NZ501571A - Novel n-substituted urea inhibitors of farnesyl-protein transferase - Google Patents
Novel n-substituted urea inhibitors of farnesyl-protein transferaseInfo
- Publication number
- NZ501571A NZ501571A NZ501571A NZ50157198A NZ501571A NZ 501571 A NZ501571 A NZ 501571A NZ 501571 A NZ501571 A NZ 501571A NZ 50157198 A NZ50157198 A NZ 50157198A NZ 501571 A NZ501571 A NZ 501571A
- Authority
- NZ
- New Zealand
- Prior art keywords
- hydrogen
- compound
- alkyl
- cells
- mixture
- Prior art date
Links
- 102000004357 Transferases Human genes 0.000 title claims description 17
- 108090000992 Transferases Proteins 0.000 title claims description 17
- 239000003112 inhibitor Substances 0.000 title description 6
- 239000004202 carbamide Substances 0.000 title 1
- 150000003672 ureas Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 229
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 44
- 125000003118 aryl group Chemical group 0.000 claims abstract description 42
- 239000001257 hydrogen Substances 0.000 claims abstract description 42
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 42
- 239000007787 solid Substances 0.000 claims abstract description 31
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 15
- 230000010261 cell growth Effects 0.000 claims abstract description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
- 230000002159 abnormal effect Effects 0.000 claims abstract description 14
- 125000001246 bromo group Chemical group Br* 0.000 claims abstract description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 11
- 150000001721 carbon Chemical group 0.000 claims abstract description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 7
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 6
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 3
- 239000012453 solvate Substances 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical class 0.000 claims abstract 11
- 239000000203 mixture Substances 0.000 claims description 79
- 238000000034 method Methods 0.000 claims description 70
- 235000011468 Albizia julibrissin Nutrition 0.000 claims description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
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- 238000002360 preparation method Methods 0.000 claims description 12
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
- -1 N-SUBSTITUTED UREA Chemical class 0.000 description 47
- 241001070944 Mimosa Species 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 239000000047 product Substances 0.000 description 37
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 35
- 239000000284 extract Substances 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
- 239000012141 concentrate Substances 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
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- 238000003756 stirring Methods 0.000 description 27
- 239000002253 acid Substances 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- 239000002585 base Substances 0.000 description 20
- 239000000010 aprotic solvent Substances 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 125000004104 aryloxy group Chemical group 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- 125000005843 halogen group Chemical group 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 12
- 235000011114 ammonium hydroxide Nutrition 0.000 description 12
- 125000004093 cyano group Chemical group *C#N 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 11
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- 239000003795 chemical substances by application Substances 0.000 description 11
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 11
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
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Classifications
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D401/14—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 three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87704997A | 1997-06-17 | 1997-06-17 | |
| PCT/US1998/011507 WO1998057948A1 (en) | 1997-06-17 | 1998-06-15 | Novel n-substituted urea inhibitors of farnesyl-protein transferase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ501571A true NZ501571A (en) | 2002-02-01 |
Family
ID=25369144
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ501571A NZ501571A (en) | 1997-06-17 | 1998-06-15 | Novel n-substituted urea inhibitors of farnesyl-protein transferase |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0989979A1 (https=) |
| JP (1) | JP2002506444A (https=) |
| KR (1) | KR20010013881A (https=) |
| CN (1) | CN1267291A (https=) |
| AR (1) | AR013094A1 (https=) |
| AU (1) | AU8253598A (https=) |
| CA (1) | CA2293706C (https=) |
| CO (1) | CO4940458A1 (https=) |
| HU (1) | HUP0002954A3 (https=) |
| IL (1) | IL133389A0 (https=) |
| NZ (1) | NZ501571A (https=) |
| PE (1) | PE82799A1 (https=) |
| WO (1) | WO1998057948A1 (https=) |
| ZA (1) | ZA985205B (https=) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7342016B2 (en) | 2000-08-30 | 2008-03-11 | Schering Corporation | Farnesyl protein transferase inhibitors as antitumor agents |
| EP1322334A2 (en) * | 2000-10-05 | 2003-07-02 | George Q. Daley | Methods of inducing cancer cell death and tumor regression |
| US20020077301A1 (en) * | 2000-10-05 | 2002-06-20 | Whitehead Institute For Biomedical Research | Effects of combined administration of farnesyl transferase inhibitors and signal transduction inhibitors |
| EP1695961A4 (en) * | 2003-12-17 | 2007-10-24 | Takeda Pharmaceutical | UREA DERIVATIVE, METHOD FOR THE PRODUCTION AND THEIR USE |
| CA2904393A1 (en) * | 2013-03-15 | 2014-09-25 | Araxes Pharma Llc | Covalent inhibitors of kras g12c |
| US9227978B2 (en) | 2013-03-15 | 2016-01-05 | Araxes Pharma Llc | Covalent inhibitors of Kras G12C |
| US9745319B2 (en) | 2013-03-15 | 2017-08-29 | Araxes Pharma Llc | Irreversible covalent inhibitors of the GTPase K-Ras G12C |
| JO3805B1 (ar) | 2013-10-10 | 2021-01-31 | Araxes Pharma Llc | مثبطات كراس جي12سي |
| JO3556B1 (ar) | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
| JP2017528498A (ja) | 2014-09-25 | 2017-09-28 | アラクセス ファーマ エルエルシー | Ｋｒａｓ ｇ１２ｃ変異体タンパク質のインヒビター |
| WO2016049568A1 (en) | 2014-09-25 | 2016-03-31 | Araxes Pharma Llc | Methods and compositions for inhibition of ras |
| ES2898765T3 (es) | 2015-04-10 | 2022-03-08 | Araxes Pharma Llc | Compuestos de quinazolina sustituidos y métodos de uso de los mismos |
| US10428064B2 (en) | 2015-04-15 | 2019-10-01 | Araxes Pharma Llc | Fused-tricyclic inhibitors of KRAS and methods of use thereof |
| US10144724B2 (en) | 2015-07-22 | 2018-12-04 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use thereof |
| EP3356349A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| EP3356351A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| WO2017058728A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| WO2017058805A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| WO2017058902A1 (en) | 2015-09-28 | 2017-04-06 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| EP3356359B1 (en) | 2015-09-28 | 2021-10-20 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| EP3356347A1 (en) | 2015-09-28 | 2018-08-08 | Araxes Pharma LLC | Inhibitors of kras g12c mutant proteins |
| WO2017070256A2 (en) | 2015-10-19 | 2017-04-27 | Araxes Pharma Llc | Method for screening inhibitors of ras |
| KR20180081596A (ko) | 2015-11-16 | 2018-07-16 | 아락세스 파마 엘엘씨 | 치환된 헤테로사이클릭 그룹을 포함하는 2-치환된 퀴나졸린 화합물 및 이의 사용 방법 |
| US9988357B2 (en) | 2015-12-09 | 2018-06-05 | Araxes Pharma Llc | Methods for preparation of quinazoline derivatives |
| WO2017172979A1 (en) | 2016-03-30 | 2017-10-05 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use |
| US10646488B2 (en) | 2016-07-13 | 2020-05-12 | Araxes Pharma Llc | Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof |
| WO2018064510A1 (en) | 2016-09-29 | 2018-04-05 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| EP3523289A1 (en) | 2016-10-07 | 2019-08-14 | Araxes Pharma LLC | Heterocyclic compounds as inhibitors of ras and methods of use thereof |
| WO2018140513A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and similar compounds as kras g12c modulators for treating cancer |
| JP7327802B2 (ja) | 2017-01-26 | 2023-08-16 | アラクセス ファーマ エルエルシー | 縮合ヘテロ－ヘテロ二環式化合物およびその使用方法 |
| US11136308B2 (en) | 2017-01-26 | 2021-10-05 | Araxes Pharma Llc | Substituted quinazoline and quinazolinone compounds and methods of use thereof |
| WO2018140599A1 (en) | 2017-01-26 | 2018-08-02 | Araxes Pharma Llc | Benzothiophene and benzothiazole compounds and methods of use thereof |
| EP3573954A1 (en) | 2017-01-26 | 2019-12-04 | Araxes Pharma LLC | Fused bicyclic benzoheteroaromatic compounds and methods of use thereof |
| CN110869357A (zh) | 2017-05-25 | 2020-03-06 | 亚瑞克西斯制药公司 | 化合物及其用于治疗癌症的使用方法 |
| WO2018218069A1 (en) | 2017-05-25 | 2018-11-29 | Araxes Pharma Llc | Quinazoline derivatives as modulators of mutant kras, hras or nras |
| US10745385B2 (en) | 2017-05-25 | 2020-08-18 | Araxes Pharma Llc | Covalent inhibitors of KRAS |
| MX2021000887A (es) | 2018-08-01 | 2021-03-31 | Araxes Pharma Llc | Compuestos espiroheterociclicos y metodos de uso de los mismos para el tratamiento de cancer. |
| CN111960990A (zh) * | 2020-07-23 | 2020-11-20 | 宿迁联盛科技股份有限公司 | 一种助剂及其制备方法 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL111235A (en) * | 1993-10-15 | 2001-03-19 | Schering Plough Corp | Medicinal preparations for inhibiting protein G activity and for the treatment of malignant diseases, containing tricyclic compounds, some such new compounds and a process for the preparation of some of them |
| US5719148A (en) * | 1993-10-15 | 1998-02-17 | Schering Corporation | Tricyclic amide and urea compounds useful for inhibition of g-protein function and for treatment of proliferative diseases |
| IL117798A (en) * | 1995-04-07 | 2001-11-25 | Schering Plough Corp | Tricyclic compounds useful for inhibiting the function of protein - G and for the treatment of malignant diseases, and pharmaceutical preparations containing them |
| IL125062A (en) * | 1995-12-22 | 2003-11-23 | Schering Corp | Tricyclic amides and pharmaceutical compositions containing them for inhibition of g-protein function and for treatment of proliferative diseases |
| JP2001500508A (ja) * | 1996-09-13 | 2001-01-16 | シェーリング コーポレイション | ファルネシルタンパク質トランスフェラーゼの阻害に有用な置換ベンゾシクロヘプタピリジン誘導体 |
| ES2234036T3 (es) * | 1996-09-13 | 2005-06-16 | Schering Corporation | Compuestos utiles para inhibir la farnesil-protein-transferasa. |
-
1998
- 1998-06-15 ZA ZA985205A patent/ZA985205B/xx unknown
- 1998-06-15 CA CA002293706A patent/CA2293706C/en not_active Expired - Fee Related
- 1998-06-15 JP JP50450299A patent/JP2002506444A/ja not_active Ceased
- 1998-06-15 AU AU82535/98A patent/AU8253598A/en not_active Abandoned
- 1998-06-15 IL IL13338998A patent/IL133389A0/xx unknown
- 1998-06-15 NZ NZ501571A patent/NZ501571A/en unknown
- 1998-06-15 WO PCT/US1998/011507 patent/WO1998057948A1/en not_active Ceased
- 1998-06-15 PE PE1998000506A patent/PE82799A1/es not_active Application Discontinuation
- 1998-06-15 CN CN98808189A patent/CN1267291A/zh active Pending
- 1998-06-15 EP EP98932717A patent/EP0989979A1/en not_active Withdrawn
- 1998-06-15 KR KR1019997011903A patent/KR20010013881A/ko not_active Withdrawn
- 1998-06-15 HU HU0002954A patent/HUP0002954A3/hu unknown
- 1998-06-16 AR ARP980102858A patent/AR013094A1/es unknown
- 1998-06-16 CO CO98034144A patent/CO4940458A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0002954A3 (en) | 2002-11-28 |
| AU8253598A (en) | 1999-01-04 |
| JP2002506444A (ja) | 2002-02-26 |
| PE82799A1 (es) | 1999-08-26 |
| KR20010013881A (ko) | 2001-02-26 |
| HUP0002954A2 (hu) | 2001-06-28 |
| ZA985205B (en) | 1998-12-15 |
| IL133389A0 (en) | 2001-04-30 |
| EP0989979A1 (en) | 2000-04-05 |
| CO4940458A1 (es) | 2000-07-24 |
| CN1267291A (zh) | 2000-09-20 |
| WO1998057948A1 (en) | 1998-12-23 |
| CA2293706C (en) | 2008-11-18 |
| CA2293706A1 (en) | 1998-12-23 |
| AR013094A1 (es) | 2000-12-13 |
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| Date | Code | Title | Description |
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| PSEA | Patent sealed |