ZA200309371B - Novel compounds and compositions as cathepsin inhibitors. - Google Patents
Novel compounds and compositions as cathepsin inhibitors. Download PDFInfo
- Publication number
- ZA200309371B ZA200309371B ZA200309371A ZA200309371A ZA200309371B ZA 200309371 B ZA200309371 B ZA 200309371B ZA 200309371 A ZA200309371 A ZA 200309371A ZA 200309371 A ZA200309371 A ZA 200309371A ZA 200309371 B ZA200309371 B ZA 200309371B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenylmethanesulfonylmethyl
- cyclohexylmethyl
- cyanomethyl
- alkyl
- compound
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 152
- 239000000203 mixture Substances 0.000 title claims description 42
- 102000005600 Cathepsins Human genes 0.000 title claims description 6
- 108010084457 Cathepsins Proteins 0.000 title claims description 6
- 239000003112 inhibitor Substances 0.000 title description 3
- -1 carbocyclic ketone Chemical class 0.000 claims description 315
- 125000000217 alkyl group Chemical group 0.000 claims description 90
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 31
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
- 150000001204 N-oxides Chemical class 0.000 claims description 25
- 201000010099 disease Diseases 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 239000000651 prodrug Substances 0.000 claims description 19
- 229940002612 prodrug Drugs 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 16
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 16
- 108090000613 Cathepsin S Proteins 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 11
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 11
- 230000007170 pathology Effects 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 102100035654 Cathepsin S Human genes 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical compound N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 claims description 10
- 125000002723 alicyclic group Chemical group 0.000 claims description 10
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical class SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 claims description 10
- 230000005764 inhibitory process Effects 0.000 claims description 10
- WRIRWRKPLXCTFD-UHFFFAOYSA-N malonamide Chemical compound NC(=O)CC(N)=O WRIRWRKPLXCTFD-UHFFFAOYSA-N 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000001931 aliphatic group Chemical group 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 125000006588 heterocycloalkylene group Chemical group 0.000 claims description 8
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 125000001118 alkylidene group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- NATUWXBMYLZRFL-UHFFFAOYSA-N n-(cyanomethyl)-n'-cyclohexyl-2-(cyclohexylmethyl)propanediamide Chemical compound C1CCCCC1NC(=O)C(C(NCC#N)=O)CC1CCCCC1 NATUWXBMYLZRFL-UHFFFAOYSA-N 0.000 claims description 6
- KKNSRBAPVIHTQK-UHFFFAOYSA-N n-benzyl-n'-(cyanomethyl)-2-(cyclohexylmethyl)propanediamide Chemical compound C=1C=CC=CC=1CNC(=O)C(C(NCC#N)=O)CC1CCCCC1 KKNSRBAPVIHTQK-UHFFFAOYSA-N 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 4
- LJQHKVXBNRSBLK-UHFFFAOYSA-N n'-(cyanomethyl)-2-(cyclohexylmethyl)-n-phenylpropanediamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(NCC#N)=O)CC1CCCCC1 LJQHKVXBNRSBLK-UHFFFAOYSA-N 0.000 claims description 4
- NITXSRBGONWVSO-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)ethyl]-n-benzyl-n'-(cyanomethyl)propanediamide Chemical compound C=1C=CC=CC=1CNC(=O)C(C(NCC#N)=O)CCS(=O)(=O)C1=CC=CC=C1 NITXSRBGONWVSO-UHFFFAOYSA-N 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 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 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
- CNSBAPWLYAFMGQ-UHFFFAOYSA-N n-(cyanomethyl)-2-(cyclohexylmethyl)-n'-(pyridin-4-ylmethyl)propanediamide Chemical compound C=1C=NC=CC=1CNC(=O)C(C(NCC#N)=O)CC1CCCCC1 CNSBAPWLYAFMGQ-UHFFFAOYSA-N 0.000 claims description 3
- ZCTSLQZUVSVXEH-UHFFFAOYSA-N n-(cyanomethyl)-2-(cyclohexylmethyl)-n'-[(4-nitrophenyl)methyl]propanediamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1CNC(=O)C(C(=O)NCC#N)CC1CCCCC1 ZCTSLQZUVSVXEH-UHFFFAOYSA-N 0.000 claims description 3
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- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 3
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- ULPMNILFDQBFDH-UHFFFAOYSA-N n-(cyanomethyl)-2-(cyclohexylmethyl)-n'-(3-phenoxyphenyl)propanediamide Chemical compound C=1C=CC(OC=2C=CC=CC=2)=CC=1NC(=O)C(C(NCC#N)=O)CC1CCCCC1 ULPMNILFDQBFDH-UHFFFAOYSA-N 0.000 claims description 2
- ZLQCGQRXILBDSY-UHFFFAOYSA-N n-(cyanomethyl)-2-(cyclohexylmethyl)-n'-(3-phenylpropyl)propanediamide Chemical compound C1CCCCC1CC(C(=O)NCC#N)C(=O)NCCCC1=CC=CC=C1 ZLQCGQRXILBDSY-UHFFFAOYSA-N 0.000 claims description 2
- CJGXYYFKCJYCCP-UHFFFAOYSA-N n-(cyanomethyl)-2-(cyclohexylmethyl)-n'-(4-phenoxyphenyl)propanediamide Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1NC(=O)C(C(NCC#N)=O)CC1CCCCC1 CJGXYYFKCJYCCP-UHFFFAOYSA-N 0.000 claims description 2
- UGTHOVYFRUNGHC-UHFFFAOYSA-N n-(cyanomethyl)-2-(cyclohexylmethyl)-n'-(6-methoxypyridin-3-yl)propanediamide Chemical compound C1=NC(OC)=CC=C1NC(=O)C(C(=O)NCC#N)CC1CCCCC1 UGTHOVYFRUNGHC-UHFFFAOYSA-N 0.000 claims description 2
- ROEYDSBTJWWOBZ-UHFFFAOYSA-N n-(cyanomethyl)-2-(cyclohexylmethyl)-n'-[(3-nitrophenyl)methyl]propanediamide Chemical compound [O-][N+](=O)C1=CC=CC(CNC(=O)C(CC2CCCCC2)C(=O)NCC#N)=C1 ROEYDSBTJWWOBZ-UHFFFAOYSA-N 0.000 claims description 2
- DLGZSPZFWDAMGP-UHFFFAOYSA-N n-[1-(1,3-benzoxazol-2-yl)-1-oxo-4-phenylbutan-2-yl]-n'-benzyl-2-(cyclohexylmethyl)propanediamide Chemical compound C1CCCCC1CC(C(=O)NC(CCC=1C=CC=CC=1)C(=O)C=1OC2=CC=CC=C2N=1)C(=O)NCC1=CC=CC=C1 DLGZSPZFWDAMGP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003431 oxalo group Chemical group 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
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- 108091008646 testicular receptors Proteins 0.000 claims 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
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- C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
- C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
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- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen 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
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen 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 with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- 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
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Applications Claiming Priority (1)
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US29574401P | 2001-06-04 | 2001-06-04 |
Publications (1)
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ZA200309371B true ZA200309371B (en) | 2005-05-27 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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ZA200309371A ZA200309371B (en) | 2001-06-04 | 2003-12-02 | Novel compounds and compositions as cathepsin inhibitors. |
Country Status (18)
Country | Link |
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EP (1) | EP1399146A4 (fr) |
JP (1) | JP2005500275A (fr) |
KR (1) | KR20040028769A (fr) |
CN (1) | CN1512880A (fr) |
BR (1) | BR0210172A (fr) |
CA (1) | CA2449021A1 (fr) |
CO (1) | CO5540292A2 (fr) |
EA (1) | EA007334B1 (fr) |
HR (1) | HRP20031092A2 (fr) |
IL (1) | IL159135A0 (fr) |
MX (1) | MXPA03011207A (fr) |
NO (1) | NO20035365L (fr) |
NZ (1) | NZ529903A (fr) |
PL (1) | PL368825A1 (fr) |
RS (1) | RS96203A (fr) |
SG (1) | SG143979A1 (fr) |
WO (1) | WO2002098406A1 (fr) |
ZA (1) | ZA200309371B (fr) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2848232B2 (ja) * | 1993-02-19 | 1999-01-20 | 武田薬品工業株式会社 | アルデヒド誘導体 |
EP1021424B1 (fr) * | 1996-06-21 | 2003-02-26 | PHARMACIA & UPJOHN COMPANY | Inhibiteurs thiadiazole amide de la metalloprotease |
WO2001019808A1 (fr) * | 1999-09-16 | 2001-03-22 | Axys Pharmaceuticals, Inc. | Composes et compositions chimiques et leur utilisation en tant qu'inhibiteurs de la cathepsine s |
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2002
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- 2002-06-04 BR BR0210172-6A patent/BR0210172A/pt not_active IP Right Cessation
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- 2002-06-04 IL IL15913502A patent/IL159135A0/xx unknown
- 2002-06-04 NZ NZ529903A patent/NZ529903A/en unknown
- 2002-06-04 CA CA002449021A patent/CA2449021A1/fr not_active Abandoned
- 2002-06-04 EA EA200301315A patent/EA007334B1/ru not_active IP Right Cessation
- 2002-06-04 JP JP2003501445A patent/JP2005500275A/ja active Pending
- 2002-06-04 CN CNA02811289XA patent/CN1512880A/zh active Pending
- 2002-06-04 RS YU96203A patent/RS96203A/sr unknown
- 2002-06-04 MX MXPA03011207A patent/MXPA03011207A/es not_active Application Discontinuation
- 2002-06-04 KR KR10-2003-7015837A patent/KR20040028769A/ko not_active Application Discontinuation
- 2002-06-04 EP EP02739721A patent/EP1399146A4/fr not_active Withdrawn
- 2002-06-04 SG SG200600505-2A patent/SG143979A1/en unknown
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2003
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- 2003-12-02 ZA ZA200309371A patent/ZA200309371B/en unknown
- 2003-12-29 HR HR20031092A patent/HRP20031092A2/xx not_active Application Discontinuation
- 2003-12-30 CO CO03113269A patent/CO5540292A2/es not_active Application Discontinuation
Also Published As
Publication number | Publication date |
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EP1399146A4 (fr) | 2006-01-18 |
SG143979A1 (en) | 2008-07-29 |
CN1512880A (zh) | 2004-07-14 |
NZ529903A (en) | 2005-09-30 |
CA2449021A1 (fr) | 2002-12-12 |
CO5540292A2 (es) | 2005-07-29 |
MXPA03011207A (es) | 2004-02-26 |
NO20035365D0 (no) | 2003-12-02 |
JP2005500275A (ja) | 2005-01-06 |
HRP20031092A2 (en) | 2004-04-30 |
EA007334B1 (ru) | 2006-08-25 |
BR0210172A (pt) | 2004-06-22 |
EP1399146A1 (fr) | 2004-03-24 |
RS96203A (en) | 2006-12-15 |
KR20040028769A (ko) | 2004-04-03 |
NO20035365L (no) | 2004-02-20 |
WO2002098406A1 (fr) | 2002-12-12 |
EA200301315A1 (ru) | 2004-06-24 |
IL159135A0 (en) | 2004-05-12 |
PL368825A1 (en) | 2005-04-04 |
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