CA2155666C - Nouveaux derives de l'acide 3-hydroxyanthranilique; methodes et produits intermediaires pour leur preparation; nouvelles compositions pharmaceutiques et leur utilisation - Google Patents

Nouveaux derives de l'acide 3-hydroxyanthranilique; methodes et produits intermediaires pour leur preparation; nouvelles compositions pharmaceutiques et leur utilisation Download PDF

Info

Publication number: CA2155666C
Authority: CA; Canada
Prior art keywords: chloro; bromo; alkyl; iodo; formula
Prior art date: 1993-02-26
Legal status (The legal status 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 status listed.): Expired - Lifetime

Application number

CA002155666A

Other languages

English (en)

Other versions

CA2155666A1 (fr

Inventor

Susanna Karin Maria Bjork

Barry K. Carpenter

Kristina Brigitta Gotthammar

Mat Torbjorn Linderberg

Per Johan Luthman

Kerstin Margareta Irma Persson

Robert Schwarcz

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Cornell Research Foundation Inc

University of Maryland College Park

Original Assignee

Cornell Research Foundation Inc

University of Maryland College Park

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.)

1993-02-26

Filing date

1994-02-24

Publication date

2006-04-18

1993-02-26 Priority claimed from SE9300658A external-priority patent/SE9300658D0/xx

1994-02-24 Application filed by Cornell Research Foundation Inc, University of Maryland College Park filed Critical Cornell Research Foundation Inc

1994-09-01 Publication of CA2155666A1 publication Critical patent/CA2155666A1/fr

2006-04-18 Application granted granted Critical

2006-04-18 Publication of CA2155666C publication Critical patent/CA2155666C/fr

2014-02-24 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 93
238000002360 preparation method Methods 0.000 title claims abstract description 23
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
WJXSWCUQABXPFS-UHFFFAOYSA-N 3-hydroxyanthranilic acid Chemical class NC1=C(O)C=CC=C1C(O)=O WJXSWCUQABXPFS-UHFFFAOYSA-N 0.000 title abstract description 11
239000000543 intermediate Substances 0.000 title abstract description 5
150000001875 compounds Chemical class 0.000 claims abstract description 133
125000000217 alkyl group Chemical group 0.000 claims abstract description 106
-1 OSO2CH3 Chemical group 0.000 claims abstract description 27
150000003839 salts Chemical class 0.000 claims abstract description 15
238000004519 manufacturing process Methods 0.000 claims abstract description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 56
125000001246 bromo group Chemical group Br* 0.000 claims description 52
125000002346 iodo group Chemical group I* 0.000 claims description 52
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 38
125000001153 fluoro group Chemical group F* 0.000 claims description 30
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims description 13
125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 claims description 10
230000004770 neurodegeneration Effects 0.000 claims description 8
125000006239 protecting group Chemical group 0.000 claims description 8
230000002265 prevention Effects 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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 5
SEAVVBUQSYHVKP-UHFFFAOYSA-N 2-amino-4,6-dibromo-3-hydroxybenzoic acid Chemical compound NC1=C(O)C(Br)=CC(Br)=C1C(O)=O SEAVVBUQSYHVKP-UHFFFAOYSA-N 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
HWQYSIQGLAQPKW-UHFFFAOYSA-N 2-amino-4,6-dichloro-3-hydroxybenzoic acid Chemical compound NC1=C(O)C(Cl)=CC(Cl)=C1C(O)=O HWQYSIQGLAQPKW-UHFFFAOYSA-N 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims 1
125000003545 alkoxy group Chemical group 0.000 abstract description 45
125000004414 alkyl thio group Chemical group 0.000 abstract description 43
125000003709 fluoroalkyl group Chemical group 0.000 abstract description 40
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract description 40
229910052736 halogen Inorganic materials 0.000 abstract description 39
150000002367 halogens Chemical class 0.000 abstract description 39
125000004093 cyano group Chemical group *C#N 0.000 abstract description 36
125000004104 aryloxy group Chemical group 0.000 abstract description 34
125000005110 aryl thio group Chemical group 0.000 abstract description 32
125000003118 aryl group Chemical group 0.000 abstract description 27
125000003710 aryl alkyl group Chemical group 0.000 abstract description 24
229910052794 bromium Inorganic materials 0.000 abstract description 12
108010072768 3-hydroxyanthranilate 3,4-dioxygenase Proteins 0.000 abstract description 10
102100029016 3-hydroxyanthranilate 3,4-dioxygenase Human genes 0.000 abstract description 8
GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 abstract description 4
230000002401 inhibitory effect Effects 0.000 abstract description 2
101710138657 Neurotoxin Proteins 0.000 abstract 1
239000002581 neurotoxin Substances 0.000 abstract 1
231100000618 neurotoxin Toxicity 0.000 abstract 1
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
238000005160 1H NMR spectroscopy Methods 0.000 description 27
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
239000000203 mixture Substances 0.000 description 26
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
239000002904 solvent Substances 0.000 description 24
235000019439 ethyl acetate Nutrition 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
239000012043 crude product Substances 0.000 description 21
238000001704 evaporation Methods 0.000 description 21
230000008020 evaporation Effects 0.000 description 21
238000000746 purification Methods 0.000 description 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
125000000896 monocarboxylic acid group Chemical group 0.000 description 18
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
239000000243 solution Substances 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
238000003818 flash chromatography Methods 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
238000001914 filtration Methods 0.000 description 11
239000002253 acid Substances 0.000 description 10
239000012267 brine Substances 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000004440 column chromatography Methods 0.000 description 9
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
239000001828 Gelatine Substances 0.000 description 7
UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 7
239000013543 active substance Substances 0.000 description 7
239000008346 aqueous phase Substances 0.000 description 7
238000010511 deprotection reaction Methods 0.000 description 7
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 7
229920000159 gelatin Polymers 0.000 description 7
235000019322 gelatine Nutrition 0.000 description 7
238000005984 hydrogenation reaction Methods 0.000 description 7
239000000047 product Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
229910004373 HOAc Inorganic materials 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000003112 inhibitor Substances 0.000 description 6
239000007788 liquid Substances 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
239000012071 phase Substances 0.000 description 6
238000006722 reduction reaction Methods 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000003826 tablet Substances 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
101150041968 CDC13 gene Proteins 0.000 description 5
238000005481 NMR spectroscopy Methods 0.000 description 5
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
238000001035 drying Methods 0.000 description 5
239000003480 eluent Substances 0.000 description 5
238000000605 extraction Methods 0.000 description 5
229910052740 iodine Inorganic materials 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 4
VWEPFJPQZFIOAU-UHFFFAOYSA-N 2-amino-4-chloro-3-hydroxybenzoic acid Chemical compound NC1=C(O)C(Cl)=CC=C1C(O)=O VWEPFJPQZFIOAU-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 4
238000003556 assay Methods 0.000 description 4
210000004556 brain Anatomy 0.000 description 4
238000007257 deesterification reaction Methods 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000010410 layer Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
229910015845 BBr3 Inorganic materials 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
201000010099 disease Diseases 0.000 description 3
230000026030 halogenation Effects 0.000 description 3
238000005658 halogenation reaction Methods 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
238000007327 hydrogenolysis reaction Methods 0.000 description 3
239000005457 ice water Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
230000001376 precipitating effect Effects 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000000725 suspension Substances 0.000 description 3
ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
WETKXFWNGCBWOH-UHFFFAOYSA-N 2-amino-6-fluoro-3-hydroxy-4-propylbenzoic acid;hydrochloride Chemical compound Cl.CCCC1=CC(F)=C(C(O)=O)C(N)=C1O WETKXFWNGCBWOH-UHFFFAOYSA-N 0.000 description 2
PXJJOILEDFTPJY-UHFFFAOYSA-N 2-fluoro-5-methoxy-4-propylphenol Chemical compound CCCC1=CC(F)=C(O)C=C1OC PXJJOILEDFTPJY-UHFFFAOYSA-N 0.000 description 2
WBJOIJXNUXOSLB-UHFFFAOYSA-N 4-(2,4-dimethoxyphenyl)butanal Chemical compound COC1=CC=C(CCCC=O)C(OC)=C1 WBJOIJXNUXOSLB-UHFFFAOYSA-N 0.000 description 2
FICLVQOYKYBXFN-VIFPVBQESA-N 6-chloro-L-tryptophan Chemical compound ClC1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 FICLVQOYKYBXFN-VIFPVBQESA-N 0.000 description 2
206010065040 AIDS dementia complex Diseases 0.000 description 2
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229920000945 Amylopectin Polymers 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
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150000004694 iodide salts Chemical group 0.000 description 2
239000008101 lactose Substances 0.000 description 2
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 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
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
CYWJACBFQMOKOQ-UHFFFAOYSA-N methyl 2-fluoro-5-methoxy-4-propylbenzoate Chemical compound CCCC1=CC(F)=C(C(=O)OC)C=C1OC CYWJACBFQMOKOQ-UHFFFAOYSA-N 0.000 description 2
229910017604 nitric acid Inorganic materials 0.000 description 2
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
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BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
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238000004611 spectroscopical analysis Methods 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
210000003568 synaptosome Anatomy 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 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
238000002560 therapeutic procedure Methods 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
235000010215 titanium dioxide Nutrition 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000001993 wax Substances 0.000 description 1

Landscapes

Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CA002155666A 1993-02-26 1994-02-24 Nouveaux derives de l'acide 3-hydroxyanthranilique; methodes et produits intermediaires pour leur preparation; nouvelles compositions pharmaceutiques et leur utilisation Expired - Lifetime CA2155666C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
SE9300658-3		1993-02-26
SE9300658A SE9300658D0 (sv)	1993-02-26	1993-02-26	New compounds
PCT/SE1994/000153 WO1994019316A1 (fr)	1993-02-26	1994-02-24	Nouveaux composes

Publications (2)

Publication Number	Publication Date
CA2155666A1 CA2155666A1 (fr)	1994-09-01
CA2155666C true CA2155666C (fr)	2006-04-18

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Application Number	Title	Priority Date	Filing Date
CA002155666A Expired - Lifetime CA2155666C (fr)	1993-02-26	1994-02-24	Nouveaux derives de l'acide 3-hydroxyanthranilique; methodes et produits intermediaires pour leur preparation; nouvelles compositions pharmaceutiques et leur utilisation

Country Status (1)

Country	Link
CA (1)	CA2155666C (fr)

1994
- 1994-02-24 CA CA002155666A patent/CA2155666C/fr not_active Expired - Lifetime

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Publication number	Publication date
CA2155666A1 (fr)	1994-09-01

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2014-04-28	MKEX	Expiry	Effective date: 20140224

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