 0.000 description 5
- 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 4
- ZEDQLIHBPGNGEC-UHFFFAOYSA-N 2-(4-oxo-3h-phthalazin-1-yl)acetic acid Chemical class C1=CC=C2C(CC(=O)O)=NNC(=O)C2=C1 ZEDQLIHBPGNGEC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 150000001323 aldoses Chemical class 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 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
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000007239 Wittig reaction Methods 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical class CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 210000003497 sciatic nerve Anatomy 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YZIFVWOCPGPNHB-UHFFFAOYSA-N 1,2-dichloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C(Cl)=C1 YZIFVWOCPGPNHB-UHFFFAOYSA-N 0.000 description 2
- ADJFSVNVKXPIAX-UHFFFAOYSA-N 2-[3-[(4-bromo-3-chlorophenyl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=CC=C(Br)C(Cl)=C1 ADJFSVNVKXPIAX-UHFFFAOYSA-N 0.000 description 2
- XMHNLZXYPAULDF-UHFFFAOYSA-N 4-bromo-1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC(Br)=CC=C1CBr XMHNLZXYPAULDF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 208000027472 Galactosemias Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000004703 alkoxides Chemical class 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
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- 230000006870 function Effects 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical class C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 2
- 229960001052 streptozocin Drugs 0.000 description 2
- VCWMRQDBPZKXKG-UHFFFAOYSA-N (2S)-O1-alpha-D-Galactopyranosyl-myo-inosit Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(O)C1O VCWMRQDBPZKXKG-UHFFFAOYSA-N 0.000 description 1
- RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 description 1
- YVVJWIIUPHLVBK-UHFFFAOYSA-N (4-bromo-2-fluorophenyl)methylhydrazine Chemical class NNCC1=CC=C(Br)C=C1F YVVJWIIUPHLVBK-UHFFFAOYSA-N 0.000 description 1
- YLOBWCNYVJFZMF-UHFFFAOYSA-N (4-oxo-3h-phthalazin-1-yl) acetate Chemical class C1=CC=C2C(OC(=O)C)=NNC(=O)C2=C1 YLOBWCNYVJFZMF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
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- YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- ZFDJCFRZDCALEA-UHFFFAOYSA-N 2-[3-[(2-fluoro-4-iodophenyl)methyl]-4-oxophthalazin-1-yl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=CC=C(I)C=C1F ZFDJCFRZDCALEA-UHFFFAOYSA-N 0.000 description 1
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- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VCWMRQDBPZKXKG-FOHCLANXSA-N Galactinol Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O1)C1[C@@H](O)[C@@H](O)C(O)[C@@H](O)[C@H]1O VCWMRQDBPZKXKG-FOHCLANXSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 239000003288 aldose reductase inhibitor Substances 0.000 description 1
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- VCWMRQDBPZKXKG-DXNLKLAMSA-N alpha-D-galactosyl-(1->3)-1D-myo-inositol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)[C@@H]1O VCWMRQDBPZKXKG-DXNLKLAMSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- AINBZKYUNWUTRE-UHFFFAOYSA-N ethanol;propan-2-ol Chemical compound CCO.CC(C)O AINBZKYUNWUTRE-UHFFFAOYSA-N 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- JBKJFMBTQMAKAL-UHFFFAOYSA-N ethyl 2-(5-fluoro-4-oxo-3h-phthalazin-1-yl)acetate Chemical compound C1=CC=C2C(CC(=O)OCC)=NNC(=O)C2=C1F JBKJFMBTQMAKAL-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical group C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 description 1
- 235000020004 porter Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000000026 trimethylsilyl group Chemical class [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS838200A CS241041B2 (cs) | 1977-12-29 | 1983-11-07 | Způsob výroby derivátů 2-benzyM^-dihydro>l-oxnftalszin-4-yloctevé kyseliny |
| CS838201A CS241042B2 (cs) | 1977-12-29 | 1983-11-07 | Způsob výroby derivátů 2-be.nzyl-l,2-dihydro-l-oxoftalazin-4-yloctové kyseliny - |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB5414277 | 1977-12-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS241015B2 true CS241015B2 (en) | 1986-03-13 |
Family
ID=10470067
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS789084A CS241015B2 (en) | 1977-12-29 | 1978-12-28 | Method of 2-benzyl-1,2-dihydro-1-oxophthalazine-4-ylacetic acid's derivatives production |
Country Status (31)
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE47592B1 (en) * | 1977-12-29 | 1984-05-02 | Ici Ltd | Enzyme inhibitory phthalazin-4-ylacetic acid derivatives, pharmaceutical compositions thereof,and process for their manufacture |
| CA1143733A (en) * | 1979-07-31 | 1983-03-29 | Masao Yoshida | Producing 7-alkoxycarbonyl-6,8-dimethyl-4- hydroxymethyl-1-phthalazone and intermediates |
| US4762839A (en) * | 1985-06-06 | 1988-08-09 | Tanabe Seiyaku Co., Ltd. | Quinazolinone copmpounds useful for the prophyloxis and treatment of diabetic complications |
| EP0222576B1 (en) * | 1985-11-07 | 1992-03-18 | Pfizer Inc. | Heterocyclic oxophthalazinyl acetic acids |
| JPS63132889A (ja) * | 1986-11-21 | 1988-06-04 | Tanabe Seiyaku Co Ltd | キナゾリノン誘導体 |
| US5011840A (en) * | 1986-11-24 | 1991-04-30 | Pfizer Inc. | Imidazolidinedione derivatives in diabetes treatment |
| GB8704569D0 (en) * | 1987-02-26 | 1987-04-01 | Ici America Inc | Therapeutic agent |
| US4868301A (en) * | 1987-06-09 | 1989-09-19 | Pfizer Inc. | Processes and intermediates for the preparation of oxophthalazinyl acetic acids having benzothiazole or other heterocyclic side chains |
| JPH0676391B2 (ja) * | 1987-06-09 | 1994-09-28 | フアイザー・インコーポレイテツド | ベンゾチアゾール等の複素環側鎖を有するオキソフタラジニル酢酸類の製造方法 |
| NZ226696A (en) * | 1987-11-02 | 1991-10-25 | Merck & Co Inc | Tablet composition comprising a phthalazine acetic acid derivative as the active ingredient present in from 83-88 wt% |
| DK607188A (da) * | 1987-11-02 | 1989-06-22 | Merck & Co Inc | Tablet indeholdende en phthalazineddikesyreforbindelse |
| US4880928A (en) * | 1987-12-21 | 1989-11-14 | Merck & Co., Inc. | Process for the preparation of 3-((4-bromo-2-fluorophenyl)methyl)-3,4-dihydro-4-oxo-1-phthalazine-acetic acid |
| US4904782A (en) * | 1988-02-29 | 1990-02-27 | Pfizer Inc. | Process for the production of phthalazineacetic acid ester derivatives and a novel intermediate |
| US4940791A (en) * | 1988-02-29 | 1990-07-10 | Pfizer Inc. | Process for the production of phthalazineacetic acid ester derivatives and a novel hydrazine containing intermediate |
| US4954629A (en) * | 1989-05-11 | 1990-09-04 | Pfizer Inc. | Process and intermediates for the preparation of oxophthalazinyl acetic acids and analogs thereof |
| US4996204A (en) * | 1989-05-11 | 1991-02-26 | Pfizer Inc. | Pyrido[2,3-d]pyridazinones as aldose reductase inhibitors |
| EP0397930A1 (en) * | 1989-05-18 | 1990-11-22 | Merck & Co. Inc. | Process for the preparation of 3-[(4-bromo-2-fluorophenyl) methyl]-3,4-dihydro-4-oxo-1-phthalazineacetic acid |
| FR2647676A1 (fr) * | 1989-06-05 | 1990-12-07 | Union Pharma Scient Appl | Nouveaux derives de pyridazinone, leurs procedes de preparation, medicaments les contenant, utiles notamment comme inhibiteurs de l'aldose reductase |
| WO1991009019A1 (en) * | 1989-12-15 | 1991-06-27 | Pfizer Inc. | Substituted oxophthalazinyl acetic acids and analogs thereof |
| US5037831A (en) * | 1990-05-21 | 1991-08-06 | American Home Products Corporation | Spiro-isoquinoline-pyrrolidines and analogs thereof useful as aldose reductase inhibitors |
| FR2682108B1 (fr) * | 1991-10-07 | 1994-01-07 | Lipha | Acide 3,4-dihydro-4-oxo-3(prop-2-enyl)-1-phtalazineacetiques et derives, leurs preparations et medicaments les contenant. |
| WO1994007867A1 (en) * | 1992-09-28 | 1994-04-14 | Pfizer Inc. | Substituted pyrimidines for control of diabetic complications |
| EP0666851A4 (en) * | 1992-11-02 | 1995-08-30 | Merck & Co. Inc. | Substituted phthalazinones as nerotensin antagonists. |
| CH683965A5 (it) * | 1993-02-19 | 1994-06-30 | Limad Marketing Exp & Imp | Composti della classe dei ftalidrazidici come sostanza attiva in agenti antinfiammatori ed antitossici. |
| JPH09506068A (ja) * | 1993-07-26 | 1997-06-17 | 藤沢薬品工業株式会社 | 悪液質治療のためのオキソフタラジン類 |
| WO1998042324A2 (en) * | 1997-03-21 | 1998-10-01 | The Regents Of The University Of California | Methods for modulating neurotrophic factor-associated activity using aldose reductase inhibitors |
| US6696407B1 (en) | 1997-03-21 | 2004-02-24 | The Regents Of The University Of California | Huntington's disease treatment comprising administering aldose reductase inhibitors to increase striatal CNTF |
| ATE344046T1 (de) * | 1997-04-15 | 2006-11-15 | Csir | Pflanzenextrakte mit appetitunterdrückender aktivität |
| AU774929B2 (en) | 1998-03-31 | 2004-07-15 | Institutes For Pharmaceutical Discovery, Llc, The | Substituted indolealkanoic acids |
| TNSN99224A1 (fr) * | 1998-12-01 | 2005-11-10 | Inst For Pharm Discovery Inc | Methodes de reduction des niveaux de glucose et triglyceride en serum et pour suppression de l'antigenese utilisant les acides la indolealkanoique |
| GB2355657B (en) * | 1999-10-27 | 2004-07-28 | Phytopharm Plc | Inhibitors Of Gastric Acid Secretion |
| DE19963607B4 (de) * | 1999-12-23 | 2005-12-15 | Schering Ag | Verfahren zur Herstellung von 4-(Heteroaryl-methyl) halogen-1(2H)-phthalazinonen |
| GB2363985B (en) | 2000-06-30 | 2004-09-29 | Phytopharm Plc | Extracts,compounds & pharmaceutical compositions having anti-diabetic activity and their use |
| AP2001002359A0 (en) * | 2000-11-30 | 2001-12-31 | Pfizer Prod Inc | Combination of gaba agonists and aldose reductase inhibitors. |
| ES2240657T3 (es) | 2001-02-28 | 2005-10-16 | Pfizer Products Inc. | Compuestos de sulfonilpiridazinona utiles como inhibidores de aldosa reductasa. |
| PL365294A1 (en) | 2001-03-30 | 2004-12-27 | Pfizer Products Inc. | Pyridazinone aldose reductase inhibitors |
| EP1392310A1 (en) * | 2001-04-30 | 2004-03-03 | Pfizer Products Inc. | Combinations of aldose reductase inhibitors and cyclooxygenase-2 inhibitors |
| AU761191B2 (en) | 2001-05-24 | 2003-05-29 | Pfizer Products Inc. | Therapies for tissue damage resulting from ischemia |
| US20050209237A1 (en) * | 2002-04-30 | 2005-09-22 | Brazzell Romulus K | Method for decreasing capillary permeability in the retina |
| CA2493755A1 (en) * | 2002-07-26 | 2004-02-05 | The Institutes For Pharmaceutical Discovery, Llc | Substituted indolealkanoic acids derivative and formulations containing same for use in treatment of diabetic complications |
| US7572910B2 (en) * | 2003-02-20 | 2009-08-11 | Pfizer, Inc. | Pyridazinone aldose reductase inhibitors |
| US20110092566A1 (en) * | 2004-11-19 | 2011-04-21 | Srivastava Satish K | Treatment of cancer with aldose reductase inhibitors |
| JP4838582B2 (ja) * | 2004-12-27 | 2011-12-14 | 岐阜プラスチック工業株式会社 | 台車用本体 |
| ES2371393T3 (es) | 2007-03-12 | 2011-12-30 | Zadec Aps | Extracto antidiabético de rooibos. |
| AU2008230949B2 (en) | 2007-03-23 | 2013-05-30 | The Board Of Regents Of The University Of Texas System | Methods involving aldose reductase inhibitors |
| US20090270490A1 (en) * | 2008-04-24 | 2009-10-29 | The Board Of Regents Of The University Of Texas System | Methods involving aldose reductase inhibition |
| JP5976010B2 (ja) | 2010-12-23 | 2016-08-23 | ザ ボード オブ リージェンツ オブ ザ ユニバーシティー オブ テキサス システム | Ｃｏｐｄを処置する方法 |
| MX372739B (es) | 2012-12-14 | 2020-05-06 | Phusis Therapeutics Inc | Metodos y composiciones para inhibir cnksr1. |
| CA2983260C (en) | 2015-04-20 | 2024-01-23 | Phusis Therapeutics, Inc. | Sulfonamide compounds, compositions and methods for inhibiting cnksr1 |
| US12090142B2 (en) | 2018-02-22 | 2024-09-17 | Board Of Regents, The University Of Texas System | Combination therapy for the treatment of cancer |
| WO2020071386A1 (ja) * | 2018-10-04 | 2020-04-09 | 日東電工株式会社 | 耐熱離型シート及び熱圧着方法 |
| JP6751974B1 (ja) * | 2019-10-16 | 2020-09-09 | 株式会社コバヤシ | 離型フィルム及び離型フィルムの製造方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3833579A (en) * | 1935-11-11 | 1974-09-03 | Inoue Michiro | 4-carbamoyl phthalazones |
| JPS5116430B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1971-08-05 | 1976-05-24 | ||
| GB1398549A (en) * | 1972-11-06 | 1975-06-25 | Boots Co Ltd | Phthalazine derivatives and their use in pharmaceutical compo sitions |
| AR205004A1 (es) * | 1973-10-30 | 1976-03-31 | Ishikawa M | Procedimiento para preparar derivados de 6,8-dialquil-7-alcoxi-carbonil-4-hidroximetil-1-ftalazona y la 7,8-lactona |
| DE2451117A1 (de) * | 1973-10-31 | 1975-05-22 | Boots Co Ltd | Therapeutisch wirksame verbindungen |
| GB1502312A (en) | 1975-03-20 | 1978-03-01 | Ici Ltd | Quinolone derivatives |
| IE43079B1 (en) * | 1975-03-20 | 1980-12-17 | Ici Ltd | Quinolone derivatives |
| JPS5214788A (en) * | 1975-07-21 | 1977-02-03 | Fuji Photo Film Co Ltd | Process for preparing phthalazinone and its derivatives |
| NL7702763A (nl) * | 1976-03-18 | 1977-09-20 | Takio Shimamoto En Masayuki Is | Werkwijze voor de bereiding van thromboxaan- -antagonisten en van preparaten die deze stof- fen bevatten. |
| IE47592B1 (en) * | 1977-12-29 | 1984-05-02 | Ici Ltd | Enzyme inhibitory phthalazin-4-ylacetic acid derivatives, pharmaceutical compositions thereof,and process for their manufacture |
| US4293553A (en) * | 1978-08-11 | 1981-10-06 | Masayuki Ishikawa | 1-Phthalazone derivatives, and use thereof |
-
1978
- 1978-11-27 IE IE2337/78A patent/IE47592B1/en not_active IP Right Cessation
- 1978-11-28 NZ NZ189034A patent/NZ189034A/xx unknown
- 1978-11-28 IN IN860/DEL/78A patent/IN150196B/en unknown
- 1978-11-29 AU AU42040/78A patent/AU516264B2/en not_active Expired
- 1978-11-29 US US05/964,725 patent/US4251528A/en not_active Expired - Lifetime
- 1978-11-30 DK DK541878A patent/DK151253C/da not_active IP Right Cessation
- 1978-11-30 IL IL56099A patent/IL56099A0/xx not_active IP Right Cessation
- 1978-12-01 EP EP78300720A patent/EP0002895B1/en not_active Expired
- 1978-12-01 CY CY1219A patent/CY1219A/xx unknown
- 1978-12-01 DE DE7878300720T patent/DE2861170D1/de not_active Expired
- 1978-12-06 PH PH21901A patent/PH15435A/en unknown
- 1978-12-12 GR GR57849A patent/GR65303B/el unknown
- 1978-12-14 FI FI783844A patent/FI64357C/fi not_active IP Right Cessation
- 1978-12-16 PL PL1978222157A patent/PL118443B1/pl unknown
- 1978-12-20 SU SU782698853A patent/SU1087075A3/ru active
- 1978-12-20 PT PT68956A patent/PT68956A/pt not_active IP Right Cessation
- 1978-12-21 CA CA318,345A patent/CA1107732A/en not_active Expired
- 1978-12-21 JP JP15695378A patent/JPS5495582A/ja active Granted
- 1978-12-22 HU HU78IE856A patent/HU182585B/hu not_active IP Right Cessation
- 1978-12-26 BG BG041857A patent/BG34336A3/xx unknown
- 1978-12-28 IT IT52480/78A patent/IT1110885B/it active
- 1978-12-28 ZW ZW249/78A patent/ZW24978A1/xx unknown
- 1978-12-28 CS CS789084A patent/CS241015B2/cs unknown
- 1978-12-28 NO NO784397A patent/NO154346C/no unknown
- 1978-12-29 ES ES476496A patent/ES476496A1/es not_active Expired
- 1978-12-29 DD DD78210284A patent/DD141021A5/de not_active IP Right Cessation
- 1978-12-29 AT AT0937678A patent/AT365581B/de not_active IP Right Cessation
- 1978-12-29 YU YU3127/78A patent/YU41607B/xx unknown
-
1980
- 1980-10-06 US US06/194,211 patent/US4393062A/en not_active Expired - Lifetime
-
1981
- 1981-12-04 SU SU813359216A patent/SU1272984A3/ru active
- 1981-12-04 SU SU813359636A patent/SU1072803A3/ru active
-
1982
- 1982-10-14 YU YU2321/82A patent/YU42807B/xx unknown
- 1982-10-14 YU YU2320/82A patent/YU42054B/xx unknown
-
1983
- 1983-11-11 SG SG68683A patent/SG68683G/en unknown
-
1984
- 1984-03-15 HK HK224/84A patent/HK22484A/en unknown
-
1985
- 1985-12-30 MY MY359/85A patent/MY8500359A/xx unknown
-
1987
- 1987-10-28 JP JP62270508A patent/JPS63119469A/ja active Granted
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