IL94302A - History of N-Arleic Acid (Il-Oxo) Theoxo (Pyrido] -D-3,2 [Pyridazinate - Google Patents

History of N-Arleic Acid (Il-Oxo) Theoxo (Pyrido] -D-3,2 [Pyridazinate

Info

Publication number: IL94302A
Authority: IL; Israel
Prior art keywords: pyrido; compound; oxo; phenyl; formula
Prior art date: 1989-05-11

Application number

IL9430290A

Other languages

English (en)

Hebrew (he)

Other versions

IL94302A0 (en

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1989-05-11

Filing date

1990-05-06

Publication date

1994-01-25

1990-05-06 Application filed by Pfizer filed Critical Pfizer

1991-03-10 Publication of IL94302A0 publication Critical patent/IL94302A0/xx

1994-01-25 Publication of IL94302A publication Critical patent/IL94302A/en

Links

150000001875 compounds Chemical class 0.000 claims abstract description 39
-1 6-substituted-5-oxo-6H-pyrido[2,3-d]pyridazine-8-ylacetic acid Chemical class 0.000 claims abstract description 37
239000002253 acid Substances 0.000 claims abstract description 29
150000003839 salts Chemical class 0.000 claims abstract description 8
125000001424 substituent group Chemical group 0.000 claims abstract description 7
150000001768 cations Chemical class 0.000 claims abstract description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
229910052794 bromium Inorganic materials 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
239000011737 fluorine Substances 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 4
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
125000004534 benzothien-2-yl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000001041 indolyl group Chemical group 0.000 claims description 2
239000011593 sulfur Chemical group 0.000 claims description 2
229910052717 sulfur Chemical group 0.000 claims description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims 1
125000005605 benzo group Chemical group 0.000 claims 1
125000000335 thiazolyl group Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 21
239000007858 starting material Substances 0.000 abstract description 11
230000001684 chronic effect Effects 0.000 abstract description 9
150000007513 acids Chemical class 0.000 abstract description 8
208000002249 Diabetes Complications Diseases 0.000 abstract description 4
206010012655 Diabetic complications Diseases 0.000 abstract description 4
239000003288 aldose reductase inhibitor Substances 0.000 abstract description 4
229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 abstract description 4
125000003710 aryl alkyl group Chemical group 0.000 abstract description 2
229910052757 nitrogen Inorganic materials 0.000 abstract description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
125000004475 heteroaralkyl group Chemical group 0.000 abstract 1
238000002560 therapeutic procedure Methods 0.000 abstract 1
239000000047 product Substances 0.000 description 40
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 18
239000012467 final product Substances 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 15
QGAQQANQFMOQTQ-UHFFFAOYSA-N acetic acid;2h-pyrido[3,2-c]pyridazin-3-one Chemical class CC(O)=O.N1=CC=CC2=NNC(=O)C=C21 QGAQQANQFMOQTQ-UHFFFAOYSA-N 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
239000007864 aqueous solution Substances 0.000 description 9
210000000695 crystalline len Anatomy 0.000 description 8
206010012601 diabetes mellitus Diseases 0.000 description 8
239000000203 mixture Substances 0.000 description 8
239000000376 reactant Substances 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
VMVSSVCXGNALAH-UHFFFAOYSA-N 2-(chloromethyl)-5-(trifluoromethyl)-1,3-benzothiazole Chemical compound FC(F)(F)C1=CC=C2SC(CCl)=NC2=C1 VMVSSVCXGNALAH-UHFFFAOYSA-N 0.000 description 7
239000002585 base Substances 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
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 6
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
125000005907 alkyl ester group Chemical group 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
239000000600 sorbitol Substances 0.000 description 6
238000000967 suction filtration Methods 0.000 description 6
102000016912 Aldehyde Reductase Human genes 0.000 description 5
108010053754 Aldehyde reductase Proteins 0.000 description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000003480 eluent Substances 0.000 description 5
239000011591 potassium Substances 0.000 description 5
229910052700 potassium Inorganic materials 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
239000012265 solid product Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
241000700159 Rattus Species 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
239000005457 ice water Substances 0.000 description 4
238000010561 standard procedure Methods 0.000 description 4
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 3
XMHNLZXYPAULDF-UHFFFAOYSA-N 4-bromo-1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC(Br)=CC=C1CBr XMHNLZXYPAULDF-UHFFFAOYSA-N 0.000 description 3
208000002177 Cataract Diseases 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
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 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 3
239000007788 liquid Substances 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
229960005235 piperonyl butoxide Drugs 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
210000003497 sciatic nerve Anatomy 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
WOEUAFRESFKHDU-UHFFFAOYSA-N 2-[5-oxo-6-[[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]pyrido[2,3-d]pyridazin-8-yl]acetic acid Chemical compound O=C1C2=CC=CN=C2C(CC(=O)O)=NN1CC1=NC2=CC(C(F)(F)F)=CC=C2S1 WOEUAFRESFKHDU-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
206010007749 Cataract diabetic Diseases 0.000 description 2
208000007342 Diabetic Nephropathies Diseases 0.000 description 2
208000032131 Diabetic Neuropathies Diseases 0.000 description 2
206010012689 Diabetic retinopathy Diseases 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
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 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
230000035508 accumulation Effects 0.000 description 2
235000011054 acetic acid Nutrition 0.000 description 2
150000001323 aldoses Chemical class 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
239000012736 aqueous medium Substances 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
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 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
239000000969 carrier Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
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239000002552 dosage form Substances 0.000 description 2
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230000008020 evaporation Effects 0.000 description 2
239000000945 filler Substances 0.000 description 2
MCQOWYALZVKMAR-UHFFFAOYSA-N furo[3,4-b]pyridine-5,7-dione Chemical class C1=CC=C2C(=O)OC(=O)C2=N1 MCQOWYALZVKMAR-UHFFFAOYSA-N 0.000 description 2
239000008103 glucose Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000000463 material Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
230000007823 neuropathy Effects 0.000 description 2
229920005862 polyol Polymers 0.000 description 2
150000003077 polyols Chemical class 0.000 description 2
238000000746 purification Methods 0.000 description 2
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229910052708 sodium Inorganic materials 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
239000003826 tablet Substances 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 1
AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 1
IFMSHCYFSBNVJL-UHFFFAOYSA-N 2-(6-benzyl-5-oxopyrido[2,3-d]pyridazin-8-yl)acetic acid Chemical class O=C1C2=CC=CN=C2C(CC(=O)O)=NN1CC1=CC=CC=C1 IFMSHCYFSBNVJL-UHFFFAOYSA-N 0.000 description 1
LLEKVIHIOONSPJ-UHFFFAOYSA-N 2-(chloromethyl)-5,7-difluoro-1,3-benzothiazole Chemical compound FC1=CC(F)=C2SC(CCl)=NC2=C1 LLEKVIHIOONSPJ-UHFFFAOYSA-N 0.000 description 1
ACVAICWJHHSMGT-UHFFFAOYSA-N 2-(chloromethyl)-5-fluoro-1,3-benzothiazole Chemical compound FC1=CC=C2SC(CCl)=NC2=C1 ACVAICWJHHSMGT-UHFFFAOYSA-N 0.000 description 1
MSXSAVPVWDXBIO-UHFFFAOYSA-N 2-[6-[(4-chloro-1-benzothiophen-2-yl)methyl]-5-oxopyrido[2,3-d]pyridazin-8-yl]acetic acid Chemical compound O=C1C2=CC=CN=C2C(CC(=O)O)=NN1CC1=CC2=C(Cl)C=CC=C2S1 MSXSAVPVWDXBIO-UHFFFAOYSA-N 0.000 description 1
KLGRUNSKORTTKE-UHFFFAOYSA-N 2-[6-[(5,7-difluoro-1,3-benzothiazol-2-yl)methyl]-5-oxopyrido[2,3-d]pyridazin-8-yl]acetic acid Chemical compound O=C1C2=CC=CN=C2C(CC(=O)O)=NN1CC1=NC2=CC(F)=CC(F)=C2S1 KLGRUNSKORTTKE-UHFFFAOYSA-N 0.000 description 1
DXTZRJXELRQNPV-UHFFFAOYSA-N 2-[6-[(5-bromo-1,3-benzoxazol-2-yl)methyl]-5-oxopyrido[2,3-d]pyridazin-8-yl]acetic acid Chemical compound O=C1C2=CC=CN=C2C(CC(=O)O)=NN1CC1=NC2=CC(Br)=CC=C2O1 DXTZRJXELRQNPV-UHFFFAOYSA-N 0.000 description 1
ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
GIQDUNZXUKYGEP-UHFFFAOYSA-N 3-(chloromethyl)-5-[2-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC=C1C1=NC(CCl)=NO1 GIQDUNZXUKYGEP-UHFFFAOYSA-N 0.000 description 1
ALDIPNAEAOQMQU-UHFFFAOYSA-N 4-chloro-2-(chloromethyl)-1-benzothiophene Chemical compound C1=CC=C2SC(CCl)=CC2=C1Cl ALDIPNAEAOQMQU-UHFFFAOYSA-N 0.000 description 1
HTDLSAGEOYDVSJ-UHFFFAOYSA-N 4-phenyloxadiazole Chemical group O1N=NC(C=2C=CC=CC=2)=C1 HTDLSAGEOYDVSJ-UHFFFAOYSA-N 0.000 description 1
FGILREBVGOSVMA-UHFFFAOYSA-N 5-bromo-2-(bromomethyl)-1,3-benzoxazole Chemical compound BrC1=CC=C2OC(CBr)=NC2=C1 FGILREBVGOSVMA-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
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FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
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SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
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KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
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ZWZUFQPXYVYAFO-UHFFFAOYSA-N Tert-butyl (triphenylphosphoranylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC(C)(C)C)C1=CC=CC=C1 ZWZUFQPXYVYAFO-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
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230000002152 alkylating effect Effects 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
150000001408 amides Chemical class 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
239000002775 capsule Substances 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000004040 coloring Methods 0.000 description 1
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229940125773 compound 10 Drugs 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
235000009508 confectionery Nutrition 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
150000003950 cyclic amides Chemical class 0.000 description 1
150000004292 cyclic ethers Chemical class 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
125000004464 hydroxyphenyl group Chemical group 0.000 description 1
230000002218 hypoglycaemic effect Effects 0.000 description 1
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
229910000103 lithium hydride Inorganic materials 0.000 description 1
SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 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
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000018791 negative regulation of catalytic activity Effects 0.000 description 1
239000002997 ophthalmic solution Substances 0.000 description 1
229940054534 ophthalmic solution Drugs 0.000 description 1
239000003538 oral antidiabetic agent Substances 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
210000000578 peripheral nerve Anatomy 0.000 description 1
210000001428 peripheral nervous system Anatomy 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
210000002826 placenta Anatomy 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
GVKZCWAHXGSMBC-UHFFFAOYSA-N pyridazin-4-yl acetate Chemical compound CC(=O)OC1=CC=NN=C1 GVKZCWAHXGSMBC-UHFFFAOYSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
210000001525 retina Anatomy 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 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
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
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 1
229960001052 streptozocin Drugs 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Emergency Medicine (AREA)
Obesity (AREA)
Hematology (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Ophthalmology & Optometry (AREA)
Neurosurgery (AREA)
Urology & Nephrology (AREA)
Reproductive Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Saccharide Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

IL9430290A 1989-05-11 1990-05-06 History of N-Arleic Acid (Il-Oxo) Theoxo (Pyrido] -D-3,2 [Pyridazinate IL94302A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US07/350,417 US4996204A (en)	1989-05-11	1989-05-11	Pyrido[2,3-d]pyridazinones as aldose reductase inhibitors

Publications (2)

Publication Number	Publication Date
IL94302A0 IL94302A0 (en)	1991-03-10
IL94302A true IL94302A (en)	1994-01-25

Family

ID=23376622

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9430290A IL94302A (en)	1989-05-11	1990-05-06	History of N-Arleic Acid (Il-Oxo) Theoxo (Pyrido] -D-3,2 [Pyridazinate

Country Status (18)

Country	Link
US (1)	US4996204A (fr)
EP (1)	EP0401981B1 (fr)
JP (1)	JPH0631235B2 (fr)
KR (1)	KR920003559B1 (fr)
AT (1)	ATE121743T1 (fr)
AU (1)	AU611610B2 (fr)
CA (1)	CA2016326C (fr)
DE (1)	DE69018876T2 (fr)
DK (1)	DK0401981T3 (fr)
ES (1)	ES2071016T3 (fr)
FI (1)	FI93013C (fr)
HU (1)	HU206714B (fr)
IE (1)	IE66029B1 (fr)
IL (1)	IL94302A (fr)
NO (1)	NO173938C (fr)
NZ (1)	NZ233599A (fr)
PT (1)	PT93984B (fr)
ZA (1)	ZA903564B (fr)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4954629A (en) *	1989-05-11	1990-09-04	Pfizer Inc.	Process and intermediates for the preparation of oxophthalazinyl acetic acids and analogs thereof
US5716954A (en) *	1991-10-09	1998-02-10	Syntex U.S.A. Inc.	Benzopyridazinone and pyridopyridazinone compounds
NZ254550A (en) *	1992-09-28	1997-08-22	Pfizer	Use of nitrogen-substituted pyrimidines to prepare medicaments useful for treatment or prevention of diabetic complications
GB9314412D0 (en) *	1993-07-13	1993-08-25	Rhone Poulenc Agriculture	New compositions of matter
SK7522001A3 (en)	1998-03-31	2002-02-05	Inst For Pharm Discovery Inc	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
HRP20030419A2 (en) *	2000-11-30	2004-08-31	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.
ATE348100T1 (de) *	2001-03-30	2007-01-15	Pfizer Prod Inc	Zwischenprodukten für die herstellung von pyridazinon aldose reductase inhibitoren.
AU2002236131B2 (en) *	2001-04-30	2005-04-14	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
US7572910B2 (en) *	2003-02-20	2009-08-11	Pfizer, Inc.	Pyridazinone aldose reductase inhibitors
PL2593456T3 (pl) *	2010-07-16	2017-06-30	The Trustees Of Columbia University In The City Of New York	Inhibitory reduktazy aldozowej i ich zastosowania
US8916563B2 (en)	2010-07-16	2014-12-23	The Trustees Of Columbia University In The City Of New York	Aldose reductase inhibitors and uses thereof
IL283809B2 (en)	2016-06-21	2024-01-01	Univ Columbia	Compounds for use in a method of treating neuropathy, retinopathy, nephropathy, or cardiomyopathy
IL272246B2 (en)	2017-07-28	2026-01-01	Applied Therapeutics Inc	History of 2-(4-oxo/thioketone/azo-3-((substituted)benzo[d]thiazol-2-yl)methyl)- 3,4-dihydrothieno[3,4-d]pyridazin-1-yl)acetic acid for use as an aldose reductase inhibitor for the treatment of galactosemia or prevention of galactosemia-related complications
AU2020254610A1 (en)	2019-04-01	2021-11-18	Applied Therapeutics Inc.	Inhibitors of aldose reductase
CN113966396A (zh)	2019-05-07	2022-01-21	迈阿密大学	遗传性神经病和相关障碍的治疗和检测

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3821383A (en) *	1972-07-10	1974-06-28	Ayerst Mckenna & Harrison	Compositions for and a method of treating diabetic complications
DE2708187A1 (de) *	1977-02-25	1978-08-31	Thomae Gmbh Dr K	Neue pyrido-pyridazin-one
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
US4209527A (en) *	1979-05-16	1980-06-24	Pfizer Inc.	Benzimidazolone derivatives
CA1160518A (fr) *	1979-07-06	1984-01-17	E. I. Du Pont De Nemours And Company	Ustensiles de cuisson a revetement de ptfe
ES2032749T3 (es) *	1985-11-07	1993-03-01	Pfizer Inc.	Acidos oxoftalazinil-aceticos heterociclicos.
US4954629A (en) *	1989-05-11	1990-09-04	Pfizer Inc.	Process and intermediates for the preparation of oxophthalazinyl acetic acids and analogs thereof

1989
- 1989-05-11 US US07/350,417 patent/US4996204A/en not_active Expired - Lifetime
1990
- 1990-05-06 IL IL9430290A patent/IL94302A/en not_active IP Right Cessation
- 1990-05-08 NZ NZ233599A patent/NZ233599A/en unknown
- 1990-05-09 PT PT93984A patent/PT93984B/pt not_active IP Right Cessation
- 1990-05-09 CA CA002016326A patent/CA2016326C/fr not_active Expired - Fee Related
- 1990-05-10 FI FI902335A patent/FI93013C/fi not_active IP Right Cessation
- 1990-05-10 DE DE69018876T patent/DE69018876T2/de not_active Expired - Fee Related
- 1990-05-10 AU AU54905/90A patent/AU611610B2/en not_active Ceased
- 1990-05-10 ZA ZA903564A patent/ZA903564B/xx unknown
- 1990-05-10 AT AT90305015T patent/ATE121743T1/de not_active IP Right Cessation
- 1990-05-10 DK DK90305015.1T patent/DK0401981T3/da active
- 1990-05-10 HU HU902996A patent/HU206714B/hu not_active IP Right Cessation
- 1990-05-10 EP EP90305015A patent/EP0401981B1/fr not_active Expired - Lifetime
- 1990-05-10 KR KR1019900006808A patent/KR920003559B1/ko not_active Expired
- 1990-05-10 ES ES90305015T patent/ES2071016T3/es not_active Expired - Lifetime
- 1990-05-10 NO NO902070A patent/NO173938C/no unknown
- 1990-05-11 IE IE170190A patent/IE66029B1/en unknown
- 1990-05-11 JP JP2122832A patent/JPH0631235B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
ES2071016T3 (es)	1995-06-16
ATE121743T1 (de)	1995-05-15
EP0401981B1 (fr)	1995-04-26
HU902996D0 (en)	1990-09-28
NO902070D0 (no)	1990-05-10
PT93984A (pt)	1991-01-08
KR920003559B1 (ko)	1992-05-04
US4996204A (en)	1991-02-26
DK0401981T3 (da)	1995-09-04
FI93013B (fi)	1994-10-31
ZA903564B (en)	1992-08-26
CA2016326A1 (fr)	1990-11-11
PT93984B (pt)	1996-11-29
NZ233599A (en)	1991-07-26
AU5490590A (en)	1990-11-15
NO173938B (no)	1993-11-15
EP0401981A1 (fr)	1990-12-12
NO902070L (no)	1990-11-12
FI902335A0 (fi)	1990-05-10
IE66029B1 (en)	1995-11-29
DE69018876T2 (de)	1995-08-24
KR900018092A (ko)	1990-12-20
IE901701L (en)	1990-11-11
DE69018876D1 (de)	1995-06-01
HUT54683A (en)	1991-03-28
JPH035481A (ja)	1991-01-11
FI93013C (fi)	1995-02-10
JPH0631235B2 (ja)	1994-04-27
CA2016326C (fr)	1995-05-30
AU611610B2 (en)	1991-06-13
IL94302A0 (en)	1991-03-10
NO173938C (no)	1994-02-23
HU206714B (en)	1992-12-28

Legal Events

Date	Code	Title	Description
1996-08-04	KB	Patent renewed
2001-06-14	RH	Patent void

Publication	Publication Date	Title
CA2016326C (fr)	1995-05-30	Acides pyrido-pyridazinone acetiques pour traiter les complications chroniques du diabete
US4668686A (en)	1987-05-26	Imidazoquinoline antithrombrogenic cardiotonic agents
IE59995B1 (en)	1994-05-18	Indolinone Derivatives
US5385931A (en)	1995-01-31	Sulfonamides derived from benzocyclic or benzoheterocyclic acids, their preparation and application in therapeutics
US5268386A (en)	1993-12-07	Certain 3,4-dihydro 4-oxospiro [2H-1 benzopyrans] useful for treating hyperuricemia
US4940708A (en)	1990-07-10	4-arylsulfonyl-3,4-dihydro-2(1H)-quinoxalinone-1-alkanoic acids, esters, and salts
JPH0825877B2 (ja)	1996-03-13	眼科治療用組成物
EP0019440B1 (fr)	1982-09-29	Dérivés de la benzimidazolone, procédé pour leur préparation et compositions pharmaceutiques les contenant
CA1140928A (fr)	1983-02-08	Quinolyhydantions inhibiteurs d'aldose reductase
KR860001581B1 (ko)	1986-10-10	스피로-3-헤테로-아졸론의 제조방법
US4574128A (en)	1986-03-04	5-(4-Chloro-3-sulfamoylbenzoyl)-2,3-dihydro-2-benzofurancarboxylic acids and their compositions having diuretic, saluretic and uricosuric activity
US4960785A (en)	1990-10-02	Indolinone derivatives
JPH04270273A (ja)	1992-09-25	チアゾリジン−２，４−ジオン誘導体とその塩及びその製造法
RO113856B1 (ro)	1998-11-30	Derivati ai sulfonamidei, procedee de preparare a acestora si preparate farmaceutice pentru terapia diabetului
KR820001929B1 (ko)	1982-10-20	프탈라진-4-일아세트산의 제조방법
WO1992012979A1 (fr)	1992-08-06	ACIDES ACETIQUES 2,4-DIOXO-PYRIDO [2,3-d] PYRIMIDINE-3- AINSI QUE LEURS ESTERS ET LEURS SELS
JPH08277266A (ja)	1996-10-22	スピロ三環式芳香族スクシンイミド誘導体、並びにヒト及び動物の糖尿病合併症治療剤
EP0112620A1 (fr)	1984-07-04	Hydantoines-5-(phényl substitués)
EP0160258A2 (fr)	1985-11-06	(6,11-dihydro-11-oxodibenzo[b,e]oxépinyl)-pentanols, un procédé et des intermédiaires pour leur préparation et leur emploi comme médicaments
NZ226030A (en)	1989-09-27	Spiro-azolone derivatives; pharmaceutical compositions