SK12572003A3 - Farmaceutická kompozícia obsahujúca 3,7-diazabicyklo [3.3.1]-deriváty ako účinnú zložku a jej použitie - Google Patents

Farmaceutická kompozícia obsahujúca 3,7-diazabicyklo [3.3.1]-deriváty ako účinnú zložku a jej použitie Download PDF

Info

Publication number: SK12572003A3
Authority: SK; Slovakia
Prior art keywords: salt; oxa; diazabicyclo; butyl; compound
Prior art date: 2001-04-12

Application number

SK1257-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Neil Barnwell

Annika BJ�RE

Lal Cheema

David Cladingboel

Adam Herring

Karin L�VQVIST

Original Assignee

Astrazeneca Ab

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.)

2001-04-12

Filing date

2002-04-12

Publication date

2004-07-07

2002-04-12 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-07-07 Publication of SK12572003A3 publication Critical patent/SK12572003A3/sk

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 286
239000000203 mixture Substances 0.000 title claims description 154
238000009472 formulation Methods 0.000 title description 7
150000003839 salts Chemical class 0.000 claims abstract description 118
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims abstract description 28
206010003119 arrhythmia Diseases 0.000 claims abstract description 18
238000011282 treatment Methods 0.000 claims abstract description 15
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 235
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 198
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 172
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 165
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 133
238000000034 method Methods 0.000 claims description 131
239000002904 solvent Substances 0.000 claims description 90
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 80
238000002425 crystallisation Methods 0.000 claims description 62
230000008025 crystallization Effects 0.000 claims description 62
238000002360 preparation method Methods 0.000 claims description 56
239000000843 powder Substances 0.000 claims description 54
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 51
-1 3,3-dimethyl-2-oxobutyl Chemical group 0.000 claims description 48
239000002253 acid Substances 0.000 claims description 43
238000000634 powder X-ray diffraction Methods 0.000 claims description 38
239000012458 free base Substances 0.000 claims description 31
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 25
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 24
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 23
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical group OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 20
230000008569 process Effects 0.000 claims description 19
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 18
239000002585 base Substances 0.000 claims description 18
229910052757 nitrogen Inorganic materials 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 15
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 14
QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical class OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 claims description 14
WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-UHFFFAOYSA-N 0.000 claims description 13
230000006793 arrhythmia Effects 0.000 claims description 13
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 12
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 12
229940092714 benzenesulfonic acid Drugs 0.000 claims description 12
238000010438 heat treatment Methods 0.000 claims description 12
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 12
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 claims description 10
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 10
229940011051 isopropyl acetate Drugs 0.000 claims description 10
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 10
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 10
LXFQSRIDYRFTJW-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonic acid Chemical class CC1=CC(C)=C(S(O)(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-N 0.000 claims description 8
MYJXSDFBYVYUCD-UHFFFAOYSA-N 2-[(4-phenylbenzoyl)amino]acetic acid Chemical compound C1=CC(C(=O)NCC(=O)O)=CC=C1C1=CC=CC=C1 MYJXSDFBYVYUCD-UHFFFAOYSA-N 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 7
TVWQKCYNJSKYOP-UHFFFAOYSA-N 2-[(3,4-dichlorobenzoyl)amino]acetic acid Chemical class OC(=O)CNC(=O)C1=CC=C(Cl)C(Cl)=C1 TVWQKCYNJSKYOP-UHFFFAOYSA-N 0.000 claims description 6
125000005233 alkylalcohol group Chemical group 0.000 claims description 6
125000004126 inden-3-yl group Chemical group [H]C1=C(*)C2=C([H])C([H])=C([H])C([H])=C2C1([H])[H] 0.000 claims description 6
238000011321 prophylaxis Methods 0.000 claims description 6
JRHUUZPSMQIWBQ-PELRDEGISA-N tert-butyl n-[2-[3-[(2s)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]ethyl]carbamate Chemical compound C([C@@H](O)CN1CC2CN(CC(C1)O2)CCNC(=O)OC(C)(C)C)OC1=CC=C(C#N)C=C1 JRHUUZPSMQIWBQ-PELRDEGISA-N 0.000 claims description 6
ZEEVEFOISWRYMK-UHFFFAOYSA-N tert-butyl n-[2-[7-[4-(4-cyanophenyl)butyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethyl]carbamate Chemical compound C1C(O2)CN(CCNC(=O)OC(C)(C)C)CC2CN1CCCCC1=CC=C(C#N)C=C1 ZEEVEFOISWRYMK-UHFFFAOYSA-N 0.000 claims description 6
XPQCDYYJHJOAIC-UHFFFAOYSA-N 2-(naphthalene-2-carbonylamino)acetic acid Chemical class C1=CC=CC2=CC(C(=O)NCC(=O)O)=CC=C21 XPQCDYYJHJOAIC-UHFFFAOYSA-N 0.000 claims description 5
150000001983 dialkylethers Chemical class 0.000 claims description 5
POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical group CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 claims description 5
150000002576 ketones Chemical class 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 4
150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
206010003130 Arrhythmia supraventricular Diseases 0.000 claims description 3
206010003658 Atrial Fibrillation Diseases 0.000 claims description 3
206010003662 Atrial flutter Diseases 0.000 claims description 3
206010047281 Ventricular arrhythmia Diseases 0.000 claims description 3
150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
239000003125 aqueous solvent Chemical class 0.000 claims description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
230000001746 atrial effect Effects 0.000 claims description 3
LAMDSCRMEIOKJI-UHFFFAOYSA-N tert-butyl n-[2-[7-[3-(4-cyanoanilino)propyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl]ethyl]carbamate Chemical compound C1C(O2)CN(CCNC(=O)OC(C)(C)C)CC2CN1CCCNC1=CC=C(C#N)C=C1 LAMDSCRMEIOKJI-UHFFFAOYSA-N 0.000 claims description 3
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical class CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims description 2
KZOCHEDMAHPYCK-UHFFFAOYSA-N 4-[3-[3-(3,3-dimethyl-2-oxobutyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound C1C(O2)CN(CC(=O)C(C)(C)C)CC2CN1CCCNC1=CC=C(C#N)C=C1 KZOCHEDMAHPYCK-UHFFFAOYSA-N 0.000 claims description 2
ASJCSAKCMTWGAH-UHFFFAOYSA-N cyclopentane-1,2-dicarboxylic acid Chemical compound OC(=O)C1CCCC1C(O)=O ASJCSAKCMTWGAH-UHFFFAOYSA-N 0.000 claims description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical class C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 2
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 claims description 2
238000001938 differential scanning calorimetry curve Methods 0.000 claims 9
NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 claims 2
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims 1
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims 1
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims 1
150000001242 acetic acid derivatives Chemical class 0.000 claims 1
WQQQISVKJCGCPL-UHFFFAOYSA-N benzenesulfonic acid;4-[3-[3-(3,3-dimethyl-2-oxobutyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl]propylamino]benzonitrile Chemical compound OS(=O)(=O)C1=CC=CC=C1.C1C(O2)CN(CC(=O)C(C)(C)C)CC2CN1CCCNC1=CC=C(C#N)C=C1 WQQQISVKJCGCPL-UHFFFAOYSA-N 0.000 claims 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
235000013847 iso-butane Nutrition 0.000 claims 1
239000000243 solution Substances 0.000 description 235
239000007787 solid Substances 0.000 description 119
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 112
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 108
239000000047 product Substances 0.000 description 64
239000013078 crystal Substances 0.000 description 57
229940126062 Compound A Drugs 0.000 description 49
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 49
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
238000005160 1H NMR spectroscopy Methods 0.000 description 40
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
239000002244 precipitate Substances 0.000 description 35
239000011541 reaction mixture Substances 0.000 description 34
238000006243 chemical reaction Methods 0.000 description 33
239000010410 layer Substances 0.000 description 30
238000003756 stirring Methods 0.000 description 27
239000012044 organic layer Substances 0.000 description 26
238000004821 distillation Methods 0.000 description 23
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
239000000706 filtrate Substances 0.000 description 22
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
239000003921 oil Substances 0.000 description 21
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 19
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
229910052943 magnesium sulfate Inorganic materials 0.000 description 18
235000019341 magnesium sulphate Nutrition 0.000 description 18
238000000113 differential scanning calorimetry Methods 0.000 description 17
238000004809 thin layer chromatography Methods 0.000 description 17
238000004458 analytical method Methods 0.000 description 16
229910052739 hydrogen Inorganic materials 0.000 description 16
239000012071 phase Substances 0.000 description 16
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
239000000463 material Substances 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
238000009835 boiling Methods 0.000 description 14
238000001816 cooling Methods 0.000 description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
239000002002 slurry Substances 0.000 description 13
239000007858 starting material Substances 0.000 description 13
238000002411 thermogravimetry Methods 0.000 description 13
239000012267 brine Substances 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
239000003054 catalyst Substances 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
239000000126 substance Substances 0.000 description 11
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
239000008346 aqueous phase Substances 0.000 description 10
238000004128 high performance liquid chromatography Methods 0.000 description 10
239000013585 weight reducing agent Substances 0.000 description 10
238000005481 NMR spectroscopy Methods 0.000 description 9
229910052763 palladium Inorganic materials 0.000 description 9
239000005909 Kieselgur Substances 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
238000001514 detection method Methods 0.000 description 8
238000001035 drying Methods 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
239000012065 filter cake Substances 0.000 description 8
239000001257 hydrogen Substances 0.000 description 8
150000004682 monohydrates Chemical class 0.000 description 8
239000012299 nitrogen atmosphere Substances 0.000 description 8
JYVLIDXNZAXMDK-UHFFFAOYSA-N pentan-2-ol Chemical compound CCCC(C)O JYVLIDXNZAXMDK-UHFFFAOYSA-N 0.000 description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 8
238000010992 reflux Methods 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
235000015165 citric acid Nutrition 0.000 description 7
229960004106 citric acid Drugs 0.000 description 7
239000012043 crude product Substances 0.000 description 7
239000012535 impurity Substances 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
239000003960 organic solvent Substances 0.000 description 7
LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 7
WYJXAGJCXWTTAH-UHFFFAOYSA-N 3-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]nonane;dihydrochloride Chemical compound Cl.Cl.C1C(O2)CNCC2CN1CC1=CC=CC=C1 WYJXAGJCXWTTAH-UHFFFAOYSA-N 0.000 description 6
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
150000008107 benzenesulfonic acids Chemical class 0.000 description 6
230000008034 disappearance Effects 0.000 description 6
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ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 6
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229910000027 potassium carbonate Inorganic materials 0.000 description 6
239000011734 sodium Substances 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
238000003860 storage Methods 0.000 description 6
DMKUNHJZZHMFFE-UHFFFAOYSA-N 3-(4-cyanoanilino)propyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCCNC1=CC=C(C#N)C=C1 DMKUNHJZZHMFFE-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
239000000908 ammonium hydroxide Substances 0.000 description 5
238000001914 filtration Methods 0.000 description 5
150000004677 hydrates Chemical class 0.000 description 5
239000012453 solvate Substances 0.000 description 5
238000010561 standard procedure Methods 0.000 description 5
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SLFJZMKCBPIOSE-UHFFFAOYSA-N 3-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]nonane Chemical compound C1C(O2)CNCC2CN1CC1=CC=CC=C1 SLFJZMKCBPIOSE-UHFFFAOYSA-N 0.000 description 4
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WREXVDPOLDOXJL-SNVBAGLBSA-N 4-[[(2s)-oxiran-2-yl]methoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OC[C@H]1OC1 WREXVDPOLDOXJL-SNVBAGLBSA-N 0.000 description 4
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
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IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 4
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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 1
238000003109 Karl Fischer titration Methods 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
238000001069 Raman spectroscopy Methods 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
208000001435 Thromboembolism Diseases 0.000 description 1
208000018452 Torsade de pointes Diseases 0.000 description 1
208000002363 Torsades de Pointes Diseases 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
238000012382 advanced drug delivery Methods 0.000 description 1
150000001345 alkine derivatives Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical group 0.000 description 1
239000003416 antiarrhythmic agent Substances 0.000 description 1
150000001499 aryl bromides Chemical class 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
238000003556 assay Methods 0.000 description 1
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
125000006267 biphenyl group Chemical group 0.000 description 1
OGODKNYCTJYXFF-HOTGVXAUSA-N bis(4-methylbenzoyl) (2s,3s)-2,3-dihydroxybutanedioate Chemical class C1=CC(C)=CC=C1C(=O)OC(=O)[C@@H](O)[C@H](O)C(=O)OC(=O)C1=CC=C(C)C=C1 OGODKNYCTJYXFF-HOTGVXAUSA-N 0.000 description 1
238000007664 blowing Methods 0.000 description 1
229940045348 brown mixture Drugs 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
SKKTUOZKZKCGTB-UHFFFAOYSA-N butyl carbamate Chemical compound CCCCOC(N)=O SKKTUOZKZKCGTB-UHFFFAOYSA-N 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
235000011089 carbon dioxide Nutrition 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
150000001734 carboxylic acid salts Chemical class 0.000 description 1
238000007675 cardiac surgery Methods 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
238000010908 decantation Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
229910021641 deionized water Inorganic materials 0.000 description 1
238000004807 desolvation Methods 0.000 description 1
239000002027 dichloromethane extract Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical class CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
229950006191 gluconic acid Drugs 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
229960004275 glycolic acid Drugs 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
150000001261 hydroxy acids Chemical class 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229960000448 lactic acid Drugs 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
229940099690 malic acid Drugs 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
239000000155 melt Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
FBBDOOHMGLLEGJ-UHFFFAOYSA-N methane;hydrochloride Chemical compound C.Cl FBBDOOHMGLLEGJ-UHFFFAOYSA-N 0.000 description 1
GXJPXWMIOFURQB-UHFFFAOYSA-N methyl 2-[(3,4-dichlorobenzoyl)amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=C(Cl)C(Cl)=C1 GXJPXWMIOFURQB-UHFFFAOYSA-N 0.000 description 1
AXGFVIISARRNQU-UHFFFAOYSA-N methyl 2-[(5,5-dichlorocyclohexa-1,3-diene-1-carbonyl)amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC(Cl)(Cl)C1 AXGFVIISARRNQU-UHFFFAOYSA-N 0.000 description 1
238000004452 microanalysis Methods 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000002107 myocardial effect Effects 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
208000031225 myocardial ischemia Diseases 0.000 description 1
VQFUCMWNUPUDHN-UHFFFAOYSA-N n-(oxiran-2-ylmethyl)benzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)NCC1CO1 VQFUCMWNUPUDHN-UHFFFAOYSA-N 0.000 description 1
YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
XNLBCXGRQWUJLU-UHFFFAOYSA-N naphthalene-2-carbonyl chloride Chemical compound C1=CC=CC2=CC(C(=O)Cl)=CC=C21 XNLBCXGRQWUJLU-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
YOEBAVRJHRCKRE-UHFFFAOYSA-N o-methylhippuric acid Chemical compound CC1=CC=CC=C1C(=O)NCC(O)=O YOEBAVRJHRCKRE-UHFFFAOYSA-N 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
NRSCPTLHWVWLLH-UHFFFAOYSA-N p-methylhippuric acid Chemical compound CC1=CC=C(C(=O)NCC(O)=O)C=C1 NRSCPTLHWVWLLH-UHFFFAOYSA-N 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000012264 purified product Substances 0.000 description 1
230000005855 radiation Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
238000004467 single crystal X-ray diffraction Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
238000007614 solvation Methods 0.000 description 1
238000000859 sublimation Methods 0.000 description 1
230000008022 sublimation Effects 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
150000008054 sulfonate salts Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
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 description 1
125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
PRINEEYGDAUNBA-IVMQYODDSA-N tert-butyl 7-[(2s)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C([C@@H](O)CN1CC2CN(CC(C1)O2)C(=O)OC(C)(C)C)OC1=CC=C(C#N)C=C1 PRINEEYGDAUNBA-IVMQYODDSA-N 0.000 description 1
WAIBGYDSVMGVJD-UHFFFAOYSA-N tert-butyl 7-benzyl-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate;hydrochloride Chemical compound Cl.C1C(O2)CN(C(=O)OC(C)(C)C)CC2CN1CC1=CC=CC=C1 WAIBGYDSVMGVJD-UHFFFAOYSA-N 0.000 description 1
LHJSYLNUEZBFED-UHFFFAOYSA-N tert-butyl 9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1NCC2CN(C(=O)OC(C)(C)C)CC1O2 LHJSYLNUEZBFED-UHFFFAOYSA-N 0.000 description 1
RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
TZRQZPMQUXEZMC-UHFFFAOYSA-N tert-butyl n-(2-bromoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCBr TZRQZPMQUXEZMC-UHFFFAOYSA-N 0.000 description 1
IDDNWXWTTIVHKC-UHFFFAOYSA-N tert-butyl n-[2-(9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl)ethyl]carbamate Chemical compound C1NCC2CN(CCNC(=O)OC(C)(C)C)CC1O2 IDDNWXWTTIVHKC-UHFFFAOYSA-N 0.000 description 1
239000012085 test solution Substances 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK1257-2003A 2001-04-12 2002-04-12 Farmaceutická kompozícia obsahujúca 3,7-diazabicyklo [3.3.1]-deriváty ako účinnú zložku a jej použitie SK12572003A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE0101327A SE0101327D0 (sv)	2001-04-12	2001-04-12	New crystalline forms
PCT/SE2002/000725 WO2002083688A1 (en)	2001-04-12	2002-04-12	3,7-diazabicyclo [3.3.1] formulations as antiarhythmic compounds

Publications (1)

Publication Number	Publication Date
SK12572003A3 true SK12572003A3 (sk)	2004-07-07

Family

ID=20283783

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1257-2003A SK12572003A3 (sk)	2001-04-12	2002-04-12	Farmaceutická kompozícia obsahujúca 3,7-diazabicyklo [3.3.1]-deriváty ako účinnú zložku a jej použitie

Country Status (29)

Country	Link
US (1)	US7217708B2 (cs)
EP (2)	EP1550663A1 (cs)
JP (1)	JP2004525970A (cs)
KR (1)	KR20030087078A (cs)
CN (1)	CN1269823C (cs)
AR (1)	AR035452A1 (cs)
AT (1)	ATE323095T1 (cs)
BR (1)	BR0208829A (cs)
CA (1)	CA2443470A1 (cs)
CZ (1)	CZ20032760A3 (cs)
DE (1)	DE60210598T2 (cs)
DK (1)	DK1389213T3 (cs)
EE (1)	EE200300504A (cs)
ES (1)	ES2261721T3 (cs)
HU (1)	HUP0303487A3 (cs)
IL (1)	IL158250A0 (cs)
IS (1)	IS6980A (cs)
MX (1)	MXPA03009206A (cs)
NO (1)	NO20034527L (cs)
NZ (1)	NZ528560A (cs)
PL (1)	PL367179A1 (cs)
PT (1)	PT1389213E (cs)
RU (1)	RU2286993C2 (cs)
SE (1)	SE0101327D0 (cs)
SK (1)	SK12572003A3 (cs)
TW (1)	TWI237025B (cs)
UA (1)	UA74629C2 (cs)
WO (1)	WO2002083688A1 (cs)
ZA (1)	ZA200307759B (cs)

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TWI259836B (en) *	2001-04-12	2006-08-11	Astrazeneca Ab	Modified release formulation suitable for antiarrhythmic compounds
SE0401539D0 (sv) *	2004-06-15	2004-06-15	Astrazeneca Ab	New compounds
SE0401540D0 (sv) *	2004-06-15	2004-06-15	Astrazeneca Ab	New compounds
KR20080021114A (ko)	2005-06-13	2008-03-06	아스트라제네카 아베	심부정맥의 치료를 위한 신규한 옥사비스피딘 화합물
KR20080028435A (ko) *	2005-06-20	2008-03-31	아스트라제네카 아베	Ｎ,ｎ’-이치환된 옥사비스피딘의 제조 방법
AR053901A1 (es) *	2005-06-20	2007-05-23	Astrazeneca Ab	Formas fisicas de oxabispidinas n,n'- disustituidas
TW200734342A (en) *	2005-12-15	2007-09-16	Astrazeneca Ab	New compounds for the treatment of cardiac arrhythmias
EP2001881A2 (en) *	2006-03-07	2008-12-17	Endacea, Inc.	Compositions and methods for treating respiratory disorders
NZ623002A (en)	2006-06-26	2015-08-28	Akebia Therapeutics Inc	Prolyl hydroxylase inhibitors and methods of use
CN103717214A (zh)	2011-06-06	2014-04-09	阿克比治疗有限公司	用于稳定低氧诱导因子-2α作为治疗癌症的方法的化合物和组合物
NO2686520T3 (cs)	2011-06-06	2018-03-17
HUE066123T2 (hu)	2013-06-13	2024-07-28	Akebia Therapeutics Inc	Készítmények és módszerek anémia kezelésére
TWI665190B (zh)	2013-11-15	2019-07-11	阿克比治療有限公司	｛［５－（３－氯苯基）－３－羥基吡啶－２－羰基］胺基｝乙酸之固體型式，其組合物及用途
CA2974691A1 (en)	2015-01-23	2016-07-28	Akebia Therapeutics, Inc.	Solid forms of 2-(5-(3-fluorophenyl)-3-hydroxypicolinamido)acetic acid, compositions, and uses thereof
NZ735973A (en)	2015-04-01	2023-06-30	Akebia Therapeutics Inc	Compositions and methods for treating anemia
US11713298B2 (en)	2018-05-09	2023-08-01	Akebia Therapeutics, Inc.	Process for preparing 2-[[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid
WO2020194260A1 (en) *	2019-03-28	2020-10-01	1ST Biotherapeutics, Inc.	Pharmaceutical salts of benzothiazol compounds, polymorphs and methods for preparation thereof
US11524939B2 (en)	2019-11-13	2022-12-13	Akebia Therapeutics, Inc.	Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino} acetic acid
US12612367B2 (en)	2019-12-10	2026-04-28	Akebia Therapeutics, Inc.	Method for producing nitrogen-containing heteroarylcarboxamide acetic acid derivative
WO2021216530A1 (en)	2020-04-20	2021-10-28	Akebia Therapeutics, Inc.	Treatment of viral infections, of organ injury, and of related conditions using a hif prolyl hydroxylase inhibitor or a hif-alpha stabilizer

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Publication number	Priority date	Publication date	Assignee	Title
DE3732094A1 (de)	1987-09-24	1989-04-06	Basf Ag	Bispidinderivate als klasse iii-antiarrhythmika
US5110933A (en) *	1989-11-13	1992-05-05	Board Of Regents Of Oklahoma State University	Salts of 3-azabicyclo[3.3.1]nonanes as antiarrhythmic agents, and precursors thereof
SE9704709D0 (sv) *	1997-12-17	1997-12-17	Astra Ab	Pharmaceutically active compounds
SE9902268D0 (sv)	1999-06-16	1999-06-16	Astra Ab	Pharmaceutically active compounds
SE9903759D0 (sv) *	1999-10-18	1999-10-18	Astra Ab	Pharmaceutically active compounds

2001
- 2001-04-12 SE SE0101327A patent/SE0101327D0/xx unknown
2002
- 2002-04-01 TW TW091106493A patent/TWI237025B/zh not_active IP Right Cessation
- 2002-04-02 AR ARP020101189A patent/AR035452A1/es not_active Application Discontinuation
- 2002-04-12 KR KR10-2003-7013320A patent/KR20030087078A/ko not_active Withdrawn
- 2002-04-12 CZ CZ20032760A patent/CZ20032760A3/cs unknown
- 2002-04-12 BR BR0208829-0A patent/BR0208829A/pt not_active IP Right Cessation
- 2002-04-12 EP EP05007851A patent/EP1550663A1/en not_active Withdrawn
- 2002-04-12 CA CA002443470A patent/CA2443470A1/en not_active Abandoned
- 2002-04-12 NZ NZ528560A patent/NZ528560A/en unknown
- 2002-04-12 PL PL02367179A patent/PL367179A1/xx unknown
- 2002-04-12 SK SK1257-2003A patent/SK12572003A3/sk not_active Application Discontinuation
- 2002-04-12 RU RU2003129231/04A patent/RU2286993C2/ru not_active IP Right Cessation
- 2002-04-12 DK DK02761972T patent/DK1389213T3/da active
- 2002-04-12 PT PT02761972T patent/PT1389213E/pt unknown
- 2002-04-12 CN CNB028116283A patent/CN1269823C/zh not_active Expired - Fee Related
- 2002-04-12 WO PCT/SE2002/000725 patent/WO2002083688A1/en not_active Ceased
- 2002-04-12 HU HU0303487A patent/HUP0303487A3/hu unknown
- 2002-04-12 AT AT02761972T patent/ATE323095T1/de not_active IP Right Cessation
- 2002-04-12 ES ES02761972T patent/ES2261721T3/es not_active Expired - Lifetime
- 2002-04-12 MX MXPA03009206A patent/MXPA03009206A/es active IP Right Grant
- 2002-04-12 DE DE60210598T patent/DE60210598T2/de not_active Expired - Fee Related
- 2002-04-12 EE EEP200300504A patent/EE200300504A/xx unknown
- 2002-04-12 IL IL15825002A patent/IL158250A0/xx unknown
- 2002-04-12 JP JP2002581443A patent/JP2004525970A/ja active Pending
- 2002-04-12 EP EP02761972A patent/EP1389213B1/en not_active Expired - Lifetime
- 2002-04-12 US US10/474,592 patent/US7217708B2/en not_active Expired - Fee Related
- 2002-12-04 UA UA2003098709A patent/UA74629C2/uk unknown
2003
- 2003-10-03 ZA ZA200307759A patent/ZA200307759B/en unknown
- 2003-10-08 IS IS6980A patent/IS6980A/is unknown
- 2003-10-09 NO NO20034527A patent/NO20034527L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
PT1389213E (pt)	2006-07-31
IL158250A0 (en)	2004-05-12
EP1389213B1 (en)	2006-04-12
IS6980A (is)	2003-10-08
UA74629C2 (en)	2006-01-16
DK1389213T3 (da)	2006-07-10
CN1514837A (zh)	2004-07-21
NO20034527L (no)	2003-12-10
WO2002083688A1 (en)	2002-10-24
ATE323095T1 (de)	2006-04-15
CA2443470A1 (en)	2002-10-24
ES2261721T3 (es)	2006-11-16
NO20034527D0 (no)	2003-10-09
EP1389213A1 (en)	2004-02-18
HUP0303487A3 (en)	2005-04-28
AR035452A1 (es)	2004-05-26
TWI237025B (en)	2005-08-01
EP1550663A1 (en)	2005-07-06
US7217708B2 (en)	2007-05-15
RU2286993C2 (ru)	2006-11-10
DE60210598T2 (de)	2007-02-08
MXPA03009206A (es)	2004-01-29
CZ20032760A3 (cs)	2004-01-14
HK1061026A1 (en)	2004-09-03
HUP0303487A2 (hu)	2004-01-28
DE60210598D1 (de)	2006-05-24
BR0208829A (pt)	2004-03-09
SE0101327D0 (sv)	2001-04-12
RU2003129231A (ru)	2005-04-10
US20040143000A1 (en)	2004-07-22
JP2004525970A (ja)	2004-08-26
EE200300504A (et)	2003-12-15
PL367179A1 (en)	2005-02-21
ZA200307759B (en)	2005-01-03
CN1269823C (zh)	2006-08-16
NZ528560A (en)	2005-05-27
KR20030087078A (ko)	2003-11-12

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Date	Code	Title	Description
2010-08-09	FC9A	Refused patent application

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