JP2003528085A - 緑内障治療のための６−ヒドロキシ・インダゾール誘導体 - Google Patents
緑内障治療のための６−ヒドロキシ・インダゾール誘導体Info
- Publication number
- JP2003528085A JP2003528085A JP2001568912A JP2001568912A JP2003528085A JP 2003528085 A JP2003528085 A JP 2003528085A JP 2001568912 A JP2001568912 A JP 2001568912A JP 2001568912 A JP2001568912 A JP 2001568912A JP 2003528085 A JP2003528085 A JP 2003528085A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- hydrogen
- independently selected
- halogen
- substituted
- Prior art date
- 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.)
- Withdrawn
Links
- 208000010412 Glaucoma Diseases 0.000 title claims abstract description 19
- NUYZVDBIVNOTSC-UHFFFAOYSA-N 1H-indazol-6-ol Chemical class OC1=CC=C2C=NNC2=C1 NUYZVDBIVNOTSC-UHFFFAOYSA-N 0.000 title description 3
- 239000001257 hydrogen Substances 0.000 claims description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims description 74
- 150000001875 compounds Chemical class 0.000 claims description 56
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 150000002431 hydrogen Chemical group 0.000 claims description 34
- 150000002367 halogens Chemical class 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- -1 C1 to 6Alkyl Chemical group 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000004962 sulfoxyl group Chemical group 0.000 claims description 6
- 230000000699 topical effect Effects 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- IUIAMNBONBRMDM-WLHGVMLRSA-N 1-(2-aminopropyl)-3-methylindazol-6-ol (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.c1cc(O)cc2c1c(C)nn2CC(N)C IUIAMNBONBRMDM-WLHGVMLRSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 3
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000000556 agonist Substances 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000004410 intraocular pressure Effects 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000004406 elevated intraocular pressure Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229940054534 ophthalmic solution Drugs 0.000 description 4
- 150000003906 phosphoinositides Chemical class 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000000862 serotonergic effect Effects 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 206010030043 Ocular hypertension Diseases 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 150000002473 indoazoles Chemical class 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000002997 ophthalmic solution Substances 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000004382 visual function Effects 0.000 description 3
- FGQUUCRNAOILHX-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-(6-methoxy-3-methylindazol-1-yl)propan-2-amine Chemical compound OC(=O)\C=C\C(O)=O.COC1=CC=C2C(C)=NN(CC(C)N)C2=C1 FGQUUCRNAOILHX-WLHGVMLRSA-N 0.000 description 2
- WSEWULCWBQDNEH-UHFFFAOYSA-N 1-(6-methoxyindazol-1-yl)propan-2-amine Chemical compound COC1=CC=C2C=NN(CC(C)N)C2=C1 WSEWULCWBQDNEH-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- RLJFTICUTYVZDG-UHFFFAOYSA-N Methiothepine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2CC1N1CCN(C)CC1 RLJFTICUTYVZDG-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- INAPMGSXUVUWAF-GCVPSNMTSA-N [(2r,3s,5r,6r)-2,3,4,5,6-pentahydroxycyclohexyl] dihydrogen phosphate Chemical compound OC1[C@H](O)[C@@H](O)C(OP(O)(O)=O)[C@H](O)[C@@H]1O INAPMGSXUVUWAF-GCVPSNMTSA-N 0.000 description 2
- OMEBHZQIIMCJGK-WLHGVMLRSA-N [1-(2-aminopropyl)indazol-6-yl] 2,2-dimethylpropanoate;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=C(OC(=O)C(C)(C)C)C=C2N(CC(N)C)N=CC2=C1 OMEBHZQIIMCJGK-WLHGVMLRSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001270 agonistic effect Effects 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
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- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 238000002825 functional assay Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 229960000367 inositol Drugs 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
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- LIHGLLXHHBMMCF-UHFFFAOYSA-N n-ethylindazol-1-amine Chemical compound C1=CC=C2N(NCC)N=CC2=C1 LIHGLLXHHBMMCF-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| US19038000P | 2000-03-17 | 2000-03-17 | |
| US60/190,380 | 2000-03-17 | ||
| PCT/US2000/031247 WO2001070702A1 (en) | 2000-03-17 | 2000-11-14 | 6-hydroxy-indazole derivatives for treating glaucoma |
Publications (2)
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| JP2003528085A true JP2003528085A (ja) | 2003-09-24 |
| JP2003528085A5 JP2003528085A5 (https=) | 2005-12-22 |
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| JP (1) | JP2003528085A (https=) |
| KR (1) | KR20030065304A (https=) |
| CN (1) | CN1450994A (https=) |
| AR (1) | AR032138A1 (https=) |
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| CA (1) | CA2402403A1 (https=) |
| GC (1) | GC0000155A (https=) |
| MX (1) | MXPA02008547A (https=) |
| PL (1) | PL358481A1 (https=) |
| TW (1) | TWI221839B (https=) |
| WO (1) | WO2001070702A1 (https=) |
| ZA (1) | ZA200206851B (https=) |
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| US6960579B1 (en) | 1998-05-19 | 2005-11-01 | Alcon Manufacturing, Ltd. | Serotonergic 5HT7 receptor compounds for treating ocular and CNS disorders |
| TW593302B (en) | 2001-12-20 | 2004-06-21 | Alcon Inc | Novel benzodifuranimidazoline and benzofuranimidazoline derivatives and their use for the treatment of glaucoma |
| AU2002360819A1 (en) * | 2001-12-28 | 2003-07-24 | Bayer Corporation | Cyclohexano- and cycloheptapyrazole derivative compounds, for use in diseases associated with the 5-ht2c receptor |
| AU2003287481B2 (en) | 2002-11-08 | 2009-04-23 | Merck & Co., Inc. | Ophthalmic compositions for treating ocular hypertension |
| US7196082B2 (en) | 2002-11-08 | 2007-03-27 | Merck & Co. Inc. | Ophthalmic compositions for treating ocular hypertension |
| CN100384827C (zh) * | 2002-11-08 | 2008-04-30 | 默克公司 | 用于治疗高眼压症的眼用组合物 |
| US7053085B2 (en) | 2003-03-26 | 2006-05-30 | Merck & Co. Inc. | EP4 receptor agonist, compositions and methods thereof |
| BR0316775A (pt) | 2002-12-13 | 2005-11-01 | Alcon Inc | Novos análogos de benzopirano e seu uso para o tratamento de glaucoma |
| JP2004262812A (ja) * | 2003-02-28 | 2004-09-24 | Rohto Pharmaceut Co Ltd | 眼圧低下剤 |
| AU2004268012B2 (en) | 2003-09-02 | 2008-11-20 | Merck & Co., Inc. | Ophthalmic compositions for treating ocular hypertension |
| DE602004020079D1 (de) | 2003-09-04 | 2009-04-30 | Merck & Co Inc | Ophthalmische zusammensetzungen zur behandlung der okularen hypertonie |
| AU2004271978B2 (en) | 2003-09-04 | 2009-02-05 | Merck & Co., Inc. | Ophthalmic compositions for treating ocular hypertension |
| TW200520760A (en) | 2003-12-15 | 2005-07-01 | Alcon Inc | Substituted [1,4] oxazino [2,3-g] indazoles for the treatment of glaucoma |
| US7338972B1 (en) | 2003-12-15 | 2008-03-04 | Alcon, Inc. | Substituted 1-alkylamino-1H-indazoles for the treatment of glaucoma |
| US7129257B1 (en) | 2003-12-15 | 2006-10-31 | Alcon, Inc. | Pyrazolo[3,4- e]benzoxazoles for the treatment of glaucoma |
| CN1988903A (zh) | 2004-07-20 | 2007-06-27 | 默克公司 | 用于治疗高眼压症的眼用组合物 |
| ATE460415T1 (de) | 2004-11-29 | 2010-03-15 | Warner Lambert Co | Therapeutische pyrazoloä3,4-büpyridine und - indazole |
| US7425572B2 (en) | 2004-12-08 | 2008-09-16 | Alcon, Inc. | Use of dioxindoindazoles and dioxoloindazoles for treating glaucoma |
| CN101704785B (zh) * | 2009-11-16 | 2012-02-29 | 东南大学 | 有机二羧酸和其盐及其制备方法 |
| CN105884687B (zh) * | 2016-04-14 | 2018-06-22 | 梯尔希（南京）药物研发有限公司 | 一种5-苄基苄达明的制备方法 |
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| CN1301161A (zh) * | 1998-05-19 | 2001-06-27 | 艾尔科实验室公司 | 用于治疗眼睛和中枢神经系统障碍的血清素激活的5ht7受体化合物 |
| ATE247963T1 (de) * | 1998-05-26 | 2003-09-15 | Pfizer Prod Inc | Medikament zur behandlung von glaukoma und ischämischer retinopathie |
| GB9819032D0 (en) * | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds IV |
| CN1269484C (zh) * | 1998-09-18 | 2006-08-16 | 艾尔科实验室公司 | 用于治疗青光眼的5－羟色胺激活性激动剂 |
| GB9820767D0 (en) * | 1998-09-23 | 1998-11-18 | Cerebrus Ltd | Chemical compounds VIII |
-
2000
- 2000-11-14 BR BR0017157-3A patent/BR0017157A/pt not_active IP Right Cessation
- 2000-11-14 WO PCT/US2000/031247 patent/WO2001070702A1/en not_active Ceased
- 2000-11-14 KR KR1020027011867A patent/KR20030065304A/ko not_active Ceased
- 2000-11-14 PL PL00358481A patent/PL358481A1/xx not_active Application Discontinuation
- 2000-11-14 MX MXPA02008547A patent/MXPA02008547A/es unknown
- 2000-11-14 AU AU2001216072A patent/AU2001216072A1/en not_active Abandoned
- 2000-11-14 EP EP00978628A patent/EP1268438A1/en not_active Withdrawn
- 2000-11-14 JP JP2001568912A patent/JP2003528085A/ja not_active Withdrawn
- 2000-11-14 CA CA002402403A patent/CA2402403A1/en not_active Abandoned
- 2000-11-14 CN CN00819346A patent/CN1450994A/zh active Pending
- 2000-11-27 TW TW089125127A patent/TWI221839B/zh not_active IP Right Cessation
- 2000-12-01 AR ARP000106394A patent/AR032138A1/es not_active Application Discontinuation
- 2000-12-03 GC GCP20001082 patent/GC0000155A/xx active
-
2002
- 2002-08-27 ZA ZA200206851A patent/ZA200206851B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2402403A1 (en) | 2001-09-27 |
| AR032138A1 (es) | 2003-10-29 |
| PL358481A1 (en) | 2004-08-09 |
| ZA200206851B (en) | 2003-10-21 |
| WO2001070702A1 (en) | 2001-09-27 |
| TWI221839B (en) | 2004-10-11 |
| CN1450994A (zh) | 2003-10-22 |
| MXPA02008547A (es) | 2003-03-12 |
| AU2001216072A1 (en) | 2001-10-03 |
| BR0017157A (pt) | 2002-11-26 |
| EP1268438A1 (en) | 2003-01-02 |
| KR20030065304A (ko) | 2003-08-06 |
| GC0000155A (en) | 2005-06-29 |
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