BG64196B1 - 3-пиридил енантиомери и използването им като аналгетици - Google Patents

3-пиридил енантиомери и използването им като аналгетици Download PDF

Info

Publication number: BG64196B1
Authority: BG; Bulgaria
Prior art keywords: compound; ethenyl; group; formula; azetidine
Prior art date: 1996-12-10

Application number

BG103556A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG103556A (en

Inventor

Mark W. Holladay

Stephen P. Arneric

Hao Bai

Michael J. Dart

Nan-Horng Lin

John K. Lynch

Yat S. Or

Keith B. Ryther

James P. Sullivan

James T. Wasicak

Paul P. Ehrich

Original Assignee

Abbott Laboratories

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.)

1996-12-10

Filing date

1999-07-06

Publication date

2004-04-30

1999-07-06 Application filed by Abbott Laboratories filed Critical Abbott Laboratories

2000-06-30 Publication of BG103556A publication Critical patent/BG103556A/xx

2004-04-30 Publication of BG64196B1 publication Critical patent/BG64196B1/bg

Links

230000000202 analgesic effect Effects 0.000 title claims abstract description 18
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 416
238000000034 method Methods 0.000 claims abstract description 83
150000003839 salts Chemical class 0.000 claims abstract description 54
208000002193 Pain Diseases 0.000 claims abstract description 43
238000002360 preparation method Methods 0.000 claims abstract description 20
241000124008 Mammalia Species 0.000 claims abstract description 7
230000002265 prevention Effects 0.000 claims abstract description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 283
239000000203 mixture Substances 0.000 claims description 122
-1 CN (S): Η Inorganic materials 0.000 claims description 120
229910052801 chlorine Inorganic materials 0.000 claims description 101
229910052731 fluorine Inorganic materials 0.000 claims description 94
229910052794 bromium Inorganic materials 0.000 claims description 67
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 67
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 62
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 44
125000000217 alkyl group Chemical group 0.000 claims description 36
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 36
229910052799 carbon Inorganic materials 0.000 claims description 28
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 26
239000003814 drug Substances 0.000 claims description 24
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 23
229960005181 morphine Drugs 0.000 claims description 22
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 21
125000001424 substituent group Chemical group 0.000 claims description 21
239000011780 sodium chloride Substances 0.000 claims description 16
CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 15
239000012267 brine Substances 0.000 claims description 15
239000003153 chemical reaction reagent Substances 0.000 claims description 15
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 15
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 14
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 14
239000003638 chemical reducing agent Substances 0.000 claims description 14
150000002148 esters Chemical class 0.000 claims description 14
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 13
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 13
UOWHCAKKYIRMSX-UHFFFAOYSA-N [N].C1CNC1 Chemical compound [N].C1CNC1 UOWHCAKKYIRMSX-UHFFFAOYSA-N 0.000 claims description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
206010061218 Inflammation Diseases 0.000 claims description 11
230000004054 inflammatory process Effects 0.000 claims description 11
229940127240 opiate Drugs 0.000 claims description 11
230000008569 process Effects 0.000 claims description 11
230000009467 reduction Effects 0.000 claims description 11
150000003512 tertiary amines Chemical class 0.000 claims description 11
229910052740 iodine Inorganic materials 0.000 claims description 9
125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 9
229910010082 LiAlH Inorganic materials 0.000 claims description 8
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 8
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 8
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 8
125000004665 trialkylsilyl group Chemical group 0.000 claims description 8
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
150000001408 amides Chemical class 0.000 claims description 6
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 6
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
230000016273 neuron death Effects 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 5
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 5
229960005261 aspartic acid Drugs 0.000 claims description 5
238000003776 cleavage reaction Methods 0.000 claims description 5
229940124641 pain reliever Drugs 0.000 claims description 5
230000007017 scission Effects 0.000 claims description 5
125000005490 tosylate group Chemical group 0.000 claims description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 4
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
150000003571 thiolactams Chemical class 0.000 claims description 4
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 3
RGURVQFYVXFVLS-UHFFFAOYSA-N [tert-butyl(methyl)silyl] trifluoromethanesulfonate Chemical compound FC(S(=O)(=O)O[SiH](C(C)(C)C)C)(F)F RGURVQFYVXFVLS-UHFFFAOYSA-N 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
239000000654 additive Substances 0.000 claims description 3
229910052782 aluminium Inorganic materials 0.000 claims description 3
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
125000000129 anionic group Chemical group 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
150000001539 azetidines Chemical class 0.000 claims description 3
239000004202 carbamide Substances 0.000 claims description 3
150000002081 enamines Chemical class 0.000 claims description 3
150000004678 hydrides Chemical class 0.000 claims description 3
239000012442 inert solvent Substances 0.000 claims description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 3
125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 3
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
HZMIWOUJIHQBTL-QMMMGPOBSA-N 2-chloro-3-[[(2s)-1-methylazetidin-2-yl]methoxy]pyridine Chemical compound CN1CC[C@H]1COC1=CC=CN=C1Cl HZMIWOUJIHQBTL-QMMMGPOBSA-N 0.000 claims description 2
YTWTVQHAWYQDBK-QMMMGPOBSA-N 2-fluoro-3-[[(2s)-1-methylazetidin-2-yl]methoxy]pyridine Chemical compound CN1CC[C@H]1COC1=CC=CN=C1F YTWTVQHAWYQDBK-QMMMGPOBSA-N 0.000 claims description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 2
230000003009 desulfurizing effect Effects 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims description 2
PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 claims description 2
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
229910052727 yttrium Inorganic materials 0.000 claims description 2
MKTAGSRKQIGEBH-SSDOTTSWSA-N tebanicline Chemical compound C1=NC(Cl)=CC=C1OC[C@@H]1NCC1 MKTAGSRKQIGEBH-SSDOTTSWSA-N 0.000 claims 2
LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 claims 1
WKZQBXASZYKYHQ-ZETCQYMHSA-N 3-bromo-2-chloro-5-[[(2s)-1-methylazetidin-2-yl]methoxy]pyridine Chemical compound CN1CC[C@H]1COC1=CN=C(Cl)C(Br)=C1 WKZQBXASZYKYHQ-ZETCQYMHSA-N 0.000 claims 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
230000000996 additive effect Effects 0.000 claims 1
SPRIOUNJHPCKPV-UHFFFAOYSA-N hydridoaluminium Chemical compound [AlH] SPRIOUNJHPCKPV-UHFFFAOYSA-N 0.000 claims 1
239000002260 anti-inflammatory agent Substances 0.000 abstract description 4
210000002569 neuron Anatomy 0.000 abstract description 3
230000001741 anti-phlogistic effect Effects 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 332
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 312
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 259
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 215
239000000243 solution Substances 0.000 description 143
238000005481 NMR spectroscopy Methods 0.000 description 142
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 132
239000000460 chlorine Substances 0.000 description 103
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 95
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 81
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 72
235000019439 ethyl acetate Nutrition 0.000 description 72
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239000000741 silica gel Substances 0.000 description 67
229910002027 silica gel Inorganic materials 0.000 description 67
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 64
238000004458 analytical method Methods 0.000 description 61
239000002904 solvent Substances 0.000 description 61
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 58
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
239000000651 prodrug Substances 0.000 description 53
229940002612 prodrug Drugs 0.000 description 53
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 52
229910000041 hydrogen chloride Inorganic materials 0.000 description 52
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235000019341 magnesium sulphate Nutrition 0.000 description 47
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
239000003921 oil Substances 0.000 description 45
235000019198 oils Nutrition 0.000 description 45
239000007787 solid Substances 0.000 description 44
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 43
239000011541 reaction mixture Substances 0.000 description 42
230000000694 effects Effects 0.000 description 41
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 38
235000019441 ethanol Nutrition 0.000 description 37
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 33
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
239000000284 extract Substances 0.000 description 32
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 30
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 30
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
238000012360 testing method Methods 0.000 description 28
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239000000047 product Substances 0.000 description 26
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239000012458 free base Substances 0.000 description 24
102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 23
108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 23
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229910052757 nitrogen Inorganic materials 0.000 description 22
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 22
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
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BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 17
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229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
239000000126 substance Substances 0.000 description 17
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238000007912 intraperitoneal administration Methods 0.000 description 16
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238000004587 chromatography analysis Methods 0.000 description 15
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239000000725 suspension Substances 0.000 description 14
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 13
IADUEWIQBXOCDZ-UHFFFAOYSA-N azetidine-2-carboxylic acid Chemical compound OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 13
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230000015572 biosynthetic process Effects 0.000 description 12
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 12
208000004296 neuralgia Diseases 0.000 description 12
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229940086735 succinate Drugs 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
210000002182 synaptic membrane Anatomy 0.000 description 1
230000005062 synaptic transmission Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 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
210000002435 tendon Anatomy 0.000 description 1
XIRUXUKRGUFEKC-SSDOTTSWSA-N tert-butyl (2r)-2-(hydroxymethyl)azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H]1CO XIRUXUKRGUFEKC-SSDOTTSWSA-N 0.000 description 1
XIRUXUKRGUFEKC-ZETCQYMHSA-N tert-butyl (2s)-2-(hydroxymethyl)azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H]1CO XIRUXUKRGUFEKC-ZETCQYMHSA-N 0.000 description 1
HRZXFEKKKPAEKF-VIFPVBQESA-N tert-butyl (2s)-2-[(5,6-dichloropyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H]1COC1=CN=C(Cl)C(Cl)=C1 HRZXFEKKKPAEKF-VIFPVBQESA-N 0.000 description 1
UEOMZNZJGRNZHA-AWEZNQCLSA-N tert-butyl (2s)-2-[(5-ethyl-6-methylpyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound N1=C(C)C(CC)=CC(OC[C@H]2N(CC2)C(=O)OC(C)(C)C)=C1 UEOMZNZJGRNZHA-AWEZNQCLSA-N 0.000 description 1
ZDRJXLFKCUCEJR-AWEZNQCLSA-N tert-butyl (2s)-2-[(5-propylpyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound CCCC1=CN=CC(OC[C@H]2N(CC2)C(=O)OC(C)(C)C)=C1 ZDRJXLFKCUCEJR-AWEZNQCLSA-N 0.000 description 1
JVPZESYAOTXMTQ-LBPRGKRZSA-N tert-butyl (2s)-2-[(6-chloro-5-ethenylpyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H]1COC1=CN=C(Cl)C(C=C)=C1 JVPZESYAOTXMTQ-LBPRGKRZSA-N 0.000 description 1
JTOWMVURJWKYCL-LBPRGKRZSA-N tert-butyl (2s)-2-[(6-chloro-5-ethylpyridin-3-yl)oxymethyl]azetidine-1-carboxylate Chemical compound N1=C(Cl)C(CC)=CC(OC[C@H]2N(CC2)C(=O)OC(C)(C)C)=C1 JTOWMVURJWKYCL-LBPRGKRZSA-N 0.000 description 1
QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
VJFXTJZJJIZRKP-UHFFFAOYSA-M tetraphenylazanium;bromide Chemical compound [Br-].C1=CC=CC=C1[N+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 VJFXTJZJJIZRKP-UHFFFAOYSA-M 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
230000000451 tissue damage Effects 0.000 description 1
231100000827 tissue damage Toxicity 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000440 toxicity profile Toxicity 0.000 description 1
230000009466 transformation Effects 0.000 description 1
YLGRTLMDMVAFNI-UHFFFAOYSA-N tributyl(prop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC=C YLGRTLMDMVAFNI-UHFFFAOYSA-N 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
229940045145 uridine Drugs 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Epidemiology (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Emergency Medicine (AREA)
Hospice & Palliative Care (AREA)
Heart & Thoracic Surgery (AREA)
Vascular Medicine (AREA)
Psychiatry (AREA)
Cardiology (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

BG103556A 1996-12-10 1999-07-06 3-пиридил енантиомери и използването им като аналгетици BG64196B1 (bg)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US76327896A	1996-12-10	1996-12-10
US3232196P	1996-12-10	1996-12-10
PCT/US1997/022811 WO1998025920A1 (en)	1996-12-10	1997-12-10	3-pyridyl enantiomers and their use as analgesics

Publications (2)

Publication Number	Publication Date
BG103556A BG103556A (en)	2000-06-30
BG64196B1 true BG64196B1 (bg)	2004-04-30

Family

ID=26708255

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG103556A BG64196B1 (bg)	1996-12-10	1999-07-06	3-пиридил енантиомери и използването им като аналгетици

Country Status (21)

Country	Link
EP (1)	EP0950057B1 (de)
JP (2)	JP4272261B2 (de)
KR (2)	KR100472154B1 (de)
CN (1)	CN1125064C (de)
AT (1)	ATE227717T1 (de)
AU (1)	AU733881B2 (de)
BG (1)	BG64196B1 (de)
BR (1)	BR9714677A (de)
CA (2)	CA2698384C (de)
DE (1)	DE69717148T2 (de)
DK (1)	DK0950057T3 (de)
ES (1)	ES2189003T3 (de)
HU (1)	HUP0001110A3 (de)
IL (1)	IL130083A0 (de)
NO (1)	NO992705L (de)
NZ (1)	NZ335810A (de)
PL (1)	PL333920A1 (de)
PT (1)	PT950057E (de)
SK (1)	SK75999A3 (de)
TR (1)	TR199901904T2 (de)
WO (1)	WO1998025920A1 (de)

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US20010031771A1 (en)	1999-05-24	2001-10-18	Gary Maurice Dull	Pharmaceutical compositions and methods for use
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US6818787B2 (en)	2001-06-11	2004-11-16	Xenoport, Inc.	Prodrugs of GABA analogs, compositions and uses thereof
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US7186855B2 (en)	2001-06-11	2007-03-06	Xenoport, Inc.	Prodrugs of GABA analogs, compositions and uses thereof
EP1511479A1 (de) *	2002-05-15	2005-03-09	Abbott Laboratories	Behandlung neuropathischer schmerzen
EP1741709A1 (de)	2005-06-28	2007-01-10	Sanofi-Aventis Deutschland GmbH	Heteroaryl substituierte Amide mit gesättigtem Linker, und deren Verwendung als Pharmaka
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DE102007058504A1 (de)	2007-12-05	2009-07-09	Acino Ag	Transdermales therapeutisches System mit einem Gehalt an einem Modulator für nikotinische Acetylcholinrezeptoren (nAChR)
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AR075988A1 (es) *	2009-04-09	2011-05-11	Lilly Co Eli	Compuesto de piridiloxi - pirrolidina inhibidor de recaptacion de serotonina y norepinefrina, composicion farmaceutica que lo comprende y su uso para la manufactura de un medicamento util para el tratamiento de dolor cronico
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CN103619354A (zh)	2011-06-30	2014-03-05	东丽株式会社	止痒剂
WO2014160783A1 (en)	2013-03-27	2014-10-02	Georgetown University	2-halo-5-alkynyl-pyridyl nicotinic ligands
JP7414529B2 (ja)	2017-06-07	2024-01-16	シファメド・ホールディングス・エルエルシー	血管内流体移動デバイス、システム、および使用方法
CN111556763B (zh)	2017-11-13	2023-09-01	施菲姆德控股有限责任公司	血管内流体运动装置、系统
EP3746149B1 (de)	2018-02-01	2025-08-06	Shifamed Holdings, LLC	Intravaskuläre blutpumpen
WO2020028537A1 (en)	2018-07-31	2020-02-06	Shifamed Holdings, Llc	Intravascaular blood pumps and methods of use
WO2020073047A1 (en)	2018-10-05	2020-04-09	Shifamed Holdings, Llc	Intravascular blood pumps and methods of use
WO2021011473A1 (en)	2019-07-12	2021-01-21	Shifamed Holdings, Llc	Intravascular blood pumps and methods of manufacture and use
WO2021016372A1 (en)	2019-07-22	2021-01-28	Shifamed Holdings, Llc	Intravascular blood pumps with struts and methods of use and manufacture
US12465748B2 (en)	2019-08-07	2025-11-11	Supira Medical, Inc.	Catheter blood pumps and collapsible pump housings
US12121713B2 (en)	2019-09-25	2024-10-22	Shifamed Holdings, Llc	Catheter blood pumps and collapsible blood conduits
WO2021062265A1 (en)	2019-09-25	2021-04-01	Shifamed Holdings, Llc	Intravascular blood pump systems and methods of use and control thereof
EP4501393A3 (de)	2019-09-25	2025-04-09	Shifamed Holdings, LLC	Katheterblutpumpen und zusammenklappbare pumpengehäuse
EP4072650A4 (de)	2019-12-11	2024-01-10	Shifamed Holdings, LLC	Absteigende aorten- und hohlvenenblutpumpen

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1997
- 1997-12-10 DE DE69717148T patent/DE69717148T2/de not_active Expired - Lifetime
- 1997-12-10 WO PCT/US1997/022811 patent/WO1998025920A1/en not_active Ceased
- 1997-12-10 JP JP52698398A patent/JP4272261B2/ja not_active Expired - Fee Related
- 1997-12-10 EP EP97952392A patent/EP0950057B1/de not_active Expired - Lifetime
- 1997-12-10 ES ES97952392T patent/ES2189003T3/es not_active Expired - Lifetime
- 1997-12-10 BR BR9714677-3A patent/BR9714677A/pt not_active IP Right Cessation
- 1997-12-10 CN CN97181628A patent/CN1125064C/zh not_active Expired - Fee Related
- 1997-12-10 HU HU0001110A patent/HUP0001110A3/hu unknown
- 1997-12-10 AT AT97952392T patent/ATE227717T1/de active
- 1997-12-10 CA CA2698384A patent/CA2698384C/en not_active Expired - Fee Related
- 1997-12-10 IL IL13008397A patent/IL130083A0/xx unknown
- 1997-12-10 SK SK759-99A patent/SK75999A3/sk unknown
- 1997-12-10 PL PL97333920A patent/PL333920A1/xx unknown
- 1997-12-10 CA CA2273917A patent/CA2273917C/en not_active Expired - Fee Related
- 1997-12-10 KR KR10-2003-7008788A patent/KR100472154B1/ko not_active Expired - Fee Related
- 1997-12-10 AU AU56010/98A patent/AU733881B2/en not_active Ceased
- 1997-12-10 PT PT97952392T patent/PT950057E/pt unknown
- 1997-12-10 KR KR10-1999-7005151A patent/KR100422995B1/ko not_active Expired - Fee Related
- 1997-12-10 TR TR1999/01904T patent/TR199901904T2/xx unknown
- 1997-12-10 NZ NZ335810A patent/NZ335810A/en unknown
- 1997-12-10 DK DK97952392T patent/DK0950057T3/da active
1999
- 1999-06-03 NO NO992705A patent/NO992705L/no not_active Application Discontinuation
- 1999-07-06 BG BG103556A patent/BG64196B1/bg unknown
2008
- 2008-12-24 JP JP2008327771A patent/JP5364872B2/ja not_active Expired - Fee Related

Also Published As

Publication number	Publication date
TR199901904T2 (xx)	1999-10-21
KR20040004476A (ko)	2004-01-13
CA2273917A1 (en)	1998-06-18
PT950057E (pt)	2003-04-30
DK0950057T3 (da)	2003-03-10
JP2001504857A (ja)	2001-04-10
CA2698384C (en)	2012-05-01
CN1245496A (zh)	2000-02-23
HUP0001110A2 (hu)	2001-04-28
SK75999A3 (en)	2000-05-16
KR20000069399A (ko)	2000-11-25
DE69717148T2 (de)	2003-10-02
HUP0001110A3 (en)	2002-04-29
BG103556A (en)	2000-06-30
AU5601098A (en)	1998-07-03
PL333920A1 (en)	2000-01-31
CN1125064C (zh)	2003-10-22
NZ335810A (en)	2001-03-30
ATE227717T1 (de)	2002-11-15
CA2698384A1 (en)	1998-06-18
BR9714677A (pt)	2000-10-03
AU733881B2 (en)	2001-05-31
KR100422995B1 (ko)	2004-03-12
ES2189003T3 (es)	2003-07-01
EP0950057B1 (de)	2002-11-13
IL130083A0 (en)	2000-02-29
JP5364872B2 (ja)	2013-12-11
NO992705L (no)	1999-08-03
JP4272261B2 (ja)	2009-06-03
DE69717148D1 (de)	2002-12-19
WO1998025920A1 (en)	1998-06-18
CA2273917C (en)	2010-05-25
KR100472154B1 (ko)	2005-02-21
JP2009143924A (ja)	2009-07-02
NO992705D0 (no)	1999-06-03
EP0950057A1 (de)	1999-10-20

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